Medicinal and Aromatic Plants—Industrial Profiles


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JULIE L.MARKHAM
188
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properties of essential oil components. J. Essent. Oil Res., 1, 119–128.
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part of The Gordon and Breach Publishing Group.

IOLOGICAL ACTIVITY
189
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results.
Mann, C.M. and Markham, J.L. (1998) A new method of determining the MIC of essential oils. J.
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Nguyen, D.C, Truong, T.X, Motl, O., Stránský, K., Presslová, J., Jedlicková, Z. and Serý, V. (1994)
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components on Staphylococcus aureus, S. epidermidis and Propionibacterium acnes. Letters in
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part of The Gordon and Breach Publishing Group.

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191
10. TOXICOLOGY OF TEA TREE OIL
MICHAEL RUSSELL
Wollongbar Agricultural Institute, Wollongbar, NSW, Australia
INTRODUCTION
For some essential oils, as little as one teaspoonful can be fatal. Wormseed, sassafras,
parsley, eucalyptus and camphor have all caused child fatalities in low doses (Tisserand
and Balacs 1995). Consequently, guarding against accidentally overdosing with certain
essential oils is important, especially with children. Storing essential oils that are known to
be harmful out of children’s reach and in child-proof bottles is a sensible way to minimise
accidental consumption. Nevertheless, it is of vital importance to understand the toxic
properties of each specific oil to be certain of the risks involved.
Toxicity can be manifested by many symptoms, beginning with a rash and redness of the
skin, extending to organ damage, especially the liver and, in the extreme, resulting in death.
Toxicity is generally dose dependant, with oral intake more significant than dermal
absorption. Also, acute toxicity results from higher doses than those responsible for longer
term chronic problems.
In this chapter, toxicology will be discussed in relation to acute oral and dermal toxicity,
to dermal irritancy and to dermal allergy responses. The amount of an essential oil needed
to bring about a response in each of these broad categories varies greatly. This variation is
due to individual human tolerance (oral or dermal), dose frequency and the oil’s intrinsic
toxicity.
TEA TREE OIL—MELALEUCA ALTERNIFOLIA
Acute Oral Toxicity
Acute oral toxicity of a substance is measured by the LD
50
 test which measures the effect of
differing amounts of a test substance given orally to a group of animals (usually rats or
mice). The group is of uniform age, size and genetic origin. Hence LD
50
 measures the
dosage which is lethal to 50% of the test animals.
The LD
50
 test is probably the prime result for any substance as it determines whether or
not the substance can be ingested safely or not. LD
50
 test results are usually expressed in the
form of grams (or ml) per kilogram of body weight, thus the heavier the person, the higher
a dose needs to be, before it becomes lethal. It is for this reason that children are particularly
susceptible to lethal poisoning. To help appreciate the significance of the LD
50
 test, 
Table
1
 converts LD
50
g/kg results for common essential oils to a lethal dose for a 70kg adult and
a 10kg child.
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MICHAEL RUSSELL
192
Tea tree oil has been reported to have an LD
50
 of 1.9g/kg (Ford 1988; Tisserand and
Balacs 1995; Table 1), 1.9–2.6ml/kg (or 1.7–2.3g/kg for an oil of density 0.9) (Bolt 1989d;
Altman 1991) and 3.0ml/kg (or 2.7g/kg) (Austteam 1995). Tisserand and Balacs (1995),
although classifying tea tree oil with oils on the borderline of safe and unsafe, place k at
the safe end of that group and state that “we have no reason to suspect any problems with
tea tree”.
Table 1 Some well known essential oils and components with their LD
50
 values (g/kg) in
Rodents, from Tisserand and Balacs (1995) with corresponding calculated doses (gm) for a
70kg adult and a 10kg young child
*FFPA=Free From Prussic Acid.
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part of The Gordon and Breach Publishing Group.

TOXICOLOGY 193
The LD
50
 test for tea tree oil conducted by Bolt (1989d) using OECD method 401 as per
the Australian Tea Tree Oil Toxicology Data Sheet No. 5 (Tea Tree Oil Growers of Australia
1989) was performed as follows:
Tea tree oil was diluted with peanut oil and tested at 20%, 25% and 33% concentrations
using groups of 5 male and 5 female Sprague Dawley SPF (specific pathogen free) and non-
SPF rats. Animals received doses of 1.7–3.0ml/kg by gavage and were observed for 14 days.
The LD
50
 was found to be 2.6ml/kg in SPF rats and 1.9ml/kg in non-SPF rats. Ingestion of
pure tea tree oil is not recommended.
For the animals surviving the above treatment, the major non lethal reaction was a
complete lack of muscular tone in the forelimbs, bloodied noses and weeping (Bolt 1989d).
These results suggest that tea tree oil is less toxic than commonly used oils like pennyroyal
(LD
50
 0.40), wintergreen (LD
50
 1.20), cornmint (LD
50
 1.25), basil (LD
50
 1.40), and bay leaf
(W. Indian) (LD
50
 1.80), (Tisserand and Balacs 1995).
Poisoning
Essential oils in general are a toxic risk especially to children and old people. Cases of
child poisoning due to overdose of essential oils such as camphor, cinnamon, citronella,
clove, eucalyptus, pennyroyal, sassafras and oil of wintergreen have been reported
(Tisserand and Balacs 1995). In America in 1973, 500 cases of camphor intoxication
alone were reported. Most of these were young children given camphorated oil instead of
castor oil. In one instance, a 16 month old boy died from consuming one teaspoon of 20%
camphorated cottonseed oil (Smith and Margolis 1954) thus making about 1 gram of
camphor the toxic dose to children. The chemical camphor is up to 60–70 times more
toxic to humans (LD
50
 0.005–0.5g/kg) than to rodents (LD
50
 0.5–15g/kg) (Tisserand and
Balacs 1995, 
Table 1
).
