SDS Abilify

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Safety Data Sheet

1. IDENTIFICATION

Product InformationProduct name Aripiprazole

Version 1.0, 04.04.2013

Jurisdiction This Safety Data Sheet was prepared in accordance with the Globally Harmonized

System of Classification and Labelling of Chemicals (GHS) for the United States ofAmerica (USA) (CFR 1910.1200), European Union (EU) (EC 1272/2008) and United

Nations (UN). The following countries utilize the UN GHS classification process:

Mexico, Brazil, China, New Zealand, Canada, Japan, Korea and Australia.

Chemical Name 2(1H)-Quinolinone,7-[4-[4-(2,3-dichlorophenyl)-1-piperazinyl]butoxy]-3,4-dihydro-

IUPAC name 7-[4-[4-(2,3-dichlorophenyl)piperazin-1-yl]butoxy]-3,4-dihydro-1H-quinolin-2-one

Synonyms Abilify; Abilify Discmelt; Abilitat; BMS-337039-01; BMS 337039-01; OPC-31;

OPC 31; OPC-14597; OPC 14597; 3D CONCORD

Intended Uses This material is the active pharmaceutical ingredient (API) in a drug product. It is used

to treat psychotic disorders.

Company/Undertaking Identification

Address USA

Bristol-Myers Squibb CompanyP.O. Box 191

New Brunswick, New Jersey 08903

United States of America

Ireland

Bristol-Myers Squibb CompanySwords Laboratories, Watery Lane

Swords, Ireland

[email protected]

Emergency Phone

Number

USA (also Canada, Puerto Rico and the

Virgin Island): 1-800-424-9300

Ireland: 353-1813-9456

Other Countries: See "Section 16" for country-specific emergency phone numbers fromCHEMTREC.

2. HAZARDS IDENTIFICATION

Classification and Labelling Common to All Jurisdictions

Classification Combustible Dust

Acute Toxicity - Oral - Category 4

Carcinogenicity - Category 2

Toxic To Reproduction - Reproductive Toxicity - Category 1A

Toxic To Reproduction - Developmental Toxicity - Category 2Effects on or via lactation

Specific Target Organ Systemic Toxicity (Repeated Exposure) - Category 1Hazardous To The Aquatic Environment - Chronic Hazard - Category 1 (M=10)

Symbol

Signal Word Danger

Hazard May form combustible dust concentrations in air (during processing).


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AripiprazoleBristol-Myers Squibb Company

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Statements Harmful if swallowed.

Suspected of causing cancer.

May damage fertility (male reproductive toxicity, female reproductive toxicity) .

Suspected of damaging the unborn child (developmental toxicity) .May cause harm to breast-fed children.

Causes damage to organs (central nervous system, cardiovascular system, endocrine system)through prolonged or repeated exposure.

Very toxic to aquatic life with long lasting effects.(M=10)

Precautionary

Statements

Minimize dust generation, accumulation, and dispersal in air.

Use personal protective equipment as required.

Do not eat, drink or smoke when using this product.

Do not breathe dust/fume/gas/mist/vapours/spray.

Obtain special instructions before use.

Avoid release to the environment.

3. COMPOSITION/INFORMATION ON INGREDIENTS

Components Concentration CAS-No.

EU only

EINECS/ELINCS/

REACHRegistration

Number

Symbol(s)/R-phrase(s)

H-code(s)

Hazardous components

Aripiprazole 100% 129722-12-9 -- T: R22,R40,

R48/25,

R60, R63,

R64, R53

H302

H351

H360FH361d

H362

H372

H410/M=10

See section 16 for Symbol, R-phrase and H-code text.

4. FIRST AID MEASURES

Eye contact Rinse immediately with plenty of water for at least 15 minutes. Keep eye wide open whilerinsing. Obtain medical attention.

Skin contact Take off contaminated clothing and shoes immediately. Wash off immediately with plenty

of water for at least 15 minutes. If skin irritation persists, call a physician.

Inhalation Move to fresh air. Oxygen or artificial respiration if needed. If exposed or concerned: Getmedical attention/advice.

Ingestion IF SWALLOWED: Call a POISON CENTER or doctor/physician if you feel unwell.

Rinse mouth.

Notes to Physician Medical conditions aggravated include: depression, diabetes, cardiovascular disease,

decreased white blood cell count, kidney disorders. This product has been reported to

interact with the following medications: drugs that inhibit cytochrome P-450,

cardiovascular agents, anti-psychotic drugs, alcohol. Refer to Section 11.


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Medical Surveillance The need for a pre-placement physical examination and history for employees with

potential exposure to this compound is to be evaluated by a physician that is thoroughly

knowledgeable about both the toxicity of this compound and the extent of work place

exposure. Baseline testing would include: a complete blood count with differential, a bloodtest for kidney function. Based on opportunity for exposure and duration of exposure a

periodic follow-up examination may be considered. This exam should be overseen by aphysician thoroughly knowledgeable about both the toxicity of this compound and the

extent of work place exposure. It is recommended that the content be similar to the pre-

placement exam.

Employees who are pregnant, are breast-feeding, or who are concerned with other

reproductive issues should be encouraged to consult with the occupational health physician

monitoring worker's health.

5. FIRE-FIGHTING MEASURES

Flammable Properties Not available

Extinguishing Media Suitable extinguishing media: Dry chemical, Water spray, FoamUnsuitable extinguishing media: Do NOT use water jet.

Protection ofFirefighters

Specific hazards: Not availableProtective equipment: Use personal protective equipment. In the event of fire, wear self-

contained breathing apparatus.

Hazardous Combustion Products: carbon oxides (COx), nitrogen oxides (NOx), and,gaseous hydrogen chloride (HCl).

Further Information: HCl gas can form flammable or explosive mixtures with alcohols or

metals. In the event of fire and/or explosion do not breathe fumes.

Other information Decontaminate protective clothing and equipment before reuse. Avoid generating dust;

fine dust dispersed in air in sufficient concentrations, and in the presence of an ignition

source is a potential dust explosion hazard.

6. ACCIDENTAL RELEASE MEASURES

Personal precautions Refer to protective measures listed in sections 7 and 8. Use personal protective equipment.Examples include tightly fitting safety goggles, lab coat and impervious gloves. Wear

respiratory protection. Depending on the nature of the spill (quantity and extent of spill)

additional protective clothing and equipment such as a self-contained breathing apparatus

may be needed.

Environmentalprecautions

Prevent release to drains and waterways. Prevent release to the environment.

Containment Methods Wet down any dust to prevent generation of aerosols, if appropriate. Cover with suitable

material.

Cleanup Methods Contain and collect spillage and place in container for disposal according to local

regulations (see Section 13). Use a HEPA vacuum or moisten materials to minimize dustgeneration during pick-up. Clean area with detergent and water after spill pick-up, if

appropriate. Handle waste materials, including gloves, protective clothing, contaminated

spill cleanup material, etc., as appropriate for chemically and pharmacologically similarmaterials.

Other information Dust deposits should not be allowed to accumulate on surfaces, as these may form an

explosive mixture if they are released into the atmosphere in sufficient concentration.

Avoid dispersal of dust in the air (i.e., clearing dust surfaces with compressed air).Nonsparking tools should be used.


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7. HANDLING AND STORAGE

Handling Precautions Avoid exposure - obtain special instructions before use. Avoid formation of dust and

aerosols. Keep away from heat and sources of ignition. Prevent release to drains and

waterways. Minimize dust generation and accumulation. Routine housekeeping should be

instituted to ensure that dusts do not accumulate on surfaces. Dry powders can build staticelectricity charges when subjected to the friction of transfer and mixing operations.

Provide adequate precautions, such as electrical grounding and bonding, or inertatmospheres. Use of inert gas should be considered for process conditions to minimize the

risk of ignition. Refer also to Section 10.

ContainerRequirements

Store in sturdy containers appropriate to maintain the integrity of this material for itsintended use. Provide anti-static bags where drum liners are used.

Storage Conditions Store at 25C Protect against light. Keep away from heat, sparks and flames.

Specific use(s) Refer to Section 1

8. EXPOSURE CONTROLS / PERSONAL PROTECTION

Exposure limit(s) Company Guideline ACGIH Germany OEL UK MEL

Aripiprazole 20 g/m3 8 hour-

TWA

-- -- --

RecommendedIndustrial Hygiene

Monitoring Methods

Contact the Bristol-Myers Squibb AIHA accredited Industrial Hygiene Laboratory at 732-227-6338.

Engineering

Controls and

Ventilation

Use process enclosures, containment technology, or other engineering controls to keep

airborne levels below recommended exposure limit. When handling quantities up to 15

milligrams, a standard laboratory with general laboratory dilution ventilation (e.g. 6-12 air

changes per hour) is appropriate. When handling quantities from 15 milligrams to 1 kilogram,work in a standard laboratory using a fume hood, biological safety cabinet(Class II, all types),

or approved vented enclosure. Quantities exceeding 1 kilogram should be handled in a

designated laboratory. A laminar flow/powder containment booth is recommended for

handling >1 kilograms of active substance. For manufacturing and pilot plant operations, use

direct coupling and closed transfer systems for all bulk transfers. Use dust tight valves asappropriate. HEPA filtration of local exhaust ventilation (LEV) is required.

