Safety Assessment of Alkyl Taurate Amides and Taurate ... amides.pdf · Safety Assessment of Alkyl Taurate Amides and Taurate Salts as Used in Cosmetics Status: Draft Report for Panel

Safety Assessment of Alkyl Taurate Amides and Taurate Salts

as Used in Cosmetics

Status: Draft Report for Panel Review Release Date: August 28, 2015 Panel Meeting Date: September 21-22, 2015

The 2015 Cosmetic Ingredient Review Expert Panel members are: Chair, Wilma F. Bergfeld, M.D., F.A.C.P.; Donald V. Belsito, M.D.; Ronald A. Hill, Ph.D.; Curtis D. Klaassen, Ph.D.; Daniel C. Liebler, Ph.D.; James G. Marks, Jr., M.D.; Ronald C. Shank, Ph.D.; Thomas J. Slaga, Ph.D.; and Paul W. Snyder, D.V.M., Ph.D. The CIR Director is Lillian J. Gill, D.P.A. This report was prepared by Lillian C. Becker, Scientific Analyst/Writer.

© Cosmetic Ingredient Review 1620 L Street, NW, Suite 1200 Washington, DC 20036-4702 ph 202.331.0651 fax 202.331.0088 [email protected]

__________________________________________________________________________________________ 1620 L Street, NW Suite 1200, Washington, DC 20036

(Main) 202-331-0651 (Fax) 202-331-0088 (Email) [email protected] (Website) www.cir-safety.org

Commitment & Credibility since 1976

MEMORANDUM

To: CIR Expert Panel and Liaisons

From: Lillian C. Becker, M.S. Scientific Analyst and Writer

Date:

August 28, 2015

Subject: Alkyl Taurate Amides and Taurate Salts

Attached is the draft report of alkyl taurate amides and taurate salts as used in cosmetics. [taurat092015rep] The twenty ingredients in this report are structurally related by having the same taurate (2-aminoethane-1-sulfonate) core. A scientific literature review was posted on June 1, 2015 with a list of data needs.

Concentration of use data [taurat092015data1; taurat092015data2] and other unpublished data have been submitted by the Council including: ingredient specifications on sodium methyl cocoyl taurate and sodium methyl oleoyl taurate, eye and skin irritation assays on sodium methyl cocoyl taurate, and safety data on sodium methyl cocoyl taurate. [taurat092015data4-7].

If the data included in this report adequately addresses the safety of the alkyl taurate amides and taurate salts, the Panel should be prepared to formulate a tentative conclusion, provide the rationale to be described in the Discussion, and issue a Tentative Report for public comment. If the data are not sufficient for making a determination of safety, then an Insufficient Data Announcement should be issued that provides a listing of the additional data that are needed.

mailto:[email protected]

http://www.cir-safety.org/

SAFETY ASSESSMENT FLOW CHART

INGREDIENT/FAMILY _____Alkyl Taurate Amides and Taurate Salts ________________________________________

MEETING ________Sept 2015______________________________________________________________________________________

Public Comment CIR Expert Panel Report Status

Priority List INGREDIENT

PRIORITY LIST

SLR

June 18, 2015

60 day public comment period

Draft Report

Table IDA TR

IDA Notice IDA

60 day public comment period Draft TR

Table

Tentative Report

60 day Public comment period

Draft FR

Table Different Conclusion

PUBLISH Final Report

DRAFT REPORT Sept 2015

DRAFT TENTATIVE REPORT

DRAFT FINAL REPORT

Issue TR

Issue FR

Table

Table

Table

History Alkyl Taurate Amides and Taurate Salts

June, 2014 – Added to the priority list for 2015.

June, 2015 – SLR posted on-line.

September, 2015 – Panel examines draft report.

Distributed for comment only -- do not cite or quote

Alkyl Taurate Amides And Taurate Salts Data Profile for September, 2015. Writer - Lillian Becker

ADME Acute toxicity Repeated dose toxicity Irritation Sensitization

Derm

al P

enetration

Log Kow

Use

Oral

Derm

al

Inhale

Oral

Derm

al

Inhale

Ocular

Irritation

Derm

al Irr. A

nimal

Derm

al Irr H

uman

Sensitization

Anim

al

Sensitization

Hum

an

Repro/D

evel toxicity

Genotoxicity

Carcinogenicity

Phototoxicity

Potassium taurate Sodium methyltaurate X X X X X

Sodium taurate Calcium lauroyl taurate X

Magnesium methyl cocoyl taurate

X

Potassium cocoyl taurate

Potassium methyl cocoyl taurate

Sodium caproyl methyltaurate

Sodium cocoyl taurate X X

Sodium methyl cocoyl taurate X X X X X X X X X

Sodium N-isostearoyl methyltaurate

Sodium lauroyl taurate X

Sodium methyl lauroyl taurate X

Sodium methyl myristoyl taurate X X

Sodium methyl oleoyl taurate X X X X X X X

Sodium methyl palmitoyl taurate

Sodium methyl stearoyl taurate X

Sodium methyltaurate isopalmitamide

Sodium methyltaurine cocoyl methyltaurate

Sodium taurine cocoyl methyltaurate

X


Search Strategy SciFinder (CAS Nos and INCI names): 880147-28-4 – 1 hit. Not useful 266994-19-8 – 2 hits. Not useful. 266994-11-0 – 3 hits. Not useful. 186132-77-4 – 1 hit. Not useful. 185549-18-2 - 2 hits. Not useful. 170150-64-8 – 1 hit. Ordered. 155114-32-2 – 18 hits. Not useful. 138705-25-6 – 23 hits. Not useful. 130976-49-7 – 14 hits. Not useful. 115049-64-4 – 3 hits. Not useful. 88265-46-7 – 6 hits. Not useful. 87111-75-9 – 2 hits. Not useful. 70609-66-4 – 68 hits. Not useful. 61791-42-2 – 0 hits. 60840-87-1 – 21 hits. Not useful. 27236-38-0 – 13 hits. Not useful. 22890-34-2 – 79 hits. 3 ordered. 20461-70-5 – 10 hits. Not useful. 18469-44-8 – 104 hits. Not useful. 12765-39-8 – 36 hits. Not useful. 7308-16-9 – 25 hits. Not useful. 4337-75-1 – 386 hits. Culled for relevant areas of interest – 259 hits. Culled for English – 44 hits. Not useful. 4316-74-9 – 528 hits. Culled for relevant areas of interest – 301 hits. Culled for English – 62 hits. Not useful. 3737-55-1 – 102 hits. Culled for relevant areas of interest – 66 hits. Culled for English – 26 hits. Not useful. 149-39-3 – 203 hits. Culled for relevant areas of interest – 162 hits. Culled for English – 25 hits. 1 useful. 137-20-2 – 587 hits. Culled for relevant areas of interest – 209 hits. Culled for English – 93 hits.

PUBMED

“Sodium Methyl Cocoyl Taurate” OR “Calcium Lauroyl Taurate” OR “Magnesium Methyl Cocoyl Taurate” OR “Potassium Cocoyl Taurate” OR “Potassium Methyl Cocoyl Taurate” OR “Potassium Taurate” OR “Sodium Caproyl Methyltaurate” OR “Sodium Cocoyl Taurate” OR “Sodium N-Isostearoyl Methyltaurate” OR “Sodium Lauroyl Taurate” OR “Sodium Methyl Lauroyl Taurate” OR “Sodium Methyl Myristoyl Taurate” OR “Sodium Methyl Oleoyl Taurate” OR “Sodium Methyl Palmitoyl Taurate” OR “Sodium Methyl Stearoyl Taurate” OR “Sodium Methyltaurate” OR “Sodium Methyltaurate Isopalmitamide” OR “Sodium Methyltaurine Cocoyl Methyltaurate” OR “Sodium Taurate” OR “Sodium Taurine Cocoyl Methyltaurate” AND tox*

1 hit. Not useful.

AND Sens* - no hits.

AND Derm* - no hits.

Google

CAS Nos. and “properties” – found a few properties for the table.


ECHA SEARCH

Searched INCI names and CAS Nos. Info available for: sodium taurate, sodium methyl cocoyl taurate, and sodium methyl taurate.

“Taurinate” – Several chemicals that were not in this report but data on ingredients in this report were present for read across purposes.

EU CosIng CALCIUM LAUROYL TAURATE; SODIUM LAUROYL TAURATE, SODIUM METHYL COCOYL TAURATE, SODIUM METHYL MYRISTOYL TAURATE, SODIUM METHYL OLEOYL TAURATE, SODIUM METHYL LAUROYL TAURATE, SODIUM METHYLTAURATE, SODIUM METHYL STEAROYL TAURATE – No restrictions NICNAS CAS Nos. – No evaluations found. EPA HPVIS CAS Nos. – No evaluations found.


Safety Assessment of Alkyl Taurate Amides and Taurate Salts

as Used in Cosmetics

Status: Draft Report for Panel Review Release Date: August 28, 2015 Panel Meeting Date: September 21-22, 2015

The 2015 Cosmetic Ingredient Review Expert Panel members are: Chair, Wilma F. Bergfeld, M.D., F.A.C.P.; Donald V. Belsito, M.D.; Ronald A. Hill, Ph.D.; Curtis D. Klaassen, Ph.D.; Daniel C. Liebler, Ph.D.; James G. Marks, Jr., M.D.; Ronald C. Shank, Ph.D.; Thomas J. Slaga, Ph.D.; and Paul W. Snyder, D.V.M., Ph.D. The CIR Director is Lillian J. Gill, D.P.A. This report was prepared by Lillian C. Becker, Scientific Analyst/Writer.

© Cosmetic Ingredient Review 1620 L Street, NW, Suite 1200 Washington, DC 20036-4702 ph 202.331.0651 fax 202.331.0088 [email protected]


INTRODUCTION This is a review of the scientific literature and unpublished data relevant to assessing the safety of alkyl taurate

amides and taurate salts as used in cosmetics. The alkyl taurate amides and taurate salts in this report are all structurally related by having the same taurate (2-aminoethane-1-sulfonate) core. While the free acid, taurine, is a cosmetic ingredient, it is not included because it functions exclusively as a fragrance, which is within the purview of the Research Institute for Fragrance Materials (RIFM). These 20 ingredients, which mostly function in cosmetics as surfactants-cleansing agent (Table 1) are:

• potassium taurate • sodium methyltaurate • sodium taurate • calcium lauroyl taurate • magnesium methyl cocoyl taurate • potassium cocoyl taurate • potassium methyl cocoyl taurate • sodium caproyl methyltaurate • sodium cocoyl taurate • sodium methyl cocoyl taurate

• sodium n-isostearoyl methyltaurate • sodium lauroyl taurate • sodium methyl lauroyl taurate • sodium methyl myristoyl taurate • sodium methyl oleoyl taurate • sodium methyl palmitoyl taurate • sodium methyl stearoyl taurate • sodium methyltaurate isopalmitamide • sodium methyltaurine cocoyl methyltaurate • sodium taurine cocoyl methyltaurate1

The Cosmetic Ingredient Review (CIR) Expert Panel (Panel) has previously concluded that many of the individual

fatty acids that are residue components of the alkyl taurate amides are safe as used in cosmetics.2-10 The safety of these fatty acids may be relevant to the safety of the amides (e.g., as residual manufacturing impurities, metabolic products of dermal amidases, etc.). Although the individual fatty acids may be relevant to the safety of the alkyl taurate amides, the available data are well-documented in the existing CIR reports and will not be summarized here. The cocoyl moieties are derived from taurine and the fatty acid of coconut acid, which is composed of various amounts of caproic acid, caprylic acid, capric acid, lauric acid, linoleic acid, myristic acid, oleic acid, palmitoleic acid, and stearic acid. The Panel has reviewed coconut acid, lauric acid, myristic acid, and oleic acid and concluded that these ingredients are safe as used. Linoleic acid has not been reviewed by the Panel.

Background information is provided on taurine, which is the starting material and potential impurity in the manufacture of these ingredients. However, extensive toxicity information for taurine is not included because taurine is ubiquitous in high concentrations throughout the animal kingdom, including in humans.

Pertinent data were discovered in the European Chemicals Agency (ECHA) database.11-16 This source provides summaries of information generated by industry, and it is those summary data that are included in this safety assessment when information from the mentioned sources is referenced.

CHEMISTRY

Definition and Structure The alkyl taurate amides and taurate salts are structurally related because these ingredients have the same taurate

core (Figure 1). They vary by N-substitution and by the counter-ion of the sulfonate functional group. For example, potassium taurate, sodium methyltaurate, and sodium taurate vary by either hydrogen or methyl N-substitution, and either sodium or potassium counter-ions.

Figure 1. The taurate salts (wherein R is hydrogen or methyl).

The remaining ingredients in this report bear a fatty acyl N-substitution that forms, together with taurate, an amide (i.e., alkyl taurate amide; Figure 2). The alkyl taurate amides share a taurate core, and vary by fatty chain length and counter-ion. Some of the ingredients in this report have names that suggest discrete fatty chain-lengths. However, all of these ingredients, regardless of the nomenclature, are likely to be mixtures of substances with different chain lengths. The length specified in the names of each of these ingredients indicates the primary, or average, chain length of the substances in the mixture obtained through the batch separation and purification procedure employed. Those ingredients with a “cocoyl” name are the result of reaction with coconut acid, which has a known composition of approximately: 0-1% caproic, 5%-9%


caprylic, 6%-10% capric, 44%-52% lauric, 13%-19% myristic, 0-1% palmitoleic, 1%-3% stearic, 5%-8% oleic, and trace-2.5% linoleic acid.7 Accordingly, not only do these alkyl taurate amides share the same taurate core and similar fatty chain lengths, but many of these ingredients have identical component overlap (e.g., there is likely some sodium methyl lauroyl taurate in sodium methyl cocoyl taurate (cocoyl means 44%-52% lauroyl) and in sodium methyl myristoyl taurate (“myristoyl” likely has some smaller [lauroyl] and longer [palmitoyl] chain lengths therein).

Figure 2. Sodium Caproyl Methyltaurate – an alkyl taurate amide.

Furthermore, the composition of plant-sourced ingredients such as sodium methyl cocoyl taurate may vary from batch to batch because the acid starting material, coconut fatty acid, has a high carbon chain-length variability, dependent on factors such as growth conditions.17 The reported ranges of the components of sodium methyl cocoyl taurate are presented in Table 2.18-23

Physical and Chemical Properties Most of the alkyl taurate amides are solids (Table 3). For example, calcium lauroyl taurate is a white powder with a high fluidity.24

The particle size of calcium lauroyl taurate is reported to be 8 µm and has a plate-like shape.24 The particle size distribution of sodium methyl cocoyl taurate were reported to be: D10 (the diameter at which 10% of a sample’s mass is comprised of smaller particles)=3.87 ± 0.16 µm; D50 (the diameter at which 50% of a sample’s mass is comprised of smaller particles)=16.58 ± 0.67 µm; and D90 (the diameter at which 90% of a sample’s mass is comprised of smaller particles)=59.97 ± 4.58 µm.16 TAURINE Taurine is a white or colorless crystal powder.25 It has high water solubility and low lipophilicity because of the zwitterionic properties.

Method of Manufacture ALKYL TAURATE AMIDES

In general, alkyl taurate amides may be manufactured by reaction of taurine, or a taurate salt, with the appropriate fatty acid. For example, manufacture of sodium methyl stearoyl taurate may be accomplished by heating triple-pressed stearic acid, sodium methyltaurate solution, and boric acid to 200˚C while stirring with a subsurface nitrogen purge, distilling off any water.26 The stirring continues at 195-200˚C for 6 h at atmospheric pressure and then for 3 h at 100 mmHg vacuum. The mass is cooled and the resulting product, an off-white waxy solid, is ground to a powder. The product is reported to be 64.0% sodium methyl stearoyl taurate as active ingredient, 29.5% free fatty acid, 2.5% sodium N-methyltaurate, and 4.0% other unspecified chemicals. The conversion of sodium methyltaurate using this method was reported to be greater than 91%. Using coconut fatty acid in place of the triple-pressed stearic acid resulted in a conversion of 97%.

In another process, calcium lauroyl taurate was reported to be synthesized by dissolving taurine in a mixture (86:14, wt/wt) of deionized water and isopropyl alcohol followed by the addition of sodium hydrate. Lauric acid chloride and 48% aqueous sodium hydrate solution is dropped into the taurine solution for 1h at 40˚C followed by stirring for 1 h at the same temperature to produce sodium lauroyl taurate. Hydrochloric acid (35%) and an aqueous calcium chloride solution (20%) are added, and the reaction mixture stirred for 1h at 40˚C. The white precipitate is filtered and the cake washed with deionized water and isopropyl alcohol, then dried.26

Sodium methyl cocoyl taurate is reported to be manufactured and sold as a mixture with sodium chloride and water with active ingredient ranging from 24.0%-33%.18-23

TAURINE AND TAURATE SALTS

Taurine may be produced by a cyclic process of reacting ethylene oxide with sodium bisulfite and ammonium to obtain sodium taurate.27 Excess ammonia is removed from the reaction mixture, and the sodium taurate is neutralized with sulfur dioxide or sulfurous acid to recover taurine. Sodium bisulfate is regenerated and is then reacted with ethylene oxide. The salt forms can then by synthesized by simply reacting with the appropriate base, such as sodium hydroxide.


Impurities

Sodium methyltaurate is reported to be 87.0% - 96.0% (w/w) pure.14 Impurities are sodium hydroxide and sodium 2-hydroxyethanesulphonate.

USE Cosmetic

The Panel assesses the safety of cosmetic ingredients based on the expected use of these ingredients in cosmetics. The Panel reviews data received from the U.S. Food and Drug Administration (FDA) and the cosmetics industry to determine the expected cosmetic use. The FDA collects data from manufacturers on the use of individual ingredients in cosmetics, by cosmetic product category, through the FDA Voluntary Cosmetic Registration Program (VCRP). Data from the cosmetic industry are submitted in response to a survey of the maximum reported use concentrations, by category, conducted by the Personal Care Products Council (Council). According to 2015 VCRP data, sodium methyl cocoyl taurate is reported to be used in 339 formulations; the majority of the uses (322) are in rinse-off formulations (Table 4).28 Only sodium methyltaurate, sodium methyl oleoyl taurate, and sodium methyl stearoyl taurate also have reported uses in the VCRP. According to the survey conducted by the Council, sodium methyl oleoyl taurate had the highest reported maximum concentration of use of 28% in bath products.29 This is followed by sodium cocoyl taurate in rinse-off products at up to 21.5%. Calcium lauroyl taurate and sodium methyl cocoyl taurate are used up to 11% and 13%, respectively. All the other ingredients with reported concentration of use are used at up to 6% or less. Sodium methyl cocoyl taurate is reported to be used in 1 baby product and in 140 products that result in exposure to mucous membranes. Sodium methyl oleoyl taurate is used in bubble baths up to 28%. Sodium methyl cocoyl taurate, sodium methyl lauroyl taurate, and sodium methyl stearoyl taurate are used in products that may be ingested up to 1.2%.

In some cases, no reported uses were received in the VCRP, but a use concentration was provided in the industry survey. For example, magnesium methyl cocoyl taurate was not reported in the VCRP to be in use, but the industry survey indicated that it is used in non-coloring shampoo formulations at up to 0.26%. It should be presumed that hydrolyzed magnesium methyl cocoyl taurate is used in at least 1 cosmetic formulation. A list of the alkyl taurate amides and taurate salts that have no reported uses are listed in Table 5.

