Registration Dossier

Diss Factsheets

Toxicological information

Skin sensitisation

Currently viewing:

Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Remarks:
Human Repeat Insult Patch Test
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
Non relevant
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods
Cross-referenceopen allclose all
Reason / purpose for cross-reference:
reference to same study
Reference
Endpoint:
sensitisation data (humans)
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions
Remarks:
Study performed in humans, in the Department of Dermatology of St John's Hospital for Diseases of the Skin in London.
Reason / purpose for cross-reference:
reference to other study
Type of sensitisation studied:
skin
Study type:
study with volunteers
Principles of method if other than guideline:
Not reported
GLP compliance:
no
Type of population:
not specified
Ethical approval:
not specified
Subjects:
Among the 5315 consecutive patients tested with the ICDRG perfume mixture:
- 86 tested with 35 essential oils
- 42 tested with the individual ingredients
Clinical history:
Not specified
Route of administration:
dermal
Details on study design:
Tests were performed with the ICDRG perfume mixture containing 1 essential oil and 7 other fragrance substances in 5315 consecutive patients at St John's Hospital for Diseases of the Skin in London and the results were positive in 299 (5.6%).
Among these 299 persons, 86 were tested with 35 essential oils (Rudzki et al., 1976).
The 42 patients positive to the perfume mixture were then tested with the individual ingredients.
Results of examinations:
- Of the 86 persons tested with 35 essentiel oils, 49 (56.9%) reacted to 1 or more essential oils, and 15 (30.6%) reacted to more than 3 oils. Positive tests were observed most frequently with cassia oil (24), oak-moss absolute (14), and clove oil (12 subjects). 3 subjects were positive to German chamomile essential oil. None were positive to bergamot or sassafras oils. The results are shown in Table 1
- Of the 42 patients positive to perfume mixture tested with the individual ingredients, most of the patients had a positive reaction to eugenol, isoeugenol and cinnamic aldehyde.
- Among the patients tested recently (1640 subjects: 890 women and 750 men) from January 1985 to May 1986, the % positive to the perfume mixture was higher than in previous years. 9.32% of all patients were positive (10.6% women and 7.7% men). In these 1640 persons, tests with balsam of Peru, turpentine, wood tar, colophony, propolis and the mixture of cassia and citronella oils are much more frequent in patients positive to the perfume mixture than in those who are negative.
See 'any other information on results incl. tables'.

Table 7.10.4/1: Sensitivity to essential oils in perfume mixture - positive patients

Essential oils

No. Positive

% of positives

Sandalwood

2

2.3

Lavender

3

3.4

Cassia

24

27.9

Thyme

4

4.6

Oak-moss absolute

14

16.2

Juniper berries

6

6.9

Calamus

7

8.1

Coriander

3

3.4

Zdrawetz concrete

4

4.6

Sweet orange

3

3.4

Petitgrain bigarade

7

8.1

Peppermint

6

6.9

Clary sage

4

4.6

Petitgrain Paraguay

4

4.6

Abies alba

2

2.3

Cananga

10

11.6

Lavandin

4

4.6

Pine needle

3

3.4

Guaiac wood

1

1.1

Vetiver

9

10.4

Spike

8

9.3

Clove

12

13.3

Angelica root

2

2.3

Rosemary

3

3.4

Bitter orange

2

2.3

German chamomile

3

3.4

Lemon

2

2.3

Himalayan cedarwood

3

3.4

Eucalyptus

1

1.1

Geranium

2

2.3

Citronella

1

1.1

Litsea cubeba

7

8

Ylang-ylang

8

9.3

Sassafras

0

-

Bergamot

0

-

Table 7.10.4/2: Sensitivity to ingredients of the perfume mixture in 42 persons

Ingredient

Positive

Eugenol

25

Isoeugenol

19

Cinnamic aldehyde

16

Geraniol

10

Cinnamic alcohol

10

Oakmoss absolute

7

Hydroxycitronellal

6

Amyl cinnamic alcohol

6
Conclusions:
In this study, German chamomile essential oil is a potential skin sensitizer for humans (3.4% positive tests).
Executive summary:

After a first experiment using a perfume mixture (ICDRG) containing 1 essential oil and 7 other fragrance substances, a group of 86 humans were tested with essential oils and 42 with individual ingredients at St John's Hospital for Diseases of the Skin in London.