It is recommended that all dust control equipment such as local exhaust ventilation and

material transport systems involved in handling of this product contain explosion relief vents

or an explosion suppression system or an oxygen deficient environment. Ensure that dust-

handling systems (such as exhaust ducts, dust collectors, vessels, and processing equipment)

are designed in an manner to prevent the escape of dust into the work area (i.e., there is no

leakage from the equipment). Use only appropriately classified electrical equipment andpowered industrial trucks.

Respiratory

protection

Use and selection of respiratory protection is based upon engineering controls in use and

potential for aerosol generation. When engineering controls are not sufficient controlexposure, wear an approved respirator with NIOSH Class 100 or high efficiency particulate

(HEPA) filters or cartridges (EN 140/EN 136) when exposures are up to 10 times the exposurecontrol guideline. Wear a loose-fitting (Tyvek or helmet type) HEPA powered-air purifying

respirator (PAPR) (EN 12941) when exposures are 10-25 times the exposure control

guideline. Wear a full facepiece negative pressure respirator with Class 100 or HEPA filters

(EN 136) when exposures are 25-50 times the exposure control guideline. Wear a tight-

fitting, full facepiece HEPA PAPR (EN 12942) when exposures are 50-100 times the exposure

control guideline. Wear a hood-shroud HEPA PAPR (EN 12941) or full facepiece supplied

air respirator (EN 139) operated in a pressure demand or other positive pressure mode when

exposures are 100-1000 times the exposure control guideline.


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Eye protection Safety glasses with side-shields are recommended (EN 166). Face shields or chemical safety

goggles (EN 166) may be required if splash potential exists or if corrosive materials are

present. Note: Choice of eye protection may be influenced by the type of respirator which is

selected.Hand protection Impervious nitrile, rubber and latex gloves are recommended (EN 420, EN 374). If material

is handled in solution, the solvent should also be considered when selecting protective clothingmaterial. Please note that employees who are allergic to natural rubber latex should use nitrile

gloves.

Skin and body

protection

Wear a laboratory coat (EN 340) when handling quantities up to 1 kilogram. For quantities

over 1 kilogram, wear laboratory coat(EN 340)or coverall of low permeability (EN 1149-1).

For manufacturing operations, wear coverall of low permeability (EN 465/1149-1). For

manufacturing operations, wear coverall of low permeability (EN 1149-1).

Hygiene Wash hands and face before breaks and immediately after handling the product.

Environmental

exposure controls

Prevent release to drains and waterways.

9. PHYSICAL AND CHEMICAL PROPERTIES

General Information

Appearance

Physical State solidColor white to off-whiteForm crystalline, powder

Odour

Odour Not availableOdor Threshold Not available

pH Not available

Other information

Bulk density Not available

Chemical Name 2(1H)-Quinolinone,7-[4-[4-(2,3-dichlorophenyl)-1-piperazinyl]butoxy]-3,4-

dihydro-Evaporation rate Not available

Molecular formula C23 H27 Cl2 N3 O2Hydrolysis/Photolysis Not available

Hygroscopicity Not available

Molecular Weight 448.39 g/mol

Log Octanol/Water Partition

Coeff [log Kow]

2.70 @ 24.9 - 25.2 C (pH 5)

2.95 @ 24.9 - 25.2 C (pH 7)2.86 @ 24.9 - 25.2 C (pH 9)

Surface Tension Not available

pKa Not available

Particle Size 95 % of particles are < 14.6 micronsSolubility, Water 0.0013 g/l @ 25 C

Solubility in other solvents Chloroform: 385 g/l @ 25 C

dimethyl sulfoxide: 17.1 g/l @ 25 Cethyl alcohol: 3.1 g/l @ 25 C

ether: 1.5 g/l @ 25 C

methanol: 0.93 g/l @ 25 C


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Specific Gravity/ Relative

density

Not available

Viscosity, dynamic Not available

Viscosity, kinematic Not available% Volatile Not available

Thermal/Stability properties

Autoignition temperature Not availableBoiling Point 139.0 - 139.5 C

Thermal decomposition Not available

Explosive Limits, LEL Not availableExplosive limits, UEL Not available

Explosiveness Non-explosive based on chemical structure.Flammability Not available

Flash point Not available

Melting Point Not available

Oxidizing Potential Non-oxidizer based on chemical structure.

Vapor Properties

Vapor Density Not availableVapor Pressure Not available

Saturated Vapor Concentration Not available

10. STABILITY AND REACTIVITY

Stability

Chemical

Stability

Stable under normal conditions.

Conditions to

avoid

Not available

Materials to

avoid

Not available

Hazardousdecomposition

products

Hazardous decomposition products formed under fire conditions.: carbon oxides (COx),nitrogen oxides (NOx), and, gaseous hydrogen chloride (HCl).

Hazardous

reactionsNone known.

Sensitivity to static discharge/Dust exp.

Explosion

Severity Factor183 m.b_/s

St1

Material exhibits weak to moderate explosion characteristics if ignited as a dust cloud.

Minimum

Ignition Energy> 3 - < 10 mJ

Material is extremely susceptible to igniting a dust cloud under certain conditions due to lowminimum ignition energy.

Volume

Resistivity

(ambient)

280.0000E+12 ohm.m

Material is highly susceptible to accumulating static charges during processing.


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Charge decay

time (ambient)

5.5 H

Ignition

temperature

> 430 - < 450 C

Layerdecomposition

No exotherm observed.

Summary

Statements

Powder handling equipment such as dust collectors, dryers, and mills may require additional

protective measures (e.g. explosion venting, inerting, etc.). Provide suitable bonding and

grounding for containers, personnel, and process equipment to control static charges. Provide

anti-static bags where drum liners are used. Use of inert gas should be considered for process

conditions to minimize the risk of ignition. NOTE: THIS DATA IS REPRESENTATIVE

FOR THE SPECIFIC PROCESS STATE OF THE MATERIAL NOTED ON THIS SDS

ONLY. Dust explosion severity risk can vary upon processing or environmental change (e.g.milling, micronizing, sieving, blending or heating can increase the risk of explosion), and may

require additional dust explosion testing.

11. TOXICOLOGICAL INFORMATION

Routes of Entry Ingestion, inhalation, Eye contact, Skin contact

Eye Irritation Not irritating to eyes.

Skin Irritation Not irritating to skin.

Respiratory

Irritation

Not available

Sensitization Not a dermal sensitizer in an experimental study

Acute ToxicityStudy

Acute OralLD50 (rat, females): 705 mg/kg High exposure effects include: CNS depression, tremors,

uncontrolled muscle movements.

LD50 (rat, males): 953 mg/kg

LD50 (monkey, males and females): > 2,000 mg/kg High exposure effects include: CNS

depression, tremors, uncontrolled muscle movements.

Acute toxicity (other routes of administration)LD50 (dog, males and females, intramuscular): > 400 mg/kg

LD50 (dog, intramuscular, 7 Weeks): > 400 mg/kg


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Repeated Dose

Toxicity

4 weeks - 2 years oral (daily) mouse, rat, monkey study with recovery period (13 weeks)

(males and females): NOAEL (1 year, monkey) = 0.5 mg/kg; Low dose effects include:

decreased responsiveness, decreased motor activity, drooping eyelids, muscle rigidity,

tremors, hyperactivity, behavioral changes, abnormal posture, clinical signs, body weight

changes, decreased food consumption, bile changes, gall stones, fecal changes, changesin clinical chemistry parameters, adrenal hormone changes, increased prolactin, altered

estrous cycling, overt toxicity, decreased organ weights included:, liver, uterus/cervix.

Low dose microscopic effects include:mammary gland, ovary, pituitary gland, lungs,

vagina, salivary gland, eyes. After recovery, most parameters returned to normal.

Genetic Toxicity In vitroAmes reverse-mutation assay -- negative

Chromosome aberration test in vitro -- positive

DNA repair assay -- negativeForward gene mutation assay -- negative

in vivooral, Mutagenicity (micronucleus test) (mouse) -- negative

oral, Unscheduled DNA synthesis assay (rat) -- negative

Carcinogenicity 2 Years Dietary (daily) mouse study : Tumor NOAEL = 1 mg/kg (males and females).

[tumor organs: pituitary gland, mammary gland] No treatment-related tumors were

observed in males.

2 Years Dietary (daily) rat study : Tumor NOAEL = 3 mg/kg (males and females). [tumor

organs: mammary gland] No treatment-related tumors were observed in males.

Carcinogenicity AssessmentThis material has limited evidence of carcinogenic potential. These tumors are believed to bedue to a prolactin-mediated mechanism.