As the oral toxicity LD
50
 test is carried out on rodents and not humans the results can
be misleading. Take for instance oil of wintergreen (methyl salicylate). In six cases of
poisoning from the oil in adult humans, three people died from ingestion of 15ml, 30ml
and 80ml and three survived after 6ml, 16ml and 24ml (Stevenson 1937) giving an
average oral lethal dose of 0.2g/kg to 0.3g/kg for humans. The LD
50
 however, is 1.2g/kg
for rodents suggesting that oil of wintergreen is some three to five times more toxic in
humans. According to Opdyke (1977) an oral dose of 4–8ml of methyl salicylate is
considered lethal for a child.
Similarly, eucalyptus oil has shown itself to be fatally toxic to humans in amounts
between 30ml and 60ml (Gurr and Scroggie 1965) thus making it 4 times more toxic to
humans than to rodents. With these figures in mind, one might be tempted to say that LD
50
tests are of limited value. The lesson here is that with the LD
50
 test, one has a comparative
assessment of an essential oil’s oral toxicity potential in humans.
Furthermore, with tea tree oil being in the borderline category when tested with rodents
(Tisserand and Balacs 1995), it is probably prudent to assume that tea tree oil is orally toxic
in reasonably large doses, so oral ingestion should be avoided. This recommendation is
even more applicable to children, who should be kept well clear of any container of essential
oil including tea tree oil.
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MICHAEL RUSSELL
194
This is well illustrated by the known cases of tea tree oil poisoning in humans (Carson
and Riley 1995).
Del Baccaro (1995) cites a case of a 17–month-old male child who developed ataxia and
drowsiness after ingestion of less than 10ml of oil of Melaleuca alternifolia. With treatment
of activated charcoal and observation, the child was discharged 7 hours later.
A similar case involving a 23–month-old boy was reported by Jacobs and Hornfeldt (1994):
A 23–month old boy became confused and unable to walk thirty minutes after ingesting
less than 10ml of T36-C7, a commercial product containing 100% Melaleuca oil. The
child was referred to a nearby hospital. His condition improved and he was asymptomatic
within 5 hours of ingestion. He was discharged to home the following day.
Adults are also susceptible with one sixty-year-old male, after ingesting half a teaspoonful
of oil, reacting with severe dermatitis in addition to feeling quite unwell (Elliot 1993). This
was thought to be “systemically induced eczema or a cutaneous reaction to an ingested
contact allergen” (Moss 1994).
On the other hand, one adult became comatose for twelve hours and semi-conscious for
a further thirty-six hours after ingesting half a cup of neat tea tree oil (Seawright 1993).
Despite abdominal pain and diarrhoea which persisted for six weeks, this patient survived a
dosage estimated at 0.5–1.0ml/kg body weight. Hence tea tree oil can be considered safer
than many other oils, including camphor, wintergreen and eucalyptus oils.
Acute Dermal Toxicity
The acute dermal toxicity test ascertains whether a specific LD
50
 dose will cause problems
if applied dermally. Some chemicals may be as toxic dermally as orally. But tea tree oil,
as with most essential oils, is not as toxic dermally as it is orally. This is most likely due
to the slow absorption of the oil into the body through the skin, thus allowing organs,
such as the liver, time to detoxify it and the kidney to eliminate the metabolites of the
toxic material.
Tea tree oil’s acute dermal toxicity was assessed by using the OECD method 402 on
rabbits as in the Australian Tea Tree Oil Toxicology Data Sheet No. 5 (Tea Tree Oil Growers
of Australia 1989):
An undiluted test sample of tea tree oil was applied dermally at the dose of 2g/kg to a group
of 5 male and 5 female albino rabbits (NZ) and held in contact for 24 hours over an
approximate skin area of 175cm
2
. Observations were made for any signs of toxicity, weight
change and abnormal behaviour. Apart from slight diarrhoea in one of the animals on day 3,
no other signs of toxicity, significant weight loss or abnormal behaviour was noted over a
two week observation period. (Bolt 1989c).
However, Villar et al. (1994) of the National Animal Poison Control Centre in USA, reports
cases involving toxicosis with tea tree oil used in veterinary products for animal dermatitis
treatment. It appears that the toxicosis occurred after topical or drenching application of
inappropriate or erroneous amounts of the products. The symptoms of the toxicosis were
ataxia, incoordination weakness, muscle tremors, behavioural disorders and depression.
Treatment was in the form of supportive care and treatment of clinical signs. It appears that
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TOXICOLOGY
195
while most animals can metabolise the components of tea tree oil, in this case it was at a rate
that was below the rate of absorption into the blood stream. Thus, it is advisable to administer
tea tree oil preparations and indeed any essential oil preparation strictly according to
manufacturer’s instructions. As for manufacturers, their product should be appropriately
tested and clearly and carefully labelled so as to instruct the purchaser that application
must only be for affected skin areas and not over total skin area. The same also applies to
products for use on humans.
Dermal Irritation
Toxicology also includes the potential for any compound to cause irritation when applied
to the skin. Traditionally this testing has been done on animals. Occasionally, however,
some compounds are mild enough to be tested on human volunteers. Before this can occur,
the substance tested must be shown to have a low irritation rating on animals.
Skin irritation for tea tree oil has been assessed using the following tests:
(1) Draize Acute Dermal Irritation in the Rabbit (OECD method 404) as in the Australian
Tea Tree Oil Toxicology Data Sheet No. 5 (Tea Tree Oil Growers of Australia 1989):
Neat tea tree oil (0.5ml) was applied to both intact and abraded skin under occlusion to 6
albino rabbits (NZ) and observed for erythema (redness) and oedema (swelling) of the skin
over a 72 hour period. The Draize index for tea tree oil is 5. Pure tea tree oil may cause
dermatitis in some users.
According to Bolt (1989a) tea tree oil, with a score of 5 out of a possible 8, places it in the
moderate to severe irritant category. However, literature and reports do not support the
result. According to Tisserand and Balacs (1995) tea tree oil is listed as a very mild irritant.
Perhaps this can be better understood with the suggestion that the Draize test cannot
distinguish well between mild and moderate irritants (Altman 1991; Phillips et al. 1972).