None of the ingredients in this report are restricted from use in any way under the rules governing cosmetic products in the European Union.30

Non-Cosmetic

SODIUM METHYL OLEOYL TAURATE Sodium methyl oleoyl taurate may be used as a component of paper and paperboard that comes into contact with dry

food without restriction. It may come into contact with aqueous and fatty foods only as an adjuvant to control pulp absorbency and pitch content in the manufacturing process.[21CFR176.170; 21CFR176.180] When sodium methyl oleoyl taurate is used in pesticides for food crops, the residues are exempted from the requirement of a tolerance when used in accordance with good agricultural practice as inert (or occasionally active) ingredients in pesticide formulations applied to growing crops or to raw agricultural commodities after harvest.[40CFR180.910] Sodium methyl oleoyl taurate is also exempt from the requirement of a tolerance when used in accordance with good agricultural practice as inert (or occasionally active) ingredients in pesticide formulations applied to animals.[40CFR180.930] TAURINE AND TAURATE SALTS The European Food Safety Authority (EFSA) Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) estimates the observed safe level in humans to be 6 g/person per day (corresponding to 100 mg/kg body weight per day).31 Taurine is used in energy drinks up to 4000 mg/L.32

Dietary taurine is a requirement for domestic cats at levels of 0.05%–0.25 % in complete feed.31 Taurine may be safely used as an additive in the feed of growing chickens when the total taurine content does not

exceed 0.054%.[21CFR573.980] In Europe, magnesium taurate, magnesium acetyl taurate, and iron (II) taurate may be used in the manufacture of

food supplements.33

TOXICOKINETICS Absorption, Distribution, Metabolism, and Excretion

OVERVIEW OF TAURINE Taurine is ubiquitous in high concentrations throughout the animal kingdom (except for protozoans).34 A human

body weighing 70 kg contains of up to 70 g of taurine. Taurine plays a part in the regulation of the cardiovascular system, brain, retina, liver, sperm motility/osmoprotection, muscle, and other general biological activities (for example, osmoregulation and calcium modulation). In general, taurine is present at high concentration in cells lacking cell walls and is


almost completely absent in cells having cell walls. Taurine levels are particularly high in electrically excitable tissues of mammals, especially in secretory structures.

After ingestion in mammals, taurine is mostly excreted unchanged or in the form of bile salts, such as taurocholate.34 Most mammals acquire taurine as an end product of sulfur metabolism (sulfur amino acids/cysteine to cysteine sulfonate to sulfate and taurine). Mammals are unable to oxidize the sulfur in taurine, cleave the C-S bond, or recycle the carbon of taurine into the general metabolic pool.

ALKYL TAURATE AMIDES AND TAURATE SALTS

Data on toxicokinetics of the alkyl taurate amides and taurate salts in this safety assessment were not found in the published literature, nor were unpublished data submitted.

TOXICOLOGICAL STUDIES

Single Dose (Acute) Toxicity The reported dermal LD50 for sodium methyl cocoyl taurate was >2000 mg/kg and values ranged from >20->2000 mg/kg for sodium methyl oleoyl taurate in rats (Table 6).11,12,16,17,35 The reported oral LD50 for sodium methyltaurate was ≥4670 mg/kg for rats and values for sodium methyl cocoyl taurate were >2000 mg/kg in rats.14,16,17 Clinical signs included hypoactivity, squatting posture, and coat bristling. An oral LD50 of 6.63 g/kg was reported for sodium methyl cocoyl taurate in mice.36 Inhalation

No acute inhalation toxicity studies were found in the published literature and no unpublished data were provided.

Repeated Dose Toxicity Dermal

No dermal repeated dose toxicity studies were found in the published literature and no unpublished data were provided.

Oral – Non-Human

The no-observed-adverse-effects-level (NOAEL) was reported to be ≥1000 mg/kg/d for both sodium methyl cocoyl taurate and sodium methyl oleoyl taurate in repeated dose oral toxicity studies in rats (Table 7).11,12,17 When 0.662 g/kg sodium methyl oleoyl taurate was administered by gavage 6 days/week for 25 doses to 10 mice, 1 mouse was dead on day 5 and 5 were dead on day 10. No additional mice died through day 25.36 Inhalation

No published repeated dose inhalation toxicity studies were found in the published literature and no unpublished data were provided.

Synergistic Effects SODIUM METHYL COCOYL TAURATE N-Ammonium thioglycolate (0.606 mg/kg/d; pH 9.32) was administered to the clipped skin of rabbits (n=11,12; strain not specified) over 15% of the body surface daily for 20 days with and without sodium methyl cocoyl taurate (3.0-4.0 mg/mL) under a rubber sleeve.37 The rabbits were observed for 3 weeks after the last administration. The LD50 was >6.5 mg/kg/d for N-ammonium thioglycolate alone; 1 rabbit died after 12 doses. The LD50 was reduced to 3.44±0.14 mg/kg/d when sodium methyl cocoyl taurate was included in the mixture; the mean number of doses before death was 11.

The entire experiment was repeated an additional 2 times with N-ammonium thioglycolate (0.600 mg/kg/d; pH 9.35) and sodium methyl cocoyl taurate (3.0 mg/mL only). In the first of the additional studies (n=11), 4 rabbits died with the mean number of doses before death at 13. In the second (n=12), 1 rabbit died with the mean number of doses before death at 20. The authors concluded that sodium methyl cocoyl taurate, because of its surfactant properties, increased the toxicity of N-ammonium thioglycolate when both were administered to the skin of rabbits compared to N-ammonium thioglycolate alone.37

REPRODUCTIVE AND DEVELOPMENTAL TOXICITY SODIUM METHYL OLEYL TAURATE A reproduction/developmental toxicity assay was performed on Sprague Dawley rats (n=10) using sodium methyl oleyl taurate (100, 300 and 1000 mg/kg/d) in accordance with Organization for Economic Cooperation and Development Test Guideline (OECD TG) 421.11,13,17 The test substance was administered by gavage starting 2 weeks before pairing, during pairing, post coitum, and through post partum day 3. The parental rats were monitored for clinical signs, body weight, feed consumption, estrous cycle and mating performance. Macroscopic observations and histopathological examinations were performed on the dams on day 4 post partum. No adverse findings were observed in life phase or at post mortem evaluation in the parental rats; however, 1 male and 1 female rat died due to possible misdosing, but not due to the prescribed


test conditions. The rats of the high-dose group showed salivation early after dosing. Body weight, body weight gain, and feed consumption were unaffected by treatment. No treatment-related findings were observed during macroscopic and microscopic examinations. No abnormalities were observed at the evaluation of the spermatogenic cycle. No differences were observed in the reproductive performance including gonadal function, mating behavior, conception, development of conceptus, and parturition. The dams had comparable length of gestation and live births. Litter and mean pup weights were also comparable between groups and no relevant findings were observed in the examination of the pups during the lactation period or at necropsy. The authors determined that the NOAEL for reproduction/developmental toxicity was >1000 mg/kg/d for both males and females.

GENOTOXICITY In Vitro

Sodium methyltaurate, sodium cocoyl taurate, sodium methyl cocoyl taurate, and sodium methyl oleoyl taurate were not genotoxic in Ames test up to 5000 µg/plate, with and without metabolic activation (Table 8).11,14,16,17 Sodium methyl cocoyl taurate was not genotoxic in Mammalian Cell Micronucleus tests genotoxic up to 320 µg/mL without metabolic activation and up to 240 µg/mL with metabolic activation.11,12,16,17 Sodium methyl cocoyl taurate, up to 100 µg/mL without metabolic activation and up to 120 µg/mL with metabolic activation, and sodium methyl oleoyl taurate, up to 9.87 µg/mL without metabolic activation and up to 265 µg/mL with metabolic activation were not genotoxic in Mammalian Cell Gene Mutation Tests.11,12

In Vivo

No published in vivo genotoxicity studies were found in the published literature and no unpublished data were provided.

CARCINOGENICITY No published carcinogenicity studies were found in the published literature and no unpublished data were provided.

IRRITATION AND SENSITIZATION

Irritation Dermal – Non-Human SODIUM METHYLTAURATE

A dermal irritation assay of sodium methyltaurate (76%- 84%; 500 mg in saline) was conducted in accordance with OECD TG 404 (Acute Dermal Irritation/Corrosion).14 The test substance was dermally administered to shaved New Zealand White rabbits (n=3) under semi-occlusion for 4 h. The test sites were observed at 0.5-1, 24, 48, 72 h and 7 and 14 d after patch removal. At observation times up to 24 h, the edema scores were between 1 and 3 of 4; edema was resolved at 48 h. The erythema score was between 1 and 3 of 6 starting at 0.5 h; erythema was fully resolved at 7 d. The test substance was a dermal irritant.

A dermal irritation assay of sodium methyltaurate (35%-37% mg in saline; 0.5 mL) was conducted in accordance with OECD TG 404 (Acute Dermal Irritation/Corrosion).14 The test substance was dermally administered to shaved New Zealand White rabbits (n=3) under semi-occlusion for 4 h. The test sites were observed at 0.5-1, 24, 48, and 72 h. The edema score was 0 of 4 at all observation times. Sodium methyltaurate was not an irritant or corrosive to rabbit skin.

Dermal-Human SODIUM METHYL COCOYL TAURATE

An occlusive patch test of sodium methyl cocoyl taurate (40% in distilled water; pH 7) was performed on subjects (n=8 females, 3 males).38 The patch was administered to the upper back for 24 h and observed at 30 min and 24 and 48 h after removal of the 50 mm2 patch. There was slight to clear erythema at 24 h in 2 subjects and 1 subject at 48 h. There were no reactions observed in 9 of the subjects.

Dermal-In Vitro SODIUM METHYL COCOYL TAURATE

An in vitro skin corrosion assay conducted in accordance with OECD TG 431 (EPISKIN™ In Vitro Skin Corrosion: Human Skin Model Test; EU Method B.40) did not predict that sodium methyl cocoyl taurate (100%; 20 mg in 100 µL sterile water to wet the test substance; >90% pure) would cause dermal irritation.11,16,17 The test was conducted on intact reconstructed human epidermis. In this assay, a positive result would have indicated that the test substance is irritating or corrosive. However, a negative result is not definitive.

An in vitro skin corrosion assay conducted in accordance with OECD TG 439 (EPISKIN™ In Vitro Skin Irritation; EU method B.46) did not predict that sodium methyl cocoyl taurate (100%; 10 mg in 5 µL sterile water to wet the test substance; >90% pure) would cause dermal irritation.11,16,17 However, as noted above, a negative result from this test is not definitive.


Ocular – In Vivo Sodium methyltaurate caused persistent corneal opacity, as well as inflammation of the iris and conjunctiva,

resulting in irreversible eye damage in rabbits at concentrations as low as 35%-37% (Table 9).14 Sodium methyl cocoyl taurate was an ocular irritant in rabbits at 100% and a mild irritant at 10%.16,17,38 Sodium methyl myristoyl taurate at 10% had a Draize score of approximately 2.2 out of 5 in rabbits.39 Sodium methyl oleoyl taurate had an irritation score of 2 out of 4 at 10% and was considered not to be an ocular irritant or a mild ocular irritant at 100% in rabbits.11-13,36

Ocular – In Vitro SODIUM METHYL COCOYL TAURATE

In a Bovine Corneal Opacity and Permeability (BCOP) test, administered in accordance with OECD TG 437, sodium methyl cocoyl taurate (20% in sodium chloride solution) was predicted to be a severe eye irritant.11,17 The calculated in vitro irritancy score (IVIS) was 53.7. The positive control (imidazole, 20% in 0.9% sodium chloride solution) induced severe irritation of the cornea (IVIS score: 90.3). The negative control (solvent) showed no irritating effect the cornea. On the basis of the test findings it was concluded that the test substance was corrosive and had severe irritation potential under the experimental conditions.

Sensitization

Dermal – Non-Human SODIUM METHYL COCOYL TAURATE In a Buehler sensitization assay conducted in accordance with OECD TG 406 (Skin Sensitization) in female Pirbright-White guinea pigs (n=20; control=10), the epicutaneous induction was conducted with sodium methyl cocoyl taurate at 100% under occlusion and the challenge was conducted at 20% (in water), also under occlusion.16 The challenge sites were observed 24 and 48 h after administration. There were no reactions observed during induction or after the challenge. It was concluded that sodium methyl cocoyl taurate was not sensitizing. SODIUM METHYL OLEOYL TAURATE In a Buehler sensitization assay conducted in accordance with OECD TG 406 (Skin Sensitization) in female Himalayan spotted guinea pigs (n=20; control=10), the epicutaneous induction and challenge was conducted with sodium methyl oleoyl taurate (50% in PEG 300).12 During the induction phase, the test material was administered to the left shoulder for 6 h, once per week for 3 weeks. The challenge involved administering the test material to the left posterior and back on day 29 for 6 h. The test site was examined 24 and 48 h after the challenge. Sodium methyl oleyl taurate was not a sensitizer under these test conditions.

Case Reports A 53-year-old woman, with a history of itching when having her hair colored, developed pruritus of the scalp followed by flushing of her entire body, dyspnea, vomiting, and hypotension while having her hair colored.40 She was treated with intravenous steroids and hydration in the hospital. A skin prick test of the ingredients of the hair dye (1% of the concentration applied to the hair) showed positive responses to p-aminophenol and sodium methyl oleoyl taurate.

SUMMARY This is a safety assessment of the scientific literature relevant for assessing the safety of 20 alkyl taurate amides and

taurate salts used as ingredients in cosmetics. The alkyl taurate amides and taurate salts in this report are all structurally related by having the same taurate core. While the free acid, taurine, is a cosmetic ingredient, it is not included in this safety assessment because it functions exclusively as a fragrance and is under the purview of RIFM; relevant data on taurine that are informative on these ingredients are included. These ingredients mostly function as surfactants – cleansing agent.

Sodium methyl cocoyl taurate is reported to be used in 339 formulations; most of these uses are in rinse-off formulations. There are no reported uses in the VCRP for most of the ingredients in this safety assessment.

Sodium methyl oleoyl taurate had the highest reported concentration of use of 28% in bath products. This is followed by sodium cocoyl taurate with a maximum concentration of use of 21.5% in rinse-off personal cleanliness products and up to 2% in leave-on skin care products. Calcium lauroyl taurate and sodium methyl cocoyl taurate are used up to 11% and 13%, respectively. All the other ingredients with reported concentrations of us are used at up to 6% or less.

The reported acute dermal LD50 for sodium methyl cocoyl taurate was >2000 mg/kg and values ranged from >20->2000 mg/kg for sodium methyl oleoyl taurate in rats. The reported oral LD50 for sodium methyltaurate was ≥4670 mg/kg for rats and values for sodium methyl cocoyl taurate were >2000 mg/kg in rats. Clinical signs included hypoactivity, squatting posture, and coat bristling. An oral LD50 of 6.63 g/kg was reported for sodium methyl cocoyl taurate in mice.

The NOAEL was ≥1000 mg/kg/d for both sodium methyl cocoyl taurate (up to 28 days) and sodium methyl oleoyl taurate (up to 25 doses) in repeated dose oral toxicity studies. There were 2 mortalities when mice were orally administered 0.662 g/kg/d sodium methyl oleoyl taurate for 25 doses.

The authors of one study concluded that sodium methyl cocoyl taurate increased the toxicity of N-ammonium thioglycolate when both were administered to the skin of rabbits for 20 days compared to N-ammonium thioglycolate alone.


The LD50 of N-ammonium thioglycolate decreased from >6.5 mg/kg/d to 3.44 mg/kg/d when combined with 3.0-4.0 mg/kg/d sodium methyl cocoyl taurate.

In a reproduction/developmental assay, the NOAEL for reproduction/developmental toxicity was ≥1000 mg/kg/d for

both male and female rats when sodium methyl oleoyl taurate was orally administered from 2 weeks before pairing through postpartum day 3.

Sodium methyltaurate, sodium cocoyl taurate, and sodium methyl cocoyl taurate was not genotoxic in an Ames test up to 5000 µg/plate. Sodium methyl oleoyl taurate was not mutagenic in an Ames test. Sodium methyl cocoyl taurate and sodium methyl oleoyl taurate were not genotoxic in Mammalian Cell Micronucleus tests.

Sodium methyltaurate at 76%-84% was dermally irritating to rabbits but was not irritating at 35%-37%. In a patch test, there was slight to clear erythema at 24 h in 2 of 11 subjects and 1 subject at 48 h when sodium

methyl cocoyl taurate was administered at 40%. There were no reactions observed in 9 of the subjects. In 2 in vitro EPISKIN™ assays, sodium methyl cocoyl taurate was not predicted to be irritating. Sodium methyltaurate at 80%-84% and 35%-37% caused persistent corneal opacity as well as inflammation of the

iris and conjunctiva resulting in irreversible eye damage. Sodium methyl cocoyl taurate at 100% was an ocular irritant to rabbits and was less irritating at 10%. In a Draize test of sodium methyl myristoyl taurate at 10% aqueous, the score was ~2.2 out of 5 in rabbits. The ocular irritation score was 2 (out of a possible 4) for sodium methyl oleoyl taurate at 1% administered to the eyes of rabbits. At 100%, sodium methyl oleoyl taurate was rated not irritating and mildly irritating in rabbits.

In a BCOP Test, sodium methyl cocoyl taurate at 20% was predicted to be corrosive to the eyes. Sodium methyl cocoyl taurate was not sensitizing to guinea pigs at 100% when challenged at 20%. Sodium methyl

oleoyl taurate was not sensitizing when induced and challenged at 50%. A woman developed sensitization to sodium methyl oleoyl taurate after repeatedly dying her hair.

DISCUSSION Discussion is scheduled to be developed at the September, 2015 Panel meeting.

CONCLUSION

To be determined.


TABLES

Table 1. Definitions, structures, and functions of the ingredients in this safety assessment.(1, CIR Staff)

Ingredient/CAS No. Definition & Structure Function

Simple Taurate Salts Potassium taurate [22890-34-2]

Potassium taurate is the organic salt that conforms to the formula:

[Potassium taurate is the potassium salt of 2-aminoethane-1-sulfonate.]

Surfactant - cleansing agent; surfactant - foam booster

Sodium methyltaurate 4316-74-9

Sodium methyltaurate is the organic compound that conforms to the formula:

[Sodium methyltaurate is the sodium salt of 2-(methylamino)ethane-1-sulfonate.]

Skin-conditioning agent - miscellaneous

Sodium taurate [7347-25-3]

Sodium Taurate is the organic salt that conforms to the formula:

[Sodium Taurate is the sodium salt of 2-aminoethane-1-sulfonate.]

Surfactant – cleansing agent; surfactant – foam booster

Alkyl Taurate Amides Calcium lauroyl taurate 138705-25-6

Calcium lauroyl taurate is the organic compound that conforms to the formula:

[Calcium lauroyl taurate is the calcium salt of 2-dodecanamidoethane-1-sulfonate.]

Surfactant – cleansing agent

Magnesium methyl cocoyl taurate

Magnesium methyl cocoyl taurate is the magnesium salt of the coconut fatty acid amide of N-methyltaurine. It conforms generally to the formula:

where RC(O)- represents the coconut acid radical. [Magnesium methyl cocoyl taurate is the magnesium salt of 2-(N-methylcocamido)ethane-1-sulfonate.*]


Potassium cocoyl taurate

Potassium cocoyl taurate is the organic salt that conforms to the formula:

where RC(O)- represents the coconut acid radical. [Potassium cocoyl taurate is the potassium salt of 2-cocamidoethane-1-sulfonate.*]


Potassium methyl cocoyl taurate

Potassium methyl cocoyl taurate is the potassium salt of the coconut acid amide of N-methyl taurine. It conforms to the formula:

where RC(O)- represents the fatty acids derived from coconut oil. [Potassium methyl cocoyl taurate is the potassium salt of 2-(N-methylcocamido)ethane-1-sulfonate.*]


Sodium caproyl methyltaurate [20461-70-5]

Sodium caproyl methyltaurate is the sodium salt of the caproic acid amide of N-methyl taurine. It conforms to the formula:

[Sodium caproyl methyltaurate is the sodium salt of 2-(N-methyldecanamido)ethane-1-sulfonate.]


Sodium cocoyl taurate

Sodium cocoyl taurate is the organic salt that conforms to the formula:

where RC(O)- represents the coconut acid radical. [Sodium cocoyl taurate is the sodium salt of 2-cocamidoethane-1-sulfonate.*]




Ingredient/CAS No. Definition & Structure Function Sodium methyl cocoyl taurate 12765-39-8 61791-42-2

Sodium methyl cocoyl taurate is the sodium salt of the coconut fatty acid amide of N-methyltaurine. It conforms generally to the formula:

where RC(O)- represents the coconut acid radical. [Sodium methyl cocoyl taurate is the sodium salt of 2-(N-methylcocamido)ethane-1-sulfonate.*]


Sodium N-isostearoyl methyltaurate [170150-64-8]

Sodium N-isostearoyl methyltaurate is the organic compound that conforms to the formula:

[This is just one example of an “iso” compound, according to the INCI definition. Sodium N-isostearoyl methyltaurate is the sodium salt of 2-(N-isooctadecanamido)ethane-1-sulfonate.]


