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TI AL Y III SIS,
TOX IC ITY
The last of a three part series based on a presentation given at Aroma ‘ 95. The full transcript is published in the conference proceedings.
the chemical compared toxicity. difficult toxicity. examines essential metabolism,
Estragole after infant
liver tumours of dietary given by et al., was
understanding and how of essential and I on and animal and the very reproductive final role part of
carcinogenicity an essential oil? 0 0 Are What
when in the context the rodent level of carcinogens risk
in mice also in
12 months mice injection when
oil composition degradation
administration in humans? is subcutaneous al., 1976).
(Miller et al., 1983) and (Drinkwater (Miller after by et
oils could have safety implications, data on human In part question This the third
Methyleugenol et al., 1983).
is similarly Asarone
acceptable/unacceptable? What evidence There are is there that carcinogens oils? found in chemicals
hepatocarcinogenic 1982; Miller hcpatocarcinogenic administration injection weakly essential Do the is no question (Wiseman carcinogenic oils. carcinogens
neurotoxicity of and
are found in essential four steam distilled be rodent safrole, These
intraperitoneal are and in
et al., 1987). There in rodents, are found
oils in cancer,
and gives some
oils which are known to - bela-asarone, liver tumours to elicit in but sometimes produced to infant liver or mice and methylcugenol.
that these substances
data on phototoxicity.
carcinogens produce rodents) Safrole tube
that the same chemicals
(the easiest type of tumour experimental It is important oil, or essential or contributing have rodents, have rodent extrapolates essential several assess a come and we do very to emphasise that there is causing other tumours by types. not one recorded case of any essential to cancer from in not good
carcinogenicity when in the context of an essential oil? Both calamus proved rodents. (containing asarone) carcinogenic, malignant after 1967). produced months, 59 duodenal weeks of (Taylor 90% but (Abbot 2) have most and sassafras oils have in oil 6&lweakly producing tumours dietary et al., oil safrole) of the to be carcinogenic Calamus 75.8% was
when given subcutaneously
in humans. All the data we experimental research
of how well to humans for
carcinogenesis oils. questions the risk In need fact
administration Dietary (containing
no tumours after 22 development et al., 1961). essential tested been
be addressed occurrence essential oils: 0 What
in order of possible evidence
to from the in that (Gleason Dietary is there liver et al., 1984) safrole tumours mice and when given et al., 1963). kidney offspring and of rodents carcinogens orally to adult rats (Long produced in the
showed tumour 1
after 24 months None of Ihe other oils (see table experimentally.
are found in essential oils?
it is not surprising containing carcinogens carcinogenesis. containing not known. other essential the equally components (increase) Since carcinogenic is much there
oils of oils is that the could other
rodent in humans?
and a compound
such high concentrations demonstrate Whether essential much lower concentrations are carcinogenic could speculate in one present However, might is no evidence inhibition One
be safely disposed of at low doses, while at high doses the detoxifying pathways amount formed. amount can of One become carcinogenic study can lead to a sudden metabolic This in the that the saturated. increase showed
This is another records nogenic compounds are partially These,
area in which there are oils or essential a carciThe oils are but they liver humans. indeed,
very few data to go on, since there are no of any essential action found in oil components demonstrating in essential
of these compounds components carcinogen.
mctabolite formed from mg/kg studies In l’ of issue of in amount
of 1 ‘ -hydroxyestragole
oil might inhibit speculate
the action of that
very weak carcinogens
frorn estragole increased from 1% to 9% as the dosage given was increased O.O5mg/kg (Zangouras have humans, urine ingested means is produced the 0.3% estragole. of to 1000 Other similar amount found the et al. 1981).
metabolised cases, table
by the are 1).
into slightly more powerful carcinogens. in most (see I’ -hydroxy This since is an it is metabolites important known efficient that
potentiate of either
the action of the carcinogen. or potentiation in this arena to be of any
consideration, in rodents than
is more is of is
in essential oils, prediction too speculative value. In the absence risk is proportionate carcinogen present.