These authors further suggest that some substances considered unsafe by rabbit tests have
been proved non-irritating to human skin. With this in mind, further tests both on rabbits
and human volunteers were undertaken.
A more recent repeat of the Acute Dermal Irritation test (OECD 404) on rabbits concluded
that “tea tree oil was found to be a mild to moderate irritant at 75%, a minimal irritant at
50% and non-irritant at 25% and 12.5% following a four hour semi-occlusive patch
application on intact skin, over a fourteen day observation period” (Rural Industries Research
and Development Corporation 1996). The maximum dermal irritation index recorded was
2.3 for the 75% oil after forty eight hours.
(2) 30-Day Dermal Irritation in the Rabbit as in the Australian Tea Tree Oil Toxicology
Data Sheet No. 5 (Tea Tree Oil Growers of Australia 1989):
Tea tree oil was diluted to 25% in paraffin oil B.P. and applied to the shaved skin of 6 female
(NZ) white rabbits on days 1–5, 8–12, 15–19 and 22–30. The irritation index was found to
be 2.2 on observation day 2 and 0 on subsequent observation days. Histological
examinations were conducted on skin samples. Although not visibly irritant, superficial
pathological changes consistent with localised irritation were observed on microscopic
examination.
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MICHAEL RUSSELL
196
This test result is consistent with the very mild irritant category into which Tisserand and
Balacs (1995) had placed tea tree oil. However, in combination with the Draize method
result, more human testing is needed to clarify the issue.
(3) Skin Irritancy Potential in Humans—Clinical Trials:
One clinical trial has been completed (Altman 1991) in which 28 human subjects were each
subjected to daily occlusive application of a 0.05ml sorbolene cream containing 1%, 2.5%,
5% and 10% tea tree oil, plus sorbolene alone onto a predetermined pattern on subject’s
backs over a 21 day period with 15 daily applications (work days only). Results showed
only 5 of 28 subjects exhibited slight irritation. Of these 5 subjects, only one reported
slight irritation with 1%, one with 2.5%, 2 with 5% and 2 with 10%. With the exception of
subject No. 23, the subjects who reported any skin irritation only did so for 1 or 2 days out
of the 15 observation days. Subject 23 reported slight irritation on 11 of the 15 days using
the 10% tea tree oil. No one reported irritation using sorbolene cream (placebo). According
to Altman (1991) the results show that a cream formulation using up to 10% w/w tea tree oil
applied for 5 days out of 7 for three consecutive weeks under occlusive dressing, produced
mainly infrequent and mild skin irritation in a small proportion of subjects. Further to this
he states “Tea tree oil used topically in dermatological formulations up to 10% w/w would
appear to pose little risk of skin irritation when applied under normal conditions”.
Furthermore a recent clinical trial (Southwell et al. 1997) investigated 25 subjects with
occlusive patch tests of 25% tea tree oil in soft white paraffin. The patches were applied
daily for 21 days (except weekends). The results indicated that no irritation was present in
any of the subjects over the 21 days. In the selection trial, 3 subjects were withdrawn because
of an allergic response to tea tree oil. This allergic reaction will be discussed more fully
later in the chapter. This trial indicated that tea tree oil even with varying concentrations of
cineole (1.5%–28.8%) and terpinen-4-ol (22.6–38.8%) is a non-irritating essential oil. Cineole
in the past has been suggested as a mucous membrane and skin irritant (Lassak and McCarthy
1983). This trial not only indicates that cineole is not a skin irritant, but also that tea tree oil
cannot be regarded as a skin irritant in concentrations up to 25%. This finding was also
confirmed by human dermal irritation studies on 306 subjects which showed no irritation to
oil at 25% concentration (Main Camp 1998).
Skin Sensitization and Contact Dermatitis
In recent years there have been several reports in dermatological journals suggesting
that tea tree oil causes contact dermatitis. Contact dermatitis is usually caused by
sensitization to a substance and at a later stage coming in contact with the same substance.
Tea tree oil has been regarded as a non-sensitizing substance (Tisserand and Balacs
1995) and this is certainly the case with guinea pigs. Bolt (1989e) carried out a skin
sensitization potential trial with guinea pigs (OECD method 406) using tea tree oil as
reported in the Australian Tea Tree Oil Toxicology Data Sheet No. 5 (Tea Tree Oil
Growers of Australia 1989):
Groups of 20 albino guinea pigs (HA strain) were tested for sensitization potential using the
method of Magnusson and Kligman (1969). The induction procedure consisted of 2
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TOXICOLOGY
197
intradermal injections and an epidermal induction application under occlusion for 48
hours. Two weeks after the induction applications the animals were challenged with 30%
tea tree oil in petroleum jelly. No sensitization reactions were noted. Tea Tree Oil could
therefore be recommended in hypoallergenic preparations.
Yet, there appears to be evidence, in humans at least, that tea tree oil can cause varying
allergic responses in certain individuals. Some case studies and clinical trial results follow:
(a)
A maximization test was conducted on 22 volunteers with a 1% tea tree oil in a
petrolatum formula and produced no sensitization reactions (Ford 1988).
(b)
A 43-year-old woman and 10–year-old boy were confirmed by patch challenge testing
to have contact dermatitis from tea tree oil (Apted 1991). Individual components of
the oil were not tested for allergic response.
(c)
A 45-year-old man, with long standing atopic dermatitis, applied tea tree oil which
exacerbated the condition after a time (de Groot and Weyland 1992). Although the oil
components were listed, no concentrations were given. The constituents listed were
more consistent with tea tree oil of the cineole genotype. This genotype was once
reported to be readily available in Europe and caused allergic responses on other
users as well (van der Valk et al. 1994). The patient gave a positive patch response
when tested with cineole (eucalyptol) in contrast with the findings of Opyke (1975b),
Knight and Hausen (1994) and Southwell et al. (1997). This chemical variety is not
normally used commercially and would not have conformed to ISO 4730:1996E
(International Standards Organisation 1996).
