Registration Dossier

Diss Factsheets

Administrative data

Description of key information

The test substance did not produce skin sensitization in a GPMT. Additionally, no sensitization was observed in a LLNA study in the read across chemical, 2,2'-azobis(isobutyronitrile).

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:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
pre-GLP study. GPMT performed similar to current scientific principles
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
Remarks:
The study was conducted according to the guideline in effect.
GLP compliance:
no
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
test was conducted before LLNA method was adopted
Specific details on test material used for the study:
Purite: 100%
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: not reported
- Age at study initiation: not reported
- Weight at study initiation: contol animals average weight - 508 g; test animals average weight - 518 g
- Housing: not reported
- Diet (e.g. ad libitum): not reported
- Water (e.g. ad libitum): not reported
- Acclimation period: not reported

ENVIRONMENTAL CONDITIONS: not reported
Route:
intradermal
Vehicle:
other: See Remark
Remarks:
Dimethyl phthalate (DMP)
Concentration / amount:
8% and 80% in DMP
Day(s)/duration:
4 weeks
Route:
other: epicutaneous
Vehicle:
other: see Remark
Remarks:
Dimethyl phthalate (DMP)
Concentration / amount:
8% and 80% in DMP
Day(s)/duration:
24 and 48 hrs
No. of animals per dose:
10
Details on study design:
RANGE FINDING TESTS: No sensitisation was observed at 10, 21, 42, or 83% (w/v) when tested in 3 guinea pigs per concentration.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 4
- Exposure period: 4 weeks
- Test groups: 1, 80% and an 8% suspension of the test material in the primary irritation test on same animal
- Control group: yes, no treatment
- Site: sacral intradermal injection
- Frequency of applications: 1 each week beginning 2 days after the test for primary irritation
- Duration: 4 weeks
- Concentrations: 0.1 ml of a 1.0% suspension in DMP,

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 2 days
- Exposure period: 24 hours and 48 hours
- Test groups: 1, 80% and an 8% suspension of the test material on same animal
- Control group: yes, At the same time 10 unexposed guinea pigs (controls) of the same age received identical topical applications.
- Site: shaved, intact shoulder skin.
- Concentrations: 0.05 ml of an 80% and an 8% suspension of test material in DMP
- Evaluation (hr after challenge): 24 hours and 48 hours
Challenge controls:
At the same time 10 unexposed guinea pigs (controls) of the same age received identical topical applications (0.05 ml of an 80% and an 8% suspension of test material in DMP).
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
all
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
all
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Remarks on result:
no indication of skin sensitisation

The test substance caused no irritation on shaved intact skin of 10 guinea pigs at 24 or 48 hours in both the primary irritation test and in the sensitization challenge. None of the test guinea pigs showed a sensitization response.

Interpretation of results:
GHS criteria not met
Remarks:
not sensitizing
Conclusions:
Not sensitising

This study and the conclusions which are drawn from it fulfill the quality criteria (validity, reliability, repeatability).
Executive summary:

The primary irritation test was conducted on 10 unexposed guinea pigs by applying and lightly rubbing in 0.05 mL of an 80% and an 8% suspension of the test material in DMP on shaved, intact shoulder skin. The induction phase began 2 days after the primary irritation test and continued for 4 weeks, one injection each week. After a 13-day rest period, the test guinea pigs were challenged for sensitization by applying and lightly rubbing in 0.05 mL of an 80% and an 8% suspension of test material in DMP on shaved, intact shoulder skin. The test substance caused no irritation on shaved intact skin of 10 guinea pigs at 24 or 48 hours. None of the test guinea pigs showed a sensitization response.

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

A maximization test in guinea pigs revealed that the test substance did not produce skin sensitization in laboratory animals. In addition, mouse local lymph node assay data is available for the read across chemical, 2,2’-azobis(isobutyronitrile). The underlying hypothesis for the read-across between the test substance and 2,2’-azobis(isobutyronitrile is that the postulated reaction scheme is driven by the azo functionality that is present in both substances. Additional documentation, provided within the IUCLID Assessment Reports section, supports the read-across approach. In the OECD guideline, GLP study, no cutaneous reactions were observed after the challenge application, while the control animals showed a satisfactory sensitization response in 75% of the animals using the positive sensitizer. Taken together the weight of evidence of these two studies support the conclusion that the test substance is not considered a skin sensitizer.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

The test substance did not produce skin sensitization in laboratory animals, and the read across chemical, 2,2’-azobis(isobutyronitrile), did not produce a sensitization response in the mouse local lymph node assay. Based on the weight of evidence provided, the test substance does not need to be classified for sensitization according EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.