Carcinogenicity ACGIH IARC NTP

Aripiprazole -- -- --

ReproductiveToxicity

oral (daily) Study of Fertility and Early Embryonic Development (rat)(parent, males) LOAEL = 2 mg/kg

(embryo/fetus, females) NOAEL = 6 mg/kg

Fetal effects include: decreased body weight. Maternal effects include: increased body

weight, increase in food consumption, altered estrous cycling, ovarian changes,

preimplantation loss, delayed time to successful copulation. Paternal effects include:increased body weight, increase in food consumption.

Assessment Reproductive Toxicity

Animal studies indicate that reproductive effects can occur.


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Developmental

Toxicity

Study of Embryo-Fetal Development (rat)

(parent, females) NOAEL = 3 mg/kg/day

(F1 offspring) NOAEL = 3 mg/kg/day

Offspring effects include: decreased body weight, changes in skeletal development,

changes in sexual development. Maternal effects include: central nervous system effects,decreased weight gain, decreased food consumption, delayed delivery. Adverse effects

on the offspring occur only at doses that also cause maternal effects.

Study of Embryo-Fetal Development (rabbit)

(parent, females) LOAEL = 10 mg/kg/day

(embryo/fetus) NOAEL = 10 mg/kg/day

Fetal effects include: decreased body weight, changes in skeletal development. Maternal

effects include: decreased food consumption, decreased body weight, postimplantationloss.

oral Study of Pre- and Postnatal Development (rat)


(F1 offspring) NOAEL = 10 mg/kg/dayFetal effects include: death. Offspring effects include: decreased viability, decreased

body weight. Maternal effects include: decreased weight gain, decreased foodconsumption, lactation effects.

Developmental Toxicity AssessmentSeveral studies were conducted. Compound produced effects on the fetus at doses similar to

those which produced effects on the maternal animal. This compound and/or its metabolites

may be excreted into the milk. Compounds in this drug class have adverse effects on

reproduction.

Human experience Experiences with Human ExposureGeneral effects low exposure - acute effects include: headache, nausea, vomiting,

constipation, incontinence, sleepiness, dizziness, weakness, restlessness, tremors,abnormal coordination, anxiety, irritability, agitation, behavioral changes, sweating,

breathing difficulties, salivation, lightheadedness, disorganized thought, suicidal

thoughts, fever, uncontrolled muscle movements, muscle rigidity, convulsions,

difficulty swallowing, pain, swelling, cough, congestion, blurred vision, changes in

blood pressure, cardiac irregularities, changes in clinical chemistry parameters,

increased weight gain. low exposure - long term exposure effects include: increased

prolactin, reproductive function changes, degeneration of skeletal muscle, kidney

failure, hyperglycemia, hepatitis.

Acute Overdose low exposure - acute effects include: vomiting, sleepiness, dizziness,tremors, uncontrolled muscle movements, difficulty swallowing, behavioral

changes, confusion, agitation, electrolyte disturbance, changes in clinical chemistryparameters, cardiac irregularities, changes in blood pressure, headache, skin

sensation changes, unconsciousness, convulsions, respiratory arrest, coma.

Target Organs central nervous system, cardiovascular system, endocrine system

Symptoms See "Human Experience".


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Pharmacokinetics/

Toxicokinetics

Absorption: Not available

Distribution: Not available

Metabolism: Not available

Elimination: Half-life = 75 Hour(s) (Human).

Other ToxicityInformation

Not available

12. ECOLOGICAL INFORMATION

Ecotoxicity effects

Acute Toxicity to Fish

LC50 (Oncorhynchus mykiss (rainbow trout), 96 H) : > 0.12 mg/l. (highest mean concentration tested)NOEC (Oncorhynchus mykiss (rainbow trout), 96 H) : 0.047 mg/l.

Acute Toxicity to Aquatic InvertebratesNOEC (Daphnia magna (Water flea), 48 H) : 0.031 mg/l.

Toxicity to aquatic plantsEC50 (Pseudokirchneriella subcapitata (formerly Selenastrum capricornutum), Algae biomass and

growth rate, 72 H) : > 0.14 mg/l (highest mean concentration tested)

NOEC (Pseudokirchneriella subcapitata (formerly Selenastrum capricornutum), Algae biomass, 72 H) :

0.026 mg/l

NOEC (Pseudokirchneriella subcapitata (formerly Selenastrum capricornutum), Algae growth rate, 72

H) : 0.14 mg/l

Toxicity to microorganisms

Respiration inhibition, EC50 (Activated Sludge, 3 H) : > 1,000 mg/l

Chronic toxicity to fishEarly-life Stage NOEC (Pimephales promelas (fathead minnow)) : 0.0058 mg/l

Chronic toxicity to aquatic invertabratesNOEC (Daphnia magna (Water flea)) : 0.00261 mg/l (reproduction rate)

Toxicity to soil dwelling organisms

EC50 (Eisenia foetida, 14 days) : > 1,000 mg/kg soil dm

Mobility Not available

Persistence and degradability

Biodegradation

Ready biodegradation (42 D) : 10 % ; Not Readily Biodegradable - unlikely to undergo rapid

biodegradation in the environment

Koc (Batch equilibrium, Activated Sludge) : 10,270 (water)

Kd (Batch equilibrium, Activated Sludge) : 2,783 (water)

immobileKoc (Batch equilibrium, Activated Sludge) : 2,850 (calcium chloride solution)

Kd (Batch equilibrium, Activated Sludge) : 772 (calcium chloride solution)

immobile

Summary Statements

Aquatic toxicityExperimental data indicate low potential for acute harm to aquatic organisms.

Chemical Fate

Not readily biodegradable. Immobile in soil.

Bioaccumulative potentialBioconcentration factor (BCF): 53.9 - 85.7


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12. ECOLOGICAL INFORMATION

PBT and vPvB Assessment: Not available

13. DISPOSAL CONSIDERATIONS

Advice On Disposal And Packaging Disposal should be in accordance with applicable regional, national and locallaws and regulations. Local regulations may be more stringent than regional

or national requirements. This information presented only applies to the

material as supplied.

Other information Disposal by incineration is recommended.

14. TRANSPORT INFORMATIONThis material is not a dangerous good for the purpose of transportation in all modes.

15. REGULATORY INFO MATION

United States of America313 Toxic ReleaseInventory

No components listed on the SARA 313 inventory.

TSCA Inventory Not listed. Food, drug and cosmetic products are exempt from TSCA.

EU Directive 67/548/EEC

Symbol(s) T: Toxic

R-phrase(s) R22: Harmful if swallowed.

R40: Limited evidence of a carcinogenic effect.

R48/25: Toxic: danger of serious damage to health by prolonged exposure if swallowed.

R60: May impair fertility.R63: Possible risk of harm to the unborn child.R64: May cause harm to breastfed babies.

R53: May cause long-term adverse effects in the aquatic environment.

S-phrase(s) S22: Do not breathe dust.

S36/37/39: Wear suitable protective clothing, gloves and eye/face protection.

S45: In case of accident or if you feel unwell, seek medical advice immediately (show label

where possible).

S53: Avoid exposure - obtain special instructions before use.

S60: This material and its container must be disposed of as hazardous waste.

S61: Avoid release to the environment. Refer to special instructions/ Safety data sheets.

Regulatory

Authorizations and

Restrictions:

Not available

16. OTHER INFORMATIONText of Symbol(s), R-phrase(s) and H-code(s) mentioned in Section 3

H302 Harmful if swallowed.H351 Suspected of causing cancer.

H360F May damage fertility

H361d Suspected of damaging the unborn child


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H362 May cause harm to breast-fed children.

H372 Causes damage to organs through prolonged or repeated exposure.

H410/M=10 Very toxic to aquatic life with long lasting effects.(M=10)

R22 Harmful if swallowed.

R40 Limited evidence of a carcinogenic effect.

R48/25 Toxic: danger of serious damage to health by prolonged exposure ifswallowed.

R53 May cause long-term adverse effects in the aquatic environment.R60 May impair fertility.

R63 Possible risk of harm to the unborn child.R64 May cause harm to breastfed babies.

T Toxic

Recommended Restrictions for Use:

Not available

SDS preparation information

Prepared by Research and Development Environment, Health and Safety 1-732-227-7380

Prepared on 04.04.2013 DD/MM/YYYYThis Safety Data Sheet has been revised. This data sheet contains changes from the

previous version in section(s): 1, 11, 12, and 16.

Other information

HMIS Health 1*

Flammability 1

Reactivity Not Determined (ND)

Personal protective equipment Not Determined (ND)

NFPA

Health 1

Fire 1

Reactivity ND

Special ND1

1

ND

ND


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Country- Specific Emergency

Phone Numbers

The information contained in this SDS is believed to be accurate and represents the best information reasonably

available at the time of preparation. However, we make no warranty, express or implied, with respect to such

information. and we assume no liability from its use. Refer to NFPA 654, Standard for the Prevention of Fire andDust Explosions from the Manufacturing, Processing, and Handling of Combustible Particle Solids, for safe handling.


