P erceptions of safety issues in

aromatherapy tend to be the

views of aromatherapy educa-

tors whose opinions appear to fall

within either of two categories:

0 Those that fail to make a clear

distinction between the hazard

and risk, but loudly proclaim near

zero risks for the widest spectrum

of essential oils using conven-

tional aromatherapy practices.

0 Those who adopt a more cautious

approach where scientific data is

insufficient, for example over

issues such as chronic toxicity and

use of oils in pregnancy

(Tisserand and Balacs, 1995).

In order to conduct risk identifi-

cation, we need to be aware of several

factors:

0 The hazardous properties of the

materials need to be identified.

?? An evaluation of exposure is

needed, i.e. the extent to which

client/ worker/ therapist is likely

to be exposed. An interpretation

must be made of what this means

in toxicological terms.

Help in identifying and assessing

e SAFETY OF ESSENTIAL OILS

TONY BURFIELD

In a world increasingly concerned with safety legislation, we have to improve our corn@-ehension of safety issues, and make this available to our respective colleagues, customers and clients. This safety knowledge may have global, continental, national and local aspects enshrined within it, and it is our duty to become familiar with these requirements and act according to the law, or the spirit of the law. This paper attempts to cover topics around safety and aromatherapy.

risks can be obtained using informa-

tion gleaned from:

1. Material Safety Data Sheets

(MSDS)

2. Professional organizations

3. Internet databases

4. Specialist safety publications,

books and scientific literature

These are a legal requirement for deliv-

ered chemical goods (e.g. essential

oils). MSDS sheets were originally

written in complex technical language

for persons responsible for Health and

Safety matters in the chemical industry.

Requirements for openness, and US

State right-to-know information and

the Control of Substances Hazardous

to Health (COSHH) regulations in

Britain has lead to a wider audience for

this sort of information. In recent years

the Chemical Manufacturers

Association (CMA) has developed a

standard aimed at international accept-

ability, and the American National

Standards Committee (ANSI) has

adopted this format. The sixteen

sections according to ANSI are as

follows:

Set 1.

Set 2.

Set 3.

Set 4.

Set 5.

Set 6.

Set 7.

Set 8.

Set 9.

Chemical product and

company information

Composition/ Information

on Ingredients

Hazards identification

First Aid measures

Fire Fighting measures

Accidental release measures

Handling and Storage

Exposure controls/

personal protection

Physical and chemical

properties

Set 10. Stability and reactivity

Set 11. Toxicological information

Set 12. Ecological information

Set 13. Disposal considerations

Set 14.Transport information

Set 15. Regulatory information

Set 16. Other information.

As a customer, you have a legal

right to return an MSDS sheet from a

supplier if you cannot understand the

information, and ask that it be re-

written in terms that you can under-

stand. Similarly, you have rights to

information where blank sections

occur or if you think that the informa-

doi:10.1054/ijar.2000.0020, available online at http://www.idealibrary.com on IOE+l@’

tion is poor, and you are legally entitled

to a re-submission.

Aromatherapists and aromatherapy

companies who supply oils are legally

bound to supply MSDS sheets to

customers. Additionally, aromathera-

pists in their work (clinical) setting are

required to have safety information to

hand. This is important. In the USA a

similar situation applies with

Occupational Safety and Health

Administration (OSHA) Hazard

Standard 1910.1200, requiring private

employees to provide information and

training to employers. OSHA legisla-

tion additionally requires that MSDSs

are kept and maintained in a marked

and accessible area.

Aromatherapists could follow the

following scheme:

1.

2.

3.

4.

5.

6.

Collect MSDS sheets; file

them and have them readily

available.

Follow up references to safety

information for each oil and

construct a written safety

assessment for each material

used.

Encourage aromatherapy

organizations to compile data

and generate their own

written assessments of every

raw material used in

aromatherapy.

If possible, ask a suitably qual-

ified person or expert on any

safety queries regarding oils.

Encourage your professional

organization, or a group of

aromatherapy associates to

produce guidelines on the use

of essential oils, preferably

with expert input.

Make links with other profes-

sional and trade organiza-

tions.

When you receive an MSDS sheet, take

into account the following observa-

tions:

0 They are constructed on a basic

template. There is an absolute

minimum of data on the proper-

ties of the individual oil.

The job of assembling the data

sheets usually falls to a clerk

rather than a chemist, and the

task is usually of low priority

within the company.

MSDS sheets are notorious for

mistakes, especially regarding

Chemical Abstracts Service (GAS)

numbers, incorrect Latin names,

incomprehensible toxicological

information and incorrect trans-

port labelling details. Do not rely

on the absolute accuracy of the

information. You have a legal

requirement to check the infor-

mation independently before use.

In any case there is usually a

disclaimer.

Downplaying information on

toxicity might have occurred in

the past to allay public fears. The

law now requires a personal

written evaluation and updating

process.

Aromatherapy organizations are

unlikely to have the individual written

assessments of the substances used in

their trade mentioned above, a neces-

sary stage in the process in order to

carry out risk assessments. Other

professional organizations that use

essential oils may be more advanced in

this respect, or can draw on expertise

within their (often extensive) member-

ship.

The R.IFM and the IFRA

The Research Institute for Fragrance

Materials (RIFM) was established in

1966 by the American Fragrance

Manufacturers Association, and is a

non-profit-making international organ-

ization, whose expert panel is wholly

independent of any manufacturing

interests. The RIFM collect, produce

and publish data on fragrance mate-

rials, which includes data on essential

oils. They then make a risk assessment

and recommendations for individual

substances used in fragrances. The

Decision Tree Approach (Cramer et al.,

19’78) underlies much of the approach

RIFM have used for toxicity assessment.

The RIFM designed a basic set of tests:

0 Skin irritation and sensitization

testing

?? Oral and dermal limit tests (at

5 g/kg) or LD50 tests

0 Phototoxicity

?? Photosensitization

?? Sensitization: originally carried

out using the Kligman (1966)

human maximization test, using

petrolatum as solvent.

In addition RIFM also carries out inves-

tigations into chronic effects, and the

metabolism of fragrant substances as

and when necessary.

The International Fragrance

Association (IFRA) receives and

considers the RIFM recommendations

and produces guidelines for individual

fragrance ingredients for its members

in the fragrance industry. We can,

therefore, say that IFRA is concerned

with the management of risk.

Some 1300 substances have been

tested by RIFM and some 50 have been

subsequently not recommended for

use in perfumes (“banned IFRA”). A

further 58 are subject to quantitative

limits in formulations, or have special

criteria governing their use. A number

of these substances, in both categories,

are essential oils. Results of the toxicity

findings are published as monographs

in the Food and Chemical Toxicology

journal. Reputable fragrance compa-

nies widely adhere to this voluntary

self-regulation (i.e. the strict following

of IFRA guidelines), especially when

selling to IFRA compliant markets. In

practice, however, some skin fragrances

have been found to be breaking the

rules.

As one of the principle investiga-

tive programs on fragrant substance

toxicology, IUFM data have been widely

adopted and referenced by industry

and, perhaps not surprisingly, by

authors of books on essential oils. This

may be because the data are widely

available, whereas other toxicological

sources may be less comprehensive and

difficult to access. It has been stated in

the public domain that KIFM is re-eval-

uating the original 1300 materials that

it investigated, as the original data are

now considerably out-dated, and is eval-

uating another 1400 materials in

common use. It is also undertaking a

worldwide survey of volume usage of all

materials on the European indicative

inventory, although it is debatable at

present whether this information will

become available to the public.

Established in 1973, members of

IFRA comprise the national associa-

tions from a number of countries,

including the USA. The fragrance

industries work loosely on a system of

voluntary self-regulation implementing

the findings of KIFM regarding

perfume ingredient use; a policy that

has avoided wholesale imposition of

legislation without consultation. Self-

policing under IFRA’s voluntary regu-

latory system is in continuous practice

as companies analyse competitors

products and customers analyse the

products from their supplier. In fact, a

major perfume launch in recent years

was perceived by other major fragrance

houses to breach the rules, and

provoked an immediate trade reaction.