(d)
Two occupational contact dermatitis subjects, one a chiropodist, the other a beautician
were said to be allergic to tea tree oil, however no challenge patch test were reported,
(de Groot and Weyland 1993).
(e)
A 33-year-old woman who had used neat tea tree oil previously with no side effects,
developed contact dermatitis confirmed by patch challenge testing with tea tree oil.
(Selvaag et al. 1994).
(f)
Knight and Hausen (1994) conducted a trial on seven patients who were treating pre-
existing skin conditions with neat tea tree oil and were challenge patch tested with tea
tree oil at 1%. All seven reacted positively. Further to this, they tested the major
components of tea tree oil at 1%. Six of seven patients reacted to limonene, 5 to a-
terpineol and aromadendrene and one to each of terpinen-4-ol,  p-cymene and a-
phellandrene. However, according to Opdyke (1975a), limonene proved negative on
23 subjects tested for sensitization. Furthermore, Knight and Hausen (1994) found
tea tree oil to be a weak sensitizer in guinea pigs as only 3 of 10 responded at 30%
challenge after 48 hr. It is interesting to note here that the terpinen-4-ol sensitized
human had a previous sensitivity to Peruvian Balsam. These authors acknowledged
that they were dealing with a population of tea tree oil sensitised patients with damaged
skin and also suggested that “other tea tree oil products containing lower concentrations
of the oil and used-on healthy skin may cause no sensitivity reactions.”
(g)
A 53-year-old patient suffered allergic airborne contact dermatitis from several essential
oils after extensive use of the oils in wet dressings, baths and room aerosols (Schaller
and Korting 1995). Although the oils used and tested included tea tree oil, only lavender,
rosewood and jasmine gave positive patch test responses.
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MICHAEL RUSSELL
198
(h) Recent investigations (Southwell et al. 1997) looked at the skin irritancy of tea tree
oil using 28 human subjects with occlusive tea tree oil 25% patch testing over 21
days. Oils of differing cineole (15–28.8%) and terpinen-4-ol (22.6–38.8%) showed
no irritancy except for 3 subjects who showed allergic responses to all the different
types of tea tree oils used. These 3 subjects were further tested with the individual
constituents or constituent blends at concentrations equivalent to their concentration
in a 25% formulation. None of the 3 subjects reacted to the monoterpenoids except
for one panellist who reacted to a-terpinene only. However, the sesquiterpene
hydrocarbon enriched blends caused reactions in all three subjects. This is consistent
with Knight and Hausen (1994) who found aromadendrene, a sesquiterpene
hydrocarbon, an allergen. Still more research is needed here.
Cytotoxicity using Human Cell Lines
All of the previous assessments of tea tree oil have been acquired from animal and human
testing. Just recently, however, cytotoxic testing of the oil has been carried out. The use of
cytotoxic (toxic to cell tissue) in vitro (test tube) testing has made testing of substances that
are quite toxic, more animal friendly and thus more acceptable. The other advantage is that
the same tissues can be used to test many substances and provide a more accurate comparison
of the relative toxicity of different substances. This approach is also being used for predictive
testing for potential allergens (Krasteva et al. 1996). According to Söderberg et al. (1996),
tea tree oil when tested at 100µg/ml had a cytotoxic effect on epithelial and fibroblast cells
for only the first hour of a 24 hour test duration.
More recently, Hayes et al. (1997) investigated tea tree oil cytotoxicity with respect to
the major oxygenated monoterpenoid constituents terpinen-4-ol, 1,8-cineole and a-terpineol.
The oil tested contained terpinen-4-ol 40%, 1,8-cineole 4%, a-terpineol 4% and results
showed that a-terpineol>tea tree oil>terpinen-4-ol>cineole for overall cytotoxicity. When
tea tree oil was compared with controls mercuric chloride (highly toxic) and aspirin (very
low toxicity) on the same cell types (liver, skin, lymph and bone marrow), ratings were
mercuric chloride>tea tree oil>aspirin. The authors state that these cytotoxicity results support
the use of tea tree oil in topical applications but not for ingestion purposes.
CINEOLE AND OTHER MELALEUCA SPECIES’ OILS
According to Tisserand and Balacs (1995), 1,8-cineole is non-toxic, non-irritant and non-
sensitising. This being the case, one would expect that high cineole content oils would be
similar. However, as mentioned earlier, eucalyptus oil, although fitting into this category, is
still regarded as potentially dangerous to small children.
Commercial cajuput oil, presumably the “cajeput” (Melaleuca leucadendron) of Tisserand
and Balacs (1995) and now known as Melaleuca cajuputi (see 
Chapter 14
), is normally a
high cineole (50–60%) oil. Tisserand and Balacs (1995) state that this “cajeput” oil has an
LD
50
 between 2–5g/kg, is non-irritant and has negligible risk of skin sensitivity.
Niaouli oil, from Melaleuca quinquenervia, also a cineole type oil, has been assessed
by Aboutabl et al. (1996) using ethanol extracts as having an LD
50
 of 147.5mg/kg while
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TOXICOLOGY 199
Tisserand and Balacs (1995) indicate that niaouli oil is safe to be used in aromatherapy
and is considered non-irritant and non-sensitizing. Linalool and nerolidol, the major
constituents in some chemotypes of Melaleuca quinquenervia, are also considered to be
safe for aromatherapy use (Tisserand and Balacs 1995) and hence non-irritant and non-
sensitising (see 
Chapter 15
).
The only Melaleuca oil that is currently considered as a potential carcinogen is the oil of
Melaleuca bracteata which contains approximately 80% methyl eugenol. According to
Randerath  et al. (1984) and Tisserand and Balacs (1995) this oil should be avoided as
currently the oil is considered carcinogenic to rodents. Until such time as it is assessed as
non-carcinogenic to humans, this advice should be heeded.