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Safety Data Sheet

1. PRODUCT AND COMPANY IDENTIFICATION

Product InformationProduct name ABILIFY 2, 5, 10, 15, 20 and 30 mg Tablets - Bulk

Version 1.0, 05.02.2010

Jurisdiction This Safety Data Sheet was prepared for the European Union (EU).

Active substance Aripiprazole

Synonyms Abilify; Abiligize; Abilitat; Otsuka Abilify, Aripiprazole

Intended Uses This material is a bulk drug product.

Registration Number: Not available


Address Swords LaboratoriesWatery Lane

Swords

Ireland

353-1813-9456

E-mail: [email protected]

Emergency Phone

NumberIn the EU, call 353-1813-9456.

2. HAZARDS IDENTIFICATIONEmergency Overview

EU Globally Harmonized System (GHS) EC Reg # 1272/2008

Classification Carcinogenicity - Category 2Toxic To Reproduction - Male Reproductive Toxicity - Category 1A

Toxic To Reproduction - Female Reproductive Toxicity - Category 1A

Toxic To Reproduction - Developmental Toxicity - Category 2Effects on or via lactation

Specific Target Organ Systemic Toxicity (Repeated Exposure) - Category

1

Labeling

Symbol

Signal Word Danger

Hazard Statements Suspected of causing cancer.

May damage fertility or the unborn child(male reproductive toxicity,

female reproductive toxicity) .

Suspected of damaging fertility or the unborn child(Developmental

Toxicity) .May cause harm to breast-fed children.

Causes damage to organs (central nervous system, cardiovascular system,

endocrine system) through prolonged or repeated exposure.


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ABILIFY 2, 5, 10, 15, 20 and 30 mgTablets - Bulk

Swords Laboratories000000126020 Page 2 of 14


Precautionary Statements Do not breathe dust/fume/gas/mist/vapours/spray. Obtain special

instructions before use. Do not handle until all safety precautions have

been read and understood. Avoid contact during pregnancy/while nursing.

Wash thoroughly after handling. Do not eat, drink or smoke when using

this product. Use personal protective equipment as required. Store locked

up.



EINECS/ELINCS

/RegistrationNumber

Symbol(s) R-phrase(s)


Aripiprazole 2 - 16 % 129722-12-9 -- T R22, R40,

R48/22,

R60, R63,

R64, R53

Corn Starch < 15 % 9005-25-8 232-679-6 -- --

Microcrystalline Cellulose < 15 % 9004-34-6 232-674-9 Xi R37Other ingredients

Magnesium Stearate < 1% 557-04-0 209-150-3 -- --

Red Iron Oxide 0 - < 0.1% 1309-37-1 215-168-2 -- --

Non-Hazardous Ingredients < 80% Not available -- -- --

See section 16 for R-Phrase text.


Eye contact IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if

present and easy to do. Continue rinsing. If eye irritation persists, get medicaladvice/attention.

Skin contact Take off contaminated clothing and shoes immediately. Wash off immediately with

plenty of water for at least 15 minutes. If skin irritation occurs, get medicaladvice/attention.

Inhalation IF exposed or concerned: Get medical attention/advice.

Ingestion IF exposed or concerned: Get medical attention/advice.

Notes to Physician This product has been reported to interact with the following medications: drugs that

inhibit cytochrome P-450, cardiovascular agents, anti-psychotic drugs, and, alcohol.

Refer to Section 11. Pregnant or nursing women should avoid exposure.

Medical Surveillance A pre-placement physical examination and history for employees with potentialexposure to this compound is recommended. Baseline testing would include: a

complete blood count with differential, a blood test for kidney function. Based on

opportunity for exposure and duration of exposure a periodic follow-up examination

may be considered. This exam should be overseen by a physician thoroughlyknowledgeable about both the toxicity of this compound and the extent of work place

exposure. It is recommended that the content be similar to the pre-placement exam.

Employees who are pregnant, are breast-feeding, or who are concerned with other

reproductive issues should be encouraged to consult with the occupational health

physician monitoring worker's health.

Other information Precautionary risk management may be different from the exposure categories in the

annex.


16/41





Extinguishing Media Suitable extinguishing media: Dry chemical, Water spray, Foam

Unsuitable extinguishing media: Do NOT use water jet.

Protection of Firefighters Specific hazards: Respiratory Irritant Developmental Toxicity

Protective equipment: Use personal protective equipment. In the event of fire, wearself-contained breathing apparatus.

Hazardous Combustion Products: carbon oxides(COx), nitrogen oxides (NOx), and,

gaseous hydrogen chloride (HCl).

Further Information: HCl gas can form flammable or explosive mixtures with

alcohols or metals. In the event of fire and/or explosion do not breathe fumes.

Other information Decontaminate protective clothing and equipment before reuse.


Personal precautions Refer to protective measures listed in sections 7 and 8. Use personal protective

equipment. Examples include tightly fitting safety goggles, lab coat and impervious

gloves. Wear respiratory protection. Depending on the nature of the spill (quantity and

extent of spill) additional protective clothing and equipment such as a self-contained

breathing apparatus may be needed.

Environmental

precautions


Containment Methods Wet down any dust to prevent generation of aerosols, if appropriate. Cover with

suitable material.

Cleanup Methods Contain and collect spillage and place in container for disposal according to localregulations (see Section 13). Use a HEPA vacuum or moisten materials to minimize

dust generation during pick-up. Clean area with detergent and water after spill pick-up,if appropriate. Handle waste materials, including gloves, protective clothing,

contaminated spill cleanup material, etc., as appropriate for chemically and

pharmacologically similar materials.


Handling Precautions Avoid exposure - obtain special instructions before use. Avoid formation of dust andaerosols. Keep away from heat and sources of ignition. Prevent release to drains and

waterways.

Container

Requirements

Store in sturdy containers appropriate to maintain the integrity of this material for its

intended use.


Specific use(s) Refer to Section 1

8. EXPOSURE CONTROLS / PERSONAL PROTECTIONExposure limit(s) Company

Guideline

ACGIH Germany OEL UK MEL

Aripiprazole 20 g/m3 -- -- --

Corn Starch -- 10 mg/m3 TWA -- --


17/41




Microcrystalline

Cellulose

-- 10 mg/m3 TWA -- --

Magnesium Stearate -- 10 mg/m3 TWA -- --

Red Iron Oxide -- 5 mg/m3 TWA

dust and

fume, as Fe

1 mg/m3 TWA

as Fe

6 mg/m3 TWA

respirable

fraction

1.5 mg/m3 MAK

respirable

fraction

10 mg/m3 STEL

fume, as Fe

2 mg/m3 STEL

as Fe

5 mg/m3 TWA

fume, as Fe1 mg/m3 TWA

as Fe

Corn Starch Occupational Exposure Limits have been established by:

- Belgium - Switzerland - Czech Republic - Spain - Greece - Ireland - Portugal

Microcrystalline

Cellulose

Occupational Exposure Limits have been established by:

- Belgium - Switzerland - Estonia - Spain - France - Ireland - Portugal

Magnesium Stearate Occupational Exposure Limits have been established by:

- Belgium - Spain - Ireland - Portugal - Sweden

Red Iron Oxide Occupational Exposure Limits have been established by:

- Austria - Belgium - Switzerland - Czech Republic - Denmark - Estonia - Spain -Finland - France - Greece - Hungary - Ireland - The Netherlands - Norway - Poland

- Portugal - Sweden

Exposure Control Band Aripiprazole

3-- The established company exposure guideline falls within Exposure

Control Band 3 (range 10-


18/41




Engineering Controls and

Ventilation

Use process enclosures, containment technology, or other engineering

controls to keep airborne levels below recommended exposure limit.

When handling quantities up to 15 milligrams, a standard laboratory withgeneral laboratory dilution ventilation (e.g. 6-12 air changes per hour) is

appropriate. When handling quantities from 15 milligrams to 1 kilogram,

work in a standard laboratory using a fume hood, biological safety

cabinet(Class II, all types), or approved vented enclosure. Quantities

exceeding 1 kilogram should be handled in a designated laboratory. A

laminar flow/powder containment booth is recommended for handling >1

kilograms of active substance. For manufacturing and pilot plantoperations, use direct coupling and closed transfer systems for all bulk

transfers. Use dust tight valves as appropriate. HEPA filtration of local

exhaust ventilation (LEV) is required.

Respiratory protection Use and selection of respiratory protection is based upon engineering

controls in use and potential for aerosol generation. When engineering

controls are not sufficient control exposure, wear an approved respirator

with NIOSH Class 100 or high efficiency particulate (HEPA) filters or

cartridges (EN 140/EN 136) when exposures are up to 10 times theexposure control guideline. Wear a loose-fitting (Tyvek or helmet type)

HEPA powered-air purifying respirator (PAPR) (EN 12941) when

exposures are 10-25 times the exposure control guideline. Wear a full

facepiece negative pressure respirator with Class 100 or HEPA filters (EN136) when exposures are 25-50 times the exposure control guideline.