This means A factor animal The
that the risk to humans to the relevance
of any useful data to the amount of
probably lower than the risk to rodents. related testing is the ‘ saturation issue’ .
levels of risk
we can do little else but assume that the
from animal tests with high doses to the human situation is not a simple matter. that the However, WC should remember
of many chemicals
most common of administration aromatherapy we know these very
route in is little of in
drops of the oil were
placed in a pot in the sauna room, the The woman’ s burns In more severe, not on skin. to were
dermal, not oral, and about metabolism chemicals the skin.
one arm and leg. a second, case serious
What level of risk
is acceptable? Taking all of the above considerations account, of the into it is possible level of in acceptable. possible Ensuring approach that to exposure safety in drops rubbed of undiluted on both essential as oils levels remain below these would be one aromatherapy.
burns were sustained following a 20 minule session on a sunbed, which bergamot application this instance, bergamot arms and both communication). followed oil (private In a few oil were legs
to give an indication carcinogens
essential oils which is likely to be safe or unsafe. In some instances contain components administration external (0.1-l%) completely carcinogens aromatherapy carcinogens (lo-go%). major
before going into a steam room. Some 15 minutes later the woman showered, went for a swim, showered bcrgamot crossed again, and then (Much Severe of the burns went on to the sunbed. the epidermis.)
In these cases oral In other cazes
would be unwise, as would
occur only at very low levels usage is likely to be Of best all the aspects by one of essential the of oil
oil, by that time, would have during the following to hospital and
and in these instances external safe. In the 2-10% area there toxicology, community understood of essential Since phototoxicity and is one of the scientific the least oils
48 hours on her arms and legs, at which time she was admitted remained there for seven days. and some blisters After leaving to
may bc some need for caution, and in this group will be found some commonly used essential oils such as fennel and nutmeg (see table 3). Oral administration recommended bear in mind or over of carcinogens. is not to oils for essential oils with 1% It is important that a few essential
by those using essential the retail is especially on this began oils
The skin on her arms and legs had a roasted appearance, were hospital, 1Ocm in diameter.
in aromatherapy; rcscarch
consumer at risk. in the and are
she was not able to return
1950’ we have a very good idea as to s, which ,essential which are not, for responsible oils are phototoxic and the phototoxicity components
work until her skin had healed and her limbs were fully mobile. Two years after the incident her limbs still have dark occasional streaks, and she experiences
contain more than one carcinogen. Conclusion The evidence that a few essential are carcinogenic although has oil in they been orally, into is little components rodents are all described Carcinogenicity seen following subcutaneously, the .abdominal doubt that carcinogens potential. rodent humans dosage risk is
largely well-known and well studied. We also have a very good idea how much is sale in humans, over what period An excessive can be induced particularly skin. occurs present, The In how much is not, and of time. reaction by certain the to sunlight chemicals, to the reaction agent tanning. will help is
burning sensations on the affected areas. Furanocoumarins The These absorb most common are polycyclic gives ultraviolet them phototoxic molecules the agents whose to store et al., are are the psoralens, structure or furanocoumarins. ability
as “weak” carcinogens. in rodents administration and by injection cavity. There oils possess
if they are applied phototoxicity,
only if the sensitising and results two in rapid cases following
them for a while, and then release them in a burst on to the skin (Caporalc 1967). present Phototoxic small components amounls, even are only in a few essential 2%. to, However,
carcinogenic extrapolating massage in levels of the oils is not easy.
tests to, for instance, with essential or exposure considered to be negligible,
illustrate what can go wrong: Two cases A woman was treated after a 20-minute taken immediately oil with lemon for minor a sauna 1992). burns bath A few session on a sunbed, after (Anon.,
oils, and normally at this oil is often effects If
in relatively less than level, diluted
As in other and there agencies
types of toxicity,
are all important, by regldatory
if the essential they phototoxic
are levels below whi&
capable of producing
if the skin is then exposed to sunlight.
such essential and/or relatively phototoxic can result. There family of is a the if the
oils are used undiluted, skin is exposed of UV to a light source
commonly lightweight protection (Dayton,
used clothing factor 1993).