CONCLUSION
Although not unduly toxic when ingested, tea tree should continue to be used mainly for
topical applications. It would appear that tea tree oil (Melaleuca alterntfolia) is non-irritating
even when used up to 10% (Altman 1991) or 25% (Southwell et al. 1997) on unabraded
healthy skin. It is not recommended that it be used on sensitive, dermatitis affected or abraded
skin for extended periods. Some people do become sensitized to tea tree oil on rare occasions
especially those that have a history of allergic responses. Generally, however, as there was
little irritation or sensitization with tea tree oil in formulations up to 25%, products of that
concentration or less are recommended.
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Altman, P. (1991) Assessment of the skin sensitivity and irritation potential of tea tree oil. Pharmaco
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Australian Tea Tree Industries Association. Pharmaceutical Consulting Services, Lindfield, Sydney.
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Australian Tea Tree Industries Association. Pharmaceutical Consulting Services, Lindfield, Sydney.
Bolt, A.G. (1989c) Acute dermal toxicity limit test of tea tree oil in the rabbit. 20th February. Report
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Bolt, A.G. (1989d) Acute oral toxicity of tea tree oil in the rat. 24th April. Report for the Australian Tea
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Bolt, A.G. (1989e) Skin sensitisation potential of tea tree oil in the guinea pig. 13th January. Report for
the Australian Tea Tree Industries Association. Pharmaceutical Consulting Services, Lindfield,
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Carson, C.F, and Riley, T.V. (1995) Toxicity of the essential oil of Melaleuca alternifolia or tea tree oil
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De Groot, A, and Weyland, W. (1992) Systemic contact dermatitis from tea tree oil. Contact Dermati-
tis, 27, 279–280.
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De Groot, A. and Weyland, W. (1993) Contact allergy to tea tree oil. Contact Dermatitis, 26, 309.
Del Baccaro, M.A. (1995) Melaleuca oil poisoning in a 17–month-old. Vet. and Human Toxicology,
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Elliot, C. (1993) Tea tree oil poisoning [Letter]. The Medical Journal of Australia, 159, 830–831.
Ford, R. (1988) Fragrance raw materials monographs. Food Cosmet. Toxicology, 26, 407.
Gurr, F.W. and Scroggie, J.G. (1965) Eucalyptus oil poisoning treated by dialysis and mannitol infu-
sion. Australian Annals of Medicine, 14, 238–249.
Hayes, A.J., Leach, D.N. and Markham, J.L. (1997) In vitro cytotoxicity of Australian tea tree oil
using human cell lines. J. Essent. Oil Res., 9, 575–582.
International Standards Organization (1996) Oil of Melaleuca, terpinen-4-ol type (Tea Tree Oil). In-
ternational Standard ISO 4730:1996(E), International Standards Organization, Geneva.
Jacobs, M.R. and Hornfeldt, M.S. (1994) Melaleuca oil poisoning. Clinical Toxicology, 32(4), 461–
464.
Knight, T.E. and Hausen, B.M. (1994) Melaleuca oil (tea tree oil) dermatitis. J. Am. Acad. Dermatol.,
30, 423–7.
Krasteva, M., Peuget-navarro, J., Moulon, C., Courtellemont, R, Redziniak, G. and Schmitt, D. (1996)
In vitro primary sensitization of hapten-specific T cells by cultured human epidermal Langerhans
cells-a screening predictive assay for contact sensitizers. Clinical and Experimental Allergy, 26,
563–570.
Lassak, E.V. and McCarthy, T. (1983) Australian Medicinal Plants, Methuen Sydney, Australia, p. 97.
Magnusson, H.C. and Kligman, A.M. (1969) The identification of contact allergens by animal assay.
The guinea pig maximization test. J. Invest. Dermatol., 52, 268–276.
Main Camp Tea Tree Oil Group Newsletter (1998), Tea Tree Oil News, 1, 3.
Moss, A. (1994) Tea tree oil poisoning [Letter]. The Medical Journal of Australia, 160, 236.
Opdyke, D.L.J. (1975a) Fragrance raw materials monographs (limonene). Food and Cosmetics Toxi-
cology, 13, 825–826.
Opdyke, D.L.J. (1975b) Fragrance raw materials monographs (eucalyptol). Food and Cosmetics Toxi-
cology, 13, 105–106.
Opdyke, D.L.J. (1977) Fragrance raw materials monographs (methyl salicylate). Food and Cosmetics
Toxicology, 15.
Phillips, L., Steinberg, M., Maibach, H.I. and Akers, W.A. (1972) A comparison of rabbit and human
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DNA adducts formed in livers of animals treated with safrole, estragole and other naturally-ocurring
alkenylbenzenes 1. Adult female CD-1 mice. Carcinogensis, 5(12), 1613–1622.
Rural Industries Research and Development Corporation (1996) Acute dermal irritation/corrosion of
75%, 50%, 25%, and 12.5% tea tree oil solutions in the rabbit . Pharmatox Project Report, T1836.A,
p. 7.
Schaller, M.S. and Korting, H.C. (1995) Allergic airborne contact dermatitis from essential oils used
in aromatherapy. Clin. & Exp. Dermatology, 20, 143–145.
Seawright, A. (1993) Tea tree oil poisoning—comment [Letter]. The Medical Journal of Australia,
159, 831.
Selvaag, E., Eriksen, B. and Thune, P. (1994) Contact allergy due to tea tree oil and cross-sensitization
to colophony. Contact Dermatitis, 31, 124–125.
Smith, A. and Margolis, G. (1954) Camphor poisoning. American Journal of Pathology, 30, 857–869.
Söderberg, T., Johansson, A. and Gref, R. (1996) Toxic effects of some conifer resin acids and tea tree
oil on human epithelial and fibroblast cells. Toxicology, 107, 99–109.
Southwell, I.A., Freeman, S. and Rubel, D. (1997) Skin irritancy of tea tree oil. J. Essen. Oil Res., 9,
47–52.
Stevenson, C.S. (1937) Oil of wintergreen (Methyl salicylate) poisoning. J. Med. Sc., 193, 772–788.