Wear a tight-fitting, full facepiece HEPA PAPR (EN 12942) when

exposures are 50-100 times the exposure control guideline. Wear a hood-

shroud HEPA PAPR (EN 12941) or full facepiece supplied air respirator

(EN 139) operated in a pressure demand or other positive pressure mode

when exposures are 100-1000 times the exposure control guideline.

Eye protection Safety glasses with side-shields are recommended (EN 166). Face

shields or chemical safety goggles (EN 166) may be required if splash

potential exists or if corrosive materials are present. Note: Choice of eyeprotection may be influenced by the type of respirator which is selected.

Hand protection Impervious nitrile, rubber and latex gloves are recommended (EN 420, EN374). If material is handled in solution, the solvent should also be

considered when selecting protective clothing material. Please note that

employees who are allergic to natural rubber latex should use nitrile

gloves.

Skin and body protection Wear a laboratory coat (EN 340) when handling quantities up to 1

kilogram. For quantities over 1 kilogram, wear laboratory coat(EN

340)or coverall of low permeability (EN 1149-1). For manufacturing

operations, wear coverall of low permeability (EN 465/1149-1). For

manufacturing operations, wear coverall of low permeability (EN 1149-1).

Hygiene Wash hands and face before breaks and immediately after handling theproduct.

Environmental exposure controls Prevent release to drains and waterways.


19/41




General Information

Appearance

Physical State solid

Color green blue pink yellow or whiteForm tablet

Odour

Odour Not available

Odor Threshold Not available

pH Not available

Other information


Evaporation rate Not available

Molecular formula Not applicable

Hydrolysis/Photolysis Not available

Hygroscopicity Not availableMolecular Weight Not available

Log Octanol/Water Partition

Coeff [log Kow]

Not available


pKa Not available

Particle Size Not availableSolubility, Water Not available


density

Not available

Viscosity, dynamic Not available

Viscosity, kinematic Not available

% Volatile Not available

Thermal/Stability propertiesAutoignition temperature Not available

Boiling Point Not available


Explosive Limits, LEL Not availableExplosive limits, UEL Not available

Explosiveness Not available

Flammability Not availableFlash point Not available


Oxidizing Potential Not available

Vapor Properties

Vapor Density Not available

Vapor Pressure Not availableSaturated Vapor Concentration Not available


Stability

Chemical Stability Stable under normal conditions.

Conditions to avoid Not available

Materials to avoid Not available


20/41




Hazardous decomposition

products

Hazardous decomposition products formed under fire conditions.: carbon

oxides(COx), nitrogen oxides (NOx), and, gaseous hydrogen chloride

(HCl).

Hazardous reactions None known.


Summary Statements Although material has not been specifically tested, fine dust suspended in

air in sufficient concentration and in the presence of an ignition source

may pose a potential explosion hazard. Provide appropriate bonding and

grounding protection to control static charge. Powder handling equipmentsuch as dust collectors, dryers, and mills may require additional protective

measures (e.g. explosion venting, inerting, etc.).


Routes of Entry Ingestion, Inhalation, Eye contact, Skin contact

Eye Irritation AripiprazoleNot irritating to eyes.

Microcrystalline Cellulose

Mildly irritating to eyes.

Skin Irritation Aripiprazole

Not irritating to skin.Microcrystalline Cellulose

Not irritating to skin.

Respiratory Irritation Microcrystalline Cellulose

Respiratory Irritant

Sensitization Aripiprazole

Not a dermal sensitizer in an experimental study

Microcrystalline CelluloseNot a dermal sensitizer


21/41




Acute Toxicity Study Acute OralAripiprazole

LD50 (rat, females): 705 mg/kg High exposure effects include: CNS depression, tremors,



LD50 (monkey, males and females): > 2,000 mg/kg High exposure effects include: CNS

depression, tremors, uncontrolled muscle movements.

Microcrystalline CelluloseLD50 (rat, males and females): > 5,000 mg/kg

Acute DermalMicrocrystalline Cellulose

LD50 (rat, males and females): > 2,000 mg/kg

Acute inhalation toxicityMicrocrystalline Cellulose

LC50 (rat, males and females): > 5350 mg/m3/4 H

Acute toxicity (other routes of administration)Aripiprazole

LD50 (dog, males and females, intramuscular): > 400 mg/kg



LD50 (rat, males, Intraperitoneal): > 3,160 mg/kg

Repeated Dose Toxicity Aripiprazole

4 weeks - 2 years Oral (daily) mouse, rat, monkey study with recovery period (13 weeks):

NOAEL = 0.5 mg/kg (males and females). Low dose effects include: decreased

responsiveness, decreased motor activity, drooping eyelids, muscle rigidity, tremors,hyperactivity, behavioral changes, abnormal posture, clinical signs, body weight

changes, decreased food consumption, bile changes, gall stones, fecal changes,

changes in clinical chemistry parameters, adrenal hormone changes, increased

prolactin, altered estrous cycling, overt toxicity, decreased organ weights included:,

liver, uterus/cervix. Low dose microscopic effects include:mammary gland, ovary,

pituitary gland, lungs, vagina, salivary gland, eyes. After recovery, most parametersreturned to normal.

Genetic Toxicity Aripiprazole

in vitroAmes reverse-mutation assay -- negative

Chromosome aberration test in vitro -- positiveDNA repair assay -- negative

Forward gene mutation assay -- negative

in vivoOral, Mutagenicity (micronucleus test) (mouse) -- negative

Oral, Unscheduled DNA synthesis assay (rat) -- negative


Mutagenicity AssessmentThis material was negative in a battery of in vivo and in vitro genotoxicity assays.


22/41




Carcinogenicity Aripiprazole

2 Years Dietary (daily) mouse study : Tumor NOAEL = 1 mg/kg (males and females).


observed in males.

2 Years Dietary (daily) rat study : Tumor NOAEL = 3 mg/kg (males and females).

[tumor organs: mammary gland] No treatment-related tumors were observed in

males.

Microcrystalline CelluloseCarcinogenicity AssessmentThis material did not show carcinogenic potential in animal studies. Not classifiable as toits carcinogenicity to humans.

Carcinogenicity ACGIH IARC NTP

Aripiprazole -- -- --

Microcrystalline

Cellulose

-- -- --

Reproductive Toxicity Aripiprazole

Oral (daily) Study of Fertility and Early Embryonic Development (rat) (parent, males andfemales) LOAEL = 2 mg/kg Effects include: increased body weight, increase in

food consumption, altered estrous cycling, ovarian changes, preimplantation loss,

delayed time to successful copulation. Fetal effects include: decreased body weight.

Oral (daily) Reproductive and developmental study (rat) (parent, males) NOAEL = 20

mg/kg Effects include: impaired spermatogenesis, atrophy of the male reproductive

organs.

Assessment Reproductive ToxicityAnimal studies indicate that reproductive effects can occur.


Assessment Reproductive ToxicityData indicate that this compound is not a reproductive hazard.


23/41




Developmental Toxicity Aripiprazole




Offspring effects include: decreased body weight, changes in skeletal development,

changes in sexual development. Maternal effects include: central nervous system

effects, decreased weight gain, decreased food consumption, delayed delivery.

Adverse effects on the offspring occur only at doses that also cause maternal effects.

Study of Embryo-Fetal Development (rabbit)(parent, females) LOAEL = 10 mg/kg/day

(embryo/fetus) NOAEL = 10 mg/kg/day

Fetal effects include: decreased body weight, changes in skeletal development.Maternal effects include: decreased food consumption, decreased body weight,

postimplantation loss.

Oral Study of Pre- and Postnatal Development (rat)



Fetal effects include: death. Offspring effects include: decreased viability, decreased

body weight. Maternal effects include: decreased weight gain, decreased foodconsumption, lactation effects.

Developmental Toxicity AssessmentSeveral studies were conducted. Compound produced effects on the fetus at doses similar

to those which produced effects on the maternal animal. This compound and/or its

metabolites may be excreted into the milk. Compounds in this drug class have adverseeffects on reproduction.


Developmental Toxicity AssessmentAvailable data do not indicate a potential for selective developmental toxicity.

Human experience Experiences with Human ExposureAripiprazole

General effects Low exposure - acute effects include: headache, nausea, vomiting,

constipation, incontinence, sleepiness, dizziness, weakness, restlessness,

tremors, abnormal coordination, anxiety, irritability, agitation, behavioral

changes, sweating, breathing difficulties, salivation, lightheadedness,

disorganized thought, suicidal thoughts, fever, uncontrolled muscle movements,muscle rigidity, convulsions, difficulty swallowing, pain, swelling, cough,

congestion, blurred vision, changes in blood pressure, cardiac irregularities,

changes in clinical chemistry parameters, increased weight gain. Low exposure -

long term exposure effects include: increased prolactin, reproductive function

changes, degeneration of skeletal muscle, kidney failure, hyperglycemia,hepatitis.