Among the 86 positive patients to the perfume mixture, 3 (3.4%) showed a positive response to German chamomile.

Reason / purpose for cross-reference:
reference to same study
Reference
Endpoint:
sensitisation data (humans)
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions
Type of sensitisation studied:
skin
Study type:
study with volunteers
Principles of method if other than guideline:
Not reported
GLP compliance:
no
Type of population:
not specified
Ethical approval:
not specified
Subjects:
- Number of subjects exposed:
- first group: 200 consecutive patients with dermatitis
- second group: 50 other subjects positive to one or more of four balsms (which comprised balsam of Peru, wood tars, colophony and turpentine)
Clinical history:
Dermatitis patients and other subjects positive to one or more of four balsms (which comprised balsam of Peru, wood tars, colophony and turpentine)
Route of administration:
dermal
Details on study design:
All the patients were tested with the 35 essential oils which were used at a concentration of 2 % in yellow soft paraffin.
Results of examinations:
- From the among 35 essential oils tested on 200 consecutive patients, 28 (14%) gave positive results. The largest number of patients was sensitive to citronella oil (5) and in diminishing order to ylang ylang (4), bitter orange, bergamot, Himalayan cedarwood, eucalyptus, geranium and litsea cubeba oil (3). One or to patients reacted to the remaining oils.
- In addition, frequent reactions were observed to star anis oil; but on account of some of its properties this oil will be the subject of a separate communication. Of the remaining seven oils to which the patients did not react, four (sandalwood,lavender, thyme and guaiac wood oil) gave positive results in the additional group of subjects sensitive to balsams.
- No patient reacted to calamus, sassafras or rosemary oil. It should be stressed that sandalwood, thyme and guaiac wood oils are used in Polish cosmetics in relatively small amounts, whereas lavender and sassafras oils are used in large quantities.
- Of the 200 consecutive patients, 187 were negative to all four balsams. Among the latter, 11 were positive to 1, 2, or 3 oils. This could not be suspected on the basis of tests with the standard series. Nevertheless, all subjects who were positive to more than three oils (5, 7 and 15) were also positive to balsams.
About half of the patients who are positive to each of the four balsams are also positive to one or several essential oils (Tables 2 to 5), the positive results with these oils showing a somewhat better agreement with the reaction to turpentine (Table 3) than with balsam of Peru (Table 2).
- Of the 20 patients positive to balsam of Peru and negative to other balsams, 12 reacted to one or more essential oils; seven were positive to cassia oil (Table 2). This may have been because 80-90 % of this oil consists of cinammic aldehyde noted that 68 % of persons positive to balsam of Peru reacted to 5 % cinammic aldehyde and 21 % of such subjects to a 2 % concentration. Thus, cinammic aldehyde could be the cause of simultaneous reactions to these substances. Subjects sensitive to balsam of Peru react less frequently to the remaining essential oils, with the exception of clove oil to which three patients were positive (Table 2).
- Of the 23 patients positive to turpentine and negative to other balsams, 15 reacted to some oils (Table 3). Twelve of these 15 reacted to pine needle oil and eight to abies alba oil. Both these oils contain alphapinene, but only pine needle oil contains delta-3-carene which is interesting in the light of views on turpentine allergens.
See 'any other information on results incl. tables'.

Table 7.10.4/1: Positive reactions to essential oil in 200 patients related to the 187 negative reactors to balsams

Essential oils

Number of positive reactions in 200 patients

Number of positive reactions in 187 patients with negative reactions to balsam

Cassia

2

1

Oak moss

1

1

Juniper

1

0

Zdrawetz

1

1

Coriander

2

0

Sweet orange

1

0

Petitgrain bigarade

1

0

Peppermint

1

1

Clary sage

1

0

Petitgrain Paraguay

1

0

Abies alba

2

0

Cananga

1

1

Lavandin

1

0

Pine needle

4

0

Vetiver

1

0

Spike

1

0

Clove

2

1

Angelica

2

1

Bitter orange

3

1

Bergamot

3

2

Chamomile

1

0

Lemon

1

0

Cedarwood

3

1

Eucalyptus

3

1

Geranium

3

2

Citronella

5

4

Litsea cubeba

3

1

Ylang-ylang

4

3

Table 7.10.4/2: Positive tests to essential oils related to positive reactions to balsam of Peru