Tea Tree Oil Growers of Australia (ca. 1989) Australian Tea Tree Oil Toxicology Data, Data Sheet 5,
Tea Tree Oil Growers of Australia, Grafton, Australia.
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Tisserand, R. and Balacs, T. (1995) Essential Oil Safety—A Guide for Health Care Professionals,
Churchill Livingstone, Edinburgh, pp. 45–55, 80, 82, 150, 187, 204, 219.
Van der Valk, P.G.M., De Groot, A.C., Bruynzeel, D.P., Coenraads P.J. en Weijland, J.W. (1994)
Allergisch contacteczeem voor ‘tea tree’-olie. Ned Tijdschr Geneeskd, 138(16), 823–825.
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Related Essential Oils Applied Topically on Dogs and Cats. Vet. Human toxicology, 36(2),
139–142.
Copyright © 1999 OPA (Overseas Publishers Association) N.V. Published by license under the Harwood Academic Publishers imprint,
part of The Gordon and Breach Publishing Group.

203
11. TEA TREE OIL IN COSMECEUTICALS:
FROM HEAD TO TOE
DON PRIEST
Main Camp Marketing Pty Ltd, Ballina NSW, Australia
INTRODUCTION
On every continent, in many countries, new cosmetics and personal care products containing
Australian tea tree oil (oil of Melaleuca alternifolia) are being launched at an ever increasing
rate.
Since the pioneering launches of personal care products in the 1980’s by companies
such as Thursday Plantations, Melaleuca Inc. and Dessert Essence, the 90’s has seen an
explosion of products containing Australian tea tree oil.
Leading the way is the Body Shop, the tea tree oil range of which has been an outstanding
success worldwide. Following closely is L’Oreal in France with the successful Ushuata
shampoo and body wash.
Numerous other companies, including Clarins, Yves Rocher, Ella Bache, Boots, Aveda,
Unilever, Carter Wallace, Colgate, Benckiser, Reckitt and Colman, Rhone Poulenc, Australian
Bodycare and Blackmores Laboratories now market cosmeceutical products containing tea
tree oil.
The reason for this is that tea tree oil is not only natural, but is one of the few active
ingredients that really works. It is a proven natural antiseptic with broad spectrum
activity, effective against a wide range of gram positive and gram negative bacteria,
yeast, moulds and fungi. At concentrations of 5% and more, it is used therapeutically
world wide for antiseptic, antifungal and acne treatment. At lower concentrations, tea
tree oil adds efficacy to a wide range of cosmetics and personal care products—products
for use from head to toe, and from baby products to treatments for aged and damaged
skin.
In addition to its germicidal properties, there have been numerous anecdotal reports of
the anti-inflammatory activity of tea tree oil—including reduction of itch and swelling from
insect bites, and erythema in pimples and sunburn. In a clinical study on tinea, Professor
Ross Barnetson, one of Australia’s leading dermatologists, reported the amelioration of
symptoms with a 10% tea tree oil cream but not the underlying fungal infection, and suggested
that these results were due to an anti-inflammatory effect rather that anti-fungal action
(Tong et al. 1992).
Investigating the potential for tea tree oil in oral hygiene, researchers at the Dental Faculty
of the University of Tennessee have found that tea tree oil suppresses superoxide which is
normally released by neutrophils in the presence of bacterial lipopolysaccharide fragments
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DON PRIEST
204
from cell walls. This superoxide release, a natural defence mechanism against invading
micro-organisms, can induce a strong inflammatory response, resulting in erythema, swelling,
pain, blisters, and initiation of free radicals which cause skin damage.
The germicidal and anti-inflammatory properties, along with excellent solvency, dermal
penetration and green image, form the basis for use of tea tree oil in cosmetics and personal
care products which typically contain 0.5–5% of the oil.
An important factor in the growth in popularity of tea tree oil is that a guaranteed supply
of ultra pure, high quality, pharmaceutical grade tea tree oil is now available from plantations.
High quality tea tree oil is crystal clear, highly active, almost non-irritant and mild in odour.
In this chapter, Australian tea tree oil is seen as an extremely versatile natural ingredient.
As one of the few natural ingredients that work, Australian tea tree oil is an important
ingredient for formulators of cosmeceutical products.
Its potential for use in a wide range of cosmeceutical products is discussed along with
rationales for use. These include hair care (including dandruff), acne and problem skin, lips
and face, oral care, shave, after sun, hand and body treatments, cleansers, leg and foot
products, natural deodorants and preservatives.
The activity of Australian tea tree oil is dose dependant. At higher doses (>5%) it is used
as a treatment for a variety of bacterial and fungal infections, and at lower doses (0.5–3%)
to control microorganisms and maintain healthy skin, hair and nails.
Consequently, this chapter outlines the widespread use of Australian tea tree oil in products
from head to toe which demonstrate the versatility of this unique ingredient.
HAIR CARE
Hair care products with tea tree oil are usually positioned for oily hair (utilising the solvent
properties of tea tree oil), or for anti-dandruff and contain 1–5%.
Recent tests have been carried out on Main Camp’s pharmaceutical grade tea tree oil by
the University of Western Sydney demonstrate a minimum inhibitory concentration (MIC)
of 0.5% against Pitryosporum ovales, the fungal cause of dandruff.
In formulating a product range, it may be necessary to position shampoos and conditioners
as products for prevention, supplemented by higher strength treatment products designed to
allow longer contact time with the scalp.
Treatment and preventative products are also marketed for use against head lice
(Pediculus capitis). Many insects and mites are either repelled or killed by tea tree oil and
the solvent properties of tea tree oil if properly formulated, should assist greatly in removal
of the eggs.
FACE AND MOUTH
Cosmetics for problem skin utilise the germicidal activity of tea tree oil against
Propionibacterium acnes in pimples and acne and other bacteria which may be involved in
secondary infection—for example Staphylococcus species. The anti-inflammatory activity
also provides a calming effect, reducing erythema and swelling around pimples. At 5%,
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TEA TREE OIL IN COSMECEUTICALS USES
205
effective treatment products can be formulated, while prevention and maintenance products
for daily use, such as night cream, moisturisers, toners and cleansers should normally contain
0.5–1%.