Other countries, such as the

Netherlands, Denmark and the USA,

have (additional) mechanisms to regu-

late at government level.

It has to be said that IFRA’s volun-

tary self-regulation system has

inevitably changed the face of

perfumery and has already influenced

some aromatherapy practice. Formerly

used materials like MOC (methyl

octine carbonate, a chemical which has

a powerful violet note), styrax resinoid

and oakmoss products, which at one

time had unrestricted status in

formulae, are now severly restricted.

Amongst others, perfumes like Miss

Dior with its high level of oakmoss,

could not be put on the market now in

original form.

IFRA recommendations are regu-

larly published in the bi-monthly trade

magazine, Perficmer and Flautist, and are

posted on the Internet (see Appendix).

The European Flavours and Fragrance

Association

This represents the interests of its

member associations to the authorities

and professional bodies of the

European Union. It works with

member states and their scientific

advisers to establish a workable legisla-

tive framework and cooperates with

associations in other countries.

Further, each member state may have

its own national trade associations, e.g.

the British Essence Manufacturers

Association (BEMA) and the British

Fragrance Association (BFA). My view

is that the European Flavours and

Fragrance Association (EFFA) has

effectively built bridges between

numerous bodies in order to achieve

common aims.

The Flavour Essence Manufacturers

Association

Of some interest to aromatherapists is

the fact that Fragrance and Flavour

Data Sheets, including many on essen-

tial oils, are produced by the USA

organizations the Flavour Essence

Manufacturers Association (FEMA),

the IUFM and the Fragrance

Manufacturers Association (FMA). A

set of 1500 is available at around $1000,

or they can be purchased in sets of 10,

choosing from a published list.

Other organizations

There are a large number of additional

organizations that are directly involved

or interact with the essential oils trade

and its user groups, e.g. the

International Federation of Essential

Oil and Aroma Trades (IFFAT), The

European Cosmetic, Toiletry and

Perfumery Association and in America

the Cosmetics Fragrance and Toiletries

Association (CFTA). Also of interest to

aromatherapy are the Food and Drugs

Administration (FDA) and the

American Medical Association (AMA).

Information about the safety and toxi-

cological properties of raw materials of

interest to aromatherapists is widely

spread. See Appendix.

See appendix.

It is sometimes advantageous for

professional bodies to associate with

one another to achieve common aims,

share information, formulate strategies

to deal with forthcoming legislation,

etc., and it will be interesting to see if

aromatherapy organizations eventually

evolve in this direction.

Various statements have been made

about essential oil inhalation toxicity.

Almost 40 years ago, a somewhat

worrying declaration was made: ‘In

view of the relatively high systemic toxi-

city of the vapours of certain essential

oils, the hazards of excessive inhalation

of these oils should not be disre-

garded”, (Kowalski et al., 1962). It is

perhaps the quantitation of “excessive”

that is important. In a search for data

on the toxic effects of Volatile Organic

Compounds (VOCs), information was

found that related to various essential

oil components, e.g. 9-14 mg/kg for

benzaldehyde, benzyl acetate, o-terpi-

neol and ethanol (Cooper et al, 1995).

The conclusion was that from the liter-

ature, health effects were unclear,

although the levels of exposure that

they were considering looked extraor-

dinarily high. It was concluded that

reductions in levels ofVOCs to substan-

tially less than 25 mg/m3 were required

if a “non-irritating” work environment

was desired (Pappas et al., 2000). In a

more extreme example of exposure in

Swedish sawmills, it was noted that the

air-levels of u-pinene, P-pinene and 6-3-

carene were found to be 80-550 mg/m3

- these are relatively high figures.

Exposure to terpenes and heating

products from coniferous woods is

significantly associated with the risk of

respiratory cancer after 5 years’ dura-

tion of exposure (Kauppinen et al.,

1986). Other studies on cl-pinene enan-

tiomers (Falk et al., 1990) indicated

that for short-term exposures of lo-450

mg/ms, no acute changes in lung func-

tion occurred after 20 minutes of expo-

sure.

In trying to calculate the likely

dosing levels in aromatherapy consider

as an example that 5 drops/hour of

eucalyptus oil (say 0.25 g) is dispensed

from a nebulizor into a room of 64mS

capacity. This would give a concentra-

tion of 3.91 mg/m5 if the whole

amount were vapourized instantly.

Note that there is a difference between

concentration and dose. In our

example above, we will assume the 1,8-

cineole content of eucalyptus oil to be

SO%, and we have a 5-minute inhala-

tion session, Even assuming 100% of

the aerially dispersed oil is actually

breathed in and absorbed by the lungs,

20.8 mg of eucalyptus oil would be

inhaled, 16.6 mg of which is 1,8-

cineole. The actual dose would only be

a small proportion of that.

Pharmokinetic studies on

prolonged inhalation are not too

common. Relevant to our example, it

was found that 1,8-cineole was easily

absorbed from breathing air and

plasma concentration peaked at 18

minutes (Jaeger, 1996). Elimination

from the blood was biphasic, with a

mean distribution half-life of 6.7

minutes and elimination half-life of

104.6 minutes. These figures are useful

in considering the metabolic fates of

substances with regard to elimination

and accumulation.

Limits for dietary intake of 1,8-

cineole had been proposed at 0.07

mg/kg bodyweight/day (private

communication) which equals 4.9

mg/day for a 70 kg adult. This

proposed (low) limit was envisaged to

cause problems for confectionery

manufacturers from dietary intake of

products containing peppermint

(Mentha piper&a) and eucalyptus oils.

Subsequently, the Council of Europe

has approved the use of eucalyptus oil

as a food additive at 15 ppm. In this

context, the likely inhalation doses of

1,8-cineole from a 5-15 minute session

from a vapourizer loaded with euca-

lyptus oil as in our example above is

over the recommended daily oral

intake, assuming a worst-case scenario.

To put this in context, however, there

are figures suggesting that eucalyptus

oil is (only) relatively orally toxic

(NIOSH, 1975) compared with other

routes of administration.

In conclusion there are some

widely scattered data on inhalation

toxicity, but little in the way of

Maximum Exposure Limit (MEL),

Optimum Exposure Standard (OES)

or Threshold Limit Value (TLV) data

for essential oils set out in a compre-

hensive manner. There is also some

data concerning individual essential oil

components such as u-pinene, but not

for a toxic compound like thujone.

Thus, we have to search out data case

by case, and taking thujone as an

example, the National Occupational

Exposure Survey (NOES) and National

Institute for Occupational Safety and

Health (NIOSH) between 1981 and

1983 noted that almost 11000 workers

were exposed to thujone via Dalmatian

sage oil, and over 43000 to cedar-leaf oil

in their workplaces. The most compre-

hensive account of thujone toxicity that

I could find seems to be the Priority-

based Assessment of Food Additives

Database (PAFA) published via the

FDA.

Inhalation and allergy

Whilst the acute toxicity effects from

inhalation might give less cause for

concern, the allergic effects of

airborne chemicals continue to pose

problems. A contact allergy in a 53.year

old woman suffering from relapsing

eczema due to sensitization from

previous exposure to lavender, jasmine

and rosewood oils was investigated

(Schaller et al., 1993). It was discovered

that she demonstrated positive sensi-

tivity testing to laurel, eucalyptus and

pomerance oils, without previous expo-

sure history. Perfume allergy has been

verified by submitting 29 asthma

patients and 13 normal subjects to 4

bronchial inhalation challenge tests

from perfume scented strips (Kumar et

al., 1995). It was found that 36, 17 and

8% of severe, moderate and mild

asthma patients respectively had exac-

erbations of symptoms and obstruction

of airways.