Sodium lauroyl taurate 70609-66-4

Sodium lauroyl taurate is the organic salt that conforms generally to the formula:

[Sodium lauroyl taurate is the sodium salt of 2-dodecanamidoethane-1-sulfonate.]


Sodium methyl lauroyl taurate 4337-75-1 [115049-64-4]

Sodium methyl lauroyl taurate is the sodium salt of the lauric acid amide of N-methyl taurine. It conforms to the formula:

[Sodium methyl lauroyl taurate is the sodium salt of 2-(N-methyldodecanamido)ethane-1-sulfonate.]


Sodium methyl myristoyl taurate 18469-44-8

Sodium methyl myristoyl taurate is the sodium salt of the myristic acid amide of N-methyl taurine. It conforms to the formula:

[Sodium methyl myristoyl taurate is the sodium salt of 2-(N-methyltetradecanamido)ethane-1-sulfonate.]


Sodium methyl oleoyl taurate 137-20-2 7308-16-9

Sodium methyl oleoyl taurate is the sodium salt of the oleic acid amide of N-methyl taurine. It conforms generally to the formula:

[Sodium methyl oleoyl taurate is the sodium salt of 2-(N-methyloleamido)ethane-1-sulfonate.]


Sodium methyl palmitoyl taurate 3737-55-1

Sodium methyl palmitoyl taurate is the sodium salt of the palmitic acid amide of N-methyl taurine. It conforms to the formula:

[Sodium methyl palmitoyl taurate is the sodium salt of 2-(N-methylpalmitamido)ethane-1-sulfonate.]


Sodium methyl stearoyl taurate 149-39-3 [87111-75-9] [27236-38-0]

Sodium methyl stearoyl taurate is the sodium salt of the stearic acid amide of N-methyl taurine. It conforms to the formula:

[Sodium methyl stearoyl taurate is the sodium salt of 2-(N-methylstearamido)ethane-1-sulfonate.]




Ingredient/CAS No. Definition & Structure Function Sodium methyltaurate isopalmitamide

Sodium methyltaurate isopalmitamide is the organic compound that conforms to the formula:

[This is just one example of an “iso” compound, according to the INCI definition. Sodium methyltaurate isopalmitamide is the sodium salt of 2-(N-isooctadecanamido)ethane-1-sulfonate.]


Sodium methyltaurine cocoyl methyltaurate

Sodium methyltaurine cocoyl methyltaurate is the organic salt that conforms to the formula:

where RC(O)- represents the cocoyl group. [Sodium methyltaurine cocoyl methyltaurate is the sodium methyltaurine salt of 2-(N-methylcocamido)ethane-1-sulfonate.*]

Surfactant – cleansing agent; surfactant – emulsifying agent

Sodium taurine cocoyl methyltaurate

Sodium taurine cocoyl methyltaurate is the organic salt that conforms to the formula:

where RC(O)- represents the cocoyl group. [Sodium taurine cocoyl methyltaurate is the sodium taurine salt of 2-(N-methylcocamido)ethane-1-sulfonate.*]

Surfactant – cleansing agent; surfactant – emulsifying agent

* The fatty acid distribution of coconut acid is 0-1% caproic, 5%-9% caprylic, 6%-10% capric, 44%-52% lauric, 13%-19% myristic, 0-1% palmitoleic, 1%-3% stearic, 5%-8% oleic, and trace-2.5% linoleic acid.7

Table 2. The reported concentration ranges of the constituents of sodium methyl cocoyl taurate.17 Constituent Typical concentration Concentration ranges Fatty acid, C8, sodium-N,N-methyl taurate ca. 3.0 % (w/w) > 0.0 — <= 8.0 % (w/w) Fatty acid, C10, sodium-N,N-methyl taurate ca. 8.0 % (w/w) > 0.0 — < 10.0 % (w/w) Sodium 2-[methyl(1-oxododecyl)amino]ethanesulphonate ca. 54.0 % (w/w) >= 40.0 — <= 62.0 % (w/w) Fatty acid, C14, sodium-N,N-methyl taurate ca. 20.0 % (w/w) >= 15.0 — <= 30.0 % (w/w) Sodium 2-[methyl(1-oxohexadecyl) amino]ethanesulphonate ca. 8.0 % (w/w) >= 5.0 — <= 15.0 % (w/w) Sodium 2-[methyloleoylamino]ethane-1-sulphonate ca. 1.0 % (w/w) > 0.0 — < 15.0 % (w/w) Sodium 2-[methyl(1-oxooctadecyl)amino]ethanesulphonate ca. 6.0 % (w/w) > 0.0 — <= 10.0 % (w/w) Sodium N-methyltaurinate 0.0 % (w/w) >= 0.0 — < 3.0 % (w/w) Sodium chloride 0.3 % (w/w) >= 0.0 — <= 1.5 % (w/w)

Table 3. Chemical and physical properties of alkyl taurate amides and taurate salts.

Property Value Reference Sodium methyl cocoyl taurate

Physical Form Solid/powder 16

Molecular Weight g/mol 287.4-427.6 17

Density/Specific Gravity @ 25oC 0.185 16

Melting Point oC 205.1 16

Boiling Point oC 378.6-385.5 16

Water Solubility g/L @ 20oC & pH 6.4 @ 20oC & pH 8.03

0.23 >250

16 16

Other Solubility g/L n-octanol @ 20oC

0.4

16

Disassociation constants pKa @ 25oC log Po/w

<1

-0.44-0.54

17 17


Table 3. Chemical and physical properties of alkyl taurate amides and taurate salts.

Property Value Reference Calcium lauroyl taurate

Physical Form Powder 24

Color White 24

Molecular Weight g/mol 803.30 41

Density/Specific Gravity Specific Gravity Bulk Specific Gravity

1.25 0.37

24 24

Water Solubility Insoluble 24

Potassium taurate Molecular Weight g/mol 163.2372 42

Sodium lauroyl taurate Molecular Weight g/mol 329.43 43

Sodium methyl lauroyl taurate Physical Form Crystalline solid 44

Color White to slight yellow 44

Odor Faint characteristic 44

Water Solubility Soluble 44

Sodium methyl myristoyl taurate Molecular Weight g/mol 371.51 45

Sodium methyl oleoyl taurate Physical Form Powder 35

Color Yellowish 35

Odor Characteristic 35


Bulk density kg/m3 600 35

Melting Point oC ~170 35

Sodium methyl palmitoyl taurate Physical Form Crystalline solid 47

Color White 47


Sodium methyl stearoyl taurate Molecular Weight g/mol 427.61 47

Sodium methyltaurate Physical Form Solid 14

Color Yellow 14


Density/Specific Gravity 1.21 48

Melting Point oC 160 14

Water Solubility g/L @ 20 oC 410 14

Sodium taurate Physical form Solid 15,49



Table 4. Frequency of use according to duration and exposure of alkyl taurate amides and taurate salts.28,29

Use type Uses

Maximum Concentration

(%) Uses


(%) Uses


(%) Uses


(%)

Sodium Methyltaurate Calcium Lauroyl

Taurate Magnesium Methyl

Cocoyl Taurate Sodium Cocoyl Taurate Total/range 2 0.11-3 NR 0.48-11 NR 0.26 NR 0.3-21.5

Duration of use Leave-on NR NR NR 0.48-11 NR NR NR 2 Rinse-off 2 0.11-3 NR NR NR 0.26 NR 0.3-21.5

Diluted for (bath) use NR NR NR NR NR NR NR 7

Exposure type Eye area NR NR NR 0.48 NR NR NR 0.3

Incidental ingestion NR NR NR NR NR NR NR NR

Incidental Inhalation-sprays NR NR NR NR NR NR NR NR

Incidental inhalation-powders NR NR NR NR NR NR NR 2c

Dermal contact 2 2 NR 0.48-11 NR NR NR 0.3-21.5 Deodorant (underarm) NR NR NR NR NR NR NR NR

Hair-noncoloring NR 0.11-3 NR NR NR 0.26 NR 0.75-9 Hair-coloring NR NR NR NR NR NR NR NR

Nail NR NR NR NR NR NR NR NR Mucous

Membrane NR NR NR NR NR NR NR 7-21.5

Baby NR NR NR NR NR NR NR NR

Sodium Methyl Cocoyl Taurate Sodium Lauroyl Taurate

Sodium Methyl Lauroyl Taurate

Sodium Methyl Myristoyl Taurate

Total/range 339 0.000095-13 NR 0.09-1 NR 0.2-0.7 NR 1-6 Duration of use

Leave-on 10 0.21-6 NR NR NR NR NR NR Rinse-off 322 0.000095-13 NR 0.09-1 NR 0.2-0.7 NR 1-6

Diluted for (bath) use 7 0.38-1.2 NR NR NR NR NR NR

Exposure type Eye area NR 2.4 NR NR NR NR NR NR

Incidental ingestion NR 0.24-1.2 NR NR NR 0.3-0.7 NR NR

Incidental Inhalation-sprays 2a; 6b 0.21-0.24a NR NR NR 0.3a NR NR

Incidental inhalation-powders 6b 6; 0.9-1.5c NR NR NR NR NR NR

Dermal contact 269 0.38-10.2 NR 1 NR 0.2 NR 6 Deodorant (underarm) NR NR NR NR NR NR NR NR

Hair-noncoloring 70 0.000095-9.7 NR 0.09 NR NR NR 1 Hair-coloring NR 0.5 NR NR NR NR NR NR

Nail NR 3.2-3.9 NR NR NR NR NR NR Mucous

Membrane 140 0.24-10.2 NR NR NR 0.3-0.7 NR NR

Baby 1 NR NR NR NR NR NR NR


Table 4. Frequency of use according to duration and exposure of alkyl taurate amides and taurate salts.28,29

Use type Uses


(%) Uses


(%) Uses


(%) Uses


(%)

Sodium Methyl Oleoyl Taurate

Sodium Methyl Stearoyl Taurate

Sodium Taurine Cocoyl Methyltaurate

Total/range 1 28 8 0.0076-4 NR 2-6 Duration of use

Leave-on NR NR 8 0.024-1 NR NR Rinse-off 1 NR NR 0.0076-4 NR 2-6

Diluted for (bath) use NR 28 NR NR NR NR

Exposure type Eye area NR NR NR 0.5-0.9 NR NR

Incidental ingestion NR NR NR 0.0076 NR NR

Incidental Inhalation-sprays NR NR 4a; 4b 1a NR NR

Incidental inhalation-powders NR NR NR 0.7-1c NR NR

Dermal contact NR 28 8 0.024-1 NR 2 Deodorant (underarm) NR NR NR 0.028d NR NR

Hair-noncoloring 1 NR NR 0.8-2 NR 6 Hair-coloring NR NR NR 0.1-4 NR NR

Nail NR NR NR NS NR NR Mucous

Membrane NR 28 NR 0.0076 NR NR

Baby NR NR NR NR NR NR NR = Not Reported; NS = Not Surveyed; Totals = Rinse-off + Leave-on Product Uses. Note: Because each ingredient may be used in cosmetics with multiple exposure types, the sum of all exposure type uses may not equal the sum total uses. a It is possible these products may be sprays, but it is not specified whether the reported uses are sprays. b Not specified whether a powder or a spray, so this information is captured for both categories of incidental inhalation. c It is possible these products may be powders, but it is not specified whether the reported uses are powders. d Not spray products.

Table 5. Alkyl taurate amides and taurate salts with no reported uses.28,29 Potassium taurate Sodium taurate Magnesium methyl cocoyl taurate Potassium cocoyl taurate Sodium caproyl methyltaurate Sodium n-isostearoyl methyltaurate Sodium methyl palmitoyl taurate Sodium methyltaurate isopalmitamide Sodium taurine cocoyl methyltaurate

Table 6. Acute toxicity studies of alkyl taurate amides and taurate salts.

Ingredient Animals Concentrations/

Dosages Methods Results Reference

Dermal Sodium Methyl Cocoyl Taurate

Male and female Wistar rats (n=5/sex)

100%; 2000 mg/kg

OECD TG 402; 10% of body under semi-occlusion for 24 h followed by 14-day observation period.

Effects level > 2000 mg/kg. No mortalities, no signs of toxicity. Residual discoloration at test site.

11,12


Wistar rats 100%; 2000 mg/kg

OECD TG 402 ; administered under semi-occlusion to 10% of the body surface

No mortalities or clinical signs. At necropsy, no specific pathology associated with test substance observed, except some residual discoloration of the skin at the test site.

16


Male and female Wistar rats

OECD TG 402; administered under semi-occlusion in a paste

LD50>2000 mg/kg 17


Rats OECD TG 402 LD50 >20 mg/kg; No signs of toxicity observed in the 14-day observation period. No effects to body weights and there were no gross pathology findings.

17


Rats >2000 mg/kg 35


Table 6. Acute toxicity studies of alkyl taurate amides and taurate salts.


Dosages Methods Results Reference

Oral Sodium Methyltaurate (80%-84% pure)

Wistar rats 4000, 4500, 4750, 5000, 6300 mg/kg

OECD TG 401 LD50≥4670 mg/kg in water (the highest dose tested). Necropsies showed unspecified changes to the intestines/ gastrointestinal tract, especially in the rats that died before the end of the experiment (number not specified).

14

Sodium Methyl Cocoyl Taurate

Sprague-Dawley rats (n=5/sex)

2000 mg/kg; 20% in water; 10 mL/kg

OECD TG 401 There were no deaths during 14-day observation period. Hypoactivity, squatting posture, and coat bristling were observed in all rats from 10-30 min to 4-6 h post administration. No signs of toxicity observed during the observation period. There were no effects to body weights and there were no gross pathology findings.

16,17


Male and female Sprague-Dawley rats

OECD TG 401 LD50>2000 mg/kg 17


Wistar rats (n=5/sex)

OECD TG 401 LD50>2000 mg/kg. No mortalities or signs of toxicity were observed during the 14-day observation period. There were no macroscopic findings at necropsy.

17


Albino Harlan mice (n=10)

The mice were observed for 72 h after dosing.

LD50=6.63 g/kg 36

OECD TG - Organization for Economic Cooperation and Development Guideline

Table 7. Repeated dose oral toxicity studies of alkyl taurate amides and taurate salts.


Dosages Methods Results Reference Sodium Methyl Cocoyl Taurate


62.5, 250, 1000 mg/kg/d. Controls received purified water.

Gavage daily for 14 days; equivalent or similar to OECD TG 407 (Repeated Dose 28-Day Oral Toxicity in Rodents)

NOAEL≥1000 mg/kg/d (actual dose received). No clinical signs with regards to mortality; feed consumption; body weight; hematology; clinical chemistry; gross pathology; organ weights; histopathology; male reproductive organs including sperm staging

12,17


Sprague-Dawley rats (n=10/sex; controls= 5/sex); 5 additional controls and high-dose rats were allowed 2 weeks of recovery before necropsy.

100, 300, 1000 mg/kg/d; 10 mL/kg

Gavage for 28 days; OECD TG 407 (Repeated Dose 28-Day Oral Toxicity in Rodents)

No clinical signs; normal weekly neurotoxicity assessment. No changes in body weights or feed consumption between groups. Increased white blood cell count was observed, especially in high-dose males; considered to be secondary to inflammatory changes due to forestomach findings in high dose animals. Increases in transaminases in high dose male animals were not considered to be indicative of liver injury but may represent adaptive changes. Macroscopic and histopathological examinations showed diffuse mucosal hyperplasia usually associated with hyperkeratosis and with focal to diffused inflammation located in the submucosa mainly in males at in the high-dose group. Focal ulcers with diffuse mucosal

17


Table 7. Repeated dose oral toxicity studies of alkyl taurate amides and taurate salts.


Dosages Methods Results Reference hyperplasia was still noted in the forestomach of the rats in the treatment/recovery subgroup. Comparable forestomach effects were not observed in the low- and mid-dose groups.



62.5, 250, or 1000 mg/kg

Gavage for 14 days NOAEL≥1000 mg/kg/d (actual dose received). No clinical signs with regards to mortality; feed consumption; body weight; hematology; clinical chemistry; gross pathology; organ weights; histopathology; male reproductive organs including sperm staging.

11


Albino Harlan mice (n=10)

0.662 g/kg ; 10% LD50

Administered by gavage for 6 days/week until 25 doses were administered

1 mouse was dead on day 5 and 5 were dead on day 10. No more mice died through the 25th dose.

36


Table 8. Genotoxicity studies of alkyl taurate amides and taurate salts. Concentration/dose Method Results Reference

Sodium Methyltaurate 4-5000 µg/plate Ames test conducted similar to OECD TG

471 (Bacterial Reverse Mutation Assay) using Salmonella typhimurium (strains TA1535, TA1537, TA98 and TA100) with and without metabolic activation

Not genotoxic. The controls had the expected results.

14

Sodium Cocoyl Taurate 4-5000 µg/ plate

Ames test conducted in accordance with OECD TG 471 using S. typhimurium (strains TA1535, TA1537, TA98, and TA100)

Not mutagenic with or without metabolic activation.

11

Sodium Methyl Cocoyl Taurate 5-5000 µg/plate in distilled water; 97.7% pure

Ames test conducted in accordance with OECD TG 471 using S. typhimurium (strains TA1535, TA1537, TA98, and TA100) and Escherichia coli (strain WP2 uvr A) with and without metabolic activation

Not genotoxic. Visible reductions in the growth of the bacterial background lawns of S. typhimurium strains at 500 µg/plate and above. The results of the controls were as expected.

16,17

4-hour without S9: 200, 240, 320 µg/mL; 4-hour with S9: 160, 200, 240 µg/mL 20-hour without S9: 40, 80, 160 µg/mL; 97.7% pure

Genotoxicity assay conducted in accordance with OECD TG 487 (In Vitro Mammalian Cell Micronucleus Test) using human lymphocytes.

Not genotoxic up to 320 µg/mL without metabolic activation and up to 240 µg/mL with metabolic activation when incubated for 4 h; test substance was cytotoxic at these concentrations and above. When incubated for 20 h without metabolic activation, there were still no genotoxic effects observed. The positive controls had the expected results; there were no negative controls.

11,16,17

Experiment 1: 4-h exposure, -S9: 10, 20, 40, 50, 60, 100 µg/mL 4-h exposure, +S9: 15, 30, 60, 70, 80, 90, 100, 120 µg/mL Experiment 2: 24-h exposure, -S9: 3.75, 7.5, 15, 30, 40, 50, 60, 80 µg/mL 4-h exposure, +S9: 3.75, 7.5, 15, 30, 60, 70, 80, 90 µg/mL (97.7% pure)

Mammalian cell gene mutation assay conducted in accordance with OECD TG 476 (In vitro Mammalian Cell Gene Mutation Test) using mouse lymphoma L5178Y cells

Not genotoxic up to 100 µg/mL without metabolic activation and up to 120 µg/mL with metabolic activation when incubated for 4 h. When incubated for 24 h without metabolic activation, there were no genotoxic effects observed up to 80 µg/mL. Cytotoxicity was observed in the 4-h exposure at 60 µg/mL and above with metabolic activation and at 50 µg/mL and above without metabolic activation. In the 24-h exposure without metabolic activation, cytotoxicity was

11,16,17


Table 8. Genotoxicity studies of alkyl taurate amides and taurate salts. Concentration/dose Method Results Reference

observed at 15 µg/mL and above. The positive controls had the expected results; there were no negative controls. The test material was cytotoxic - Experiment 1: 4-h exposure, +S9: at 60 µg/mL and above; 4-h exposure, -S9: at 50 µg/mL and above; Experiment 2: 4-h exposure, +S9: at 60 µg/mL: 24-h exposure, -S9: at 15 µg/mL and above.