Lip balms and sticks containing 1–3% tea tree oil are particularly effective in the prevention
and treatment of sore and cracked lips resulting from sun and windburn.
Australian tea tree oil is increasingly being found in oral hygiene products—as a natural
anti-plaque agent in toothpastes and mouthwashes. Although taste can be difficult to mask
at concentrations over 0.5%, higher levels are predicted for use in products for sensitive
teeth due to efficacy against the microflora of the mouth (Walsh and Longstaff 1987; Carson
and Riley 1993), anti-inflammatory action and local anaesthetic properties on mucous
membranes.
Obviously shave products would benefit from the germicidal and soothing properties of
tea tree oil. The addition of 1% tea tree oil to shave creams, sticks, foams and after shave
products will sooth irritated skin caused by the action of shaving.
BODY PRODUCTS
After-sun lotions containing 1% Australian tea tree oil are effective in reducing redness and
soreness of sunburn. The inclusion of tea tree oil in sunscreen products could enhance its
Sun Protection Factor by suppression of erythema, although the benefit of this might be
debatable.
The broad spectrum germicidal activity provides excellent cleansing and deodorancy at
1–2% in bar soaps, liquid soaps, bath oils and shower gels. In addition, the anti-fungal
activity assists in the prevention and control of various fungal-based conditions prevalent in
hot, humid climates of Asia, Africa and Central and South America.
Australian tea tree oil is also finding application as a natural deodorant in underarm
antiperspirants and deodorants. Usually concentrations of 2–3% are required together with
suitable perfume type fixatives to reduce the vapour pressure and extend time of effectiveness.
Products include aerosols, sticks, roll-ons, deo-sprays, and talcs.
HANDS
Protective barrier creams (1%) and treatment creams for hands and nails (3–5%) are both
applications for tea tree oil. In treatment creams, tea tree oil’s antifungal and anti-
inflammatory properties can be of great benefit to dry and cracked hands and nails.
FEET AND LEGS
The irritation caused by hair removal products for legs and bikini line—shave, wax and
depilatory creams—is substantially reduced by the addition or tea tree oil (1–2%).
Powders, creams and sprays containing tea tree oil (1–3%), can provide excellent
deodorancy and assist in prevention of ‘athletes foot’.
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DON PRIEST
206
NATURAL PRESERVATIVE
Finally, formulating tea tree oil into a product at 0.5% or greater may eliminate the need to
add a preservative. Studies previously reported by the author demonstrated that Main Camp
pharmaceutical grade tea tree oil could be successfully used in a range of formulations as a
natural preservative at 0.5% and meet the requirements of both the USP and BP Preservative
Challenge Tests.
SUMMARY
In summary, tea tree oil is an effective active ingredient due to its broad spectrum antimicrobial
properties, anti-inflammatory action and low toxicity. This versatile ingredient has a place
in cosmetic and personal care products from head to toe.
It is an active ingredient that happens to be natural—particularly suited to products for
problem skin. It is used in treatment products at higher concentration of 3–5% and as a
preventative, deodorant and natural preservative at lower concentrations (0.5–34%).
Modern plantation oil is pure, colourless and low in odour. It can be easily perfumed to
be virtually undetectable to the consumer or it can be left unperfumed to capitalise on its
natural clean, green, environmental image.
REFERENCES
Carson, C.F. and Riley, T.V. (1993) Anti-microbial activity of the essential oil of Melaleuca alternifolia.
Lett. Appl. Microbiol., 16, 49–55.
Tong, M.M., Altman, P.M. and Barnetson, R.St.-C. (1992) Tea tree oil in the treatment of Tinea pedis.
Australasian J. Dermatol., 33, 145–149.
Walsh, L.J. and Longstaff, J. (1987) The anti-microbial effects of an essential oil on selected oral
pathogens. Periodontology, 8, 11–15.
Copyright © 1999 OPA (Overseas Publishers Association) N.V. Published by license under the Harwood Academic Publishers imprint,
part of The Gordon and Breach Publishing Group.

207
12. FORMULATING FOR EFFECT
JAMES S.ROWE
Technical Consultancy Services Pty Ltd, Rockdale NSW, Australia
INTRODUCTION
The use of tea tree oil in Australia spans many centuries. There is evidence to show that
the leaves have been used by aborigines for thousands of years for a variety of ailments.
When Australia was discovered by the British, log book entries show the leaves were
used as an infusion or tea in an attempt to control the scurvy from which the first fleet
suffered and hence the name tea tree oil. Unfortunately Melaleuca leaves contain no
vitamin C but the name remained. In the 1920’s scientists became aware of its antiseptic
properties and it was issued to Australian Army personnel during the second world war.
With the discovery of antibiotics its use declined until recently. It has now been rediscovered
as an effective natural antiseptic with a wide variety of uses in the pharmaceutical and
personal care industry.
FEATURES OF TEA TREE OIL
Tea tree oil is a natural product, has a broad spectrum of activity and is environmentally safe
with a long history of use. It has excellent antiseptic and wound cleansing properties and a
low incidence of skin irritation. These features make it a versatile ingredient in
pharmaceuticals, cosmetics, toiletries, pet care and household sanitation.
The oil consists of a complex mixture with over one hundred fractions identified, consisting
of a mixture of monoterpenes, sesquiterpenes and terpene alcohols. The germicidal effect is
mainly due to terpinen-4-ol although other compounds may act synergistically. Research
indicates that the anti-microbial activity increases markedly as the terpinen-4-ol concentration
increases up to 35%, then marginally to 40% concentration. No further increase in activity
is observed at concentrations in excess of 40% terpinen-4-ol.