Millqvist followed this in 1996 in a

study where nine patients with respira-

tory symptoms after non-specific irri-

tant stimuli were subjected to perfume

provocation or placebo, with and

without a carbon filter mask (nose

clamped). The conclusion was that

hyper-reactivity of the respiratory tract

could be produced by perfume, and

that a carbon filter had no effect. The

mechanism was independent of the

olfactory nerve, but perhaps operated

via a trigeminal reflex of the respira-

tory tract or by the eyes. It was shown

that for perfumes at least, subchronic

inhalation of complex fragrance

mixtures did not constitute a risk even

when inhaled under repeated and

exaggerated exposure levels

(Fukayama et al., 1999).

Attempts have also been made to

quantitate the inhalation dose of

applied perfumes (Pybus and Sell,

1999). They tried to estimate the

inhalation dose where 0.2 ml of 10%

fragrance in ethanol was applied

behind the ear. Assuming that the

fragrance could be detected at 1

metre’s distance, then 0.02 ml

fragrance volatizing immediately into

8 m3 of air would give a concentration

of 2.5 mg/m3. Since the perfume might

be detectable for several hours, obvi-

ously the concentration will be much

lower than this. The authors’ remark

that if perfumes were toxic at this level,

they would be classified as chemical

warfare agents. As a comparison,

camphor has a long term OES level of

12 mg/ms (Reynolds, 1993).

In an aromatherapy context, we

are taking a scenario where 5-25 ml of

massage oil would be used in a whole-

body application, at a maximum level

of 2.5% essential oil concentration.

Using the maximum 25 ml, this would

give us a total of 0.625 g of essential oil

applied to the body. If the oil were all

suddenly volatized at once into 8 ms of

air, a concentration of 78.1 mg/litre

would be achieved. Clearly this does

not happen as we would be choking

and our eyes would be streaming at this

level. In practice, say the skin absorbed

25% of the essential oil, and if 5% of

this oil evaporated in the first minute,

again using the same air volume, the

concentration would be a more reason-

able 2.93 mg/litre, at that point in

time. The actual concentration would

be much lower in reality, and in relative

terms would represent a low toxicity

body-burden. Tisserand and Balacs

have stated, however, that because

giving a massage involves physical

effort, the aromatherapist may absorb

more essential oil than the client.

We are left assuming that,

although essential oil doses from

inhalation in conventional

aromatherapy procedures (massage,

nebulizers) may be small, where higher

exposure levels are regularly employed

there might be a small risk of accumu-

lation of essential oil components,

which may lead to chronic toxicity. This

could be of concern where neurotoxic

oils are regularly used; however, this is

pretty unlikely in normal practice. A

more realistic risk scenario concerns

the airborne levels of essential oils that

are present in the aromatherapist’s

workplace being sufficient to cause

allergic inhalation reactions in suscep-

tible clients. These individuals may be

identified as often having a predisposi-

tion to atopic skin conditions, having

respiratory problems such as asthma or

respiratory allergy, or having a history

of perfume sensitivity.

Adaptation

Koala bears thrive on a diet of euca-

lyptus leaves and branches. Their diges-

tive metabolic processes have presum-

ably evolved to tolerate and safely

metabolize the large amounts of essen-

tial oil that they consume daily. This is

a simple example of adaptation. A

graphic illustration of this effect

concerns the oral administration of

myrtle essential oil to rats. Its toxicity

was reduced considerably by adaptive

liver stimulation induced by 3 weeks

pretreatment feeding of myrtle oil in

the daily diet (Uehleke, 1979). This

does not always happen and depending

on the nature of the oils and the

species involved etc., toxicity can actu-

ally increase when oils are consumed

regularly.

General Remarks

Glossing over possible gastric irritation

effects from oral dosing of essential

oils, as they pass through the digestive

tract, solubilization with bile acids

occurs, and proportion of ingested

essential oil will be absorbed and trans-

ported to the liver. Here phase 1 P-450

reactions take place and some conver-

sion to alcohols or carboxylic acids

occurs. Conjugation with glycine for

carboxylic acid containing metabolites,

or glucuronic acid for metabolites with

alcohol groupings is common, and

elimination may occur via the bile or

urine.

LDso Issues

To decide our tolerance of oils and

chemicals we have to rely on testing

procedures. The determinations of

LD,, values are one of the major

factors in deciding the acute toxicity of

substances including essential oils.

Data exist for different doses that are

administered to matched pairs of

animals (rats, guinea pigs, rabbits, mice

etc.). The dose that kills 50% of the

animals is the LD50 value, and is calcu-

lated on body weight of the animal and

expressed as mg/kg. Data are often

available for oral, dermal and intraperi-

toneal methods of administration.

Determinations of LD50 values

seemingly vary from source to source,

but we can construct a table of relative

toxicity’s that would range from less

than 1 g/kg to over 5 g/kg (e.g. boldo

oil from Peumus boldus at 0.3 mg/kg at

one end of the scale, to say rose oil at

over 5 g/kg at the other). Some of the

oils with LD,, values of less than 1 g/kg

are not recommended for use in

perfumery by IFRA. These include

mustard oil, boldo, chenopodium, and

calamus oils. Similarly, the same oils are

not recommended for use in

aromatherapy.

Assumptions are made when

interpreting animal data to the human

situation, i.e. more toxic/ less toxic.

The differences in metabolism between

species are quantitative rather than

qualitative, but this may mean different

metabolic routes are favoured in one

species over another. It would be more

appropriate, therefore, given sufficient

resources, to choose a particular

animal model for a particular essential

oil. In the absence of appropriate

modelling, we start to draw conclusions

on the relative toxicity of the material

from poisoning records, i.e. by estima-

tion of the (fatal) dose received, or

better by clinical measurement of

substrates in target organs. In this

manner we are sometimes able to

derive the relative toxicity of animals to

humans and derive a ratio.

LDLo is often seen quoted in toxi-

cological data. It is the lowest dose of

material introduced by any route over a

given period of time reported to have

caused death. Lo is frequently used

where the number of subjects is low.

TDLo is the lowest dose of material

resulting in a toxic death.

In an old but important paper, hyssop

oil was found to be more toxic than

sage oil (Millet et al., 1981) working on

diet-induced convulsions in rats. The

dose at which cortical events became

sub-clinical was 0.08 g/kg for hyssop;

0.3 g/kg for sage; i.e. 0.8 g dose for

10 kg child for hyssop oil if

animal/human child toxicity were

similar. Convulsions occurred at 0.13

g/kg for hyssop and 0.5 g/kg for sage

oil that became lethal above 1.25 g/kg

for hyssop and 3.25 g/kg for sage.

Interestingly, repeated daily injection

of a subclinical dose revealed a cumu-

lative toxic effect. This paper indicated

the neurotoxicity of thujone and

pinocamphone in rats for the first time

but also indicated untoward effects

occurring at levels well below (6.4% of)

the lethal dose. This is possibly the

reason behind Tisserand and Balacs’s

statement that thujone containing oils

such as armoise (Artemisia hcrrbealba)

and wormwood (Artemisia absinthium)

should not be used in aromatherapy.

Presumably the same remarks should

apply to hyssop (Hyssopus officinalis) ,

which appears even more toxic from

the above data (Miller, 1981).

An evaluation of 109 pediatric

poisoning accidents involving euca-

lyptus oil in Australia (Day et al., 1997)

revealed that 74% gained access via a

home vapourizer unit, often placed at

ground level, and in most instances

between 5 and 10 ml was consumed. In

fact eucalyptus oil is much more toxic

by the oral route than by any other i.e.

oral-child TDLo=218 mg/kg; oral-man

TDLo= 375 mg/kg (NIOSH, 1975).

Potential countermeasures proposed

by Day et al. included discontinuing

use of eucalyptus oil as a therapeutic

agent, improving child resistant

closures and discouraging vapourizer

use for respiratory infections in chil-

dren.