Sodium Methyl Oleoyl Taurate TA97a: 1.6-160 µg/plate (-S9), 16-1600 µg/plate (+S9) TA98: 50-5000 µg/plate (+/-S9) TA100: 16-1600 µg/plate (+/-S9) TA102: 50-5000 µg/plate (+/-S9) TA1535: 16-1600 µg/plate (+/-S9) in bidistilled water

OECD TG 471 using S. typhimurium (strains TA97a, TA 100, TA102, TA1535) with and without metabolic activation

Not mutagenic 12

Experiment 1: 32.3, 23.1, 16.5, 11.8, 8.40 and 6.00 µg/mL without S9; 600, 462, 355, 273, 210 and 162 µg/mL with S9 Experiment 2: 28.2, 21.7, 16.7, 12.8 and 9.87 µg/mL without S9; 500, 458, 382, 318 and 265 µg/mL with S9

Mammalian cell gene mutation assay conducted in accordance with OECD TG 476 (In vitro Mammalian Cell Gene Mutation Test) and Guideline EU Method B.17 (Mutagenicity - In Vitro Mammalian Cell Gene Mutation Test) Using Chinese hamster lung fibroblast (V79)

Not genotoxic 11,12

First experiment: 5000, 2500, 1250, 625, 313, 156, 78.1, 39.1 and 19.5 µg/mL with and without S9 metabolism. Second experiment: 270, 180, 120, 80.0, 53.3, 35.6, 23.7, 15.8, 10.5 and 7.02 µg/mL without S9

Mammalian chromosome aberration test OECD TG 473 (In vitro Mammalian Chromosome Aberration Test) and Guideline EU Method B.10 (Mutagenicity - In Vitro Mammalian Chromosome Aberration Test) using human lymphocytes

Not genotoxic. Marked toxicity was observed at 313 µg/mL, where the relative mitotic index was 18% and 22% of the control in the absence and presence of S9 metabolism respectively. Moderate toxicity was observed at 156 g/mL, where the relative mitotic index was 48% and 52% of the concurrent negative control with and without metabolic activation, respectively. No remarkable toxicity was observed at 78.1, 39.1 and 19.5 µg/mL for both treatment series.

11,12

Table 9. In vivo ocular studies of alkyl taurate amides and taurate salts. Dose/concentration Method Results Reference

Sodium Methyltaurate 80%-84% in saline; 100 mg

OECD TG 405 (Acute Eye Irritation/ Corrosion) in New Zealand White rabbits (n=3)

There was persistent corneal opacity as well as inflammation of the iris and conjunctivae. The iris irritation scores was between 0 and 1 of 2 up to 72 h; then the irritation was resolved at the next observation. There was conjunctiva irritation at all observation times and was not fully reversed at 21 d. Conclusion: sodium methyltaurate caused persistent corneal opacity as well as inflammation of the iris and conjunctiva resulting in irreversible eye damage.

14

35%-37% aqueous; 0.1 mL

OECD TG 405 in New Zealand White rabbits (n=3)

There was persistent corneal opacity as well as inflammation of the iris and conjunctivae at all observation times, and was not fully reversed by 7 d. The iris irritation scores were between 0 and 1 of 2 up to 72 h; the irritation was resolved by 7 d. The conjunctiva irritation score was between 2 and 3 of 3 at all observation times and irritation was not fully reversed at 7 d. Conclusion: sodium methyltaurate caused persistent corneal opacity as well as inflammation of the iris and conjunctiva resulting in irreversible eye damage.

14


Table 9. In vivo ocular studies of alkyl taurate amides and taurate salts. Dose/concentration Method Results Reference

Sodium Methyl Cocoyl Taurate 100% in a paste as provided; 100 mg

OECD TG 405 (Acute Eye Irritation/Corrosion) in New Zealand White rabbits (n=3)

The conjunctivae were swollen above normal, including swellings with lids about half closed and definitely injected blood vessels up to a diffuse red color from 1 h to 3 days after administration. The iris was reddened in 2 rabbits up to day 2 and in the remaining rabbit until day 3. The overall irritation score was 0.67 of 4. The iris irritation score was 0.78 of 2. The conjunctiva irritation score was 2.8 of 3. The chemosis score was 2.1 of 4. All signs of irritation were fully resolved by day 7. Conclusion: sodium methyl cocoyl taurate was an ocular irritant under these conditions.

16,17

10%; 0.1 mL in distilled water

Ocular irritation assay with and without rinsing. Rabbits (n=3). The eyes were observed at 1 h and 1, 2, 3, 4, and 7 days post administration

Unrinsed eyes-the maximum irritation index was 49.7 at 1 h, which was resolved at 4 days. Rinsed eyes-the maximum irritation index was 25.3 at 1 h, which was resolved at day 4.

38

Sodium Methyl Myristoyl Taurate 10% aqueous; 0.1 mL

Draize test, Japanese albino rabbits (n not specified)

Draize score ~2.2 out of 5 39

Sodium Methyl Oleoyl Taurate 1% Rabbits (n and species not

specified). The eyes were observed at 5 and 10 min, and 1 and 24 h.

The irritation score was 2 out of 4. Inflammation was observed, but not photophobia, discharge or clouded corneas.

36

100%; 0.1 g ; 0.1 mL

OECD TG 405 (Acute Eye Irritation/Corrosion)

Mild to moderate, early-onset and transient ocular changes, such as corneal opacity, reddening of the conjunctivae and sclerae, discharge and chemosis; resolved at 7 days after treatment. The individual mean scores for corneal opacity was 0.67 for all 3 rabbits. The individual mean scores for the conjunctivae were 2.00 for reddening and 0.67, 0.33 and 0.67 for chemosis for each rabbit. No abnormal findings were observed in the iris of any rabbit at any time. No corrosion was observed at any of the measuring intervals. White test item remnants were evident in the eye or conjunctival sac of 1 female 1 h after instillation. No staining of the treated eyes by the test item was observed and no clinical signs were observed. Based on the findings and in accordance with the classification criteria of Directive 67/548 EEC (DSD), the registration substance is considered to be "not irritating" to the rabbit eye. However, based on the criteria of Directive (EC) 1272/2008 (GHS-CLP) the registration substance should be considered to be "mildly irritating to eyes" (category 2B).

11-13



REFERENCES 1. Nikitakis, J and Breslawec HP. International Cosmetic Ingredient Dictionary and Handbook. 15 ed. Washington, DC: Personal Care Products

Council, 2014.

2. Andersen, FA. Annual review of cosmetic ingredient safety assessments 2002/2003. International Journal of Toxicology. 2005;24(Suppl. 1):1-102.

3. Andersen, FA. Annual review of cosmetic ingredient safety assessments - 2004/2005. International Journal of Toxicology. 2006;26(Suppl. 2):1-89.

4. Becker LC, Bergfeld WF, Belsito DV, Hill RA, Klaassen CD, Marks JG, Shank RC, Slaga TJ, Snyder PW, and Andersen FA. Final report of the amended safety assessment of myristic acid and its salts and esters as used in cosmetics. Int J Toxicol. 2010;29(Suppl 3):162-186.

5. Bergfeld, WF, Belsito, DV, Hill, RA, Klaassen, CD, Liebler, DC, Marks Jr, JG, Shank, RC, Slaga, TJ, Snyder, PW, Andersen, FA, Burnett, CL, and Fiume, M. Final report: Plant-derived fatty acid oils as used in cosmetics. Washington, DC, Cosmetic Ingredient Review. 2011. pp. 1-100.

6. Burnett, CL, Bergfeld, WF, Belsito, DV, Klaassen, CD, Marks Jr, JG, Shank, RC, Slaga, TJ, Snyder, PW, and Andersen, FA. Final report on the safety assessment of Cocos nucifera (coconut) oil and related ingredients. International Journal of Toxicology. 2011;30(Suppl 1):5S-16S.

7. Elder, RL. Final report on the safety assesment of coconut oil, coconut acid, hydrogenated coconut acid, and hydrogenated coconut oil. Journal of the American College of Toxicology. 1986;5(3):103-121.

8. Elder, RL. Final report on the safety assessment of oleic acid, lauric acid, palmitic acid, myrisitic acid, and stearic acid. Journal of the American College of Toxicology. 1987;6(3):321-401.

9. Elder, RL. Final report on the safety assessment of isoproyl linoleate. Journal of the American College of Toxicology. 1992;11(1):51-56.

10. Fiume, M, Bergfeld, WF, Belsito, DV, Hill, R, Klaassen, CD, Liebler, D, Marks Jr, JG, Shank, RC, Slaga, TJ, Snyder, PW, and Andersen, FA. Final report on stearyl heptanoate and related stearyl alkanoates as used in cosmetics. International Journal of Toxicology. 2012;31(Suppl. 2):141S-146S.

11. European Chemicals Agency (ECHA). Fatty acid chlorides, C12-18 (even numbered) and C18 unsatd., reaction products with sodium N-methyltaurinate. http://echa.europa.eu. Last Updated 2013.

12. European Chemicals Agency (ECHA). Fatty acid chlorides, C18 unsatd., reaction products with sodium N-methyltaurinate . http://echa.europa.eu. Last Updated 2013. Date Accessed 7-22-2015.

13. European Chemicals Agency (ECHA). Fatty acid chlorides, C12-18 (even numbered) and C18 unsatd., reaction products with sodium N-methyltarinate. http://echa.europa.eu. Last Updated 2015. Date Accessed 7-21-0015.

14. European Chemicals Agency (ECHA). Sodium N-methyltaurinate. http://echa.europa.eu. Last Updated 2015. Date Accessed 3-10-2015.

15. European Chemicals Agency (ECHA). Sodium taurinate. http://echa.europa.eu. Last Updated 2015. Date Accessed 3-10-2015.

16. European Chemicals Agency (ECHA). Sodium methyl cocoyl taurate. http://echa.europa.eu. Last Updated 2015. Date Accessed 3-10-2015.

17. CRODA Europe Limited. 2015. Chemical safety report: Ethanesulfonic acid, 2-(methylamino)-, N-coco acyl derivs., sodium salts (Sodium Methyl Cocoyl Taurate). Unpublished data submitted by Personal Care Products Council.

18. Jeen. 2013. Specifications JEEPON T-33 (33% Sodium Methyl Oleoyl Taurate). Unpublished data submitted by Personal Care Products Council.

19. Jeen. 2013. Specifications JEEPON 30 A (30% Sodium Methyl Cocoyl Taurate). Unpublished data submitted by Personal Care Products Council.

20. Jeen. 2013. Specifications JEEPON 24 A (24% Sodium Methyl Cocoyl Taurate). Unpublished data submitted by Personal Care Products Council.

21. Jeen. 2015. JEEPON T-33 (Sodium Methyl Oleoyl Taurate) Compositional breakdown. Unpublished data submitted by Personal Care Products Council.

22. Jeen. 2015. JEEPON 30-A (Sodium Methyl Cocoyl Taurate): Compositional breakdown. Unpublished data submitted by Personal Care Products Council.

23. Jeen. 2015. JEEPON 24-A (Sodium Methyl Cocoyl Taurate): Compositional breakdown. Unpublished data submitted by Personal Care Products Council.

24. Nonomura, Yoshimune, Kurita, Kenkou, Kashimoto, Akio, Hotta, Hajime, Kaneko, Yohei, and Iitaka, Kazuhiro. The internal structure and tribology of calcium lauroyl taurate. Chemistry Letters. 2002;31(2):216-217.


http://echa.europa.eu/






25. O'Neil, MJ. The Merck Index - An encyclopedia of chemicals, drugs, and biologicals. Cambridge, UK: Royal Society of Chemistry, 2013.

26. Day, JF; inventor. Preparation of N-acyl taurates. 5,496,959. 3-5-1996.

27. Hu, S; inventor. Cyclic process for the production of taurine. US 8,609,890. 12-17-2013.

28. Food and Drug Administration (FDA). Frequency of use of cosmetic ingredients; FDA Database. Washington, DC, FDA. 2015.

29. Personal Care Products Council. 7-7-2015. Concentration of Use by FDA Product Category: Alkyl Taurate Amides and Salts. Unpublished data submitted by Personal Care Products Council.

30. European Commission. CosIng database; following Cosmetic Regulation No. 1223/2009. http://ec.europa.eu/consumers/cosmetics/cosing/. Last Updated 2014. Date Accessed 1-14-0015.

31. European Food Safety Authority (EFSA) Panel on Additives and Products or Substances Used in Animal Feed (FEEDAP. Scientific Opinion on the safety and efficacy of taurine as a feed additive for all animal species. EFSA Journal. 2012;10(6):2736

32. European Union Scientific Committee on Food. Opinion on Caffeine, Taurine and D-Glucurono - g -Lactone as constituents of so-called "energy" drinks (expressed on 21 January 1999). http://ec.europa.eu/food/fs/sc/scf/out22_en.html. Last Updated 1999. Date Accessed 7-27-2015.

33. European Parliment and of Council and Regulations (EC). Commision regulations (EC). Official Journal of the European Union. 11-30-2009;314:36-42. http://eur-lex.europa.eu/legal-content/EN/TXT/PDF/?uri=CELEX:32009R1170&from=EN.

34. Huxtable, RJ. Physiological actions of taurine. Physiological Reviews. 1992;72(1):101-163.

35. Solvay. Safety Data Sheet: GEROPON T 77 [pamphlet]. Santo André, São Paulo: Rhodia Poliamida e Especialidades Ltda; 2013.

36. Hopper, SS, Hulpieu, HR, and Cole, VV. Some toxicological properties of surface-active agents. Journal of the American Parmaceutical Association. 1949;38(8):428-432.

37. Gershbein, LL. Percutaneous toxicity of thioglycolate mixtures in rabbits. Journal of Pharmaceutical Sciences. 1979;68(10):1230-1235.

38. Anonymous. 2015. Summary of eye and skin irritation tests of Sodium Methyl Cocoyl Taurate. Unpublished data submitted by Personal Care Products Council.

39. Okahata, Yoshio and Ebato, Hiroshi. Absorption behaviors of surfactant molecules on a lipid-coated quartz-crystal microbalance. An alternative to eye-irritant tests. Analytical Chemistry. 1991;63(3):203-207.

40. Uehara, S, Inomata, N, Suzuki, A, Matsuura, M, and Aihara, M. Severe contact urticarial syndrome due to oxidative hair dye containing para-aminophenol and sodium-methyl-oleoyl-taurate. The Journal of Dermatology. 2014;41(6):560-561.

41. Guidechem. Calcium lauroyl taurate (CAS No. 138705-25-6). http://www.guidechem.com/reference/dic-462936.html. Last Updated 2010.

42. ChemNet.com. CAS, cas.ChemNet.com: 22890-34-2 potassium 2-aminoethanesulfonate. http://www.chemnet.com/cas/en/22890-34-2/potassium-2-aminoethanesulfonate.html. Last Updated 2015. Date Accessed 3-30-2015.

43. ChemNet.com. 70609-66-4, Sodium 2[(1-oxododecyl)amino]ethanesulphonate [pamphlet]. 2015.

44. Nikko Chemicals Col, Ltd. Material safety data sheet, Sodium Methyl Lauroyl Taurate [pamphlet]. Tokyo, Japan: Barnet Products Corp.; 2015.

45. National Center for Biotechnology Information. PubChem Compound Database; CID 23664339. http://pubchem.ncbi.nlm.nih.gov/compound/23664339. Last Updated 2015.

46. Guidechem. Chemical Trading Guide: Sodium2-[methyl(1-oxo-9-octadecenyl)amino]ethanesulphonate (CAS No. 7308-16-9). http://www.guidechem.com/reference/dic-311112.html. Last Updated 2015.

47. Guidechem. Chemical Trading Guide: CAS No. 3737-55-1 (Ethanesulfonic acid,2-[methyl(1-oxohexadecyl)amino]-, sodium salt (1:1) ). http://www.guidechem.com/cas-373/3737-55-1.html. Last Updated 2015.

48. Chemical Book. Chemical Book, N-methyltaurine sodium salt. http://www.chemicalbook.com/CAS_4316-74-9.htm. Last Updated 2010.

49. Biosynth Chemistry & Biology. Safety data sheet: Sodium taurinate. 2014. pp.1-4.

50. Chemical Book. Chemical Book, Taurine sodium. http://www.chemicalbook.com/ChemicalProductProperty_EN_CB4841014.htm. Last Updated 2010.


http://ec.europa.eu/consumers/cosmetics/cosing/

http://ec.europa.eu/food/fs/sc/scf/out22_en.html

http://eur-lex.europa.eu/legal-content/EN/TXT/PDF/?uri=CELEX:32009R1170&from=EN

http://www.guidechem.com/reference/dic-462936.html

http://www.chemnet.com/cas/en/22890-34-2/potassium-2-aminoethanesulfonate.html

http://www.chemnet.com/cas/en/22890-34-2/potassium-2-aminoethanesulfonate.html

http://pubchem.ncbi.nlm.nih.gov/compound/23664339

http://www.guidechem.com/reference/dic-311112.html

http://www.guidechem.com/cas-373/3737-55-1.html

http://www.chemicalbook.com/CAS_4316-74-9.htm

http://www.chemicalbook.com/ChemicalProductProperty_EN_CB4841014.htm

Memorandum

TO: Lillian Gill, D.P.A.Director - COSMETIC INGREDIENT REVIEW (CIR)

FROM: Beth A. Lange, Ph.D. Industry Liaison to the CIR Expert Panel

DATE: July 7, 2015

SUBJECT: Concentration of Use by FDA Product Category: Alkyl Taurate Amides and Salts


Concentration of Use by FDA Product Category – Alkyl Taurate Amides and Salts*

Sodium Methyl Cocoyl Taurate Calcium Lauroyl Taurate Magnesium Methyl Cocoyl Taurate Potassium Cocoyl Taurate Potassium Methyl Cocoyl Taurate Potassium Taurate Sodium Caproyl Methyltaurate Sodium Cocoyl Taurate Sodium N-Isostearoyl Methyltaurate Sodium Lauroyl Taurate Sodium Methyl Lauroyl Taurate

Sodium Methyl Myristoyl Taurate Sodium Methyl Oleoyl Taurate Sodium Methyl Palmitoyl Taurate Sodium Methyl Stearoyl Taurate Sodium Methyltaurate Sodium Methyltaurate Isopalmitamide Sodium Methyltaurine Cocoyl Methyltaurate Sodium Taurate Sodium Taurine Cocoyl Methyltaurate

Ingredient Product Category Maximum Concentration of Use

Sodium Methyl Cocoyl Taurate Bubble baths 0.38-1.2% Sodium Methyl Cocoyl Taurate Other bath preparations 0.68% Sodium Methyl Cocoyl Taurate Eyeliner 2.4% Sodium Methyl Cocoyl Taurate Shampoos (noncoloring) 0.000095-9.7% Sodium Methyl Cocoyl Taurate Tonics, dressings and other hair

grooming aids 0.21%

Sodium Methyl Cocoyl Taurate Other hair preparations (noncoloring) 1.6% Sodium Methyl Cocoyl Taurate Hair dyes and colors 0.5% Sodium Methyl Cocoyl Taurate Face powders 6% Sodium Methyl Cocoyl Taurate Foundations 1.2% Sodium Methyl Cocoyl Taurate Basecoats and undercoats (manicuring

preparations) 3.2%

Sodium Methyl Cocoyl Taurate Cuticle softeners 3.9% Sodium Methyl Cocoyl Taurate Dentifrices (aerosol, liquid, pastes and

powders) 1.2%

Sodium Methyl Cocoyl Taurate Mouthwashes and breath fresheners (liquids and sprays)

0.24%

Sodium Methyl Cocoyl Taurate Bath soaps and detergents 4.5-10.2% Sodium Methyl Cocoyl Taurate Other personal cleanliness products 0.6-2% Sodium Methyl Cocoyl Taurate Skin cleansing (cold creams, cleansing

lotions, liquids and pads) 2.4-6%

Sodium Methyl Cocoyl Taurate Face and neck products Not spray

1.3-1.5%

Sodium Methyl Cocoyl Taurate Body and hand products Not spray

0.9%

Sodium Methyl Cocoyl Taurate Foot products Not spray, not powder, rinse-off

13%

Calcium Lauroyl Taurate Eye shadow 0.48% Calcium Lauroyl Taurate Foundations 11% Magnesium Methyl Cocoyl Shampoos (noncoloring) 0.26%


Taurate Sodium Cocoyl Taurate Bath oils, tablets and salts 7% Sodium Cocoyl Taurate Eye makeup removers 0.3% Sodium Cocoyl Taurate Hair conditioners 3% Sodium Cocoyl Taurate Shampoos (noncoloring) 9% Sodium Cocoyl Taurate Wave sets 0.75% Sodium Cocoyl Taurate Other personal cleanliness products

Not spray 21.5%

Sodium Cocoyl Taurate Shaving cream (aerosol, brushless and lather)

3%

Sodium Cocoyl Taurate Skin cleansing (cold creams, cleansing lotions, liquids and pads)

20%

Sodium Cocoyl Taurate Face and neck products Not spray

2%

Sodium Cocoyl Taurate Body and hand products Not spray

2%

Sodium Cocoyl Taurate Paste masks and mud packs 0.3% Sodium Cocoyl Taurate Other skin care preparations 2% Sodium Lauroyl Taurate Shampoos (noncoloring) 0.09% Sodium Lauroy Taurate Skin cleansing (cold creams, cleansing

lotions, liquids and pads) 1%

Sodium Methyl Lauroyl Taurate Dentifrices 0.7% Sodium Methyl Lauroyl Taurate Mouth washes and breath fresheners 0.3% Sodium Methyl Lauroyl Taurate Skin cleansing (cold creams, cleansing

lotions, liquids and pads) 0.2%


Shampoos (noncoloring) 1%


Skin cleansing (cold creams, cleansing lotions, liquids and pads)

6%

Sodium Methyl Oleoyl Taurate Bubble baths 28% Sodium Methyl Stearoyl Taurate Eye lotion 0.5-0.9% Sodium Methyl Stearoyl Taurate Hair conditioners 2% Sodium Methyl Stearoyl Taurate Rinses (noncoloring) 1% Sodium Methyl Stearoyl Taurate Tonics, dressings and other hair

grooming aids 1%

Sodium Methyl Stearoyl Taurate Wave sets 0.8% Sodium Methyl Stearoyl Taurate Hair tints 2% Sodium Methyl Stearoyl Taurate Hair bleaches 0.1-4% Sodium Methyl Stearoyl Taurate Dentifrices (aerosol, liquid, pastes and

powders) 0.0076%

Sodium Methyl Stearoyl Taurate Deodorant Not spray

0.028%

Sodium Methyl Stearoyl Taurate Skin cleansing (cold creams, cleansing lotions, liquids and pads)

0.35%

Sodium Methyl Stearoyl Taurate Face and neck products Not spray

1%


Sodium Methyl Stearoyl Taurate Body and hand products Not spray

0.7%

Sodium Methyl Stearoyl Taurate Moisturizing products Not spray

0.024-1%

Sodium Methyltaurate Hair conditioners 0.11% Sodium Methyltaurate Rinses (noncoloring) 0.11% Sodium Methyltaurate Shampoos (noncoloring) 3% Sodium Methyltaurate Skin cleansing (cold creams, cleansing

lotions, liquids and pads) 2%


Shampoos (noncoloring) 6%


Skin cleansing (cold creams, cleansing lotions, liquids and pads)

2%

*Ingredients included in the title of the table but not found in the table were included in the concentration of use survey, but no uses were reported.