Essential oils

Positive reactions of patients positive to balsam of Peru only (20)

Positive reactions of all patients positive to balsam of Peru (31)

Cassia

7

9

Thyme

1

1

Oak moss

1

1

Juniper

1

1

Zdrawetz

0

1

Coriander

1

1

Peppermint

0

1

Clary sage

1

2

Abies alba

1

2

Pine needle

1

4

Vetiver

0

1

Spike

0

1

Clove

3

5

Chamomile

0

1

Lemon

0

1

Geranium

1

1

Citronella

0

3

Litsea cubeba

0

1

Ylang-ylang

1

1

Table 7.10.4/3: Positive tests to essential oils related to turpentine reactions

Essential oils

Positive reactions in patients positive to turpentine only (23)

Positive reactions in all patients positive to turpentine (31)

Lavender

1

1

Cassia

3

5

Oak moss

1

1

Juniper

1

1

Coriander

1

1

Sweet orange

1

1

Petitgrain bigarade

2

2

Abies alba

8

9

Cananga

1

1

Pine needle

13

14

Guaiac wood

1

1

Vetiver

1

1

Spike

1

1

Clove

0

1

Angelica

1

1

Bitter orange

3

3

Bergamot

1

1

Chamomile

1

2

Lemon

1

2

Cedarwood

3

3

Eucalyptus

2

2

Geranium

1

1

Citronella

1

2

Litsea cubeba

1

1

Ylang-ylang

1

1

Table 7.10.4/4: Positive tests to essential oils related to colophony reactions

Essential oils

Positive reactions to essential oils in patients positive to colophony only (4)

Positive reactions to essential oils in all patients positive to colophony (7)

Sandalwood

1

1

Cassia

0

2

Zdrawetz

0

1

Sweet orange

1

1

Peppermint

0

1

Clary sage

1

2

Pine needle

1

2

Guaiac wood

1

1

Vetiver

1

2

Spike

0

1

German chamomile

1

1

Citronella

0

1

Litsea cubeba

1

2

Table 7.10.4/5: Positive tests to essential oils related to wood tars sensitivity

Essential oils

Nuumber of positive reactions to essential oils in patients positive to wood tars only (4)

Number of positive reactions to essential oils in all patients positive to wood tars (11)

Cassia

0

1

Coriander

2

2

Clary sage

2

2

Petitgrain Paraguay

1

1

Lavandin

1

1

Pine needle

0

1

Clove

0

1

Citronella

1

2

Ylang-ylang

1

1

Other oils

0

0

Table 7.10.4/6: Number of patients reacting to none or more than one of the 35 essential oils tested related to the various groups of balsam reactors

 

Patients positive to none or more than one oil

200 + 50 patients

0

1

2

3

4

5

6

7

8

9

15 oils

200 patients

183

6

2

6

0

1

0

1

0

0

1

Negative to balsams (187)

176

5

1

5

0

0

0

0

0

0

0

All balsam of Peru reactors (31)

13

12

3

0

0

1

1

0

0

1

0

Positive to balsam of Peru only (20)

8

9

2

0

0

0

1

0

0

0

0

All turpentine reactors (31)

12

8

4

2

0

3

0

1

0

0

1

Positive to turpentine only (23)

8

5

4

2

0

2

0

1

0

0

1

All wood tars reactors (11)

6

2

1

1

0

1

0

0

0

0

0

Positive to wood tars only (4)

2

0

0

1

0

1

0

0

0

0

0

All colophony reactors (7)

3

1

0

1

0

1

0

0

0

1

0

Positive to colophony only (4)

2

0

0

1

0

1

0

0

0

0

0
Conclusions:
In this study, German chamomile essential oil at concentration of 2% is a potential skin sensitiser for humans.
Executive summary:

Two hundred consecutive patients and 50 subjects positive to balsams were tested with the 35 essential oils most frequently used in Polish cosmetics. The essential oils were tested at concentration of 2% in yellow soft paraffin.

The frequency of sensitivity to the particular oils is noted and the index of sensitization calculated as the amount of oil/kg used annually for the production of Polish cosmetics per one patient positive to this oil.

The correlation of positive tests to essential oils with positive tests to four balsams of the standard series is shown.