If aromatherapy had widely

promoted the use of pennyroyal oil

instead of eucalyptus as an acceptable

mucolytic, we would be looking at far

more serious misadventure conse-

quences in this one example alone. I

would suggest, therefore, there is a

global social responsibility here. Either

the universal promotion of childproof

closures on bottles and equipment has

to be more effective, or aromatherapy

as a profession, needs to discourage the

use of hazardous essential oils. With

numerous reported accidents with

essential oils now documented globally,

potential hazard is now equating with

unacceptable risk in the minds of many

of those who are dealing with the

consequences of essential oil ingestion.

THE INTERN.4TIONAL .lO”RNAL OF AROMATHERAPY 2000 wol(Dnos QD

Key points to remember about LDsOs:

They are not absolute biological

constants (for example estimates

will vary from lab to lab).

The LDso value alone is insuffi-

cient for comparisons of relative

toxicity.

Dose-response curves and

degrees of slope, for example can

furnish more information. This

may, in turn, provide information

on the mechanism.

Other indexes are also useful.

The ratio of the pharmacologi-

cally effective dose to the LDsO

gives the therapeutic index value;

the larger the ratio the greater

the safety factor.

Oral dosing

Many practicing aromatherapists will

find themselves unable to legally

prescribe essential oils for oral intake

within the country/state in which they

operate, unless they are appropriately

medically qualified. In any case, oils

should be carefully administered in the

correct manner, as intake of concen-

trated and volatile substances into the

mouth should not be embarked upon

casually. Oils should generally be

administered in minute amounts and

by appropriate dilution. A suitable

vehicle for this can be difficult to find

because of the poor water solubility of

most oils. Sometimes one or two drops

of oil can be dissolved in strong sugar

syrup, and then quickly stirred into a

full tumbler of water, and the oil will

stay ‘dissolved’. Other factors to take

into account are the toxicity of the oils

(many oils should never be taken

orally, e.g. hyssop, wormwood, winter-

green etc.), the possibility of interac-

tion with medications and whether the

treatment is appropriate (during preg-

nancy, for example). In conclusion, my

message is that unless you are very clear

on what you are doing, stay away from

oral prescribing.

Dermal Toxicity

Dermal LDso (Limit test rabbit) is

concerned with mortality following

apphcahon of a toxin to the skin as

opposed to oral dosing. The ability to

penetrate the skin and the metabolic

changes that occur in the skin vary

from substance to substance. For

example, coumarin is rapidly absorbed

by the skin and passes through the

barrier unchanged (Yourick, 1997),

but some esters may be totally modi-

fied. We now realise that LDsO values

tell us more about systemic toxicity

than anything else. There are worries

that data from rabbit skin LD,, tests

may give a distorted view when applied

to the human situation, due to the

greater apparent permeability of rabbit

skin to a variety of chemicals. Curiously,

dermal LDso studies, however flawed,

must be potentially of great interest to

aromatherapists, because they are

closely allied to what is carried out in

aromatherapy massage practice. Yet

they have been omitted from ‘Essential

Oil Safety’ (Tisserand and Balacs,

1995), and results obtained elsewhere

have been described as not relevant to

human exposure (Schnaubelt, 1986).

However, we do know that the skin as a

target organ is capable of being

damaged. Phototoxicity is one

example; other oils that are dermal

toxins include wormseed, bitter

almond and wintergreen oils.

Permeation of substances

through the skin (specifically across the

stratum corneum) is a diffusion-

controlled process where absorption of

individual substances is related to

lipophilicity (represented by the parti-

tion coefficient for an octanol/ water

mixture) and molecular weight. The

effect of one substance on another

must also be taken into account, i.e. for

coumarin absorption it was found that

the uptake was greater from an oil-in-

water emulsion than from an ethanolic

solution.

Additional evidence that bioavail-

ability was proportional to the method

of application was provided by Weyers

in 1989. Application under occlusion

has been shown to alter the perme-

ation kinetics because:

a loss of volatiles through evapora-

tion is reduced

?? skin hydration increases

0 skin temperature increases.

All these factors may increase the

absorption of the applied substance.

Thus we have the following important

factors in skin absorption:

degree of skin hydration

skin temperature

application vehicle

idiosyncratic factors

lipophilicity of materials

volatility of the materials

molecular volume of individual

components

time of contact

dose and concentration applied

(relationship between applied

dose and absorption is compound

and species specific)

surface area and region applied

to

occlusion/ non occlusion of skin

surface

degree of skin barrier, compro-

mised by skin disease/ physical

damage etc.

age of skin

number of hair follicles and their

thickness etc.

skin metabolism of components.

For the mixture of substances

present in an oil, many small lipophilic

materials may quickly permeate the

skin and eventually pass into the

receptor fluid and on to the systemic

circulation. Smaller amounts more

polar components with high molecular

weights may penetrate much slower,

perhaps infinitely slowly, resulting in

the “fractional absorption” of essential

oil components. Counter to this,

smaller, more volatile components

evaporate more quickly from the skin

surface. Some aromatherapy writers

who have been quick to dismiss the

skin absorption route as being of little

significance in terms of physiological

effects. However coumarin, present in

cassia and other oils is rapidly absorbed

to 46% (human unoccluded), p-

phenylethanol 64% (rat unoccluded),

benzyl acetate 12% (human unoc-

eluded) and cinnamaldehyde to 24%

(human unoccluded)

In more detail, some components

will accumulate to form a cutaneous

reservoir pool (Hewitt, 1993) in the

lipid-rich stratum corneum. Others

components permeate deeper into the

skin to be biotransformed by the P-450

enzyme systems in the dermis and

epidermis. Eventually, this mixture of

biotransformed and unchanged mole-

cules will reach the systemic circulation

via the dermal microvasculature. The

cutaneous reservoir model of a pool of

applied substances, which are slowly

released into the systemic circulation is

an important concept as it allows for

continued systemic exposure after

dermal application has ceased.

One of the original RIFM tests was the

determination of the potential for skin

sensitization. The 1966 Kligman

human maximization test (Kligman,

1966) was used as a screening method

using petrolatum as a solvent. The

word ‘potential’ is important: this is a

predictive test and does not indicate

hazard. The word maximization refers

to a maximum level of exposure to

identify even weak sensitizers that

might have been previously missed in

former procedures. Ten times the

maximum use levels of the substance in

consumer products was used in order

to give a safety margin and to account

for the fact that only 25 volunteers were

used in the test, and also to compen-

sate for the fact that the material was

applied under semi-occlusion. In a

modification (Magnussan, 1969),

guinea pigs replaced humans when

finding volunteers became problem-

atic. A number of problems with the

test subsequently came to light:

0 Irritants were often been misiden-

tified as sensitizers.

?? Common vehicles (carriers)

could be sensitizers.

?? Inter-laboratory variability was

very high.

0 Private sector information on the

subject remains unpublished.

0 There was little distinction

between mild and severe sensi-

tizers.

Further, epicutaneous testing has

suffered from the use of impure mate-

rials and many substances classed as

sensitizers may have been wrongly

described on the basis of impurities

they contained. Mixtures of

compounds can lead to increased or

decreased reactivity.

In 1985 the RIFM switched to the

modified Draize procedure (Human

Repeat Injury Patch Test, HRIPT).

Volunteers were treated with 24hour

patch test on Mondays, Wednesdays

and Fridays over a S-week period

followed by a 2-week rest, then a 24

hour challenge under total occlusion.

In fact the original Draize procedure

used ten applications, but for conven-

ience three applications for 3 weeks has

more often been used. RIFM relies on

this human screening for final decision

on sensitivity potential. It is important

to note this latter fact as there is confu-

sion in the aromatherapy community

on this point. Some writers have erro-

neously maintained that these tests are

not carried out on humans, and have,

therefore, dismissed RIFM data as irrel-

evant. Materials are initially screened,

however, using Buerler’s guinea pig

sensitization test (1965) where mate-

rials are applied under total occlusion.

This procedure was said to give better

predictions of eventual performance in

HRIPT tests than other tests. An

external review tells a different story,

however, of poor result compatibility

between RIFM’s maximization data and

the Draize HRIPT test (Marzulli and

Maibach, 1980).