Information collected in 2015 Table prepared July 2, 2015


2015 VCRP Data for Taurate Amides and Taurate Salts

01C - Other Baby Products SODIUM METHYL COCOYL TAURATE 1

02B - Bubble Baths SODIUM METHYL COCOYL TAURATE 7

05F - Shampoos (non-coloring) SODIUM METHYL COCOYL TAURATE 68

05G - Tonics, Dressings, and Other Hair Grooming Aids

SODIUM METHYL COCOYL TAURATE 2

10A - Bath Soaps and Detergents SODIUM METHYL COCOYL TAURATE 101

10E - Other Personal Cleanliness Products SODIUM METHYL COCOYL TAURATE 32

11E - Shaving Cream SODIUM METHYL COCOYL TAURATE 4

11G - Other Shaving Preparation Products SODIUM METHYL COCOYL TAURATE 2

12A - Cleansing SODIUM METHYL COCOYL TAURATE 112

12C - Face and Neck (exc shave) SODIUM METHYL COCOYL TAURATE 1

12D - Body and Hand (exc shave) SODIUM METHYL COCOYL TAURATE 5

12H - Paste Masks (mud packs) SODIUM METHYL COCOYL TAURATE 3

12J - Other Skin Care Preps SODIUM METHYL COCOYL TAURATE 1

339

05F - Shampoos (non-coloring) SODIUM METHYL OLEOYL TAURATE 1

12C - Face and Neck (exc shave)

SODIUM METHYL STEAROYL TAURATE 3

12D - Body and Hand (exc shave)

SODIUM METHYL STEAROYL TAURATE 1

12F - Moisturizing SODIUM METHYL STEAROYL TAURATE 4

8 12A - Cleansing SODIUM METHYLTAURATE 2


No uses were reported for: Calcium Lauroyl Taurate Magnesium Methyl Cocoyl Taurate Potassium Cocoyl Taurate Potassium Methyl Cocoyl Taurate Potassium Taurate Sodium Caproyl Methyltaurate Sodium Cocoyl Taurate Sodium N-Isostearoyl Methyltaurate Sodium Lauroyl Taurate Sodium Methyl Lauroyl Taurate Sodium Methyl Myristoyl Taurate Sodium Methyl Palmitoyl Taurate Sodium Methyltaurate Isopalmitamide Sodium Methyltaurine Cocoyl Methyltaurate Sodium Taurate Sodium Taurine Cocoyl Methyltaurate











Memorandum

TO: Lillian Gill, D.P.A.Director - COSMETIC INGREDIENT REVIEW (CIR)

FROM: Beth A. Lange, Ph.D. Industry Liaison to the CIR Expert Panel

DATE: July 20, 2015

SUBJECT: Sodium Methyl Cocoyl Taurate

Croda Europe Limited. 2015. Chemical safety report: Ethanesulfonic acid, 2-(methylamino) -, N-cocoacyl derivs., sodium salts (Sodium Methyl Cocoyl Taurate).


CHEMICAL SAFETY REPORT

Substance Name: Ethanesulfonic acid, 2-(methylamino) -, N-coco acyl derivs., sodium salts

EC Number: 263-174-9

CAS Number: 61791-42-2

Registrant's Identity: Croda Europe Limited


EC number:

263-174-9

Ethanesulfonic acid, 2-(methylamino)-, N-coco acyl derivs., sodium salts CAS number:

61791-42-2

2015-06-05 CSR-PI-5.4.0 CHEMICAL SAFETY REPORT 2

1. IDENTITY OF THE SUBSTANCE AND PHYSICAL

AND CHEMICAL PROPERTIES

1.1. Name and other identifiers of the substance

The substance Ethanesulfonic acid, 2-(methylamino) -, N-coco acyl derivs., sodium salts is a UVCB (origin:

organic) having the following characteristics and physical–chemical properties (see the IUCLID dataset for

further details).

Table 1. Substance identity

EC number: 263-174-9

EC name: Ethanesulfonic acid, 2-(methylamino)-, N-coco acyl derivs., sodium salts

CAS number (EC inventory): 61791-42-2

IUPAC name: Ethanesulfonic acid, 2-(methylamino)-, N-coco acyl derivs., sodium salts

Description: UVCB - due to C chain variability associated with the coconut fatty acid

starting material.

Molecular formula: UVCB

Molecular weight range:

Structural formula:

1.2. Composition of the substance

Name: Ethanesulfonic acid, 2-(methylamino) -, N-coco acyl derivs., sodium salts

Description: UVCB - due to C chain variability associated with the coconut fatty acid starting material. The final

product has a compostion that varies from batch to batch.

Degree of purity: ca. 100.0 % (w/w)

Table 2. Constituents

Constituent Typical concentration Concentration range Remarks

Fatty acid, C8, sodium-N,

N-methyl taurate

ca. 3.0 % (w/w) > 0.0 — <= 8.0 % (w/w) Ref analytical report in

section 1.4


N-methyl taurate

ca. 8.0 % (w/w) > 0.0 — < 10.0 % (w/w) Ref analytical report in

section 1.4

sodium

2-[methyl(1-oxododecyl)a

mino]ethanesulphonate

EC no.: 224-388-8

ca. 54.0 % (w/w) >= 40.0 — <= 62.0 %

(w/w)

Ref analytical report in

section 1.4


N-methyl taurate

ca. 20.0 % (w/w) >= 15.0 — <= 30.0 %

(w/w)

Ref analytical report in

section 1.4

sodium

2-[methyl(1-oxohexadecyl

)amino]ethanesulphonate

EC no.: 223-114-4

ca. 8.0 % (w/w) >= 5.0 — <= 15.0 % (w/w) Ref analytical report in

section 1.4


EC number:

263-174-9


61791-42-2


Constituent Typical concentration Concentration range Remarks

sodium

2-[methyloleoylamino]eth

ane-1-sulphonate

EC no.: 205-285-7

ca. 1.0 % (w/w) > 0.0 — < 15.0 % (w/w) Ref analytical report in

section 1.4

sodium

2-[methyl(1-oxooctadecyl)

amino]ethanesulphonate

EC no.: 205-738-9

ca. 6.0 % (w/w) > 0.0 — <= 10.0 % (w/w) Ref analytical report in

section 1.4

sodium N-methyltaurinate

EC no.: 224-339-0

0.0 % (w/w) >= 0.0 — < 3.0 % (w/w) Ref analytical report in

section 1.4, including

certificate of analysis for

batch tested.

sodium chloride

EC no.: 231-598-3

0.3 % (w/w) >= 0.0 — <= 1.5 % (w/w) Ref analytical report in

section 1.4, including

certificate of analysis for

batch tested


EC number:

263-174-9


61791-42-2


5. HUMAN HEALTH HAZARD ASSESSMENT

5.1. Toxicokinetics (absorption, metabolism, distribution and

elimination)

5.1.1. Non-human information

5.1.2. Human information

5.1.3. Summary and discussion of toxicokinetics

There were no experimental studies available investigating the toxicokinetic properties of Sodium methyl cocoyl

taurate. Therefore, whenever possible, toxicokinetic behavior was assessed taking into account the available

information on physico-chemical and toxicological characteristics of Sodium methyl cocoyl taurate according to

the “Guidance on information and chemical safety assessment Chapter R.7c: Endpoint specific guidance (ECHA,

2012) ”.

Absorption

Sodium methyl cocoyl taurate is a UVCB substance and has a molecular weight of 287.4 - 427.6 g/mol. It is a

white solid powder with a moderate to high water solubility (0.23 – 250 g/L), a vapour pressure of < 1 Pa at 25 °C

and a log Po/w of -0.44 - 0.54.

The molecular weight, the water solubility and the moderate log Po/w value favour an absorption along the

gastrointestinal tract. The acute oral toxicity study of Sodium methyl cocoyl taurate and also of the read-across

substance Sodium methyl oleyl taurate has been investigated in rats (Clariant, 1987). The LD50 from these studies

was determined to be > 2000 mg/kg bw for male and female animals, respectively. Therefore, Sodium methyl

cocoyl taurate is considered to be easily absorbed after oral ingestion but of low toxicity.

The particle size determination of Sodium methyl cocoyl taurate revealed percentile values of D10: 3.87 µm, D50:

16.58 µm and D90: 59.97 µm. Particles with and aerodynamic diameter below 100 µm have the potential to be

inhaled and may reach the thoracic region of the respiratory tract if they are < 50 µm and the alveolar region if they

are < 15 µm. Therefore, inhalation of Sodium methyl cocoyl taurate is generally possible. However, since the

substance is a solid with a very low vapour pressure (<1 Pa at 25 °C), it is probably not available for inhalation as

vapour. Furthermore, the use of the substance is not anticipated to result in the formation of aerosols, particles or

droplets of inhalable size. Thus, exposure of humans via inhalation is unlikely.

Regarding the water solubility (0.23 - 250 g/L) and the lipophilic properties of Sodium methyl cocoyl taurate (log

Po/w-0.44 - 0.54), dermal absorption is anticipated to be generally possible. However, due to its solid state and the

moderate molecular weight close to 500 g/mol, dermal uptake is overall considered to be low. This result is

underpinned by a Dermwin v2.0 QSAR modeling which estimated a dermal permeability constant Kp 9.38E-006

cm/h for Sodium methyl cocoyl taurate. Similar to the approach taken by Kroes et al. (2007), the maximum flux

Imax (Imax = Kp [cm/h] x water solubility [mg/cm³]) was calculated, resulting in dermal absorption of 0.002 and

2.345 µg substance/cm²/h.

Distribution

Distribution within the body depends on the molecular weight, the lipophilic character and water solubility of a

substance. In general, the smaller the molecule, the wider is the distribution. If the molecule is lipophilic, it is

likely to distribute into cells and the intracellular concentration may be higher than extracellular concentration

particularly in fatty tissues (ECHA, 2012). With a molecular weight of 287.4 - 427.6 g/mol and the slight

lipophilic character (log Po/w >0), Sodium methyl cocoyl taurate is considered to distribute within the body and to

enter particularly in fatty tissues to a certain but low extent.

Metabolism and Excretion

Following the accepted metabolic pathways for alkylamides, the amide linkage of Sodium methyl cocoyl taurate

will initially be hydrolyzed to generate sodium N-methyl taurine and fatty acids by fatty acid amide hydrolase, the

principal catabolic enzyme for fatty acid amides having both, esterase and amidase activity (EPA, 2009). This


EC number:

263-174-9


61791-42-2


metabolism step was also observed after modeling of potential metabolites with the hydrolysis simulator of the

OECD toolbox Vs. 3.2. The resulting anionic sulfonate may be either directly excreted in the urine or converted to

a dianionic salt with glucuronic acid that is excreted. The fatty acid moiety is metabolized in a second step via the

ß-oxidation pathway (Stryer, 1996). This metabolic behaviour was also demonstrated for sodium

N-oleoyl-N-methyltaurine in Pseudomonas alcaligenes (Denger et al. 2008).

Denger, K., Mayer, J., Hollemeyer, K., Cook, A. M. (2008), FEMS Microbiol. Lett. 288: 112-117

EPA (2009), Final Rule, Federal Register 74, 2009 [EPA-HQ-OPP-2008-0725; FRL-8426-8]

Stryer, L. (1996). Biochemie. 4. Auflage. Heidelberg Berlin Oxford: Spektrum Akademischer Verlag.

The following information is taken into account for any hazard / risk assessment:

No studies adressing toxicokinetics are available for the test substance. However, structure related consideration

suggests enzymatic degradation in analogy to accepted metabolic pathways for amide hydrolysis and fatty acid

ß-oxidation. The metabolism will not generate metabolites of toxicological concern. Excretion of postulated

metabolites is considered fast and complete. Due to its solid state, the moderate molecular weight close to 500 and

the ionic nature, only limited dermal penetration is expected.

5.2. Acute toxicity


5.2.1.1. Acute toxicity: oral

The results of studies on acute toxicity after oral administration are summarised in the following table:

Table 3. Studies on acute toxicity after oral administration

Method Results Remarks Reference

rat (Sprague-Dawley) male/female

oral: gavage

OECD Guideline 401 (Acute Oral

Toxicity)

LD50: > 2000 mg/kg bw

(male/female) based on: test

mat.

1 (reliable without

restriction)

weight of evidence

experimental result

Test material

(Common name):

Fatty acid chlorides,

C12-18 (even

numbered) and C18

unsatd., reaction

products with

sodium

N-methyltaurinate

Form: paste

Hoechst AG

(1987a)

rat (Wistar) male/female

oral: gavage

OECD Guideline 401 (Acute Oral

Toxicity)

LD50: > 2000 mg/kg bw


mat.

2 (reliable with

restrictions)

weight of evidence

read-across from

supporting substance

(structural analogue

or surrogate)

Hoechst AG

(1987b)


EC number:

263-174-9


61791-42-2



Test material (CAS

number): 137-20-2

(See endpoint

summary for

justification of

read-across)

Form: solid

5.2.1.2. Acute toxicity: inhalation

Data waiving

Information requirement: Acute toxicity after inhalation exposure

Reason: other justification

Justification: In accordance with Column 2 of Annex VIII, Section 8.5.2 of Regulation (EC) 1907/2006,

testing by the inhalation route is appropriate if exposure of humans via inhalation is likely taking into account

the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an

inhalable size.

The substance is a solid with negligible vapour pressure (4.4E-5 Pa at 25 °C). The use of the substance is not

anticipated to result in the formation of aerosols, particles or droplets of inhalable size. Thus, exposure of

humans via inhalation is unlikely.

Therefore, testing for acute toxicity by the inhalation route is not appropriate and should be avoided for

reasons of animal welfare.

5.2.1.3. Acute toxicity: dermal

The results of studies on acute toxicity after dermal administration are summarised in the following table:

Table 4. Studies on acute toxicity after dermal administration


rat (Wistar) male/female

Coverage: semiocclusive

OECD Guideline 402 (Acute Dermal

Toxicity)

LD50: > 2000 mg/kg bw


mat.

2 (reliable with

restrictions)

key study

read-across from



or surrogate)

Test material (CAS

number): 137-20-2

(See endpoint

summary for

justification of

read-across)

Form: paste

Battelle Europe

(1991)

5.2.1.4. Acute toxicity: other routes



EC number:

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61791-42-2


5.2.3. Summary and discussion of acute toxicity

Acute oral toxicity

Data requirement on acute oral dose toxicity of Sodium methyl cocoyl taurate is covered in a weight of evidence

approach with data on Sodium methyl cocoyl taurate and the source substance Sodium methyl oleyl taurate. Both,

the target and the source substance are chemically reaction products of fatty acid chlorides with Sodium N-methyl

taurinate. The only difference between both substances is seen in the origin of the fatty acid, which represents a

C12 -18(even numbered, C18 unsaturated) -alkyl chain in the target and a C18 -(unsaturated) -alkyl chain in the

source molecule. The molecular structure ofboth materials is characterized by the hydrophobic aliphatic alkyl

chain with N-methyl taurine as hydrophilic head group, giving the whole molecule amphiphilic properties.

The acute oral toxicity of Sodium methyl cocoyl taurate was tested in 5 male and 5 female Sprague Dawley rats at

a dose level of 2000 mg/kg body weight (limit test) according to OECD Guideline 401 under GLP conditions

(Clariant, 1987). The animals received the compound once as a 20% suspension in water via gavage and the

administration volume was 10 mL/kg body weight. The observation period following treatment lasted 14 days. No

mortality occurred. Unspecific clinical symptoms like hypoactivity, squatting posture and coat bristling were

observed in all animals from 10 - 30 minutes up to 4 - 6 hours post application. From day 1 until the end of the

observation period no clinical signs were observed. The development of body weight was not impaired. None of

the animals showed macroscopically visible changes at gross pathology. Based on the study results, the LD50 of

Sodium methyl cocoyl taurate is greater than 2000 mg/kg body weight in rats.

The acute oral toxicity of the source substance Sodium methyl oleyl taurate was tested in 5 male and 5 female

Sprague Dawley rats at a dose level of 2000 mg/kg body weight (limit test) according to OECD Guideline 401

under GLP conditions (Clariant, 1987). The animals received the compound once as a 20% suspension in water

via gavage and the administration volume was 10 mL/kg body weight. The observation period following

treatment lasted 14 days. No mortality occurred. Unspecific clinical symptoms like hypoactivity, squatting

posture and coat bristling was observed in all animals from 10 - 60 minutes post application. From 1 hour after

adminstration onwards no clinical symptoms of toxicity were observed until the end of the observation period.

Body weight development was not impaired. None of the animals showed macroscopically visible changes at

gross pathology. Based on the study results, the LD50 for Sodium methyl oleyl taurate is greater than 2000 mg/kg

body weight in rats.

Acute dermal toxicity

Data requirement on acute dermal dose toxicity of Sodium methyl cocoyl taurate is covered by a read-across to the

source substance Sodium methyl oleyl taurate. Both, the target and the source substance are chemically reaction

products of fatty acid chlorides with Sodium N-methyl taurinate. The only difference between both substances is

seen in the origin of the fatty acid, which represents a C12 -18(even numbered, C18 unsaturated) -alkyl chain in

the target and a C18 -(unsaturated) -alkyl chain in the source molecule. The molecular structure ofboth materials is

characterized by the hydrophobic aliphatic alkyl chain with N-methyl taurine as hydrophilic head group, giving

the whole molecule amphiphilic properties.

