Registration Dossier

Administrative data

Description of key information

The test item is not considered a skin sensitiser under OECD 406 (Hatoum & Johnson 1991)

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:
24 July 1991 to 31 August 1991
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail
Justification for type of information:
Please refer to Section 13.2 for full read-across justification
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes
Type of study:
Buehler test
Justification for non-LLNA method:
The study was performed prior to the validation and adoption of the LLNA as OECD TG 429.
Species:
guinea pig
Strain:
Hartley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS- Source: Murphy Breeding laboratories, Plainfield, IN, USA- Age at study initiation: 9 weeks of age- Weight at study initiation: Weight at arrival was 281-370 g- Fasting period before study: Not stated- Housing: Housed individually in stainless steel cages measuring 24.9 x 17.8 x 39.8 cm. Polyzorb pads were placed in the pan below the stainles steel mesh of each animals cage to absorb liquids.- Diet (e.g. ad libitum): Guinea Pigs Chow 5025 (Ralston Purina Co., St. Louis, MO, USA) ad libitum- Water (e.g. ad libitum): Purified water ad libitum- Acclimation period: 3 weeksENVIRONMENTAL CONDITIONS- Temperature (°C): 22 - Humidity (%): 63- Air changes (per hr): Not stated- Photoperiod (hrs dark / hrs light): 12/12
Route:
epicutaneous, occlusive
Vehicle:
DMSO
Concentration / amount:
The test article was prepared as a 30% (w/w) solution in DMSO, and 0.3 mL was applied for the induction phase.
Day(s)/duration:
Once a week for three weeks
Adequacy of induction:
not specified
No.:
#10
Route:
epicutaneous, occlusive
Vehicle:
DMSO
Concentration / amount:
The test article was prepared as a 30% (w/w) solution in DMSO, and 0.3 mL was applied for the induction phase.
Day(s)/duration:
6 hours
Adequacy of challenge:
not specified
No. of animals per dose:
10e.
Details on study design:
The test article was prepared as a 30% (w/w) solution in DMSO. Solutions were prepared fresh for each induction and challenge dose.Undiluted DMSO was applied to the vehicle control guinea pigs during the induction phase. A 70% (w/w) solution of DMSO in reverse osmosis-purifed water was prepared and applied to the vehicle control guinea pigs for the challenge dose.Induction: Using a Hill Top Chamber, 0.3 ml of the 30% test article/DMSO solution, or undiluted DMSO was applied to the upper left quadrant of the backs of the ten guinea pigs in the treated and control groups respectively, once/week for a period of three weeks. Elastoplast was wrapped around the midsection of the guinea pigs to keep the Hill Top Chamber in place. All wrapping materials were removed 6 hours after each application. The 10 control guinea pigs were handled in the same manner (without the addition of isophthalic acid to the chamber). Challenge: Two weeks following application of the last induction dose, 0.3 ml of the 30% test article/DMSO solution was applied to the lower left quadrant of the backs of the 10 treated guinea pigs. Challenge control guinea pigs also received a challenge dose of 0.3 ml of the 30% test article/DMSO solution. Vehicle control guinea pigs each received a challenge dose of 0.3 ml of a 70% aqueous DMSO solution. The challenge dose for all sham and control guinea pigs was applied at the same site as the treated guinea pigs (lower left quadrant). The test materials were applied in an identical manner to that used in the induction phase, all wrappings were removed 6 hours after the challenge application.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 Draize method. To facilitate scoring, all animals were shaved immediately prior to scoring during the induction phase, while all of the guinea pigs were depilated with Neet Hair Remover approximately 2 hours prior to the 24 hour scoring during the challenge phase.All guinea pigs were observed daily for mortality and morbidity. Body weights were measured weekly. Necropsies were not performed.
Challenge controls:
Yes - guinea pigs that received repeated applications of undiluted DMSO in the induction phase were challenged with 30% (w/w) test article/DMSO solution.
Positive control substance(s):
no
Positive control results:
A positive control was not included in this study.
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
Not included
No. with + reactions:
0
Total no. in group:
0
Remarks on result:
other: Positive control grous was not included in the study
Reading:
1st reading
Hours after challenge:
24
Group:
other: Sham control group
Dose level:
0.3 ml of 30% solution in DMSO
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0.3 ml of 30% solution in DMSO
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
0.3 ml of 30% solution in 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% solution in DMSO. No with. + reactions: 1.0. Total no. in groups: 10.0.

Summation of individual erythema scores

Time of scoring after challenge Dose.

 

24 hours

48 hours

Group 

Erythema score

Erythema score

0

1

2

3

4

0

1

2

3

4

Treated

2

7

1

0

0

3

7

0

0

0

Vehicle Control

3

7

0

0

0

8

2

0

0

0

Sham Control

3

7

0

0

0

4

6

0

0

0

Interpretation of results:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
No evidence of sensitisation was seen under the conditions of this study.
Executive summary:

In a Buehler study, isophthalic acid 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 the test article. 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 dose and the challenge dose.

A positive erythema reaction (score greater than or equal to 2) was observed in one test article-treated guinea pig during the challenge phase of the study. Positive erythema reactions were not observed in any vehicle or sham control guinea pigs after challenge.

Based on the statistical analyses, neither the primary effect of treatment with isophthalic acid nor the secondary effect of time of scoring was a significant factor; the effect of treatment for the vehicle versus sham control comparison was also not significant. These results indicate that sensitization was not induced in guinea pigs following repeated dermal application of isophthalic acid.

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

No data are available for TPA, however a negative Buehler study is reported for the read-across substance isophthalic acid (IPA). The OECD QSAR Toolbox does not report any structural alerts for protein binding activity (relevant for skin sensitisation) for TPA or IPA. TPA (benzene-1,4 -dicarboxylic acid) and IPA (benzene-1,3 -dicarboxylic acid) are structurally highly similar (isomers), differing only in the position of the two carboxylic acid sidechains on the benzene ring. As such, the potential for protein binding is likely to be comparable fo the two substances and read-across for the skin sensitisation endpoint is scientifically justified.


Migrated from Short description of key information:
No evidence of skin sensitisation was noted in a Buehler study with the read-across compound isophthalic acid (IPA). The OECD QSAR Toolbox does not report any structural alerts for protein binding activity (relevant for skin sensitisation) for TPA.

Justification for selection of skin sensitisation endpoint:
Only one study is available for this endpoint.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

No classification for skin sensitisation is proposed on the basis of a negative Buehler study with the read-across substance isophthalic acid.