Sensitization results (for example

on MSDS sheets) are given in mg or

other appropriate unit/ duration

period of exposure, i.e. 500 mg/24

hour. Skin reaction result tests are

expressed as:

0 MLD: (“mild”) well defined

erythema and slight oedema

0 MOD: (“moderate”) moderate to

severe erythema and slight

oedema

0 SEV: (“severe”) severe to slight

escher form and severe oedema.

The protocols of Bueler and the

maximization test are recommended in

European Union and the Organisation

for Economic Co-operation and

Development (OECD) guidelines, but

variable results are still encountered.

The Mouse Local Lymph Node Assay

(LLNA) (Kimber and Basketter, 1992)

depends on measuring cell growth in

lymph nodes draining the dermal site

to which the potential sensitizer has

been applied. This test gives good inter-

laboratory correlation, although may

be less sensitive than the maximization

test and can still yield false positive

results. It has had full international

validation and gives data on relative

sensitizing abilities of different

substances.

Low-molecular-weight allergens, called

haptens, are present in a number of

essential oils; these can be removed by

physical treatment rendering the oils

non-sensitising. However, the aroma

industry has not adopted this practice

to any great extent commercially in

order to use the IFRA banned or

restricted materials freely.

After being first absorbed into the

epidermis, the hapten is either metab-

olized by cutaneous enzymes or other

processes to form a reactive metabolite,

or often may be chemically modified

through the reaction of ultra-violet

light, or remains unchanged. Haptens

are often electrophilic and can bind

covalently with -NH2 groups and -SH

groups on dermal proteins. The modi-

fied protein, when presented to the

immune system, reacts with antigen

presenting cells in the dermis. An

inflammatory response is subsequently

stimulated.

Attempts have been made to

define sensitization potential from

structure, and at an elementary level

we can classify haptens from their func-

tional groups: this listing include epox-

ides, and may partly explain why

oxidized bitter orange and turpentine

oils have an associated sensitizing

potential. Oxidation of d-limonene,

present at up to 96% in bitter orange

oil, leads to the formation of cis- and

tram-limonene oxides, and limonene

hydroperoxide, carve01 ancl I-carvone

amongst others, all of which except

carve01 have been found to be sensi-

tizing.

Banned IFRA:

Costus root oil, absolute and

concrete, elecampane oil, Thea

sinesis absolute, verbena oil, fig

leaf absolute.

Restricted by IFRA:

Cinnamon bark oil Sri Lanka,

cassia oil, oakmoss extracts,

treemoss extracts, fennel oil,

Opoponax derivatives, Peru

balsam, Styrax, verbena absolute,

Pinaceae derivatives. Oakmoss

products have come under a

temporary restriction to a

concentration 0.1% in the final

product until new methods of

extraction can produced mate-

rials that are not (so) sensitizing.

Pinaceue derivatives including oils of the Pinus and Abies genera should only be

used when the level of peroxides is kept

to the lowest practical level, preferably by adding anti-oxidants at the time of production. They should in any case

only be used when the level of perox-

ides is less than 10 mmol/l determined by the Essential Oils Association (EOA)

method. Quenching is a phenomenon

where the sensitization properties of fragrant substances may be quenched

when other compounds are present,

e.g. cinnamic aldehyde is quenched by

an equivalent amount of eugenol. Studies of even simple mixes of

fragrance chemicals have shown non- predictive sensitization behaviour. It is presumptuous, therefore, to predict

the likely sensitizing potential of a complex mix of hundreds of compo-

nents, as is the case with an essential oil, based on the inclusion of one or

more chemicals with known sensitivity

problems. In Japan, Nakayama (19741984)

embarked on a screening program to identify the contact allergens in

cosmetics. The findings have been widely discussed and the essential oils

considered to be sensitizing include jasmine, patchouli, geranium, cananga

and ylang ylang, sandalwood, and costus amongst others. By omitting these substances in perfume formula- tions, cosmetics could be produced

with a built-in allergen-control system.

It will be interesting to see if IFRA even-

tually validate these findings.

An irritant is an agent that can cause

cell damage if applied in sufficient

concentration and for a long enough period. Immunological processes are

not involved, and basically the chem- ical insult releases histamine from mast

cells producing erythma and increased

vascular permeability, accompanied by

eventual migration of polymorphonu- clear leucocytes to the area. Dermatitis

can follow without prior sensitization. Those with fair skin are more easily irri-

tated, but the irritant reaction can also be shown to decline with increasing

age, and to increase with increasing

temperature, such that irritant

dermatitis may only occur in some indi-

viduals in summer. The irritant must exceed a certain threshold to produce

a reaction, but the dose-response curve is less acute for allergens. Based around

the original 1944 Draize test, the FDA report of the procedure uses albino

rabbits clipped free of hair. A

minimum of six animals is used in abraded and intact skin tests. Materials

are introduced under a square surgical

gauze (skin or eyes) and the entire trunk of the animal is wrapped up in an impervious material for 24 hours to

keep the patch in place and to prevent

the easy evaporation of the volatile substance. After 24 hours the patch is removed to predict irritation potential.

The test often failed to distin- guish between marginal and low-grade

irritants. In the Philipis modification,

cumulative low-grade irritants are tested with a cumulative irritancy test,

the application time of which may be up to 21 days. The test gives good results for single application testing

because strong and moderate irritants are easily recognized. Other animals

besides rabbits have been tried, but good comparisons between human and

rabbit test results have made a major change unlikely. Alternatives to animal

testing are likely to become a European Union requirement soon. A validation study is being conducted on eye irrita-

tion which converts results from in- vitro tests to in viva standards via a

number of prediction model algo-

rithms. Irritation effects may be encoun-

tered with neat undiluted essential oils

containing components such as

eugenol (e.g. clove bud, pimento),

menthol (e.g. cornmint, peppermint)

and aldehydes (e.g. cassia). In general, the following oils have been found to be strongly irritant: horseradish, mustard, garlic and massoia. A larger

number of essential oils have a

moderate irritant risk, including the essential oils of savory and thyme.

Many perfume companies self-impose a final O-0.576 skin concentration limit

on phenolic oils in fragrances.

Sunlight is responsible for a number of

cutaneous pathologies including

phototoxicity and skin cancer. Phototoxicity itself is a light-related irri-

tation that is due to the percutanous

penetration of a light activated chem- ical (the phototoxic agent) followed by

skin exposure to light of the appro-

priate intensity and wavelength. It does not involve the immune system. In

more simple terms, it is can be regarded as accelerated tanning of the skin by a chemical ultra-violet absorber.

The carrier or solvent in which the

material is dissolved strongly affects the percutanous penetration and chemical

release. Testing is, therefore, carried out with carriers likely to release the

phototoxic agent effectively, such as ethanol.

Furanocoumarins (also called

psoralens) in expressed citrus oils and certain other oils, like rue, are perhaps

the most investigated phototoxins (e.g. bergaptene). The time following chem- ical exposure and the intensity of the

light exposure are also variables.

Animals produce maximum responses

to phototoxins after a few minutes; in humans 1 hour is usually optimal,

fading away to zero response at 24 hours. Human testing is usually carried

out on areas on the back or arm. As the phototoxic response is common to

most persons, only small testing panels

are employed. The body test site, the treatment protocol, test concentration,

application frequency and the time and duration of chemical/ light exposure

affect the response.

An important original finding was

that following a screening of 161 raw

materials used in fragrances, 21 gave a

phototoxic response; 20 of these were

from the Rutuceue (citrus oils) or the

Apiaceue botanical families (Forbes et

al., 1977). For cosmetic safety profes-

sionals, this leaves a very large number

of cosmetic ingredients to test, so that

even at this stage the overall potential

and frequency of the phototoxic

response is still unclear.

We can rank phototoxic oils in

common aromatherapy use. Fig leaf

absolute and verbena oil are “banned

IFRA” and these products are not

recommended for aromatherapy use.