The source substance Sodium methyl oleyl taurate was tested for acute dermal toxicity in 5 male and 5 female rats

according to OECD guideline 402 following the principles of GLP (Leuna-Tenside, 1991). After administration of

a single dermal dose of 2000 mg/kg body weight, no specific test item related findings were observed during the

subsequent 14 day observation period. Body weight gain was not adveresly effected througout the study period.

At necropsy, no specific compound-associated pathology was found, except some residual discoloration of the

skin at the application site. Based on the study results, the acute dermal toxicity (LD 50) of sodium methyl oleyl

taurate in the rat was determined to be greater than 2000 mg/kg body weight.


Oral (OECD 401), rat: LD50 >2000 mg/kg bw

Dermal (OECD 402), rat: LD50 >2000 mg/kg bw

Value used for CSA:

Acute oral toxicity: No adverse effect observed

Acute dermal toxicity: No adverse effect observed


EC number:

263-174-9


61791-42-2


Acute inhalation toxicity: No study available

Justification for classification or non classification

The available data on acute oral and dermal toxicity of the test substance do not meet the criteria for classification

according to Regulation (EC) No 1272/2008 and Directive 67/548/EEC, and are therefore conclusive but not

sufficient for classification.

No data is available on acute inhalation toxicity.

5.3. Irritation

5.3.1. Skin

5.3.1.1. Non-human information

The results of studies on skin irritation are summarised in the following table:

Table 5. Studies on skin irritation


in vitro study

human (EPISKIN™

model kit 0.38 cm²;

reconstructed

three-dimensional human

epidermis)

Coverage: open in vitro

system (intact

reconstructed human

epidermis)

OECD Guideline 431 (In

Vitro Skin Corrosion:

Human Skin Model Test)

EU Method B.40 (Skin

Corrosion)

not corrosive (in vitro)

cell viability (%): 100 (mean value of

negative controls (0.9% sodium chloride

solution)) (Time point: 240 min) (not

applicable)

cell viability (% of negative control): 12.8

(mean value of the positive controls

(glacial acetic acid (50 µL))) (Time point:

240 min) (not applicable)


(mean value of the test item (20 mg))

(Time point: 240 min) (not applicable)







1 (reliable without

restriction)

key study

experimental result

Test material (EC

name):

Ethanesulfonic

acid,

2-(methylamino)-,

N-coco acyl derivs.,

sodium salts

Warren, N.

(2013a)

in vitro study

human (EPISKIN™

reconstructed human

epidermis model)

Coverage: open in vitro

system (intact

reconstructed human

epidermis)

OECD Guideline 439 (In

Vitro Skin Irritation)

EU method B.46 (In vitro

skin irritation:

reconstructed human

not irritating (in vitro)

cell viability (%): 100 (mean (value of

negative controls)) (Time point: 15 min)

(reversibility: not applicable) (standard

deviation: 3.8%)


(mean (value of positive control)) (Time

point: 15 min) (reversibility: not

applicable) (standard deviation: 1.0%)


(mean (value of the test item (100%)))

(Time point: 15 min) (reversbility: not

applicable) (standard deviation: 6.2%)

1 (reliable without

restriction)

key study

experimental result

Test material (EC

name):

Ethanesulfonic

acid,

2-(methylamino)-,


sodium salts

Warren, N.

(2013b)


EC number:

263-174-9


61791-42-2



epidermis model test)

Data waiving

Information requirement: Skin irritation

Reason: study scientifically unjustified

Justification: In accordance with Annex XI of Regulation (EC) 1907/2006, if the results obtained from the

use of in vitro methods do not indicate a certain dangerous property, the relevant test shall nevertheless be

carried out at the appropriate tonnage level to confirm the negative result, unless testing is not required in

accordance with Annexes VII to X or the other rules in Annex XI.

Such confirmation may be waived, if the following conditions are met:

(1) results are derived from an in vitro method whose scientific validity has been established by a validation

study, according to internationally agreed validation principles;

(2) results are adequate for the purpose of classification and labelling and/or risk assessment; and

(3) adequate and reliable documentation of the applied method is provided.

The substance was tested for in vitro skin corrosion in a GLP-compliant study according to OECD guideline

431 / EU Method B.40. The tissue viability was more than 50% after a 3 minutes exposure time and more than

15 % after a 60 minutes exposure time. The test substance was therefore considered as non-corrosive to skin

and hence fulfils the test method criteria for non-classification.

The substance was furthermore tested for in vitro skin irritation in a GLP-compliant study according to OECD

guideline 439 / EU Method B.46. The tissue viability after exposure and post-treatment incubation was more

than 50%. The test substance was therefore considered as non-irritant to skin and hence fulfils the test method

criteria for non-classification.

The results are derived from scientific valid in vitro methods, are adequate for the purpose of classification and

labelling, and adequate and reliable documentation is provided in the technical dossier and the chemical safety

report. Thus, all conditions for waiving a test confirming the negative result are met and further testing on

vertebrate animals for that property shall be omitted.

5.3.1.2. Human information

5.3.2. Eye


The results of studies on eye irritation are summarised in the following table:

Table 6. Studies on eye irritation


rabbit (New Zealand

White)

OECD Guideline 405

(Acute Eye Irritation /

Corrosion)

irritating

Cornea score:

0.67 of max. 4 (mean (all animals))

(Time point: 24 h, 48 h , 72 h) (fully

reversible within: 7 days)

0 of max. 4 (animal #1 (mean)) (Time

point: 24 h, 48 h, 72 h) (no irritation

observed)

1.67 of max. 4 (animal #2 (mean))

(Time point: 24 h, 48 h, 72 h) (fully




1 (reliable without

restriction)

key study

experimental result

Test material

(Common name):

Fatty acid chlorides,

C12-18 (even

numbered) and C18

unsatd., reaction

products with

sodium

Hoechst AG

(1987c)


EC number:

263-174-9


61791-42-2



reversible within: 48 hours)

Iris score:

0.78 of max. 2 (mean (al animals))







point: 24 h, 48 h, 72 h) (fully reversible

within: 7 days)




Conjunctivae score:




2.7 of max. 3 (animal #1 (mean)) (Time


within: 7 days)



within: 7 days)



within: 7 days)

Chemosis score:






within: 7 days)



within: 7 days)




N-methyltaurinate

Form: paste

in vitro study

cattle

OECD Guideline 437

(Bovine Corneal Opacity

and Permeability Test

Method for Identifying

Ocular Corrosives and

Severe Irritants)

non-corrosive

: 53.7 (mean (of all 3 eyes)) (Time point:

240 min + 90 min) (reversibility: not

applicable) (Test substance)






1 (reliable without

restriction)

supporting study

experimental result

Test material (EC

name):

Ethanesulfonic

acid,

2-(methylamino)-,

Warren, N.

(2013c)


EC number:

263-174-9


61791-42-2




: 59 (mean (of all 3 eyes)) (Time point:


applicable) (Positive control)









applicable) (Solvent control)








sodium salts


5.3.3. Respiratory tract



5.3.4. Summary and discussion of irritation

Skin irritation/corrosion

In a GLP-compliant study according to OECD Guideline 431, the skin corrosion potential of Sodium methyl

cocoyl taurate was evaluated using the EPISKIN™ reconstructed human epidermis model after a treatment period

of 3, 60 and 240 min (Warren, 2013). The principle of the assay is based on the measurement of cytotoxicity in

reconstructed human epidermal cultures following topical exposure to the test item (20 mg/tissue) by means of the

colourimetric MTT reduction assay. Cell viability was measured by enzymatic reduction of the yellow MTT

tetrazolium salt to a blue formazan salt (within the mitochondria of viable cells) in the test item treated tissues

relative to the negative controls (treated with 0.9% sodium chloride solution). Positive control tissues were treated

with 50 µL glacial acetic acid.

After the exposure period, the relative mean tissue viability for the test item compared to the control was 99.4,

95.5 and 97.4% for the 3, 60 and 240 min exposure periods, respectively. The relative mean tissue viability for the

positive control treated tissues compared to the control was 12.8% after an exposure period of 240 min.

Based on the study results, the test item was considered to be non-corrosive in vitro.

In a GLP-compliant study according to OECD Guideline 439, the skin irritation potential of Sodium methyl

cocoyl tauratewas evaluated using the EPISKIN™ reconstructed human epidermis model after a treatment period

of 15 min followed by a post-exposure incubation period of 42 h (Warren, 2013). The principle of the assay is

based on the measurement of cytotoxicity in reconstructed human epidermal cultures following topical exposure

to the test item (10 mg/tissue) by means of the colourimetric MTT reduction assay. Cell viability was measured by

enzymatic reduction of the yellow MTT tetrazolium salt to a blue formazan salt (within the mitochondria of viable

cells) in the test item treated tissues relative to the negative controls (treated with Dulbecco’s Phosphate Buffered


EC number:

263-174-9


61791-42-2


Saline (DPBS) with Ca2+ and Mg2+). Positive control tissues were treated with Sodium Dodecyl Sulphate (SDS),

5% w/v.

After the 15 min exposure period, the relative mean tissue viability for the test item and positive control treated

tissues compared to the control was 90.9% (± SD = 6.2%) and 5.5% (± SD = 1.0%), respectively.

Based on the study results, the test item was considered to be non-irritant in vitro.

Eye irritation/corrosion

The potential of Sodium methyl cocoyl taurateto cause ocular corrosivity or severe irritation was assessed by

conducting a bovine corneal opacity and permeability test (BCOP) according to OECD Guideline 437 and GLP

(Warren, 2013). Freshly prepared bovine corneas were obtained from slaughtered cattles.

The test substance (20% in 0.9% w/v sodium chloride solution) was incubated on the cornea for 240 minutes at 32

± 1 °C. After removal of the test item and 90 min post-incubation, opacity and permeability values were

measured.

The calculated IVIS (in vitro irritancy score) was 53.9. The positive control (imidazole, 20% in 0.9% sodium

chloride solution) induced severe irritation of the cornea (IVIS score: 90.3), and the negative control (the solvent

control) showed no irritating effect the cornea. On the basis of the test findings it can be concluded that the test

item under the experimental condition displayed no corrosion or severe irritation potential.

The primary eye irritation potential of the test substance was furthermore evaluated according to OECD Guideline

405 in the New Zealand albino rabbit (Clariant, 1987). Only animals without ocular abnormalities were used for

the study. 100 mg of undiluted test material was applied once to the conjunctival sac of the left eye of three rabbits.

The untreated eyes served in each case as a control. The exposure period was 24 hours. 24 hours after instillation

and at all the designated examination times at which a corneal examination with fluorescein sodium solution took

place, the treated eyes were washed out thoroughly with isotonic saline at approx. 37 °C. The eyes were examined

1, 24, 48 and 72 hours after application of the test substance. At 24 and 72 hours the eyes were also examined for

corneal lesions under UV light after instillation of one drop of 0.01% fluorescein-sodium solution. From 1 hour up

to 3 days after administration the conjunctivae of the animals showed swellings above normal up to swellings with

lids about half closed and definitely injected blood vessels up to a diffuse beefy red colour. The iris was reddened

in two animals up to day 2 and in the remaining animal until day 3 p. a. The cornea of two animals showed

scattered areas of opacity up to easily discernible translucent areas. Over the 24, 48 and 72 h observation period, a

mean corneal opacity score of 0.67, a mean iris score of 0.78, a mean conjunctival redness score of 2.8 and a mean

chemosis score of 2.1 was observed. All signs of irritation were reversible within 7 days post exposure. Based on

the results of this study, the test substance is considered to be irritating to rabbit eyes.


Skin irritation: not corrosive (OECD 431), not irritating (OECD 439)

Eye irritation: irritating (OECD 405)

Value used for CSA:

Skin irritation / corrosion: No adverse effect observed (not irritating)

Eye irritation / corrosion: Adverse effect observed (irritating)

Respiratory irritation / corrosion: No study available


The available data on skin irritation do not meet the criteria for classification according to Regulation (EC) No

1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.

The available data on eye irritation do meet the criteria for classification according to Regulation (EC) No

1272/2008 and Directive 67/548/EEC. Therefore the substance is classified as Eye irritant (Cat. 2, H319)

according to Regulation (EC) No 1272/2008 and Xi (R36) according to Directive 67/548/EEC.

5.4. Corrosivity


EC number:

263-174-9


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5.4.3. Summary and discussion of corrosion

5.5. Sensitisation

5.5.1. Skin


The results of studies on skin sensitisation are summarised in the following table:

Table 7. Studies on skin sensitisation


guinea pig (Pirbright-White)

female

Buehler test

Induction: epicutaneous,

occlusive

Challenge: epicutaneous,

occlusive

OECD Guideline 406 (Skin

Sensitisation)

not sensitising

No. with positive reactions:

1st reading: 0 out of 20 (test group); 24

h after chall.; dose: 100%

1st reading: 0 out of 20 (test group); 48

h after chall.; dose: 100%

1st reading: 0 out of 10 (negative

control); 24 h after chall.; dose: 100%

1st reading: 0 out of 10 (negative

control); 48 h after chall.; dose: 100%

1 (reliable

without

restriction)

key study

experimental

result

Test material

(Common

name): Fatty

acid chlorides,

C12-18 (even

numbered) and

C18 unsatd.,

reaction

products with

sodium

N-methyltaurin

ate

Form: paste

Hoechst AG

(1994)


5.5.2. Respiratory system



5.5.3. Summary and discussion of sensitisation

Skin sensitisation

Sodium methyl cocoyl taurate was evaluated for potential skin sensitising effects in guinea pigs according to

OECD Guideline 406 under GLP conditions using the methodology of Buehler (Clariant, 1994). Dermal

induction was performed using 100% test material. The control group was exposed to the vehicle water only.

Challenge treatment was carried out using a 20% test material solution (in water). Under the conditions of the

present study, none of the 20 animals of the treatment group showed a positive skin response after the challenge

procedure (sensitisation incidence = 0%). Also none of the 10 control animals exhibited skin responses.

Sensitivity of the test system is periodically confirmed using alpha-hexylcinnamaldehyde as positive control.


EC number:

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61791-42-2


Based on the results of this study, the test substance is considered to not be a skin sensitiser.


Skin sensitisation (Buehler): not sensitising

Value used for CSA: No adverse effect observed (not sensitising)

Respiratory sensitisation

Value used for CSA: No study available


The available data on skin sensitisation of the test substance do not meet the criteria for classification according to

Regulation (EC) 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for

classification.

5.6. Repeated dose toxicity


5.6.1.1. Repeated dose toxicity: oral

The results of studies on repeated dose toxicity after oral administration are summarised in the following table:

Table 8. Studies on repeated dose toxicity after oral administration



subacute (oral: gavage)

100, 300, 1000 mg/kg bw/day (actual

ingested)

Exposure: a minimum of 4

consecutive weeks (daily, 7

days/week)

OECD Guideline 407 (Repeated

Dose 28-Day Oral Toxicity in

Rodents)

NOAEL: >= 1000 mg/kg

bw/day (actual dose received)


mat. (overall effects with

regard to systemic toxicity

(forestomach effects are

considered `first site of

contact`and thus local effects

which are not relevant for

human health hazard / risk

assessment))

2 (reliable with

restrictions)

key study

read-across from



or surrogate)

Test material (CAS

number): 137-20-2

(See endpoint

summary for

justification of

read-across)

Form: solid

Research

Toxicology Centre

(2012a)


subacute (oral: gavage)

62.5, 250, 1000 mg/kg bw/day

(actual ingested)

Exposure: 14 days (daily, 7

days/week)

equivalent or similar to OECD

Guideline 407 (Repeated Dose

28-Day Oral Toxicity in Rodents)

NOAEL: >= 1000 mg/kg



mat. (clinical signs; mortality;

food consumption; body

weight; haematology; clinical

chemistry; gross pathology;

organ weights; histopathology

(male reproductive organs

including sperm staging))

2 (reliable with

restrictions)

supporting study

read-across from



or surrogate)

Test material (CAS

number): 137-20-2

(See endpoint

summary for

RTC (2012)


EC number:

263-174-9


61791-42-2



justification of

read-across)

Form: solid

Data waiving

Information requirement: Repeated dose toxicity after oral administration


Justification: In addition to the available 28-day oral repeated dose toxicity study performed with the source

substance Sodium methyl oleyl taurate, the requirement for this endpoint is waived based on the intention to

perform a 90-day repeated dose toxicity study (OECD 408) using a substance similar to Sodium methyl cocoyl

taurate.

There are no data available on the 90-day repeated dose toxicity of Sodium methyl cocoyl taurate. In order to

fulfil the standard information requirements, a GLP-compliant repeated dose toxicity study in the rat via the

oral route following OECD 408 for the source substance Sodium methyl oleyl taurate (CAS 137-20-2) is

proposed, according to Regulation (EC) 1907/2006, Annex IX, Column I, 8.6.2.

Sodium methyl oleyl taurate (CAS 137-20-2) has been selected as read-across substance because of the close

structural and functional similarities. Both, the target substance Sodium methyl cocoyl taurate and the source

substance Sodium methyl oleyl taurate are chemical reaction products of fatty acid chlorides with sodium

N-methyl taurinate and as such a close structural relationship exists. The only difference between both

substances is found in the origin of the fatty acid, which represents a C12-18-(even numbered, C18

unsaturated) -alkyl chain in the target molecule and a C18-(unsaturated) -alkyl chain in the source molecule.

The molecular structure of both materials is characterized by the hydrophobic aliphatic alkyl chain with

N-methyl taurine as hydrophilic head group, giving the whole molecule amphiphilic properties. Regarding

metabolism, catabolic degradation of both, target and source molecule, is anticipated involving amide

hydrolysis and subsequent fatty acid ß-oxidation. The physico-chemical properties data are also consistent,

varying in some endpoints according to the increase in chain length of the side chain.

Therefore, read-across will be performed based on an analogue approach, in accordance with the Regulation

(EC) No 1907/2006 to avoid tests in terms of animal welfare.

The study will be conducted after a decision on the requirement to carry out the proposed test has been taken in

accordance with the procedure laid down in Regulation (EC) No 1907/2006, and a deadline to submit the

information required has been set by the Agency. Approximately 12 months will be needed to perform the

study and finalise the study report.

5.6.1.2. Repeated dose toxicity: inhalation

5.6.1.3. Repeated dose toxicity: dermal

5.6.1.4. Repeated dose toxicity: other routes


5.6.3. Summary and discussion of repeated dose toxicity

Discussion

Data requirement on repeated dose toxicity of Sodium methyl cocoyl taurate is covered by a read-across to the






the whole molecule amphiphilic properties. No information on repeated dose toxicity of Sodium methyl cocoyl

taurate is available.


EC number:

263-174-9


61791-42-2


Sub-acute

The toxicity of the source substance Sodium methyl oleyl taurate was investigated in a preliminary study in rats

after daily oral administration for 2 weeks, in order to select dose levels for subsequent toxicity studies. The study

consisted of 4 groups of 6 rats each (3 males and 3 females). Animals in the low-, mid- and high-dose groups

received the test item at doses of 62.5, 250 and 1000 mg/kg bw/day, respectively, while animals in the control

group received the vehicle (purified water). The following investigations were performed: daily clinical signs,

body weight, food consumption as well as after termination of the study clinical pathology investigations,

necropsy, organ weights and evaluation of spermatogenic cycle of the seminiferous tubules of testes. During the

course of the study no substance-related clinical signs, no effects on body weight development and no mortalities

occurred. Food consumption was not influenced. No changes of toxicological significance were recorded in

haematological and coagulation parameters. Clinical chemistry revealed no adverse effects. With regard to

terminal organ weights no differences were found between the dose groups. No macroscopic findings related to

the administration of the test item were observed during necroscopy. Morphological evaluation of the

seminiferous tubules with respect to their stages in the spermatogenic cycle and to the integrity of the various cell

types within the different stages revealed no treatment-related changes. A regular layering in the germinal

epithelium was noted. No treatment-related changes were seen in testes and epididymides of male animals during

histopathology. On the basis of these results, the NOAEL was considered to be ≥ 1000 mg/kg bw/day.

