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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
not specified
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1981

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: Guinea pig topical sensitisation test
GLP compliance:
no
Type of study:
other: guinea pig topical sensitisation test
Justification for non-LLNA method:
Study was carried out before LLNA was considered a requirement. It is considered sufficient for the endpoint, so there was no need for an additional LLNA study, which would involve more animals.

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
additive
Test material form:
solid: particulate/powder
Details on test material:
Moisture content 0.16% w/w (Karl FIscher) as supplied to laboratory.
Batch Number: G309569
Specific details on test material used for the study:
Batch No: RJ1173

In vivo test system

Test animals

Species:
guinea pig
Strain:
not specified
Sex:
male/female
Details on test animals and environmental conditions:
Five male and five female guinea pigs, initially weighing 250-300 g.

Study design: in vivo (non-LLNA)

Induction
Route:
other: epicutaneous, no other information mentioned
Vehicle:
other: saline:2-methoxyethanol:Tween 80 (45:45:10)
Concentration / amount:
not mentioned
Day(s)/duration:
not mentioned
Adequacy of induction:
not specified
Challenge
No.:
#1
Route:
other: epicutaneous, not specified
Vehicle:
other: saline:2-methoxyethanol:Tween 80 (45:45:10)
Concentration / amount:
Not specified
Day(s)/duration:
Not specified
Adequacy of challenge:
not specified
No. of animals per dose:
5
Positive control substance(s):
yes
Remarks:
Benzyl penicillin

Results and discussion

Positive control results:
At 24 hours, only 2/9 animals treated with Benzyl Penicillin gave positive results. This increased to 5/9 animals at 48 hours. This is a low result for the positive control substance, as sensitisation usually occurs in >80% of the animals.

In vivo (non-LLNA)

Resultsopen allclose all
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
Not available
No. with + reactions:
1
Total no. in group:
10
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
Not available
No. with + reactions:
2
Total no. in group:
10
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
Not available
No. with + reactions:
2
Total no. in group:
9
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
Not available
No. with + reactions:
5
Total no. in group:
9

Applicant's summary and conclusion

Interpretation of results:
Category 1 (skin sensitising) based on GHS criteria
Conclusions:
Skin sensitising potential of 1132/4 DMF (CQ Intermediate) is low, but cannot be ignored.
Over 20% of the animals showed positive responses to the challenge after 48 hours, which is sufficient to classify the substance as a Skin Sensitiser Category 1, according to the criteria set for animal studies in section 3.4.2.2.4.1 of Annex I of the CLP Regulation.
Executive summary:

The skin sensitisation potential of 0/4 dihydrochloride dihydrate, 1132/4 DMF and 1132/4 bis hydrochloride was assessed in the guinea pig topical sensitisation test. The results indicate that repeated contact of the human skin with 0/4 dihydrochloride dihydrate might produce contact dermatitis. The contact allergenic potential of 1132/4 DMF although low, cannot be ignored, and that of 1132/4 bis hydrochloride, if any, is very low.