Tagete, bergamot oil expressed, lime

oil expressed and angelica root oil are

all phototoxic and should not be used

at concentrations greater than recom-

mended by IFRA. In my opinion, rue

oil and tagete oil should not be used at

all in this situation. Bitter orange oil,

lemon oil expressed and grapefruit oil

expressed are less phototoxic and IFRA

guidelines reflect this. Distillation or

chemical treatments are available

options to bring the furanocoumarin

concentration down to very low levels

(often below 0.05% for distilled berg-

amot oil).

Bergamot oil is carcinogenic in the

presence of ultra-violet (UV) light

when applied to mouse skin, but when

applied with a sunscreen the carcino-

genic effect disappears. Little data are

available in the public domain for oils

other than bergamot at present.

Photoallergy is similar to allergy but

involves the binding of a protein with a

metabolite which has penetrated the

skin and been transformed by UV light.

Many photoallergens are also contact

allergens. The former fragrance

compound 6methylcoumarin is a well-

known example here.

Many oils have a direct action on the

central nervous system (CNS) such as

hyssop, camphor, cedarleaf, tansy, etc.,

and the worrying element here is irre-

versible damage of over-exposure as

spontaneous self-repair is not generally

possible. With the same perception of

possible CNS damage in mind, The No

Observable Adverse Effect Level

(NOFAL) was used by RIFM for consid-

ering the possible neurotoxic effects of

the synthetic perfumery musk chem-

ical 6-acetyl-7-ethyl-1,1,4,4tetramethyl-

tetralin. The material was subsequently

“banned IFRA”.

This minimum level concept at

which there are “no observable effects”

is generally used in setting exposure

limits such as Acceptable Daily Intake

(ADI) for chemicals used as food addi-

tives, or Threshold Limit Values for

chemicals used in an industrial

context. Usually a built-in safety factor

of xl00 applies, to account for differ-

ence between species, and to account

for idiosyncratic metabolism and other

factors. Where these figures are avail-

able, this would seem to be a very

useful concept to apply to the

aromatherapy situation with regard to

neurotoxic/ toxic compounds in essen-

tial oils, such as 01- and B-thujones,

rather than rely on computations based

on LDBO values. Children are especially

vulnerable from CNS effects.

I am concerned about those

aromatherapy authors who proclaim

the “no risk” scenario in using poten-

tially neurotoxic oils such as hyssop,

armoise and, to some extent, sage oils.

Also of concern are the herbals in

circulation that mention the use of

pennyroyal as an abortifacient with no

mention of inevitable cellular injury, or

recommend pennyroyal tea with no

mention of the potential of fulminant

hepatic failure to young children.

It is probable that essential oil metabo-

lites cross the placenta due to the inti-

mate (but not direct) contact between

maternal and embryonic or foetal

blood. Lipophilic substances can

migrate by passive diffusion between

these two circulations and reach equiv-

alent levels in foetal blood. If these

substances are biotransformed into

polar compounds, they can accumulate

in the foetus. In addition, the high

water:lipid ratio in the foetus, the lower

amount of available plasma protein for

binding foreign compounds, and the

reduced rate of glomerular filtration

are all factors, amongst others, which

mitigate against toxin clearance in

neonates. We, therefore, do not know

the consequences of direct exposure to

many substances during pregnancy and

oral, vaginal and rectal administration

of essential oils should be avoided.

Teratogens

A teratogen is a substance that inter-

feres with the normal development of

either the embryo or foetus in utero,

giving rise to abnormalities in the

neonate. Teratogens that have been

positively identified amongst the essen-

tial oils have included the embryotoxic

Savin oil fromJuni@rus satina (Pages et

al., 1989) and Spanish lavender from

Sulviu luvunduluefoliu oil (Fournier et

al., 1993). Here the offending

substance appears to be sabinyl acetate,

which may occur up to 24% in Spanish

lavender oil. Sabina oil is “banned

IFRA” and its sale in the UK is contrary

to The Medicines (Retail Sale or

Supply of Herbal Remedies) Order

1977. Spanish lavender oil is not simi-

larly restricted.

To my thinking the responsible

attitude is to discourage the use of

essential oils completely during the

first few months of pregnancy. Critics

of this policy have said that the amount

of dietary essential oil intake (in

flavourings) outweighs intake from

aromatherapy practice. I might think

that dietary intake of essential oils was

undesirable under these circumstances

anyway, but in any case, current

aromatherapy practice uses oils that are

not used in flavourings and involves

different routes of absorption. It has

always to be considered that the

greatest number of mitoses take place

in the foetus, and exposure to

substances which might possibly act as

mutagens should particularly be

avoided in the first trimester of preg-

nancy.

A carcinogen is a chemical that may

give rise to tumour production, which

is an unrestrained malignant prolifera-

tion of a somatic cell, resulting in a

progressively growing mass of

abnormal tissue.

At the simplest level carcinogenic

testing might involve adding substances

to rodent diets over a period of time, at

the end of which they are killed and

examined for tumors etc. This in-vivo

approach still accounts for a consider-

able proportion of pharmacological

testing at least (for screening new

drugs, etc.). Ethical demands have

driven the wider use of in-vitro alterna-

tives to animal tests. Unfortunately, the

standard of information given by in-

vitro testing falls below that offered by

in-vivo tests. Quantitative Structure-

Activity Relationship (QSAR) model-

ling - which relates the magnitude of

one particular property of a series of

related chemicals to one or more other

physiochemical or structural parame-

ters of the chemicals in question - is

helping to complement in&o testing.

It is hoped that this approach will even-

tually get to a stage that will be

accepted by regulatory authorities.

A mutagen is a substance that may

cause inheritable defects arising from

their action on mammalian germ cells.

Tumour formation may result from

their action on somatic cells via cellular

disruption. Many mutagens are

carcinogens, but not all carcinogens

are mutagens.

A mutation is defined as any heri-

table change in generic material. In-

vitro testing methods for mutagens

include examining the action of the

substance on chromosomal DNA and

bacterial testing for gene mutation

(e.g. Ames test). The problem with

using the Ames test to predict potential

carcinogens is that the mutagens iden-

tified in the Ames test are not neces-

sarily carcinogens, and some carcino-

gens are not mutagenic. Interpretation

of data in this whole area is frequently

both complex and controversial.

Safrole-containing oils

These cannot be legally used in many

countries. Sassafras oil is controlled (as

Safrole) under the Controlled Drugs

(Scheduled Substances Used in

Manufacture) (Irma-Community

Trade) Regulations 1993 in conformity

with subsequent European Directives

3677/90 as amended by Council

Regulation 900/92 as a Category 1

substance. It is controlled together with

a number of other substances, as it is a

pre-cursor to the illicit manufacture of

psychotropic and narcotic drugs (espe-

cially in this case Ecstasy), as part of a

worldwide effort to restrict unautho-

rized movement of these substances.

Licenses are required to engage in the

import/ export of these substances,

and end-user declarations have to be

filled in annually. As a hazard, safrole is

categorised as a Category 2 carcinogen.

P_asarone

Calamus oil is (severely) restricted by

the IFRA. Triploid and tetroid varieties

of Acorns calamus contain B-asarone,

which damages human lymphocytes,

has mutagenic effects on bacteria, and

has demonstrable carcinogenic activity

in rats. Although diploid varieties are

claimed to have little or no R-asarone

content, calamus oil should not be used

in aromatherapy.

Citral

This is known to be a powerful contact

allergen and occurs in Backhousia citri-

odora, lemongrass, Litsea cububa and

melissa oils. Restricted by the IFRA, it

should be used with a quencher, e.g.

lemongrass SO%, citrus terpenes 20%.

