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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
This study is used for read-across and therefore has been assigned a reliability of 2 (reliable with restrictions). The study, if used in support of isophthalic acid, has a reliability of 1 (reliable without restriction). This study was selected as the key study because the information provided for the hazard endpoint is sufficient for the purpose of classification and labelling and/or risk assessment.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1991
Report Date:
1991

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes
Type of study:
Buehler test

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Purity: Not reported

In vivo test system

Test animals

Species:
guinea pig
Strain:
Hartley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: 6 weeks
- Weight at study initiation: 281-370 g
- Housing: individually in stainless steel cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 3 weeks


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C
- Humidity (%): 63%
- Air changes (per hr): Not reported
- Photoperiod (hrs dark / hrs light): 12-hour light/12-hour dark

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
other: occlusive
Vehicle:
DMSO
Concentration / amount:
0.3 mL of a 30% (w/w ) test substance/DMSO
Challengeopen allclose all
Route:
other: occlusive
Vehicle:
DMSO
Concentration / amount:
0.3 mL of a 30% (w/w ) test substance/DMSO
No. of animals per dose:
3 groups of ten males
Details on study design:
MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 30
- Exposure period: 2 weeks
- Test groups: 10
- Vehicle Control group: 10
- Sham Control group: 10
- Site: Upper left quadrant of the backs
- Frequency of applications: once/week
- Duration: 3 weeks
- Concentrations: 0.3 ml of a 30% (w/w) test article/DMSO solution (Test group) or undiluted DMSO (Vehicle control), Nothing (Sham group)


B. CHALLENGE EXPOSURE
- No. of exposures: 30
- Exposure period: 6 hours
- Test groups: 10
- Control group: 10
- Sham Control group: 10
- Site: lower left quadrant of the backs
- Concentrations: 0.3 ml of the 30% (w/w) test article/DMSO (Test group and Sham group), Vehicle control guinea pigs each received a challenge dose of 0.3 ml of a 70% aqueous DMSO solution
- Evaluation (hr after challenge): 24 hours and 48 hours

-OTHER
Approximately 24 and 48 hours after application of the first induction dose and of the challenge dose, the test sites were scored for erythema according to the method of Draize. To facilitate scoring, all animals were shaved immediately prior to scoring during the induction phase, while all of the guinea pigs were depilated with hair remover approximately 2 hours prior to the 24-hour scoring during the challenge phase.

Study design: in vivo (LLNA)

Statistics:
Two-factor log-linear models (Bishop, Fienberg and Holland, Discrete Multivariate Analysis, The MIT Press, Cambridge, MA, 1975) were used to assess the effects of treatment (treated vs. sham control, treated vs. vehicle control and vehicle control vs. sham control) and time of scoring (24 hr vs. 48 hr) on erythema reactions. For the purpose of interpretation, the log-linear model is an analogue of the analysis of variance procedures where a qualitative response, such as a rating scale of erythema, is the focus of investigation. A Chi-square statistic is generated to test the significance of overall treatment vs. control differences and the combination of treatment and time of scoring. These statistical analyses were performed using SYST AT software (Wilkinson, L., SYSTAT: The System for Statistics. Systat, Inc., Evanston, IL, Verso 5.0, 1990) on personal computer. A minimum significance level of p < 0.05 was used in the comparison.

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
0.3 ml of 30% (w/w) test substance/DMSO
No. with + reactions:
1
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 0.3 ml of 30% (w/w) test substance/DMSO . No with. + reactions: 1.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
0.3 ml of 30% (w/w) test substance/DMSO
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 0.3 ml of 30% (w/w) test substance/DMSO . No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
24
Group:
other: vehicle control
Dose level:
0.3 ml of 70% aqueous DMSO
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: other: vehicle control. Dose level: 0.3 ml of 70% aqueous DMSO . No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
other: vehicle control
Dose level:
0.3 ml of 70% aqueous DMSO
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: other: vehicle control. Dose level: 0.3 ml of 70% aqueous DMSO. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
24
Group:
other: Sham Control
Dose level:
0.3 ml of 30% (w/w) test substance/DMSO
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: other: Sham Control. Dose level: 0.3 ml of 30% (w/w) test substance/DMSO . No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
other: Sham Control
Dose level:
0.3 ml of 30% (w/w) test substance/DMSO
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: other: Sham Control. Dose level: 0.3 ml of 30% (w/w) test substance/DMSO. No with. + reactions: 0.0. Total no. in groups: 10.0.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
This study and the conclusions which are drawn from it fulfil the quality criteria (validity, reliability, repeatability).

The findings indicate that dermal sensitisation did not result from repeated dermal application of test substance.
Executive summary:

The test substance was applied once a week at a dose of 0.3 ml of a 30% (w/w) solution in dimethyl sulfoxide (DMSO) to the shaved backs of ten male guinea pigs during an induction period of three weeks. Another group of 10 male guinea pigs served as a vehicle control and was similarly dosed with 0.3 ml of undiluted DMSO. A third group of ten sham control guinea pigs was handled in the same manner, but was not treated with test article or vehicle. Two weeks following application of the third induction dose, the treated and sham control guinea pigs each received a challenge dose of 0.3 ml of the 30% (w/w) test article/DMSO solution; the vehicle control guinea pigs each received a challenge dose of 0.3 ml of a 70% (w/w) aqueous DMSO solution. All guinea pigs were scored for erythema approximately 24 and 48 hours following application of the first induction dose and the challenge dose. Positive erythema reactions (i.e., a score > 2) were observed in only one test article-treated guinea pig, compared to no vehicle or sham control guinea pigs during the challenge phase. Thus, the primary effect of treatment (treated vs. control) and the secondary effect of time of scoring (24 hr vs. 48 hr) were not statistically significant. These findings indicate that dermal sensitisation did not result from repeated dermal application of test substance.