manufacture 5 and 15 use in of a
as carrying a risk. A number they are
only have a sun
of citrus oils are not phototoxic; listed in table 6.
of between The potentially phototoxic preparation, reduce Common tells risk us
(sunbeds or strong sunlight) effects whole best in The and are nonmolecules or
will risk of
known is bergapten found primarily oil. bergamot psoralens coumarins relatively volatile
phototoxicity. sense that the of will with time to the the the of
phototoxicity diminish following application skin. intensity phototoxic response more correctly, in oil is known or bergamot This as having an When there is no risk, or a reduced risk, of phototoxicity There applied is no risk of phototoxicity if the foils are used in a product off the skin, preparations such bergamot, distilled as citrus such which is not bath during next the hour, first remains and then hour the bergapten application, the following This is certainly (Zaynoun timescale other and citrus then will In reality
and, in the cast found (cold
citrus oils, tend to be in expressed pressed) oils, in distilled (or, reduce)
but not to
oils. It is also possible remove considerably bergamot FCF
increases following over 5). oil for
at a peak for the decreases (see table
oil. The resulting bergamot,
as bergaptenless bergamot
(furanocoumarin-free). oil is regarded
to the skin, or which is washed as shampoo, citrus or soap. There is no risk
true for bergamot probably gradual hold
et al., 1977) oils. The mirrors then
and the same steady increase decrease time taken the it. the the the in to reach
inferior fragrance state (Dubertret
IL is clear
to the oil in its natural et al., 1990). rrom the essential by from 1 for and oil The the published
oils are used, oils. However, and
furanocoumarin-free oils tend To be used in
monographs Research Materials consequent Fragrance ociation depends, presence type Some several and
presumably dermis, and (A
Institute (KIFM), Research YIFRA) not
for the furanocoumarins phototoxic
Ikavourings rather than fragrances,
to pass beyond reaction until crossed take place has
International Assguidelines, mere furathe
that the risk of phototoxicity on the but on of phototoxic amount
epidermis dermis. As table oil are not impact. much used in aromatherapy, relatively poor fragrance phototoxic arter 8 hours, 10 hours. is no risk iI the parts of the the
and reached can 5, produced be a seen
0.5% no was out safe on
present. fura-nocolimarins to photo-
concentration reactions, Tests were
of bergamot I% carried
oils contain all contribute due CO their There skin to applied should safety,
and 2.5% was sale after
toxicity of the oils. We are concerned which essential Taget also with their degree oil, for instance, grapefruit not only with but to be than of phototoxicity. appears oils are phototoxic,
human has been at levels
volunteers. that skin which oils to This and the maximum treated higher should zone with phototoxic than not be exposed 12 hours. of 2 hours,
It is recommend
are covered in such a way as to them. It sake of clothing is UV fabrics substantial Most bc that assumed, typical lightly whereas blocks for the
prevent UV rays from reaching summer coloured) more
around 100 times more phototoxic expressed phototoxic on the the percentage skin, dilution based on
use levels, UV light gives of 5% assumes
oil. Table 4 shows at which each safe to USC IFRA current
for at least a maximum
(lightweight, permeable, clothing
a safety essential
oil is considered
concentration or 20%
oil. A 15%
concentration still produce after 12 hours xanthotoxin 10 undiluted phototoxic produce hours, (Zaynoun Individual but
can The great majority quite safe as used but the danger to of essential which oils arc do exist it is the
mutagenicity bacteria. in aromatherapy, The photobiology perfume Journal 0 Clinical products, Wilktins, attitude seems oil essential of hazards, some of and 0 tumors safrole. 604 0 metabolic carcinogenicily that occur Carcinogens 0 of this as Miller, OJ be ignored. of 0
of I’ -acetoxycstragole
a phototoxic application A 0.5%
reaction (Zaynoun 01 equivalent
Jourrlal Duberlret, of
of the National Caww L. et bergamot an al. (1990) and oil as a a,nd overview.
>~~st%tute 57: 1323-1331 photochemistry ingredient:
et al., 1977).