Methyl chavicol

This occurs as a major component in

tropical basil and tarragon oils. Methyl

chavicol (estragole) has been shown to

produce hepatocellular carcinomas in

mice (Drinkwater et al., 1976), but

investigations of the genotoxicity of two

basil oils and one tarragon oil demon-

strated that whilst tarragon was geno-

toxic, the basil oils were not (Tateo,

1989). The author here concluded that

methyl chavicol was not the only factor

in considering the genotoxic effects in

basil oil, and in another study highly

purified methyl chavicol was found free

from mutagenic effects to Salmonella

TlOO, whereas 96% was positive to

Salmonella strains in the Ames test

(Sekizawa, 1982). There are not

enough data to predict the carcino-

genic effects of methyl chavicol in basil

oil reliably, but when considering expo-

sure of the oil to children, caution is

advised. Tarragon and high methyl

chavicol type basil oils are important

contributors to the top notes in men’s

fragrances.

Geraniol

This is a sensitizer and consistently

causes problems as a component ot

perfumes and cosmetics. Geraniol

occurs in many oils including

palmarosa, geranium, and rose. It is

not currently restricted by the IFRA

(Nakayama et al., 1974).

Flung ylang oil

A 5-year worldwide study of cosmetics

reactions shows frequent allergic reac-

tion to this material (Nakayama et al.,

1974.)

Methyl eugenol

This component is genotoxic. It occurs

in a few oils as a major component

(Huon pine and Melaleuca bracteata)

and in a number of essential oils as a

minor component, e.g. nutmeg,

Russian tarragon, rose oils, ylang ylang

and laurel leaf. Investigations have

confirmed genotoxicity and carcino-

genicity in rats (Chan et al., 1992)),

probably due to strong DNA-binding

reactions. Many perfume companies

impose in-house restrictions on the use

of this material in perfume formula-

tions, and will be pressurizing profes-

sional bodies for a position statement.

Owing to the risk, it is suggested that

aromatherapists should not use high

methyl eugenol containing oils.

Eugenol

This is a component of clove and

cinnamon leaf oils and causes frequent

allergic reactions when used as an

ingredient of fragrance formulations.

There is no current IFRA restriction

(Loveless et al., 1996).

R-(+)-Pulegone

This component is hepatotoxic. It is a

major constituent of both European

and American pennyroyal oil and

buchu oil and is also present in

spearmint, catnip, peppermint and

cornmint oils. The acute oral LD,, for

pennyroyal oil in rats is 0.5 g/kg.

Reports have indicated that the

substance is hepatotoxic, but it would

appear that the damaging effect on the

liver of large oral doses might involve

the depletion of glutathione, needed in

one of several detoxification steps. This

depletion leads to the overwhelming of

the liver by excess pulegone and

centrilobar necrosis of the hepatocytes

occurs.

The food regulations in the EC

limit the amount of pulegone in food

flavourings to 0.025 g/kg food (The

Flavourings in Food Regulations

Statutory Instrument no. 1971, 1992).

It is probably important that the

aromatherapy profession is not seen to

be out of step with regulations imposed

in other sectors. Co-incidentally

Tisserand and Balacs (1995) indicate

that the oil should not be used in

aromatherapy, especially in pregnancy.

Sandalwood oil

A 5-year worldwide study of cosmetic

reactions showed that sandalwood

caused frequent allergic reactions. This

may be related to the J3-santalol

content, which is thought to be a sensi-

tiser (Nakayama et al., 1974).

Menthofuran

This component is hepatotoxic. Newer

legislation limits its concentration in

chewing-gum, where is occurs as a

component of mint oils. It has previ-

ously been found to be hepatotoxic

and lung-toxic, and occurs in water

mint and in many other wild mints, and

formerly in Japanese peppermint oil.

Western consumers have never cared

much for the taste of high mentho-

fur-an-containing peppermint oils, and

this characteristic has been successfully

curtailed in many commercial strains

of peppermint oil, so that mentho-

furan occurs at much lower levels.

Menthofuran is also a metabolite of

pulegone detoxification in the liver

(for example from pennyroyal oil), and

contributes to the toxicity of this

substance.

Anethole

Trans-anethole occurs in high amounts

in aniseed oil, where levels may exceed

95%. There has been much debate

about the toxicity of anethole. Much of

this is to be centered around its

commercial purity. The cis-form is

much more toxic, and can form in

aging, especially in the presence of

light. Anethole is the principle

flavouring agent in Pernod and Ouzo,

but there are no current restrictions on

its use in beverages. Other substances

such as photoanethol may be respon-

sible for the alleged toxicity of anet-

hole. It would seem prudent in the

absence of further data to only use

fresh oils, with caution, and to restrict

intakes for children.

Methyl salicylate

Methyl salicylate occurs at up to 98% in

wintergreen and sweet birch oils, the

former being commercially obtainable

from countries such as China. Most oils

on the market are actually synthetic

methyl salicylate. Methyl salicylate is

used as a counter-irritant in many over-

the-counter preparations. Its use in

topical rubefacients for the relief of

muscle pain by their action in

producing a feeling of relief and

‘glowing-skin’ has been estimated at

generating &7 million in UK sales

alone. There is some evidence that

absorption from the intestines is

erratic, and hence we get a range of

toxicity estimations and variability in

fatalities and effects. The lethal dose

for a 70 kg man has been estimated at

between 5 and 30 ml (Gleason et al.,

1969). NIOSH (1975) recorded a

human oral LDLo value of 170 mg/kg

(LD,, oral-rat for methyl salicylate is

887 mg/kg). It has been noted tha!

children under 5 years are especial11

susceptible to salicylate poisoning, am

can quickly exhibit physiological symp

tams associated with advanced

poisoning (Pribble et al., 1988). The

substance directly interferes with

glucose metabolism, and exhibits CNS

toxicity.

There are a large number of

studies on skin absorption of methyl

salicylate from skin (e.g. Brown and

Scott, 1934; Levine, 1984). Absorption

through the skin is much more rapid

that intestinal absorption and metabo-

lism seems to occur mainly in the liver.

Evidence suggests that blood salicylate

levels are highest at 20-30 minutes after

application. Collins et al. (1984) did

some interesting work on topical

absorption of “Deep-Heat” (an aerosol

preparation for relief of rheumatic

pain) that includes methyl and ethyl

salicylate in its formulation. After a

one-shot 500 microlitre spray on the

forearm, erythma production was

correlated with salicylate concentration

and blood salicylate levels reached a

maximum after 20 minutes. In their

work, blood salicylates appeared to

tifect the prostaglandin system. The

Norst-case scenario is that methyl salicy-

ate is a CNS poison with acute salicy-

ate poisoning manifesting in disorien-

.ation, irritability, hallucinations,

impor, coma, etc. Therefore, winter-

;reen oil should not be ingested and

should only be used for topical applica-

ion and not full body massage. Do not

rse wintergreen in cases where the

:lient is receiving anti-coagulant drugs

uch as warfarin. We know there are

rroblems with chronic salicylate inges-

t ion in pregnancy that makes morbid

eading (Turner et al., 1975), so preg-

tant and lactating women should avoid

nethyl salicylate/wintergreen.

It can be very difficult for aromathera

pists to decide about the safety o

particular oils, especially where there i:

conflicting advice. It is as well to bc

aware of what the problems are, ant

exercise caution if you decide to use

these oils. It is always an idea to debate

“personal professional use” and posi

tive and negative lists of oils with fellow

therapists.

Although many procedura;

aspects of safe working practices are

based on common sense, safety date

must in the first instance be derived

from an authoritative source. Some 01

these sources have been outlined in the

above text, and it is hoped that you may

be able to find others for yourselves.

Armed with this data, safe working poli-

cies and procedures can then be

constructed. As we learn more about

toxicology and its health implications

we are able to modify our views on

hazard and risk accordingly.

?? Brown and Scott. (1934) Journal 01

Pharmacology and Experimental

Therapeutics 50: 3250.

?? Chan, V.S.W., et al. (1992)

Comparative induction of unscheduled

DNA synthesis in cultured rat hepato-

cytes by allylbenzenes and their l-

hydroxy metabolites. Food and Chemical

Toxicology 30(10): 831-836.