Acute Overdose Low exposure - acute effects include: vomiting, sleepiness,dizziness, tremors, uncontrolled muscle movements, difficulty swallowing,

behavioral changes, confusion, agitation, electrolyte disturbance, changes in

clinical chemistry parameters, cardiac irregularities, changes in blood pressure,

headache, skin sensation changes, unconsciousness, convulsions, respiratory

arrest, coma.


24/41




Target Organs Aripiprazole

central nervous system, cardiovascular system, endocrine system

Symptoms Aripiprazole

See "Human Experience".Microcrystalline Cellulose

labored respiration, noisy respiration, chest pain, breathing difficulties, shortness of breath,

lung inflammation

Pharmacokinetics/Toxic

okinetics

Aripiprazole




Elimination: Half-life = 75 hours (Human).

Other Toxicity

Information

Not available

12. ECOLOGICAL INFORMATIONEcotoxicity effects

Acute Toxicity to FishAripiprazole

LC50 (Oncorhynchus mykiss (rainbow trout), 96 H) : > 0.12 mg/l. (highest mean concentrationtested)

NOEC (Oncorhynchus mykiss (rainbow trout), 96 H) : 0.047 mg/l.

Acute Toxicity to Aquatic Invertebrates

Aripiprazole

NOEC (Daphnia magna (Water flea), 48 H) : 0.031 mg/l.

Toxicity to aquatic plants

AripiprazoleEC50 (Pseudokirchneriella subcapitata (formerly Selenastrum capricornutum), Algae biomass and


NOEC (Pseudokirchneriella subcapitata (formerly Selenastrum capricornutum), Algae biomass, 72

H) : 0.026 mg/lNOEC (Pseudokirchneriella subcapitata (formerly Selenastrum capricornutum), Algae growth rate,

72 H) : 0.14 mg/l


Aripiprazole


Chronic toxicity to fish

AripiprazoleEarly-life Stage NOEC (Pimephales promelas (fathead minnow)) : 0.0058 mg/l

Chronic toxicity to aquatic invertabrates

AripiprazoleNOEC (Daphnia magna (Water flea)) : 0.00261 mg/l (reproduction rate)

Mobility Not available

Persistence and degradabilityBiodegradation

Aripiprazole


biodegradation in the environment

Aripiprazole


25/41



12. ECOLOGICAL INFORMATIONKoc (Batch equilibrium, Activated Sludge) : 10,270 (water)

Kd (Batch equilibrium, Activated Sludge) : 2,783 (water)immobile

Koc (Batch equilibrium, Activated Sludge) : 2,850 (calcium chloride solution)


immobile

Summary Statements

Aquatic toxicityAripiprazole

Experimental data indicate low potential for acute harm to aquatic organisms.

Chemical FateAripiprazole


PBT and vPvB Assessment: Not available


Advice On Disposal And Packaging Disposal should be in accordance with applicable regional, national and

local laws and regulations. Local regulations may be more stringent than

regional or national requirements. This information presented onlyapplies to the material as supplied.


14. TRANSPORT INFORMATIONThis material is not a dangerous good for the purpose of transportation.

15. REGULATORY INFORMATION

EINECS/ELINCS/RegistrationNumber

Corn Starch: 232-679-6Microcrystalline Cellulose: 232-674-9

Magnesium Stearate: 209-150-3

FD&C Blue No. 2 Aluminum Lake: 240-589-3

Yellow Iron Oxide: 257-098-5

Red Iron Oxide: 215-168-2

EU Globally Harmonized System (GHS) EC Reg # 1272/2008

Classification Carcinogenicity - Category 2

Toxic To Reproduction - Male Reproductive Toxicity - Category 1A

Toxic To Reproduction - Female Reproductive Toxicity - Category 1A

Toxic To Reproduction - Developmental Toxicity - Category 2

Effects on or via lactation


1

Labeling

Symbol

Signal Word Danger


26/41




Hazard Statements Suspected of causing cancer.

May damage fertility or the unborn child(male reproductive toxicity,

female reproductive toxicity) .

Suspected of damaging fertility or the unborn child(DevelopmentalToxicity) .

May cause harm to breast-fed children.Causes damage to organs (central nervous system, cardiovascular system,

endocrine system) through prolonged or repeated exposure.

Precautionary Statements Do not breathe dust/fume/gas/mist/vapours/spray. Obtain special


been read and understood. Avoid contact during pregnancy/while

nursing. Wash thoroughly after handling. Do not eat, drink or smoke

when using this product. Use personal protective equipment as required.Store locked up.

R&S Labeling

Symbol(s) T: Toxic

R-phrase(s) R40: Limited evidence of a carcinogenic effect.R48/22: Harmful: danger of serious damage to health by prolonged

exposure if swallowed.

R60: May impair fertility.

R63: Possible risk of harm to the unborn child.

R64: May cause harm to breastfed babies.

S-phrase(s) S22: Do not breathe dust.

S36/37/39: Wear suitable protective clothing, gloves and eye/face

protection.S38: In case of insufficient ventilation, wear suitable respiratory

equipment.

S45: In case of accident or if you feel unwell, seek medical adviceimmediately (show label where possible).

S53: Avoid exposure - obtain special instructions before use.

Regulatory Authorizations and

Restrictions:

Not available

UN Globally Harmonized System (GHS)

Classification Acute Toxicity - Oral - Category 5

Mild Eye Irritation - Category 2B

Carcinogenicity - Category 2

Toxic To Reproduction - Male Reproductive Toxicity - Category 1A

Toxic To Reproduction - Female Reproductive Toxicity - Category 1AToxic To Reproduction - Developmental Toxicity - Category 2

Effects On Or Via Lactation


1Hazardous To The Aquatic Environment - Chronic Hazard - Category 1

Labeling

Symbol

Signal Word Danger


27/41




Hazard Statements May be harmful if swallowed.

Causes eye irritation.

Suspected of causing cancer.

May damage fertility or the unborn child (male reproductive toxicity,female reproductive toxicity) .

Suspected of damaging fertility or the unborn child (DevelopmentalToxicity) .

May cause harm to breast-fed children.

Causes damage to organs (central nervous system, cardiovascular system,endocrine system) through prolonged or repeated exposure.

Very toxic to aquatic life with long lasting effects.

Precautionary Statements Refer to HAZARDS IDENTIFICATION section.

16. OTHER INFORMATIONText of R phrases mentioned in Section 3

R22: Harmful if swallowed.

R40: Limited evidence of a carcinogenic effect.R48/22: Harmful: danger of serious damage to health by prolongedexposure if swallowed.




R53: May cause long-term adverse effects in the aquatic environment.

R37: Irritating to respiratory system.

Recommended Restrictions for Use:Not available

MSDS preparation information

Prepared by Research and Development Pharmaceutical Quality and Environment,Health and Safety 1-732-227-7380

Prepared on 05.02.2010

This is the first EU Safety Data Sheet issued for this material.

The information contained in this MSDS is believed to be accurate and represents the best information

reasonably available at the time of preparation. However, we make no warranty, express or implied, with respect

to such information. and we assume no liability from its use.


28/41

Continued

Material Safety Data Sheet

1. PRODUCT AND COMPANY IDENTIFICATION

Product InformationProduct name ABILIFY 2, 5, 10, 15, 20 and 30 mg Tablets - Bulk

Version 1.0, 02/05/2010

Jurisdiction This Material Safety Data Sheet was prepared for the jurisdiction USA.

Active substance Aripiprazole

Synonyms Abilify; Abiligize; Abilitat; Otsuka Abilify, Aripiprazole

Intended Uses This material is a bulk drug product.


Address Bristol-Myers Squibb CompanyP.O. Box 191

New Brunswick, New Jersey 08903United States of America

1-732-227-7380

Emergency Phone

Number

CHEMTREC 1-800-424-9300. For all international transportation emergencies call

CHEMTREC at 1-703-527-3887. Collect calls accepted.




Aripiprazole 2 - 16% 129722-12-9

Corn Starch


29/41


Bristol-Myers Squibb Company000000126020 Page 2 of 14

Continued


Precautionary Measures Do not breathe dust/fume/gas/mist/vapours/spray. Obtain special


been read and understood. Avoid contact during pregnancy/while

nursing. Wash thoroughly after handling. Do not eat, drink or smoke

when using this product. Use personal protective equipment as required.

Store locked up.

Potential Health Effects

Eyes Possible mild eye irritant

Skin Experimental data indicate that this material has low potential to cause

skin reactions.

Ingestion Causes damage to organs through prolonged or repeated exposure.

Inhalation May cause respiratory irritation.

Target Organs central nervous system, cardiovascular system, endocrine system

Signs and Symptoms Refer to Section 11.

Medical Conditions Aggravated

Include:

depression, diabetes, cardiovascular disease, decreased white blood cell

count, kidney disorders

Environmental Effects Very toxic to aquatic life with long lasting effects. Refer to Section 12


Eye contact IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if

present and easy to do. Continue rinsing. If eye irritation persists, get medical

advice/attention.