The fact that the amount of oils per one positive test is smallest in the case of German camomile oil may be the result of frequent application in Poland of camomile compresses. An example of 'false cross-reaction' is probably responsible for simultaneous sensitivity to turpentine and pine needle oil.

Reason / purpose for cross-reference:
reference to same study
Reference
Endpoint:
sensitisation data (humans)
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions
Type of sensitisation studied:
skin
Study type:
study with volunteers
Principles of method if other than guideline:
Not reported
GLP compliance:
no
Type of population:
not specified
Ethical approval:
not specified
Subjects:
- Number of subjects exposed: 450 patients with dermatitis
Clinical history:
Dermatitis patients
Route of administration:
dermal
Details on study design:
The standard series (comprising beside balsam of Peru, colophony, turpentine and wood tards) and 35 essential oils used in 2% concentration in yellow soft paraffin were tested on 450 patients with dermatitis.
Results of examinations:
- From among 450 patients 106 were positive to one or more essential oils.
Of these 106 patients only 32 were positive to balsam of Peru and 74 were negative. Table 1 shows the results of skin tests with 35 essential oils of all the patients and of those positive and negative to balsam of Peru. All patients were negative only to sassafras oil. From among those sensitive to 10 oils not one patient reacted to balsam of Peru, and only among the patients sensitive to 3 oils - thyme, clove and ylang ylang - more than half were positive to balsam of Peru. Table 2 indicates to how many oils patients negatively or positively reacted to this contactant. As seen in table 2, patients reacting to as many as 15 and 16 essential oils were netagive to balsam of Peru.
- From among 74 patients positive to one or more esesntial oils and negative to balsam of Peru, 40 were positive to other balsams. Talble 3 shows that among the subjects sensitive to as many as 22 oils, more than half were positive to other balsams. It results from Table 4 that all those positive ro more than 5 essential oils are also positive to other balsams.
- Among subjects negative to all the 4 balsams, those positive to cassia oil ans citronella oil were mort numerous. Table 5 gives the results of patch tests with other essential oils in patients positive and negative to both these oils and table 6 indicates to how many oils these subjects reacted.

Table 7.10.4/1: Positive reactions to essential oils

Oils

Positive reactions in

All patients

Positive to balsam of Peru

Negative to balsam of Peru

Sandalwood

5

1

4

Lavender

1

-

1

Cassia

43

15

28

Thyme

4

3

1

Oak moss absolute

7

2

5

Juniper berries

6

3

3

Calamus

1

-

1

Coriander

4

1

3

Zdrawetz concrete

4

2

2

Sweet orange

3

1

2

Petitgrain bigarade

3

-

3

Peppermint

7

3

4

Clary sage

8

3

5

Petitgrain Paraguay

1

-

1

Abies alba

13

2

11

Cananga

6

-

6

Lavandin

3

1

2

Pine needle

35

7

28

Guaiac wood

4

1

3

Vetiver

7

2

5

Spike

6

2

4

Clove

15

10

5

Angelica root

3

-

3

Rosemary

3

-

3

Bitter orange

6

-

6

Bergamot

5

1

4

German chamomile

5

2

3

Lemon

4

1

3

Cedarwood

6

-

6

Eucalyptus

5

-

5

Geranium

12

2

10

Citronella

24

8

16

Litsea cubeba

13

2

11

Ylang-ylang

9

5

4

Table 7.10.4/2: Reactions to none or more than one of the 35 essential oils in all patients tested

 

Patients positive to none or more than one oil

Patients

0

1

2

3

4

5

6

7

8

9

10

13

15

16

All patients

344

57

17

14

2

9

2

1

 

1

 

1

1

1

Positive to balsam of Peru

31

20

4

1

 

3

2

 

 

1

 

1

 

 

Negative to balsam of Peru

313

37

13

13

2

6

 

1

 

 

 

 

1

1

Table 7.10.4/3: Positive reactions to essential oils in patients negative to balsam of Peru

