Registration Dossier

Data platform availability banner - registered substances factsheets

Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Toxicological information

Endpoint summary

Currently viewing:

Administrative data

Description of key information

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Non-GLP, near guideline study, available as unpublished report, acceptable with restrictions
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
GLP compliance:
no
Type of study:
guinea pig maximisation test
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Animal Breeding Unit, Imperial Chemical Industries PLC, Pharmaceuticals Division, Alderley Park, Macclesfield, Cheshire, UK
- Age at study initiation: 5-11 weeks
- Weight at study initiation: 354-579 g
- Housing: individually (2 per divided cage), in stainless steel and polycarbonate cages (370 mm x 320 mm x 200 mm)
- Diet: Labsure RGP Guinea Pig Diet ad libitum
- Water: ad libitum
- Acclimation period: at least 6 days

ENVIRONMENTAL CONDITIONS
- Temperature: approximately 21°C
- Humidity: approximately 55%
- Air changes: 20-30 per hr
- Photoperiod: 12hrs dark / 12hrs light

IN-LIFE DATES: January and February 1984
Route:
intradermal and epicutaneous
Vehicle:
corn oil
Concentration / amount:
intradermal induction 5.0% w/v; topical induction 100% (undiluted), challenge 50%, 25% and 5 % w/v, rechallenge 50% and 5%
Route:
epicutaneous, occlusive
Vehicle:
corn oil
Concentration / amount:
intradermal induction 5.0% w/v; topical induction 100% (undiluted), challenge 50%, 25% and 5 % w/v, rechallenge 50% and 5%
No. of animals per dose:
20 test and 10 control animals (plus 10 additional controls used for rechallenge)
Details on study design:
RANGE FINDING TESTS: up to 2 dose levels tested on groups of 2 or more guinea pigs to determine dose levels for main study.

MAIN STUDY
A. INDUCTION EXPOSURE (test animals)
- No. of exposures / exposure period: 3 pairs of intradermal injections (0.1 mL each) per guinea pig as follows: (i) Freund's complete adjuvant plus corn oil (1:1), (ii) 5% w/v Aromasol H in corn oil, (iii) 5% w/v Aromasol H, followed one week later by topical application of 0.25 mL of undiluted Aromasol H for 48 hours under an occlusive dressing
- Site: scapular region

INDUCTION EXPOSURE (control animals)
- No. of exposures / exposure period: 3 pairs of intradermal injections (0.1 mL each) per guinea pig as follows: (i) Freund's complete adjuvant plus corn oil (1:1), (ii) corn oil, (iii) Freund's complete adjuvant plus corn oil (1:1), the topical applications were as above except that nothing was applied to the skin
- Site: scapular region

B. CHALLENGE EXPOSURE (test and control animals)
- No. of exposures / exposure period: single 24 hour application of 0.05-0.1 mL of each of a 50%, 25% and 5% solution of Aromasol H in corn oil
- Day(s) of challenge: two weeks after topical induction application
- Site: shorn flank
- Evaluation (hr after challenge): 24 and 48 hours