The Minimum Inhibitory Concentration (MIC) against commonly encountered gram
positive and negative bacteria is typically in the range of 0.5–1.0%. Tea tree oil exerts its
action by causing structural damage to the cell wall of the organism followed by
denaturation of the cell contents. Unlike antibiotics, there is no evidence of genetically
acquired immunity and the oil is effective in the presence of blood, pus, necrotic tissue
and mucous discharge.
Copyright © 1999 OPA (Overseas Publishers Association) N.V. Published by license under the Harwood Academic Publishers imprint,
part of The Gordon and Breach Publishing Group.

JAMES S.ROWE
208
FORMULATION CONSIDERATIONS
Selection of the Oil
Perhaps the most important consideration in the development of products containing tea
tree oil is to select an oil of suitable quality. It has been noted that the activity of the oil
depends in part on the terpinen-4-ol content. However high cineole levels have been
mistakenly associated with irritation of the mucous membranes. The chemical variants of
Melaleuca alternifolia have been described as low, intermediate and high cineole forms.
For optimal activity, only the low cineole level form should be utilised. On standing and
after exposure to light and air, the terpenes convert to p-cymene by an oxidative process.
Anti-oxidants should thus be considered in formulated products. The pure oil is a clear,
mobile liquid. If discolouration occurs then inferior distillation or contamination from the
holding vessel should be suspected. The presence of weed or other impurities in the harvest
will affect the colour. Odiferous compounds may also result from poor distillation techniques.
The factors most affecting the quality of the oil include post harvest factors such as the
conditions of the extraction process, the storage conditions of the oil and most importantly,
the formulation and storage of the formulated products. It is this latter consideration on
which I now wish to focus.
Solubilisation of Tea Tree Oil
Tea tree oil can be solubilised in water using a variety of surfactants. In our laboratories we
found it necessary to use four parts of polysorbate 20 to one part of tea tree oil to produce a
clear solution on subsequent dilution with water. This is in contrast to about one to one and
a half parts of the surfactant polyoxyl 35 castor oil. The method of preparation is of vital
importance. The method can be summarised as follows:
1.
The tea tree oil is first mixed with the surfactant and allowed to stand for several minutes.
2.
Add small aliquots of water gradually with constant stirring. This results in a thick gel
due to hydration.
3.
Further gradual additions of water result in a lowering of the viscosity and a clear liquid.
Should the initial addition of water be done too quickly or the tea tree oil not adequately
mixed, then at best an opalescent solution results.
The addition of polyhydroxy alcohols such as glycerol or propylene glycol can effect
solubilisation without having to go through the initial gelling phase. This can be achieved
by triturating the glycerol with the mixture of the surfactant and tea tree oil, prior to the
addition of water. The addition of alcohol to the formulation greatly enhances solubilisation
producing a clear solution. Typically a range of 5 to 10% alcohol is employed.
Effect of Solubiliser on Antimicrobial Activity
The effects of various surfactants and solubilising agents on the anti-microbial activity of a
range of disinfectant and antiseptic products have been well documented in the literature.
Copyright © 1999 OPA (Overseas Publishers Association) N.V. Published by license under the Harwood Academic Publishers imprint,
part of The Gordon and Breach Publishing Group.

FORMULATING
209
Our investigations aimed to determine the effect of varying the concentration of surfactants
on the anti-microbial activity of tea tree oil. The concentration of tea tree oil remained
constant at 0.5% and the surfactants were varied to achieve a ration of Oil: Surfactant of
between 1:1 to 1:5 on a weight to weight basis.
1.
Polyoxyl 35 castor oil had no effect on tea tree oil activity when used as the solublising
agent in the range of concentrations studied (up to 2.5% surfactant with 0.5% oil). All
formulations passed the British Pharmacopoeia (BP) Preservative Efficacy Test with
the exception of Aspergillus niger. All passed the United States Pharmacopoeia (USP)
Preservative Efficacy Test.
2.
Increasing the polysorbate 20: tea tree oil ratio from 1:1 to 5:1, decreased the activity
of tea tree. Higher levels of this surfactant result in failure of the BP/USP test for
some bacteria, yeasts and moulds.
These findings are in simple aqueous solution. In formulated products it can be anticipated
that the situation will be even more complex.
Effect of Oil Concentration on Antimicrobial Activity
In this series the surfactant was polyoxyl 35 castor oil at a constant concentration of 1.0% to
solubilise the tea tree oil. The oil concentration was varied between 0.1% and 1.0%. Again
simple aqueous solutions were prepared and subjected to a combined BP/ USP test.
A summary of the results is as follows:
Tea tree oil concentration
Result (combined BP/USP test)
0.1%
Fails some bacteria
Fails Candida and A. niger
0.3%
Passes bacteria
Passes Candida
Fails A. niger
0.5%
As for 0.3%
1.0%
As for 0.3%
These results indicate that in colloidal systems and formulated products the nature of the
surfactant employed is important with respect to the anti-microbial activity of the oil. It
appears that polyoxyl 35 castor oil is superior to polysorbate 20 in that less surfactant is
required to achieve satisfactory solubilisation of the oil and it has less effect on the anti-
microbial activity of the solubilised oil. Simple aqueous solutions of tea tree oil solubilised
with polyoxyl 35 castor oil will pass the USP Preservative Efficacy Test at a level of 0.3%.
This level of oil passes the BP test with the exception of A. niger as there was no two-log
reduction in the count in 14 days. Higher concentrations of tea tree oil up to 1.0% do not
appear to improve the activity against A. niger.
Effect of Other Additives on Antimicrobial Activity
Other commonly used excipients were examined for their effect on the anti-microbial activity
of tea tree oil. Simple 0.5% aqueous solutions, solubilised with polyoxyl 35 castor oil, were
Copyright © 1999 OPA (Overseas Publishers Association) N.V. Published by license under the Harwood Academic Publishers imprint,
part of The Gordon and Breach Publishing Group.

JAMES S.ROWE
210
again used. The materials examined included EDTA, oil of thyme, propylene glycol and
butylene glycol. All materials were examined in a range of concentrations, and it was found
that none of the materials examined had any observable effect on the anti-microbial activity
of the oil.

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