Skin contact Take off contaminated clothing and shoes immediately. Wash off immediately with

plenty of water for at least 15 minutes. If skin irritation occurs, get medical

advice/attention.

Inhalation IF exposed or concerned: Get medical attention/advice.

Ingestion IF exposed or concerned: Get medical attention/advice.

Notes to Physician This product has been reported to interact with the following medications: drugs that

inhibit cytochrome P-450, cardiovascular agents, anti-psychotic drugs, and, alcohol.Refer to Section 11. Pregnant or nursing women should avoid exposure.

Medical Surveillance A pre-placement physical examination and history for employees with potential

exposure to this compound is recommended. Baseline testing would include: acomplete blood count with differential, a blood test for kidney function. Based onopportunity for exposure and duration of exposure a periodic follow-up examination

may be considered. This exam should be overseen by a physician thoroughlyknowledgeable about both the toxicity of this compound and the extent of work place

exposure. It is recommended that the content be similar to the pre-placement exam.

Employees who are pregnant, are breast-feeding, or who are concerned with otherreproductive issues should be encouraged to consult with the occupational health

physician monitoring worker's health.



Extinguishing Media Suitable extinguishing media: Dry chemical, Water spray, Foam

Unsuitable extinguishing media: Do NOT use water jet.


30/41



Continued


Protection of Firefighters Specific hazards: Respiratory Irritant Developmental Toxicity

Protective equipment: Use personal protective equipment. In the event of fire, wear

self-contained breathing apparatus.Hazardous Combustion Products: carbon oxides(COx), nitrogen oxides (NOx), and,

gaseous hydrogen chloride (HCl).

Further Information: HCl gas can form flammable or explosive mixtures with

alcohols or metals. In the event of fire and/or explosion do not breathe fumes.

Other information: Decontaminate protective clothing and equipment before reuse.


Personal precautions Refer to protective measures listed in sections 7 and 8. Use personal protective

equipment. Examples include tightly fitting safety goggles, lab coat and imperviousgloves. Wear respiratory protection. Depending on the nature of the spill (quantity andextent of spill) additional protective clothing and equipment such as a self-contained

breathing apparatus may be needed.

Environmental

precautions


Containment Methods Wet down any dust to prevent generation of aerosols, if appropriate. Cover with

suitable material.

Cleanup Methods Contain and collect spillage and place in container for disposal according to local

regulations (see Section 13). Use a HEPA vacuum or moisten materials to minimize

dust generation during pick-up. Clean area with detergent and water after spill pick-up,

if appropriate. Handle waste materials, including gloves, protective clothing,

contaminated spill cleanup material, etc., as appropriate for chemically and

pharmacologically similar materials.


Handling Precautions Avoid exposure - obtain special instructions before use. Avoid formation of dust andaerosols. Keep away from heat and sources of ignition. Prevent release to drains and

waterways.


Container

Requirements

Store in sturdy containers appropriate to maintain the integrity of this material for its

intended use.


Exposure limit(s) Company

Guideline

ACGIH OSHA NIOSH

Aripiprazole 20 g/m3 -- -- --

Corn Starch -- 10 mg/m3 TWA 15 mg/m3 TWAtotal

5 mg/m3 TWA

10 mg/m3 TWA5 mg/m3 TWA

Microcrystalline

Cellulose

-- 10 mg/m3 TWA 15 mg/m3 TWA

total

5 mg/m3 TWA

10 mg/m3 TWA

5 mg/m3 TWA


31/41



Continued


Magnesium Stearate -- 10 mg/m3 TWA -- --

Red Iron Oxide -- 5 mg/m3 TWA

dust and fume,

as Fe1 mg/m3 TWA

as Fe

10 mg/m3 TWA 2,500 mg/m3

IDLH

dust and fume,as Fe

5 mg/m3 TWA

dust and fume,

as Fe1 mg/m3 TWA

as Fe

Exposure Control Band Aripiprazole

3-- The established company exposure guideline falls within Exposure

Control Band 3 (range 10-1

kilograms of active substance. For manufacturing and pilot plant

operations, use direct coupling and closed transfer systems for all bulk

transfers. Use dust tight valves as appropriate. HEPA filtration of local

exhaust ventilation (LEV) is required.


32/41



Continued


Respiratory protection Use and selection of respiratory protection is based upon engineering

controls in use and potential for aerosol generation. When engineering

controls are not sufficient to control exposure, wear an approvedrespirator with NIOSH Class 100 or high efficiency particulate (HEPA)

filters or cartridges when exposures are up to 10 times the exposure

control guideline. Wear a loose-fitting (Tyvek or helmet type) HEPA

powered-air purifying respirator (PAPR) when exposures are 10-25 times

the exposure control guideline. Wear a full facepiece negative pressure

respirator with Class 100 or HEPA filters when exposures are 25-50 times

the exposure control guideline. Wear a tight-fitting, full facepiece HEPAPAPR when exposures are 50-100 times the exposure control guideline.

Wear a hood-shroud HEPA PAPR or full facepiece supplied air respirator

operated in a pressure demand or other positive pressure mode when

exposures are 100-1000 times the exposure control guideline.

Eye protection Safety glasses with side-shields are recommended. Face shields or

chemical safety goggles may be required if splash potential exists or if

corrosive materials are present. Note: Choice of eye protection may be

influenced by the type of respirator which is selected.Hand protection Impervious nitrile, rubber and latex gloves are recommended. If material

is handled in solution, the solvent should also be considered when

selecting protective clothing material. Please note that employees who areallergic to natural rubber latex should use nitrile gloves.

Skin and body protection Wear a laboratory coat when handling quantities up to 1 kilogram. For

quantities over 1 kilogram, wear laboratory coat or coverall of low

permeability. For manufacturing operations, wear coverall of low

permeability.

Hygiene Wash hands and face before breaks and immediately after handling the

product.


Appearance

Physical State solid

Color green blue pink yellow or white

Form tablet

Other information

Molecular Weight Not available

Molecular formula Not applicable


Evaporation rate Not available

Hydrolysis/Photolysis Not available

Hygroscopicity Not availableLog Octanol/Water Partition

Coeff [log Kow]

Not available


Odor Not available

Odor Threshold Not available

pH Not available

pKa Not available

Particle Size Not available

Solubility, Water Not available


33/41



Continued



density

Not available

Viscosity Not available

Thermal/Stability properties

Autoignition temperature Not availableBoiling Point Not available


Explosive Limits, LEL Not available

Explosive limits, UEL Not available

Explosiveness Not available

Flammability Not available

Flash point Not available


Oxidizing Potential Not available

Vapor Properties

Vapor Density Not available

Vapor Pressure Not availableSaturated Vapor Concentration Not available


Stability

Chemical Stability Stable under normal conditions.

Conditions to avoid Not available

Incompatible products Not available

Hazardous decomposition

productsHazardous decomposition products formed under fire conditions.: carbon

oxides(COx), nitrogen oxides (NOx), and, gaseous hydrogen chloride

(HCl).

Hazardous reactions None known.


Summary Statements Although material has not been specifically tested, fine dust suspended in

air in sufficient concentration and in the presence of an ignition source

may pose a potential explosion hazard. Provide appropriate bonding andgrounding protection to control static charge. Powder handling equipment

such as dust collectors, dryers, and mills may require additional protective

measures (e.g. explosion venting, inerting, etc.).


Routes of Entry Ingestion, Inhalation, Eye contact, Skin contact

Eye Irritation AripiprazoleNot irritating to eyes.

Microcrystalline CelluloseMildly irritating to eyes.


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Skin Irritation Aripiprazole




Respiratory Irritation Microcrystalline Cellulose

Respiratory Irritant

Sensitization Aripiprazole

Not a dermal sensitizer in an experimental study


Not a dermal sensitizer

Acute Toxicity Study Acute OralAripiprazoleLD50 (rat, females): 705 mg/kg High exposure effects include: CNS depression, tremors,



LD50 (monkey, males and females): > 2,000 mg/kg High exposure effects include: CNSdepression, tremors, uncontrolled muscle movements.


LD50 (rat, males and females): > 5,000 mg/kg

Acute Dermal

Microcrystalline CelluloseLD50 (rat, males and females): > 2,000 mg/kg

Acute inhalation toxicityMicrocrystalline Cellulose

LC50 (rat, males and females): > 5350 mg/m3/4 H

Acute toxicity (other routes of administration)Aripiprazole

LD50 (dog, males and females, intramuscular): > 400 mg/kg



LD50 (rat, males, Intraperitoneal): > 3,160 mg/kg

Repeated Dose Toxicity Aripiprazole

4 weeks - 2 years Oral (daily) mouse, rat, monkey study with recovery period (13 weeks):

NOAEL = 0.5 mg/kg (males and females). Low dose effects include: decreased

responsiveness, decreased motor activity, drooping eyelids, muscle rigidity, tremors,

hyperactivity, behavioral changes, abnormal posture, clinical signs, body weightchanges, decreased food consumption, bile changes, gall stones, fecal changes,

changes in clinical chemistry parameters, adrenal hormone changes, increased


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prolactin, altered estrous cycling, overt toxicity, decreased organ weights included:,

liver, uterus/cervix. Low dose microscopic effects include:mammary gland, ovary,

pituitary gland, lungs, vagina, salivary gland, eyes. After recovery, most parameters

returned to normal.