C. RECHALLENGE EXPOSURE:
- No. of exposures / exposure period: single 24 hour application of 0.05-0.1 mL of each of a 50% and 5% solution of Aromasol H in corn oil
- Day(s) of challenge: 7 days after first challenge
- Site: shorn flank (different from area used for initial challenge)
- Evaluation (hr after challenge): 24 and 48 hours
- A fresh group of 10 negative controls (previously injected with Freund's complete adjuvant) were used
Positive control substance(s):
not specified
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
50%
No. with + reactions:
7
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 50%. No with. + reactions: 7.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
50%
No. with + reactions:
1
Total no. in group:
20
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 50%. No with. + reactions: 1.0. Total no. in groups: 20.0.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
50%
No. with + reactions:
3
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 50%. No with. + reactions: 3.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
50%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 50%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
25%
No. with + reactions:
3
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 25%. No with. + reactions: 3.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
25%
No. with + reactions:
2
Total no. in group:
20
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 25%. No with. + reactions: 2.0. Total no. in groups: 20.0.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
25%
No. with + reactions:
1
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 25%. No with. + reactions: 1.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
25%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 25%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
5%
No. with + reactions:
11
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 5%. No with. + reactions: 11.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
5%
No. with + reactions:
10
Total no. in group:
20
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 5%. No with. + reactions: 10.0. Total no. in groups: 20.0.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
5%
No. with + reactions:
1
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 5%. No with. + reactions: 1.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
5%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 5%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
other: rechallenge 1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
50%
No. with + reactions:
9
Total no. in group:
20
Remarks on result:
other: Reading: other: rechallenge 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 50%. No with. + reactions: 9.0. Total no. in groups: 20.0.
Reading:
other: rechallenge 2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
50%
No. with + reactions:
6
Total no. in group:
20
Remarks on result:
other: Reading: other: rechallenge 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 50%. No with. + reactions: 6.0. Total no. in groups: 20.0.
Reading:
other: rechallenge 1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
50%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: other: rechallenge 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 50%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
other: rechallenge 2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
50%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: other: rechallenge 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 50%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
other: rechallenge 1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
5%
No. with + reactions:
8
Total no. in group:
20
Remarks on result:
other: Reading: other: rechallenge 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 5%. No with. + reactions: 8.0. Total no. in groups: 20.0.
Reading:
other: rechallenge 2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
5%
No. with + reactions:
7
Total no. in group:
20
Remarks on result:
other: Reading: other: rechallenge 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 5%. No with. + reactions: 7.0. Total no. in groups: 20.0.
Reading:
other: rechallenge 1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
5%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: other: rechallenge 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 5%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
other: rechallenge 2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
5%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: other: rechallenge 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 5%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Interpretation of results:
Category 1 (skin sensitising) based on GHS criteria
Conclusions:
Aromasol H appeared to be a sensitiser to guinea pig skin. The response may have been due to irritation.
Executive summary:

Guinea pigs were challenged with 5 % Aromasol H in corn oil, with occlusion. Following challenge with either a 50 % or 25 % preparation in corn oil, a weak sensitisation response was elicited but irritation was also noted. The animals were rechallenged 7 days later with either a 50 % or a 5 % preparation in corn oil and a moderate sensitisation response was recorded.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

There is no information on sensitisation in humans after exposure to trimethylbenzenes.

In animals a key study is provided by Shell Toxicology Laboratory (1977). Guinea pigs were challenged with Shellsol A (a mixture of trimethylbenzenes CAS No 64742 -95 -6) in a maximization test. No sensitisation response was elicited immediately, 24 or 48 hours after the challenge. The test was therefore negative. This result is supported by a poorly reported guinea pig maximization test (IUCLID 4 record; EBSI, 1983) where no sensitisation occurred after exposure to 1,2,4-trimethylbenzene (study unavailable).

In contrast, dermal responses were reported when Aromasol H (a mixture of C8 aromatics (xylenes and benzenes), C9 aromatics (trimethylbenzenes and ethyl toluenes), and C10 aromatics (diethyl ethyl benzenes and diethyl benzenes)) was tested in a guinea pig maximization test (CTL1984). The study report concluded that Aromasol H was a weak sensitizer but irritation was also noted. Irritation has been reported to be a factor in false positive results obtained on other substances in the guinea pig maximization test (Basketter, 2008). The substituted aromatics present in Aromasol H are known to be non-sensitising, hence the weight of evidence therefore indicates that this result is a false positive.

In conclusion, the available evidence indicates that 1,3,5-trimethylbenzeneis not a skin sensitiser.

References

Basketter D (2008). Information derived from sensitization test methods: Test sensitivity, false positives, and false negatives. Reg. Tox. Pharm. 50, 68–169.

Migrated from Short description of key information:

A weight of evidence evaluation indicates that of 1,3,5- trimethylbenzene is not-sensitising. Two guinea pig maximization tests with mixtures containing trimethylbenzenes were negative. One study gave a positive result but this is believed to be a false positive due to irritation.

Justification for selection of skin sensitisation endpoint:

Results from a guinea pig maximisation test performed using trimethylbenzenes indicate that 1,3,5-trimethylbenzene is unlikely to induce or elicit skin sensitisation

Justification for classification or non-classification

1,3,5-Trimethylbenzene is not considered to be sensitizing. It does not therefore warrant classification under DSD or CLP.