Registration Dossier

Administrative data

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:
other: GLP compliant, guideline study, available as unpublished report, no restrictions, fully adequate for assessment
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1987
Report Date:
1987

Materials and methods

Test guideline
Qualifier:
according to
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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): CGA185072 technical
- Analytical purity: 91.6%

In vivo test system

Test animals

Species:
guinea pig
Strain:
Pirbright-Hartley
Sex:
not specified
Details on test animals and environmental conditions:
TEST ANIMALS
- 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

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
epicutaneous, open
Vehicle:
other: Induction phase 20% propylene glycol and 80% physiological saline (plus Freund's complete adjuvant during 2nd and 3rd weeks). For intracutaneos challenge - 20% propylene glycol and 80% physiological saline. For epicutaneous challenge - vaseline
Concentration / amount:
0.1% for induction phase
0.1% for intradermal challenge
1% for epicutaneous challenge
Challengeopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
other: Induction phase 20% propylene glycol and 80% physiological saline (plus Freund's complete adjuvant during 2nd and 3rd weeks). For intracutaneos challenge - 20% propylene glycol and 80% physiological saline. For epicutaneous challenge - vaseline
Concentration / amount:
0.1% for induction phase
0.1% for intradermal challenge
1% for epicutaneous challenge
No. of animals per dose:
20 test animals for intracutaneous challenge
10 controls and 20 test animals for epicutaneous challenge


Details on study design:
RANGE FINDING TESTS: no data


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 every 6 months using Paraphenylene-diamine or Potassium dichromate as positive controls.
Positive control substance(s):
yes
Remarks:
See challenge controls above

Results and discussion

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 posiitive control assessments.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
1%
No. with + reactions:
1
Total no. in group:
10
Clinical observations:
None
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 1%. No with. + reactions: 1.0. Total no. in groups: 10.0. Clinical observations: None.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
1%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
None
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 1%. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: None.
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
1%
No. with + reactions:
20
Total no. in group:
20
Clinical observations:
Erythema
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 1%. No with. + reactions: 20.0. Total no. in groups: 20.0. Clinical observations: Erythema.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
1%
No. with + reactions:
20
Total no. in group:
20
Clinical observations:
Erythema
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 1%. No with. + reactions: 20.0. Total no. in groups: 20.0. Clinical observations: Erythema.

Any other information on results incl. tables

Table 1: Cloquintocet-mexyl - Optimization test - Number of animals with signs of allergic skin reactions

Control group

Test group

Scored after

24 h

48 h

24 h

48 h

Intradermal challenge

- Vehicle control

- Cloquintocet-mexyl


1/20
not tested


not tested

2/20

Epicutaneous challenge

- Vehicle control

- Cloquintocet-mexyl


0/10

1/10


0/10

0/10


0/20

20/20


0/20

20/20

After epicutaneous challenge a number of females in the test group also had oedema, 3 after 24 hours and 2 after 48 hours.

Maximum erythema score 2 (maximum possible 4)

Maximum edema score 1 (maximum possible 4)

Applicant's summary and conclusion

Interpretation of results:
sensitising
Remarks:
Migrated information
Conclusions:
Cloquintocet-mexyl was found to have skin sensitising potential in the guinea pig (optimization test), 20/20 responded positively to the epicutaneous challenge.
Executive summary:

CGA185072 technical, purity 91.6%, batch P. 607001/002 was tested in a open epicutaneous maximisation test for sensitising potential. Guinea Pigs were allocated to control and test groups. In the induction phase: 0.1% CGA185072 in 20% propylene glycol + 80% physiological saline was injected in to 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% CGA185072 in 20% propylene glycol + 80% physiological saline. Epicutaneous challenge: 1% of the test article in vaseline. It was shown in a pretest that this was the highest non-irritating concentration. Dosing procedure: During the induction phase, every second day one intracutaneous injection was made into the back skin of the animals (total of 10 injections). After three injections without adjuvants, the seven following injections were made with complete Freund’s adjuvants. Fourteen days after the induction, intradermal challenge was made by a single injection into the skin of the left flank. Ten days after intracutaneous challenge, epicutaneous challenge was done by 24 hours dermal administration of the test article in vaseline under occlusive dressing (right flank). After epidermal challenge application of cloquintocet-mexyl, all treated animals showed positive skin reactions.

Cloquintocet-mexyl was assessed in the guinea pup using an optimisation test protocol - 20/20 responded positively to the epicutaneous challenge indicating that the test substance has sensitisation potential by skin contact.