Genetic Toxicity Aripiprazole

in vitroAmes reverse-mutation assay -- negativeChromosome aberration test in vitro -- positive

DNA repair assay -- negative

Forward gene mutation assay -- negative

in vivoOral, Mutagenicity (micronucleus test) (mouse) -- negative

Oral, Unscheduled DNA synthesis assay (rat) -- negative


Mutagenicity AssessmentThis material was negative in a battery of in vivo and in vitro genotoxicity assays.

Carcinogenicity Aripiprazole2 Years Dietary (daily) mouse study : Tumor NOAEL = 1 mg/kg (males and females).


observed in males.

2 Years Dietary (daily) rat study : Tumor NOAEL = 3 mg/kg (males and females).

[tumor organs: mammary gland] No treatment-related tumors were observed in

males.

Carcinogenicity AssessmentThis material has limited evidence of carcinogenic potential. These tumors are believed to

be due to a prolactin-mediated mechanism.


Carcinogenicity AssessmentThis material did not show carcinogenic potential in animal studies. Not classifiable as to

its carcinogenicity to humans.

Carcinogenicity ACGIH OSHA NTP IARC

Aripiprazole -- -- -- --

Microcrystalline

Cellulose

-- -- -- --


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Continued


Reproductive Toxicity Aripiprazole

Oral (daily) Study of Fertility and Early Embryonic Development (rat) (parent, males and

females) LOAEL = 2 mg/kg Effects include: increased body weight, increase in

food consumption, altered estrous cycling, ovarian changes, preimplantation loss,

delayed time to successful copulation. Fetal effects include: decreased body weight.

Oral (daily) Reproductive and developmental study (rat) (parent, males) NOAEL = 20

mg/kg Effects include: impaired spermatogenesis, atrophy of the male reproductive

organs.

Assessment Reproductive ToxicityAnimal studies indicate that reproductive effects can occur.


Assessment Reproductive ToxicityData indicate that this compound is not a reproductive hazard.

Developmental Toxicity Aripiprazole



(F1 offspring) NOAEL = 3 mg/kg/dayOffspring effects include: decreased body weight, changes in skeletal development,

changes in sexual development. Maternal effects include: central nervous system

effects, decreased weight gain, decreased food consumption, delayed delivery.

Adverse effects on the offspring occur only at doses that also cause maternal effects.

Study of Embryo-Fetal Development (rabbit)

(parent, females) LOAEL = 10 mg/kg/day

(embryo/fetus) NOAEL = 10 mg/kg/dayFetal effects include: decreased body weight, changes in skeletal development.

Maternal effects include: decreased food consumption, decreased body weight,

postimplantation loss.

Oral Study of Pre- and Postnatal Development (rat)

(parent, females) NOAEL = 10 mg/kg/day(F1 offspring) NOAEL = 10 mg/kg/day

Fetal effects include: death. Offspring effects include: decreased viability, decreased

body weight. Maternal effects include: decreased weight gain, decreased food

consumption, lactation effects.

Developmental Toxicity AssessmentSeveral studies were conducted. Compound produced effects on the fetus at doses similar

to those which produced effects on the maternal animal. This compound and/or itsmetabolites may be excreted into the milk. Compounds in this drug class have adverse

effects on reproduction.

Microcrystalline CelluloseDevelopmental Toxicity Assessment

Available data do not indicate a potential for selective developmental toxicity.

Human experience Experiences with Human ExposureAripiprazole

General effects Low exposure - acute effects include: headache, nausea, vomiting,

constipation, incontinence, sleepiness, dizziness, weakness, restlessness,

tremors, abnormal coordination, anxiety, irritability, agitation, behavioral

changes, sweating, breathing difficulties, salivation, lightheadedness,disorganized thought, suicidal thoughts, fever, uncontrolled muscle movements,


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muscle rigidity, convulsions, difficulty swallowing, pain, swelling, cough,

congestion, blurred vision, changes in blood pressure, cardiac irregularities,

changes in clinical chemistry parameters, increased weight gain. Low exposure -

long term exposure effects include: increased prolactin, reproductive function

changes, degeneration of skeletal muscle, kidney failure, hyperglycemia,

hepatitis.

Acute Overdose Low exposure - acute effects include: vomiting, sleepiness,

dizziness, tremors, uncontrolled muscle movements, difficulty swallowing,

behavioral changes, confusion, agitation, electrolyte disturbance, changes inclinical chemistry parameters, cardiac irregularities, changes in blood pressure,

headache, skin sensation changes, unconsciousness, convulsions, respiratory

arrest, coma.

Target Organs Aripiprazolecentral nervous system, cardiovascular system, endocrine system

Symptoms Aripiprazole

See "Human Experience".


labored respiration, noisy respiration, chest pain, breathing difficulties, shortness of breath,

lung inflammation

Pharmacokinetics/Toxic

okinetics

Aripiprazole




Elimination: Half-life = 75 hours (Human).

Other Toxicity

Information

Not available


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12. ECOLOGICAL INFORMATIONEcotoxicological Information (Aquatic)

Acute Toxicity to FishAripiprazole

LC50 (Oncorhynchus mykiss (rainbow trout), 96 H) : > 0.12 mg/l. (highest mean concentration

tested)

NOEC (Oncorhynchus mykiss (rainbow trout), 96 H) : 0.047 mg/l.Acute Toxicity to Aquatic Invertebrates

Aripiprazole

NOEC (Daphnia magna (Water flea), 48 H) : 0.031 mg/l.

Toxicity to aquatic plantsAripiprazole

EC50 (Pseudokirchneriella subcapitata (formerly Selenastrum capricornutum), Algae biomass and


NOEC (Pseudokirchneriella subcapitata (formerly Selenastrum capricornutum), Algae biomass, 72H) : 0.026 mg/l

NOEC (Pseudokirchneriella subcapitata (formerly Selenastrum capricornutum), Algae growth rate,

72 H) : 0.14 mg/l


Aripiprazole


Chronic toxicity to fishAripiprazole

Early-life Stage NOEC (Pimephales promelas (fathead minnow)) : 0.0058 mg/l

Chronic toxicity to aquatic invertabrates

AripiprazoleNOEC (Daphnia magna (Water flea)) : 0.00261 mg/l (reproduction rate)

Ecotoxicological Information (Terrestrial) Not available

Chemical fate information

Biodegradation

Aripiprazole


biodegradation in the environmentsorption/desorption

Aripiprazole

Koc (Batch equilibrium, Activated Sludge) : 10,270 (water)

Kd (Batch equilibrium, Activated Sludge) : 2,783 (water)

immobileKoc (Batch equilibrium, Activated Sludge) : 2,850 (calcium chloride solution)


immobile

Summary Statements

Aquatic toxicityAripiprazole

Experimental data indicate low potential for acute harm to aquatic organisms.Chemical Fate

Aripiprazole



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Advice On Disposal And Packaging Disposal should be in accordance with applicable regional, national and

local laws and regulations. Local regulations may be more stringent than

regional or national requirements. This information presented only

applies to the material as supplied.


14. TRANSPORT INFORMATIONThis material is not a dangerous good for the purpose of transportation.

15. REGULATORY INFORMATIONUnited States of America

OSHA Hazard Classification Respiratory Irritant

Reproductive Toxicity

Developmental ToxicityTarget Organs

313 Toxic Release Inventory.

Listed Chemicals/Compounds

No components listed on the SARA 313 inventory.

TSCA Inventory Not listed. Food, drug and cosmetic products are exempt from TSCA.

International

Canada

WHMIS D2A: Very Toxic Material Causing Other Toxic Effects

D2B Toxic Material Causing Other Toxic Effects

DSL/NDSL Not listed.

Mexico

Mexico Classification Health classification - Moderate Hazard 2 - Substances that may cause

temporary disability or residual harm under emergency conditions

Carcinogenicity

Reproductive Toxicity

Developmental Toxicity

Europe

EINECS/ELINCS/Registra

tion Number

Corn Starch: 232-679-6

Microcrystalline Cellulose: 232-674-9

Magnesium Stearate: 209-150-3

FD&C Blue No. 2 Aluminum Lake: 240-589-3

Yellow Iron Oxide: 257-098-5

Red Iron Oxide: 215-168-2

Symbol(s) T: Toxic

R-phrase(s) R40: Limited evidence of a carcinogenic effect.

R48/22: Harmful: danger of serious damage to health by prolongedexposure if swallowed.




S-phrase(s) S22: Do not breathe dust.S36/37/39: Wear suitable protective clothing, gloves and eye/face

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