The repeated dose toxicity of the source substance was investigated following daily oral administration for 4

weeks according to OECD Guideline 407 under GLP conditions (Clariant 2012). The test item was given orally by

gavage at 100, 300 and 1000 mg/kg bw/day formulated in purified water to 10 rats of each sex. Control animals (5

males and 5 females) received the vehicle water. Control and high dose groups comprised 5 additional animals per

sex, which were sacrificed after 2 weeks of recovery. Animals of the control, low-, mid- and high-dose groups

received the test item at the dose volume of 10 mL/kg bw. The following parameters were monitored: mortality,

body weight, clinical signs, including neurotoxicity assessment, food consumption and clinical pathology

investigation. The animals were subjected to detailed macroscopic observations at necropsy, including organ

weights and histopathological examination. In addition, identification of the stages of the spermatogenic cycles

was carried out.

No adverse signs were recorded at daily clinical examination and at the neurotoxicity assessment (weekly detailed

observations, sensory reactivity to stimuli and activity monitor). No significant changes were noted in body

weight and food consumption between the groups. Increase in white blood cell count was noted especially in high

dose males which is considered to be secondary to inflammatory changes due to the observed forestomach

findings in high dose animals. Increases in transaminases in high dose male animals were not considered to be

indicative of liver injury but may represent adaptive changes.

Macroscopically and histopathologically test item related findings were restricted to changes in the forestomach

of animals (mainly males) at 1000 mg/kg bw/day. These changes consisted of mostly diffuse mucosal hyperplasia

usually associated with hyperkerathosis and with focal to diffused inflammation located in the submucosa. In two

males receiving 1000 mg/kg bw/day focal ulcers were noted. Diffuse mucosal hyperplasia usually associated with

hyperkerathosis was still noted in the forestomach of the animals previously treated with the high dose and

sacrificed at the end of the 2 weeks of recovery. Comparable forestomach effects were not seen in rats from the

low- and mid-dose groups.

Application of rodent forestomach effect data for predicting risk or even hazard for humans is in general not

justified, given that a human counterpart for the rodent forestomach does not exist. In assessing the relevance of

such findings in rodents aspects like the method of administration (e. g. gavage versus feeding) and the

applicability of the forestomach to human organs (e. g. tissue concordance) have to be considered. Direct doses to

the forestomach as it is the case via oral gavage, promotes the irritation of the epithelial lining of the forestomach

due to a physical trauma by the gavage needle and/or chemical-induced irritation associated with

the deposition of high doses of test material which then comes directly in contact with the forestomach epithelium

for long periods of time. Besides the absence of a forestomach in humans, both aspects are neither representative

of natural pathways of exposure nor relevant to human exposure conditions. Local irritation to the forestomach

mucosa as such may cause local injury that stimulates compensatory cell proliferation.

Taken together, since the forestomach effects are considered to be `site of first contact` and thus local effects

which are not relevant for human hazard / risk assessment, the NOAEL of the source substance with regard to

systemic toxicity was determined to be ≥ 1000 mg/kg bw/day.


EC number:

263-174-9


61791-42-2



Oral (OECD 407), sub-acute, rat: NOAEL (systemic), males/females ≥ 1000 mg/kg bw/day

Value used for CSA (via oral route - systemic effects):

No adverse effect observed

Value used for CSA (dermal - systemic effects):

No study available

Value used for CSA (dermal - local effects):

No study available

Value used for CSA (inhalation - systemic effects):

No study available

Value used for CSA (inhalation - local effects):

No study available


The available data on oral repeated dose toxicity of the test substance do not meet the criteria for classification

according to Regulation (EC) No 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not

sufficient for classification.

5.7. Mutagenicity


5.7.1.1. In vitro data

The results of in vitro genotoxicity studies are summarised in the following table:

Table 9. In vitro genotoxicity studies


bacterial reverse mutation assay

(e.g. Ames test) (gene mutation)

S. typhimurium TA 1535, TA

1537, TA 98 and TA 100 (met.

act.: with and without)

E. coli WP2 uvr A (met. act.: with

and without)

Test concentrations: Preliminary

Toxicity Test: 0, 0.15, 0.5, 1.5, 5,

15, 50, 150, 500, 1500 and 5000

µg/plate

Main test:

Experiment 1: 5, 15, 50, 150, 500,

1500 and 5000 µg/plate

Experiment 2: 5, 15, 50, 150, 500,

1500 and 5000 µg/plate

Evaluation of results:

negative

Test results:

negative for S. typhimurium

TA 1535, TA 1537, TA 98, TA

100 and E. coli WP2(all

strains/cell types tested) ; met.

act.: with and without ;

cytotoxicity: yes (Salmonella

tester strains: visible reduction

in the growth of the bacterial

background lawns and/or

substantial reductions in the

revertant colony frequency

from 500 µg/plate onwards

with and without S9 –mix; no

toxicity in E. coli strain

WP2UvrA) ; vehicle controls

valid: yes; negative controls

1 (reliable without

restriction)

key study

experimental result

Test material (EC

name):

Ethanesulfonic

acid,

2-(methylamino)-,


sodium salts

Thompson, P.W.

(2012)


EC number:

263-174-9


61791-42-2



OECD Guideline 471 (Bacterial

Reverse Mutation Assay)

EU Method B.13/14

(Mutagenicity - Reverse Mutation

Test Using Bacteria)

EPA OPPTS 870.5100 - Bacterial

Reverse Mutation Test (August

1998)

valid: yes; positive controls

valid: yes

in vitro mammalian cell

micronucleus test (chromosome

aberration)

lymphocytes: human origin of

healthy men at the age of 28 and

32 (met. act.: with and without)

Test concentrations: 40, 80, 160,

200, 240, 320 µg/mL

Dose levels selected for analysis

of binucleate cells for

micronuclei:

4-hour without S9: 200, 240, 320

µg/mL

4-hour with S9: 160, 200, 240

µg/mL

20-hour without S9: 40, 80, 160

µg/mL

OECD 487 (In Vitro Mammalian

Cell Micronucleus Test)


negative

Test results:

negative for lymphocytes:

human(all strains/cell types

tested) ; met. act.: with and

without ; cytotoxicity: yes (4-h

treatment, -S9: at 240 µg/mL

and above; 4-h treatment, +S9:

at 320 µg/mL; 20-h treatment,

-S9: at 160 µg/mL and above) ;

vehicle controls valid: yes;

negative controls valid: not

examined; positive controls

valid: yes

1 (reliable without

restriction)

key study

experimental result

Test material (EC

name):

Ethanesulfonic

acid,

2-(methylamino)-,


sodium salts

Morris, A. (2013)

mammalian cell gene mutation

assay (genome mutation)

mouse lymphoma L5178Y cells

(met. act.: with and without)

Test concentrations: Experiment

1:

4-h exposure, -S9: 10, 20, 40, 50,

60, 100 µg/mL

4-h exposure, +S9: 15, 30, 60, 70,

80, 90, 100, 120 µg/mL

Experiment 2:

24-h exposure, -S9: 3.75, 7.5, 15,

30, 40, 50, 60, 80 µg/mL

4-h exposure, +S9: 3.75, 7.5, 15,

30, 60, 70, 80, 90 µg/mL

OECD Guideline 476 (In vitro

Mammalian Cell Gene Mutation

Test)

EU Method B.17 (Mutagenicity -


negative

Test results:

negative for mouse lymphoma

L5178Y cells(all strains/cell

types tested) ; met. act.: with

and without ; cytotoxicity: yes

(Experiment 1: 4-h exposure,

+S9: at 60 µg/mL and above;

4-h exposure, -S9: at 50 µg/mL

and above; Experiment 2: 4-h

exposure, +S9: at 60 µg/mL:

24-h exposure, -S9: at 15

µg/mL and above) ; vehicle

controls valid: yes; negative

controls valid: no; positive

controls valid: yes

1 (reliable without

restriction)

key study

experimental result

Test material (EC

name):

Ethanesulfonic

acid,

2-(methylamino)-,


sodium salts

Brown, R. (2013)


EC number:

263-174-9


61791-42-2



In Vitro Mammalian Cell Gene

Mutation Test)

EPA OPPTS 870.5300 - In vitro

Mammalian Cell Gene Mutation

Test

5.7.1.2. In vivo data


5.7.3. Summary and discussion of mutagenicity

Discussion

Genetic toxicity in vitro

Gene mutation in bacteria

Sodium methyl cocoyl taurate was tested for its potential induction of gene mutation in bacteria in an Ames test

conducted according to OECD Guideline 471 and under GLP conditions (Thompson, 2012). S. typhimurium and

E. coli tester strains (TA 1535, TA 1537, TA 98, TA 100 and WP2uvrA) were treated with the test material

dissolved in distilled water at seven concentrations up to 5000 µg/plate, using both the plate incorporation and

pre-incubation methods and in the presence and absence of metabolic activation (S9-mix). Negative, vehicle and

appropriate positive controls were included.

The test item caused a visible reduction in the growth of the bacterial background lawns and/or substantial

reductions in the revertant colony frequency of all of the Salmonella tester strains, initially from 500 µg/plate in

both the presence and absence of S9-mix. No toxicity was noted to Escherichia coli strain WP2uvrA in either the

absence or presence of S9-mix at any test item dose level. No test item precipitate was observed at any of the doses

tested in either the presence or absence of S9-mix. No significant increases in the frequency of revertant colonies

were recorded for any of the tester strains, at any concentration either in the presence or absence of metabolic

activation. The negative, vehicle and positive controls yielded the expected results and the respective frequency of

revertant colonies was within the range of the reported historical control values.

Based on the study results, the test substance was considered to be non-mutagenic under the conditions of the test.

Cytogenicity in mammalian cells

Cytogenicity of Sodium methyl cocoyl taurate was investigated in an in vitro micronucleus test with human

lymphocytes according to OECD guideline 487 and under GLP conditions (Morris, 2013). Duplicate cultures of

cells were treated with 40, 80, 160, 200, 240, and 320 µg/mL test substance dissolved in medium for 4 hours with

and without metabolic activation and for 20 hours without metabolic activation. Controls were treated with the

vehicle or appropriate positive control substances. Three dose levels per approach were evaluated for micronuclei

in binucelated cells: 4-hour exposure without S9: 200, 240, 320 µg/mL, 4-hour exposure with S9-mix: 160, 200,

240 µg/mL and 20-hour without S9: 40, 80, 160 µg/mL. No precipitation of the test substance was observed.

Cytotoxicity was observed during the 4 -hour treatment without S9-mix at 240 µg/mL and above as well as with

S9-mix at 320 µg/mL and within the 20-hour treatment at 160 µg/mL and above. The test item did not induce any

increases in the frequency of cells with micronuclei, in either the absence or presence of metabolic activation after

both the 4- and 20 -hour exposure period. All vehicle controls had frequencies of cells with micronuclei within the

range expected for normal human lymphocytes. The positive control items induced statistically significant

increases in the frequency of cells with micronuclei, indicating the satisfactory performance of the test and of the

activity of the metabolising system.

Based on the study results, the test substance was considered to be non-cytogenic under the conditions of the test.

Gene mutation in mammalian cells

Mutagenic effects of Sodium methyl cocoyl taurate on the thymidine kinase, TK +/-, locus of the L5178Y mouse

lymphoma cell line were assessed in a GLP-compliant study conducted according to OECD guideline 476


EC number:

263-174-9


61791-42-2


(Brown, 2013). L5178Y TK +/- 3.7.2c mouse lymphoma cells were treated with the test material at concentrations

of 15 to 120 µg/mL with metabolic activation and at 10 to 100 µg/mL without metabolic activation system

(S9-mix). Vehicle and appropriate positive controls were included. Two independent experiments were

performed. In the first experiment, cells were exposed to the test material for 4 hours in the presence and absence

of S9-mix. In the second experiment, cells were treated for 4 hours with metabolic activation and for 24 hours

without metabolic activation.

Cytotoxicity was observed in experiment 1 at 90 µg/mL and above with metabolic activation and at 70 µg/mL and

above without metabolic activation. In experiment 2, cytotoxic effects were observed at 90 µg/mL in the presence

of metabolic activation and at 50 µg/mL and above in the absence of metabolic activation. No precipitate of the

test item was observed at any dose level.

The test material did not induce any toxicologically relevant increases in the mutant frequency at any

concentration, either with or without metabolic activation. The vehicle controls had acceptable mutant frequency

values that were within the normal range for the L5178Y cell line at the TK +/- locus. The positive control items

induced marked increases in the mutant frequency.

The test material was thus considered to be non-mutagenic in L5178Y cells under the conditions of the test.


In vitro gene mutation in bacteria: negative (with and without S9-mix)

In vitro cytogenicity in mammalian cells: negative (with and without S9-mix)

In vitro gene mutation in mammalian cells: negative (with and without S9-mix)

Value used for CSA: Genetic toxicity: No adverse effect observed (negative)


The available data on genetic toxicity of the test substance do not meet the criteria for classification according to

Regulation (EC) No 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for

classification.

5.8. Carcinogenicity


5.8.1.1. Carcinogenicity: oral

5.8.1.2. Carcinogenicity: inhalation

5.8.1.3. Carcinogenicity: dermal

5.8.1.4. Carcinogenicity: other routes


5.8.3. Summary and discussion of carcinogenicity

5.9. Toxicity for reproduction

5.9.1. Effects on fertility


The results of studies on fertility are summarised in the following table:

Table 10. Studies on fertility



EC number:

263-174-9


61791-42-2




screening

oral: gavage

100, 300, 1000 mg/kg bw/day

(nominal in water)

Exposure: Males: about 28 days

(Animals were dosed once a day, 7

days a week, for 2 consecutive weeks

prior to pairing and thereafter

through the day before necropsy.)

Females: about 50 days (Animals

were dosed once a day, 7 days a

week, for 2 consecutive weeks prior

to pairing, and thereafter during

pairing, post coitum and post partum

periods until Day 3 post partum.

(Once a day)

OECD Guideline 421 (Reproduction

/ Developmental Toxicity Screening

Test)

NOAEL (P): >= 1000 mg/kg



mat. (NOAEL corresponding

to the highest dose tested.)

NOAEL (F1): >= 1000 mg/kg



mat. (NOAEL corresponding

to the highest dose tested.)

2 (reliable with

restrictions)

key study

read-across from



or surrogate)

Test material (CAS

number): 137-20-2

(See endpoint

summary for

justification of

read-across)

Form: powder

Research

Toxicology Centre

(2012b)

Data waiving

Information requirement: Toxicity for reproduction / fertility


Justification: In accordance to Regulation (EC) No 1907/2006 Annex IX Column I 8.7.3, a two-generation

reproductive toxicity study is required, if the 28-day or 90-day study indicates adverse effects on reproductive

tissues or organs.

There are no information available on repeated dose and reproductive/developmental toxicity of Sodium

methyl cocoyl taurate. However, there are reliable data available on repeated dose and

reproductive/developmental toxicity of Sodium methyl oleyl taurate which were considered suitable for

read-across. Both, the target and the source substance are chemically reaction products of fatty acid chlorides

with Sodium N-methyl taurinate. The only difference between both substances is seen in the origin of the fatty

acid, which represents a C12 -18(even numbered, C18 unsaturated) -alkyl chain in the target and a C18

-(unsaturated) -alkyl chain in the source molecule. The molecular structure of both materials is characterized

by the hydrophobic aliphatic alkyl chain with N-methyl taurine as hydrophilic head group, giving the whole

molecule amphiphilic properties.

In a GLP guideline study performed according to OECD guideline 407, Sodium methyl oleyl taurate was

administered at doses of 100, 300 and 1000 mg/kg bw/day. No effects on reproductive organs were observed at

gross- and histopathology of both sexes. In addition to the subacute study, a testing proposal for an OECD 408

90-day repeated oral toxicity study is forwarded for the read-across source substance Sodium methyl oleyl

taurate.

In a GLP guideline study performed according to OECD guideline 421, rats were administered Sodium methyl

oleyl taurate at doses of 100, 300 and 1000 mg/kg bw/day. Reproductive performance and reproductive

indices of the parent animals were not adversely affected. In addition, no adverse effects on estrous cyclicity

and sperm parameters were observed. Gross pathology and histopathology revealed no effects on gonadal

tissues.

Therefore, Sodium methyl cocoyl taurate is considered not to have any adverse effect on reproductive tissues

or organs at and thus a two-generation study does not need to be conducted.



EC number:

263-174-9


61791-42-2


5.9.2. Developmental toxicity


Data waiving

Information requirement: Developmental toxicity / teratogenicity


Justification: The requirement for this endpoint is waived based on the intention to perform a prenatal

developmental toxicity study (OECD 414) using a substance similar to Sodium methyl cocoyl taurate.

There are no data available on the developmental toxicity/teratogenicity of Sodium methyl cocoyl taurate. In

order to fulfil the standard information requirements, a GLP-compliant prenatal development study in the rat

via the oral route following OECD 414 for the source substance Sodium methyl oleyl taurate (CAS 137-20-2)

is proposed, according to Regulation (EC) No 1907/2006, Annex IX, Column I, 8.7.2.

Sodium methyl oleyl taurate (CAS 137-20-2) has been selected as source substance because of the close

structural and functional similarities. Both, the target substance Sodium methyl cocoyl taurate and the source

substance Sodium methyl oleyl taurate are chemically reaction products of fatty acid chlorides with sodium

N-methyl taurinate and as such a close structural relationship exists. The only difference between both

substances is found in the origin of the fatty acid, which represents a C12-18-(even numbered, C18

unsaturated) -alkyl chain in the target molecule and a C18-(unsaturated) -alkyl chain in the source molecule.

The molecular structure of both materials is characterized by the hydrophobic aliphatic alkyl chain with

N-methyl taurine as hydrophilic head group, giving the whole molecule amphiphilic properties. Regarding

metabolism, catabolic degradation of both, target and source molecule, is anticipated involving amide

hydrolysis and subsequent fatty acid ß-oxidation. The physico-chemical properties data are also consistent,

varying in some endpoints according to the increase in chain length of the side chain.

Therefore, read-across will be performed based on an analogue approach, in accordance with the Regulation

(EC) No 1907/2006 to avoid tests in terms of animal welfare.


accordance with the procedure laid down in Regulation (EC) No 1907/2006, and a deadline to submit the

information required has been set by the Agency. Approximately 12 months will be needed to perform the

study and finalise the study report.


5.9.3. Summary and discussion of reproductive toxicity

Effects on fertility

Data requirement on repeated dose toxicity of Sodium methyl cocoyl taurate is covered by a read-across to the






the whole molecule amphiphilic properties. No information on reproduction toxicity of Sodium methyl cocoyl

taurate is available.

The source substance Sodium methyl oleyl taurate was investigated according to OECD Guideline 421 under GLP

conditions (Clariant, 2012). The purpose of the study was to evaluate the reproduction/developmental toxicity of

the test item in Sprague Dawley rats up to Day 4 post partum. The test item was administered orally, by gavage, at

dosages of 100, 300 and 1000 mg/kg bw/day. The treatment schedule included 2 weeks before pairing, during

pairing, post coitum and post partum Day 3. Animals were administered for approximately 5 and 7 weeks for

males and females, respectively. The parental animals were monitored for daily clinical signs, body weight, food

consumption, oestrous cycle and mating performance. The dams were allowed to give birth and rear their

offspring until Day 4 post partum. Macroscopic observation and histopathological examination were also

performed. In parental animals, no adverse findings were found in life phase or at post mortem evaluation. The

animals of the high dose group showed salivation early after dosing as major clinical sign. Body weight, body


EC number:

263-174-9


61791-42-2


weight gain and food consumption were unaffected by treatment. No treatment-related findings were found at

macroscopic and microscopic examinations. No abnormalities were found at the evaluation of the spermatogenic

cycle. Likewise, no differences were noted in the reproductive performance including gonadal function, mating

behaviour, conception, development of conceptus and parturition. The females had indeed comparable length of

gestation and gave births. Litter and mean pup weights were also comparable between groups and no relevant

findings were observed in pups during the lactation period nor at post mortem examination. On the basis of the

results obtained in the study, the NOAEL for reproduction/developmental toxicity was determined to be ≥ 1000

mg/kg bw/day for both males and females.