(very roughly bergamot potential)
oil in terins of continued reactions after 48 for 36 hours
are very real and cannot very agree the much in the
As I have said on many occasions, interests to, aromatherapy on safety trade and to industry guidelines the implement
firstly, Par both and, those
Photobiolo~~ 7: 362365 Gleason, toxicology 5th edn. M. N. et al. (1984) of commercial Williams & Liver
et al., 1977). differences diflerences phototoxic but skin factor was no
secondly, guidelines. The
In a study on 63 volunteers, did not significantly responses colour (Zaynoun statistical brown. bergamot phototoxic individuals average colour black of was a affect
in eye colour, age, sex and ability to tan to bergamot ct al., 1977). difference The average oil, There
Long E. L. et al. (1963) produced
aromatherapists ignoring pretending This attitude. thorough hazards retailers, teachers to essential subjecl something increase oil should for It
to be one
in rats by feeding
Archives of Pathology 75: 595Miller, J. A. et al. (1982) activation of and E. naturally in many Mutagens C. et al. The and spices. in the
they simply is only
do not exist. through very that the real
is an unhealthy research from
between those with concentration to produce in compared those with brown of a these to an skin or
as fair, sallow and light
of the subject ones.
we will be able to distinguish Ihe illusory writers, or practitioners, our safety. not I be Whether
oil required response was 2.4%, 15% in
we are manuracturers, researchers, we all need believe regarded ‘ advanced be basic to training. knowledge
Environ.ment 1: 83-96 (1983) of mouse the and and Structure-activity carcinogenicities rat of some synthetic relaled 0 Toxicity variety). 0 (1979) to studies in the naturally safrole J. of M.
as dark et al., 1977).
occurring and et
gave light skin some extra protection. When There Firstly, used there are
derivatives estragole. al. (1967) (Jammu A$plied D. et al.
is an increased scenarios
courses’ it should aromatherapy
Cancer Research 43: 1124-l 134 Taylor, of oil calamus and S. safrolc.
phototoxicity in which oils risk of phototoxicity if several together, may be increased. phototoxic the For risk are if the increases
Essen.tial Oil Safety, by Robert Tisserand and ?&1y Balacs, is published
ToxicoloSq Vesselinovitch, Transplaccntal by
Pharmecology 10: 405 and lactational Cancer
proportionally. bergamot maximum in a product
s Ch.urchill by ISBN: 0443 052h0 3.
and cumin oils are both used in equal proportions, safe percentage if will be 0.2% concentrated 01 essential Citrus a oil oils large or 0 Chronic 0 warning. 0 Abbot, D. D. et al. (1961)
carcinogenesis 0 Wiseman.
Research 39: 4378-4380 R. W. et al. (1987) studies of safrole of the to on male (1981) of to the l’ alkenylStructure-activity hepatocarcinogenicities benzene estragole administration mice. 0 G et al. (1967) of some activily estragole q/ derivatives and oral toxicity Anon (1992) of oil of sassafras
for each, not 0.4% for each. Secondly, (deterpenated) maximum degree generally amount of (rdeterpenised, tcrpcncfree) possess (including much larger concentrated all the citrus their of citrus oils are used, the in proporlion to the
Pharmacologist 3 (73) Lemon lnternation.al
should be reduced
to preweanling A. et al. conversion metabolite
concentration. contain terpcnes.
Cancer Research 47: 2275-2283 Zangouras,
Aromatherafiy 4 (4) Caporale,
Deterpenated oils therefore components in (1976) of oil will of So, a 10 times lemon
Dose-dependent carcinogenic hydroxyestragole.
Skin photosensitizing methylpsoralens. 986 0 Drinkwater, cstragole
in the rat and mouse
Exfiewntia 23: 985 N.R. et al.
Biochemical S. T. el al. (1977) and its importance agent. Contact A
Pharmacology 30: 1383-1386
Hcpatocarcinogenicity (1.allyl-4and in the l’ -hydroand mouse as
study of bcrgamot a
have a maximum
0.2%, instead of 2%.
Dermatitis 3: 225-239
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