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Description of key information

Sensitising to skin (OECD TG 406, Schoch 1987)

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
11 May 1987 to 02 July 1987
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
This study was performed to meet the regulatory data requirements under a different legislation long before REACH came into force.
Species:
guinea pig
Strain:
Pirbright-Hartley
Sex:
not specified
Details on test animals and environmental conditions:
TEST ANIMALS
- Source of test animals: Animal Production, Ciba-Geigy Ltd., Stein, Switzerland
- Age at study initiation: circa 10 weeks
- Weight at study initiation: 300 to 398 g
- Housing: conventional laboratory caging, not otherwise specified

IN-LIFE DATES: From: 11.05.1987 To: 02.07.1987
Route:
intradermal
Vehicle:
other: Test substance was dissolved in 20% propylene glycol and 80% physiological saline. During second and third week of induction, a mixture of the normal vehicle with complete Bacto adjuvant in a ratio 1:1 was used.
Concentration / amount:
0.1% test substance applied in 0.1 mL solution
Day(s)/duration:
Every second day (except weekends), in total 10 intracutaneous injections
Adequacy of induction:
not specified
No.:
#2
Route:
epicutaneous, occlusive
Vehicle:
other: Vaseline
Concentration / amount:
1%
Day(s)/duration:
10 days after the intradermal challenge injection
Adequacy of challenge:
other: Sub-irritant dose
No.:
#1
Route:
intradermal
Vehicle:
other: 20% propylene glycol plus 80% physiological saline
Concentration / amount:
0.1% of test material dissolved in vehicle
Day(s)/duration:
14 days after after the last injection during induction period.
Adequacy of challenge:
not specified
No. of animals per dose:
20 test animals for intracutaneous challenge
10 controls and 20 test animals for epicutaneous challenge


Details on study design:
MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 10
- Exposure period: three weeks
- Test groups: 20 animals for intracutaneous challenge and 20 animals for epicutaneous challenge
- Control group: 10 animals
- Site: Dorsum of guinea pig
- Frequency of applications: 10 intracutaneous injections - the first three without adjuvant and seven including adjuvant
- Duration: Injections made every second day
- Concentrations: 0.1%


B. CHALLENGE EXPOSURE
- No. of exposures: Two. An intracutaneous challenge was made 14 days after last induction injection, into the left flank. Ten days later an epicutaneous challenge was applied (topical exposure for 24 hours) under an occlusive dressing
- Day(s) of challenge:
- Exposure period:
- Test groups:
- Control group:
- Site:
- Concentrations: 0.1% and 1% for intracutaneous and epicutaneous challenges respectively
- Evaluation (hr after challenge): Reactions evalauted 24 hours after intracutaneous challenge and 24 and 48 hours after epicutaneous challenge


OTHER:
Challenge controls:
Concomitant control animals were treated with the vehicle only. The sensitivity of the test system was tested in an independent test every 6 months using Paraphenylene-diamine or Potassium dichromate as positive controls.
Positive control substance(s):
no
Positive control results:
The sensitivity of the test system was tested at six monthly intervals with paraphenylene-diamine or potassium dichromate. Historical positive control study results are not presented but the methods are assumed to be validated by the six-monthly positive control assessments.
Group:
positive control
Remarks on result:
not measured/tested
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
Not applicable
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
No relevant clinical signs observed.
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
Not applicable
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
No relevant clinical signs observed.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
1%
No. with + reactions:
20
Total no. in group:
20
Clinical observations:
No relevant clinical signs observed.
Remarks on result:
positive indication of skin sensitisation
Remarks:
Epicutaneous challenge
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
1%
No. with + reactions:
20
Total no. in group:
20
Clinical observations:
No relevant clinical signs observed.
Remarks on result:
positive indication of skin sensitisation
Remarks:
Epicutaneous challenge
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
Not applicable
No. with + reactions:
1
Total no. in group:
20
Clinical observations:
No relevant clinical signs observed.
Remarks on result:
no indication of skin sensitisation
Remarks:
Intradermal injection challenge
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
0.1%
No. with + reactions:
2
Total no. in group:
20
Clinical observations:
No relevant clinical observations reported.
Remarks on result:
no indication of skin sensitisation
Remarks:
Intradermal injection challenge
Interpretation of results:
sensitising
Conclusions:
Cloquintocet-mexyl was found to have skin sensitising potential in the guinea pig (optimization test).
Executive summary:

The skin sensitising properties of the substances were tested under GLP to OECD TG 406 in an open epicutaneous maximisation test for sensitising potential. Guinea Pigs were allocated to control and test groups. In the induction phase, 0.1% test substance in 20% propylene glycol + 80% physiological saline was injected into the skin of the dorsum on three occasions in week 1. During the second and third week of the induction period, the test article was admixed to the vehicle and complete Freund’s adjuvant (1:1 v/v). A further 7 injections were administered every other day to give a total induction injection schedule of ten injections. Intracutaneous challenge was done with an injection of 0.1% test substance in 20% propylene glycol + 80% physiological saline 14 days after the last induction injection. There was no significant statistical difference of responses between the vehicle control group and the test group. A second, epicutaneous challenge was done 10 days after the intradermal injection challenge. 1% of the test article in vaseline was applied to the skin of the animals in the test group and was kept under occlusion for 24 hours. It was shown in a pretest that this was the highest non-irritating concentration. All animals treated treated in this way showed positive skin reactions in the skin readings after 24 and 48 hours. Cloquintocet-mexyl was found to be a skin sensitiser in this skin sensitisation maximisation test.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)
Additional information:

Cloquintocet-mexyl has been tested in a maximisation study in guinea pigs conducted according to OECD test guideline 406 (Schoch M, 1987). Groups of 20 guinea pigs were treated with 0.1% cloquintocet-mexyl for induction and challenged with 1% cloquintocet-mexyl. All 20 guinea pigs in the treated group showed a positive reaction 24 and 48 hours after challenge. Cloquintocet-mexyl was found to be a skin sensitiser.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Data on cloquintocet-mexyl indicate that it causes an allergic skin reaction in guinea pigs and should therefore be classified as a sensitiser by skin contact under Regulation (EC) 1272/2008, Annex I, Part 3, 3.4.2.2.

There are no data on the respiratory sensitisation potential of cloquintocet-mexyl.

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