Oils

Patients

Positive to one or more of the other three balsams

Negative to all four balsams

Sandalwood

2

2

Lavender

1

-

Cassia

19

9

Thyme

-

1

Oak moss absolute

3

2

Juniper berries

2

1

Calamus

1

-

Coriander

3

-

Zdrawetz concrete

1

1

Sweet orange

2

-

Petitgrain bigarade

3

-

Peppermint

3

1

Clary sage

5

-

Petitgrain Paraguay

1

-

Abies alba

10

1

Cananga

2

4

Lavandin

1

1

Pine needle

28

-

Guaiac wood

3

-

Vetiver

5

-

Spike

3

1

Clove

3

2

Angelica root

1

2

Rosemary

1

2

Bitter orange

4

2

Bergamot

1

3

German chamomile

3

-

Lemon

3

-

Cedarwood

4

2

Eucalyptus

2

3

Geranium

3

7

Citronella

8

8

Litsea cubeba

6

5

Ylang-ylang

1

3

Table 7.10.4/4: Reactions to none or more than one of the 35 essential oils in patients negative to balsam of Peru

 

Patients positive to none or more than one oil

Patients

0

1

2

3

4

5

6

7

15

16

Positive to one or more of other three balsams

26

16

10

6

 

5

2

1

1

1

Negative to all four balsams

287

21

3

7

2

1

 

 

 

 

Table 7.10.4/5: Positive reactions to essential oils in patients negative to all four balsams

Oils

Patients

Positive to citronella oil

Negative to citronella oil

Positive to cassia oil

Negative to cassia oil

Sandalwood

 

2

 

2

Cassia

1

8

9

25

Thyme

 

1

 

1

Oak moss absolute

 

1

 

1

Juniper berries

 

1

 

1

Zdrawetz concrete

1

 

 

1

Peppermint

1

 

 

1

Cananga

1

3

1

3

Lavandin

 

1

 

1

Spike

 

1

 

1

Clove

 

2

 

2

Angelica root

 

2

 

2

Rosemary

 

2

 

2

Bitter orange

 

2

 

2

Bergamot

 

3

 

3

Cedarwood

 

2

 

2

Eucalyptus

 

3

 

3

Geranium

2

5

1

6

Citronella

8

26

1

7

Litsea cubeba

2

3

1

4

Ylang-ylang

1

2

 

3

Table 7.10.4/6: Reactions to none or more than one of the 35 essential oils, patients negative to all four balsams

 

Patient positive to none or more than one oil

Patients

0

1

2

3

4

Positive to citronella oil

3

1

3

 

1

Negative to citronella oil

 

18

1

5

2

Positive to cassia oil

8

 

 

 

1

Negative to cassia oil

 

13

3

7

2
Conclusions:
In this study, German chamomile essential oil is a potential skin sensitizer for humans.
Executive summary:

The standard series and 35 essential oils were tested on 450 patients with dermatitis. It was found that those simultaneously sensitive to essential oils are more frequently negative than positive to balsam of Peru. The remaining 3 balsams, however (colophony, turpentine and wood tars), are also screening agents for essential oils. All four balsams reveal sensitivity to essential oils in most of the subjects tested.

In patients negative to all 4 balsams of the standard series, attempts to find an essential oil with which tests would be simultaneously frequently positive with those for other essential oils failed.

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Unnamed
Year:
1976
Reference Type:
publication
Title:
Unnamed
Year:
1986
Reference Type:
publication
Title:
Unnamed
Year:
1977

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Non specified
GLP compliance:
no
Type of study:
other: Human Repeat Insult Patch Test
Justification for non-LLNA method:
Available publications

Test material

Constituent 1
Reference substance name:
Matricaria recutita, ext.
EC Number:
282-006-5
EC Name:
Matricaria recutita, ext.
Cas Number:
84082-60-0
Molecular formula:
Not relevant, UVCB substance
IUPAC Name:
Essential oil of Matricaria recutita (Asteraceae) obtained from flower tops by steam distillation of Egypt origin

In vivo test system

Test animals

Species:
other: Human
Strain:
other: Non relevant
Sex:
male/female
Details on test animals and environmental conditions:
Refer to point 7.10.4

Results and discussion

Positive control results:
Non performed

In vivo (non-LLNA)

Resultsopen allclose all
Key result
Group:
test chemical
Remarks on result:
positive indication of skin sensitisation
Reading:
other: Non performed, non documented
Group:
negative control
Remarks on result:
not measured/tested
Reading:
other: Non performed, non documented
Group:
positive control
Remarks on result:
not measured/tested

Applicant's summary and conclusion

Interpretation of results:
Category 1B (indication of skin sensitising potential) based on GHS criteria
Conclusions:
Refer to point 7.10.4
Executive summary:

Refer to point 7.10.4