Oral (OECD 421), rat: NOAEL (fertility), males/females ≥ 1000 mg/kg bw/day

Value used for CSA (route: oral):

No adverse effect observed

Value used for CSA (route: dermal):

No study available

Value used for CSA (route: inhalation):

No study available

Developmental toxicity

The requirement for this endpoint is waived based on the intention to perform a prenatal developmental toxicity

study (OECD 414) using a substance similar to Sodium methyl cocoyl taurate.

There are no data available on the developmental toxicity/teratogenicity of Sodium methyl cocoyl taurate. In order

to fulfil the standard information requirements, a GLP-compliant prenatal development study in the rat via the oral

route following OECD 414 for the read-across substance Sodium methyl oleyl taurate (CAS 137-20-2) is

proposed, according to Regulation (EC) 1907/2006, Annex IX, Column I, 8.7.2.

Sodium methyl oleyl taurate has been selected as read-across substance because of the close structural and

functional similarities. Both, the target substance Sodium methyl cocoyl taurate and the source substance Sodium

methyl oleyl taurate (CAS 137-20-2) are chemically reaction products of fatty acid chlorides with sodium

N-methyl taurinate and as such a close structural relationship exists. The only difference between both substances

is seen in the origin of the fatty acid, which represents a C12-18-(even numbered, C18 unsaturated) -alkyl chain in

the target molecule and a C18-(unsaturated) -alkyl chain in the source molecule. The molecular structure of both

materials is characterized by the hydrophobic aliphatic alkyl chain with N-methyl taurine as hydrophilic head

group, giving the whole molecule amphiphilic properties. Regarding metabolism, catabolic degradation of both

N-acyl-N-methyl taurates (target and source molecule) is anticipated involving amide hydrolysis and subsequent

fatty acid ß-oxidation. The physico-chemical properties data are also consistent, varying in some endpoints

according to the increase in chain length of the side chain.

Therefore, data-gap filling will be conducted based on a read-across approach, in accordance with the Regulation

(EC) 1907/2006 to avoid tests in terms of animal welfare.


accordance with the procedure laid down in Regulation (EC) 1907/2006, and a deadline to submit the information

required has been set by the Agency. Approximately 12 months will be needed to perform the study and finalise

the study report.

Value used for CSA (route: oral)

No study available

Value used for CSA (route: dermal):

No study available

Value used for CSA (route: inhalation):

No study available


EC number:

263-174-9


61791-42-2



The available data on toxicity to reproduction of the test substance do not meet the criteria for classification

according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient

for classification.

5.10. Other effects


5.10.1.1. Neurotoxicity

5.10.1.2. Immunotoxicity

5.10.1.3. Specific investigations: other studies


5.10.3. Summary and discussion of other effects

5.11. Derivation of DNEL(s) and other hazard conclusions

5.11.1. Overview of typical dose descriptors for all endpoints

Table 11. Available dose-descriptor(s) per endpoint as a result of its hazard assessment

Endpoint Route Dose descriptor or qualitative effect

characterisation; test type

Reference to selected study

(see footnotes for justification)

Acute toxicity oral No adverse effect observed

Acute toxicity dermal No adverse effect observed

Acute toxicity inhalation No study available

Irritation /

Corrosivity

skin No adverse effect observed (not irritating)

Irritation /

Corrosivity

eye Adverse effect observed

irritating

Irritation /

Corrosivity

respiratory

tract

No study available

Sensitisation skin No adverse effect observed (not sensitising)

Sensitisation respiratory

tract

No study available

Repeated dose

toxicity

oral No adverse effect observed

Repeated dose

toxicity

dermal

(systemic

effects)

No study available

Repeated dose

toxicity

dermal

(local

effects)

No study available

Repeated dose

toxicity

inhalation

(systemic

effects)

No study available

Repeated dose

toxicity

inhalation

(local

effects)

No study available


EC number:

263-174-9


61791-42-2


Endpoint Route Dose descriptor or qualitative effect

characterisation; test type

Reference to selected study

(see footnotes for justification)

Mutagenicity in vitro / in

vivo

No adverse effect observed (negative)

Reproductive

toxicity: effects

on fertility

oral No adverse effect observed

Reproductive

toxicity: effects

on fertility

dermal No study available

Reproductive

toxicity: effects

on fertility

inhalation No study available

Reproductive

toxicity:

developmental

toxicity

oral No study available

>>>CAUTION: "No study available" in

corresponding IUCLID endpoint summary,

although an Effect level is provided.<<<

Reproductive

toxicity:

developmental

toxicity

dermal No study available

Reproductive

toxicity:

developmental

toxicity

inhalation No study available

Justification for endpoint selection:

- Acute toxicity (oral): Hazard assessment is based on the weight of evidence from acute oral toxicity studies.

- Acute toxicity (dermal): There is only one study available.

- Irritation / Corrosivity (skin): Hazard assessment is based on the weight of evidence from in vitro skin

corrosion and irritation studies.

- Irritation / Corrosivity (eye): The selected study is the most adequate and reliable study based on overall

quality assessment (refer to the endpoint discussion for further details).

- Sensitisation (skin): There is only one study available.

- Repeated dose toxicity (oral): Hazard assessment is conducted by means of a read-across from a structural

analogue. The selected study is the most adequate and reliable study based on the identified similarities in

structure and intrinsic properties between source and target substance and overall assessment of quality,

duration and dose descriptor level (refer to the endpoint discussion for further details).

- Mutagenicity: No study was selected, since all available in vitro genetic toxicity studies were negative.

- Reproductive toxicity: effects on fertility (oral): Hazard assessment is conducted by means of read-across from

a structural analogue. The selected study is the most adequate and reliable study based on the identified

similarities in structure and intrinsic properties between source and target substance and overall assessment of

quality, duration and dose descriptor level (refer to the endpoint discussion for further details).


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5.11.2. Selection of the DNEL(s) or other hazard conclusion for critical health effects

Table 12. Hazard conclusions for workers

Route Type of effect Hazard conclusion Most sensitive endpoint

Inhalation Systemic

effects -

Long-term

DNEL (Derived No Effect Level): 58.77 mg/m³ repeated dose toxicity (Oral)

Inhalation Systemic

effects - Acute

No hazard identified

Inhalation Local effects -

Long-term

Hazard unknown (no further information

necessary)


Acute


necessary)

Dermal Systemic

effects -

Long-term

DNEL (Derived No Effect Level): 8.33 mg/kg

bw/day

repeated dose toxicity (Oral)

Dermal Systemic

effects - Acute


Dermal Local effects -

Long-term


necessary)


Acute


Eyes Local effects Low hazard (no threshold derived)

Further explanation on hazard conclusions:

- Inhalation Systemic effects - Long-term: See discussion section for correction of NOAEL and for a detailed

justification of assessment factors used.

- Inhalation Systemic effects - Acute: Assessment of hazard is sufficiently covered by derivation of the

respective DNEL for long-term exposure

- Inhalation Local effects - Long-term: No dose-response data are available.

- Inhalation Local effects - Acute: No dose-response data are available.

- Dermal Systemic effects - Long-term: See discussion section for correction of NOAEL and for a detailed

justification of assessment factors used.

- Dermal Local effects - Long-term: The available toxicological data show that the test substance does not

need be classified for local skin effects. Thus, a DNEL for local effects does not need to be derived and the

assessment of the hazard is sufficiently covered by derivation of the DNEL for long-term systemic exposure.

- Eyes Local effects: The available toxicological data show that the test substance has to be classified for local

effects. No DNEL for effects on the eyes could be derived. Therefore, the hazard is covered in a qualitative

assessment.

Table 13. Further explanation on DNEL derivation for workers

Route / Type of

effect

DNEL derivation Assessment factors (AF) for DNEL

derivation

Inhalation DNEL derivation method: ECHA AF for difference in duration of


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Route / Type of

effect

DNEL derivation Assessment factors (AF) for DNEL

derivation

Systemic effects -

Long-term

REACH Guidance

Dose descriptor starting point: NOAEC

1763.16 mg/m³

exposure: 6 (sub-aute (28-day repeated

dose) to chronic)

AF for intraspecies differences: 5 (default

for worker)

Overall Assessment Factor: 30

Dermal

Systemic effects -

Long-term

DNEL derivation method: ECHA

REACH Guidance

Dose descriptor starting point: NOAEL

1000 mg/kg bw/day

AF for difference in duration of

exposure: 6 (sub-acute (28-day repeated

dose) to chronic)

AF for interspecies differences

(allometric scaling): 4 (the study was

conducted with rats)

AF for intraspecies differences: 5 (default

for worker)

Overall Assessment Factor: 120

Justification for route-to-route extrapolation:

- Inhalation Systemic effects - Long-term: No study on long term inhalation toxicity available.

- Dermal Systemic effects - Long-term: No study on long term dermal toxicity available.

Discussion

Workers - Hazard via inhalation route

No route-specific acute and/or repeated inhalation toxicity studies are available for Sodium methyl cocoyl taurate

and/or for the read-across substance Sodium methyl oleyl taurate. Route-to-route extrapolation is performed using

the NOAEL of 1000 mg/kg bw/day from a 28-day oral toxicity study performed with the read-across substance

Sodium methyl oleyl taurate, which was identified as key study for repeated dose toxicity. This NOAEL is used as

starting point for the derivation of the worker DNEL "long-term inhalation exposure - systemic effects".

The corrected inhalatory NOAEC is obtained according to ECHA Guidance R.8 (ECHA, 2012) as 1763.16 mg/m³

(1000 mg/kg bw/day * (1/0.38 m³/kg bw/day) * (1/1) * 6.7 m³/ 10 m³). The assessment factors were chosen as

described in ECHA Guidance R.8. Despite no systemic toxic relevant effects were noted and thus the point of

departure (POD) used can be considered to be conservative, an assessment factor of 1 for dose-response is chosen.

Since the assessment is based on the outcome of a 28 -day repeated dose toxicity study, time extrapolation to

chronic exposure conditions generally have to be considered and the default factor of 6 (sub-acute to chronic) is

used. With regard to interspecies differences, allometric scaling concerning oral-to-inhalation extrapolation is not

appropriate and no assessment factor is applied. A factor of 1 for remaining interspecies differences is also

supported, because toxicokinetic is considered to not differ between species. With regard to intraspecies

variations, a default assessment factor of 5 was used to accommodate the variability in the human population.

Since the available data on repeated dose toxicity are considered reliable and adequate, the quality of the data base

is judged sufficient for evaluation and thus, an assessment factor of 1 is applied. Both, the target substance Sodium

methyl cocoyl taurate and the read-across substance Sodium methyl oleyl taurate are chemically reaction products

of fatty acid chlorides with sodium N-methyl taurinate and as such a close structural relationship exists. The only

difference between both substances is seen in the origin of the fatty acid, which represents a C12-18-(even

numbered, C18 unsaturated) -alkyl chain in the target molecule and a C18-(unsaturated) -alkyl chain in the source

molecule.

The resulting overall assessment factor is 30 (6 x 5) resulting in a DNEL "long term inhalation exposure - systemic

effects" of 58.77 mg/m³.


EC number:

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Workers - Hazard via dermal route

No route-specific repeated dermal toxicity data is available for Sodium methyl cocoyl taurate and/or the

read-across substance Sodim methyl oleyl taurate. As default, route-to-route extrapolation is performed using the

NOAEL of 1000 mg/kg bw/day from a 28-day oral toxicity study performed with the read-across substance

Sodium methyl oleyl taurate, which was identified as key study for repeated dose toxicity. This NOAEL is used as

starting point for the derivation of the worker DNEL "long term dermal exposure - systemic effects". The

assessment factors were chosen based on the ECHA Guidance R.8 (ECHA, 2012). Despite no systemic toxic

adverse effects were noted and thus the POD used can be considered to be conservative, assessment factors of 1

for dose-response and quality of data base seem to be appropriate. Since the assessment is based on the outcome of

a 28-day repeated dose toxicity study, time extrapolation to chronic exposure conditions generally have to be

considered and the default factor of 6 (sub-acute to chronic) is used. With regard to interspecies differences and to

correct for differences in metabolic rate for the experimental animals, the default allometric scaling factor of 4 is

chosen. A factor of 1 for remaining interspecies differences is also supported, because toxicokinetic is considered

to not differ between species. With regard to intraspecies variations, a default assessment factor of 5 was used to

accommodate the variability in the human population. The resulting overall assessment factor is 120 (6 x 4 x 5)

leading to a DNEL "long-term dermal exposure - systemic effects" of 8.33 mg/kg body weight per day.

Additional information

No DNELs are derived for systemic toxicity and for local effects following acute exposure. It is concluded that

short-term exposures are well-controlled by conditions for long-term exposure. Additionally, proper technical and

personal risk management measures are in place to protect against local effects and ensure safe use conditions.

Table 14. Hazard conclusions for the general population

Route Type of effect Hazard conclusion Most sensitive endpoint

Inhalation Systemic

effects -

Long-term


Inhalation Systemic

effects - Acute



Long-term



Acute


Dermal Systemic

effects -

Long-term


Dermal Systemic

effects - Acute



Long-term



Acute


Oral Systemic

effects -

Long-term


Oral Systemic

effects - Acute


Eyes Local effects No hazard identified

Further explanation on hazard conclusions:

- Inhalation Systemic effects - Long-term: With regard to consumer exposure, Sodium methyl cocoyl taurate


EC number:

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is used only in cosmetic products. Therefore, derivation of DNELs, assessment of exposure and risk

characterisation are not required under REACh. These uses are under the scope of Regulation (EC) No

1223/2009 on cosmetic products.

- Inhalation Systemic effects - Acute: With regard to consumer exposure, Sodium methyl cocoyl taurate is

used only in cosmetic products. Therefore, derivation of DNELs, assessment of exposure and risk



- Inhalation Local effects - Long-term: With regard to consumer exposure, Sodium methyl cocoyl taurate is




- Inhalation Local effects - Acute: With regard to consumer exposure, Sodium methyl cocoyl taurate is used

only in cosmetic products. Therefore, derivation of DNELs, assessment of exposure and risk characterisation

are not required under REACh. These uses are under the scope of Regulation (EC) No 1223/2009 on cosmetic

products.

- Dermal Systemic effects - Long-term: With regard to consumer exposure, Sodium methyl cocoyl taurate is




- Dermal Systemic effects - Acute: With regard to consumer exposure, Sodium methyl cocoyl taurate is used



products.

- Dermal Local effects - Long-term: With regard to consumer exposure, Sodium methyl cocoyl taurate is used



products.

- Dermal Local effects - Acute: With regard to consumer exposure, Sodium methyl cocoyl taurate is used only

in cosmetic products. Therefore, derivation of DNELs, assessment of exposure and risk characterisation are

not required under REACh. These uses are under the scope of Regulation (EC) No 1223/2009 on cosmetic

products.

- Oral Local effects - Long-term: With regard to consumer exposure, Sodium methyl cocoyl taurate is used



products.

- Oral Local effects - Acute: With regard to consumer exposure, Sodium methyl cocoyl taurate is used only in

cosmetic products. Therefore, derivation of DNELs, assessment of exposure and risk characterisation are not

required under REACh. These uses are under the scope of Regulation (EC) No 1223/2009 on cosmetic

products.

- Eyes Local effects: With regard to consumer exposure, Sodium methyl cocoyl taurate is used only in cosmetic

products. Therefore, derivation of DNELs, assessment of exposure and risk characterisation are not required

under REACh. These uses are under the scope of Regulation (EC) No 1223/2009 on cosmetic products.

Discussion

With regard to consumer exposure, the registered substance is used only in cosmetic products. Therefore,

derivation of DNELs, assessment of exposure and risk characterisation are not required under REACh. These uses

are under the scope of Regulation (EC) No 1223/2009 on cosmetic products.


EC number:

263-174-9


61791-42-2


REFERENCES Battelle Europe (1991). Acute dermal toxicity study (OECD-Guideline 402) of Metaupon-Paste in rats. Testing

laboratory: Battelle Europe. Report no.: BE-MT-114-91-02-ADR-02. Owner company: Leuna-Tenside. Report

date: 1991-11-20.

Brown, R. (2013). L5178Y Mouse Lymphoma Assay. Testing laboratory: Harlan Laboratories Ltd, Shardlow,

UK. Report no.: 41204205. Owner company: Croda Europe Limited, Goole, UK. Report date: 2013-02-21.

Hoechst AG (1987a). Hostapon CT Teig - Akute Toxizität per os an der Ratte. Testing laboratory: Hoechst AG.

Report no.: 87.1427. Owner company: Clariant. Study number: 1987.1427. Report date: 1987-10-05.

Hoechst AG (1987b). Hostapon T Pulver - Akute Toxizität per os in der Wistar Ratte. Testing laboratory: Hoechst

AG. Report no.: 87.1503. Owner company: Clariant. Study number: 1987.1503. Report date: 1987-10-05.

Hoechst AG (1987c). Hostapon CT Teig - Augenreizung am Kaninchen. Testing laboratory: Hoechst AG. Report

no.: 87.1455. Owner company: Clariant. Study number: 1987.1455. Report date: 1987-10-05.

Hoechst AG (1994). Hostapon CT Teig - Prüfung auf sensibilisierende Eigenschaften an Pirbright-White

Meerschweinchen nach Buehler. Testing laboratory: Hoechst AG. Report no.: 94.0962. Owner company:

Clariant. Study number: 1994.0962. Report date: 1994-12-05.

Morris, A. (2013). Micronucleus test in human lymphocytes in vitro: OECD Method 487. Testing laboratory:

Harlan Laboratories Ltd, Shardlow, UK. Report no.: 41204204. Owner company: Croda Europe Limited, Goole,

UK. Report date: 2013-02-25.

Noack, M. (2013). Sodium methyl cocoyl taurate, Daphnia magna Reproduction Test (Semi-Static, 21 d). Testing

laboratory: Dr. U. Noack-Laboratorien, Kaethe-Paulus Str.1, 31157 Sarstedt, Germany. Owner company:

Clariant. Study number: DRE15129. Report date: 2013-03-25.

RTC (2012). Hostapon TPHC - 2 week preliminary oral toxicity study in rats. Testing laboratory: RTC, Italy.

Report no.: 91260EXT. Owner company: Clariant. Study number: 91260EXT. Report date: 2012-07-29.

Research Toxicology Centre (2012a). 4 WEEK ORAL TOXICITY STUDY IN RATS FOLLOWED BY A 2

WEEK RECOVERY PERIOD. Testing laboratory: Research Toxicology Centre S. p. A. Via Tito Speri, 12/14

00040 Pomezia (Rome) Italy. Report no.: 91460. Owner company: Clariant.

Research Toxicology Centre (2012b). REPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING

TEST IN RATS. Testing laboratory: Research Toxicology Centre S. p. A. Via Tito Speri, 12/14 00040 Pomezia

(Roma) Italy. Report no.: 91480. Owner company: Clariant. Report date: 2013-02-13.

Thompson, P. W. (2012). Reverse Mutation Assay "Ames Test" using Salmonella typhimurium and Escherichia

coli. Testing laboratory: Harlan Laboratories Ltd, Shardlow, UK. Report no.: 41204203. Owner company: Croda

Europe Limited, Goole, UK. Report date: 2012-12-05.

Warren, N. (2013a). In vitro skin corrosion in the EPISKIN reconstructed human epidermis model. Testing

laboratory: Harlan Laboratories Ltd, Shardlow, UK. Report no.: 41204200. Owner company: Croda Europe

Limited, Goole, UK. Report date: 2013-01-06.

Warren, N. (2013b). Determination of skin irritation potential using the EPISKIN™ reconstructed human

epidermis model. Testing laboratory: Harlan Laboratories Ltd, Shardlow, UK. Report no.: 41204201. Owner

company: Croda Europe Limited, Goole, UK. Report date: 2013-03-25.

Warren, N. (2013c). The bovine corneal opacity and permeability assay. Testing laboratory: Harlan Laboratories

Ltd, Shardlow, UK. Report no.: 41204202. Owner company: Croda Europe Limited, Goole, UK. Report date:

2013-01-06.

Younis, S. (2012). Flammability Testing on a Sample of [Trade name] (CAS 61791-42-2). Testing laboratory:

Chilworth Technology Limited, Southampton, United Kingdom. Report no.: GLP108524R1V1/12. Owner

company: Croda Europe Limited, Goole, UK. Report date: 2012-09-04.


EC number:

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61791-42-2




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