?? Collins, et al. (1984) Annals of the

Rheumatic Diseases 43: 411-415.

?? Conway, G.A., et al. (1979). Journal

of Ethnopharmacology l(3) : 241-246.

?? Cooper, S.D., et al. (1995) The iden-

tification of polar organic compounds

found in consumer products and their

toxicological properties. Journal of

Exposure Analysis and Environmental

Epidemiology 5 (1) : 57-75.

?? Cramer, G.M., Ford, R.A., Hall, R.L.

(1978) Estimation of Toxic Hazard - a

Decision Tree Approach. Food anzL

Chemical Toxicology 16: 255-276.

?? Ford, R.A. (1990) Metabolic and

kinetic criteria for assessment of repro.

ductive hazard. In Volans, G.F., Sis J.

Sullivan, F.M. and Turner, P. (eds) Basic

Science in Toxicology. NY: Tylor and

Francis.

?? Falk, A.A., et al. (1990) Uptake,

distribution and elimination of a-

pinene in man after exposure by

inhalation. Scandinavian Journal of Work

and Environmental Health 16: 372-378.

?? Fukayama, M.Y., et al. Subchronic

inhalation studies of complex

Fragrance mixtures in rats and

hamsters Toxicology Letters 20: 111 (l-2)

175-187.

?? Gleason, et al. (1969): Clinical toxi-

cology of acute poisoning 3rd Edition.

?? Hewitt, P.G., et al. (1993) Cutaneous

retopical application of 4,4’-methylene

-his-(Bcloroaniline) and 4,4’-methyl;

znedianiline to rat and human skin in

Vitro. Prediction of percutaneous penetra-

tion: methods, measurements and modeling.

Zardiffi STS.

) Jaeger, W., et al. (1996)

‘harmokinetic studies of the fragrance

:ompound 1,8-cineol in humans

luring inhalation. Chemical Senses 21:

L77-480.

B Kauppinen, T.P. et al. (1986)

Respiratory cancers and chemical

:xposure in the wood industry: a

rested case-control study. British Journal

qlndustrial Medicine 43: 8490.

) Kimber,I., Basketter, D.A. (1992)

:he Murine Local Lymph Node Assay:

L commentary on collaborative studies

.nd new directions. Food and Chemical

bxicoligy 30: 165-169.

1 Kligman, A.M. (1966) The identifi-

ation of Human Contact Allergens by

Iuman Exposure. Journal of

nvestigative Derm,atology 47: 399.

?? Kowalski, Z. et al. (1962) Medycync

Pr. 13: 69.

?? Kumar, P., et al. (1995) Inhalation

challenge effects of perfume scent

strips in patients with asthma. Annals 0~

Allergy Asthma and Immunology 75(5) :

429433.

?? Levine. (1984) Skin absorption.

Journal of Analytical Toxicology 8: 239.

241.

0 Loveless, SE et al. (1996) Further

evaluation of the Local Lymph Node

Assay in the final phase of an interna-

tional collaborative trial. Toxicology 108:

141-152. 235-244.

0 Millet, Y., et al (1981) Clinical

Toxicology 1981 lS(12): 1485-1498.

?? Millqvist (1996) Placebo controlled

challenges with perfume in patients

with asthma-like symptoms. Allergy

51(6): 434439.

?? Nakayama, H. (1974) Perfume

allergy and cosmetic dermatitis. Japan

Journal of Dermatology 84: 659-667.

?? Nakayama, H., et al. Allergen

controlled system: l-42 Kanehara

Shuppan, Tokyo

?? Nakayama, H., et al. (1984)

Pigmented Cosmetic Dermatitis.

International Journal of Dermatology 23:

299-305.

?? Pages, N., Fournier, G., Chamorro,

G., Slazar, M., Paris, M. and Boudene,

2. (1989) Teratological evaluation of

runiperus sabina essential oil in mice.

Planta Medicus 55(2): 1446.

@ Pappas, G.P., Herbert, R.J.,

senderson, W., Koenig, J., Stover, B.

md Barnhart, S. (2000) The respira-

.ory effects of volatile organic

:ompounds. International Journal of

kupational and Environmental Health

i(1): 1-8.

’ Pribble, J.P., et al. (1988) Poisoning.

n Applied Therapeutics. Vancouver:

ipplied Therapeutics Inc.

’ Pybus, D., Sell, C. (1999) The

yhemistry ofFragrances. RSC Paperbacks.

?? Reynolds, J.E.F. (Ed) (1993) The

Extra Pharmacopoeia. The

Pharmaceutical Press: London.

?? Schnaulbelt, K. (1986) Aromatherafi

Course, 2nd Edn. San Raphel.

?? Schaller, M.M., Korting, H.C. (1993)

Allergic airborne contact dermatitis

from essential oils used in

aromatherapy. Clinical and Experimental

DermatoloB 20: 143-145.

?? Uehleke, H., Brinkschulte-Freitas,

M. (1979) Oral toxicity of an essential

oil from myrtle and adaptive liver stim-

ulation. Toxicology lZ(3): 335-342.

?? Tateo, F. (1989) Journal of Essential

OilResearch 1: 111-118

?? Tisserand, R. and BaIacs, T. (1995)

Essential Oil Safety- a guide for Health Care

Professionals. Edinburgh: Churchill

Livingstone.

?? Turner, G., Collins, E. (1975) Fetal

effects of regular salicylate ingestion in

pregnancy. Lancet 2: 338-339).

?? Weyers, W. (1989) Skin absorption

of Volatile Oils. Pharmokinetics.

Pharmazie Unserer &it 18(3): 82-86.

?? Yourick, J.J. (1997) Journal of Applied

Toxicologyl7(3): 153-158.

lnternet databases:

A useful database list may be

obtainable by searching the NAHA

site: (http://www.naha.org).

Botanical Dermatolog Database -

http://bodd.cf.ac.uk/search/all_

bodd

Medline

http://www.nlm.nih.gov/medlin

eplus/ A searchable database of

some 9 million medical papers.

Abstracts are available to many

documents.

IFRA Guidelines -

http://www.ifraorg.org/GuideLi

nesasp. See below.

ToxLine

http://toxnet.nlm.nih.gov/cgi-

bin/sis/htmlgen?TOXLINE. A

searchable database containing

2.1 million toxicity related papers,

0 Dialog OneSearch

http://library.dialog.com/prod-

ucts/datastar/4002-3.html

Safety Literature:

N.B. Some of these publications may

only have small sections that are

directly relevant to aromatherapy.

Tisserand, R. and Balacs, T.

(1995) Essential Oil Safety- a guide

for Health Care Professionals.

Edinburgh: Churchill Livingstone.

Gosselin R.E., et al (1976) Clinical

Toxicology of Commercial Products:

Acute Poisoning. 4th Edn.

Baltimore: Williams and Wilkins.

Wren R.C., revised by Williamson,

E.M., Evans, F.J. (1988) Potters New

Cyclopaedia of Botanical Drugs and

Preparations. Essex: C.W. Daniel

co.

De Smet, K., Keller, R., Hansel,

R.F. and Chandler, R.F. Adverse

Effects of Herbal Drugs Vol 1-3.

P.A.G.M. Springer-Verlag.

Lewis, R.J. (1987) Sax’s Dangerous

Properties of Industrial Materials, 9th

Edn. Van Nostrand Reinhold.

Lawrence, KH., et al. Compendium

of SDS sheets for Research and

Industrial Chemists. Part VI1

Flavour and Fragrance

Substances. Ed. T.C. Zebovitz.

Opdyke D.L.J. Monographs on

Fragrance Raw Materials: Food and

Cosmetics Toxicology Special

Issues I-VII.

Flavour and Fragrance Extract

Manufacturers Association of U.S.

Inc. Flavour and Fragrance

Mate+als. Illinois: Allured

Publishing Co., 1987.

Food Chemicals Codex IV Edn.

National Academy Press,

Washington.