Isophthalic acid

Skin sensitisation

Administrative data

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:

other: Proprietary GLP study, comparable to guidelines.

Cross-reference

Reason / purpose for cross-reference:

reference to same study

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

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Deviations:

yes

Remarks:

: no positive control group

Principles of method if other than guideline:

The methodology was broadly comparable to OECD 406, with the following exceptions: observation times were not in line with those recommended in the guidelines. No analytical tests were conducted to determine the test substance/DMSO mixtures concentration. These deficiencies were not believed to have affected the overall outcome of the study.

GLP compliance:

yes

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

The study was performed prior to adoption of the LLNA as preferred test method

Test material

Test material information

Constituent 1

Reference substance name:

Isophthalic acid

EC Number:

204-506-4

EC Name:

Isophthalic acid

Cas Number:

121-91-5

Molecular formula:

C8H6O4

IUPAC Name:

isophthalic acid

Details on test material:

- Name of test material (as cited in study report): Isophthalic acid 220
- Substance type: Organic acid
- Physical state: White powder
- Identification no: ATTA 91-30(TA 313C)
The test material was stored at room temperature (approximately 22°C), the sponsor indicated that the test material was stable under these conditions.

In vivo test system

Test animals

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 weeks


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22
- Humidity (%): 63
- Air changes (per hr): Not stated
- Photoperiod (hrs dark / hrs light): 12 hours followed by 12 hours of darkness.

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

epicutaneous, occlusive

Vehicle:

DMSO

Induction 2

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.

Challenge

Challenge 1

Route:

epicutaneous, occlusive

Vehicle:

DMSO

Challenge 2

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.

No. of animals per dose:

10 animals per group

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

Results and discussion

Positive control results:

A positive control was not included in this study.

In vivo (non-LLNA)

Results

Results 1

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

No. with + reactions:

1

Total no. in group:

10

Clinical observations:

Grade 2 erythema

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. No with. + reactions: 1.0. Total no. in groups: 10.0. Clinical observations: Grade 2 erythema.

Results 2

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. No with. + reactions: 0.0. Total no. in groups: 10.0.

Results 3

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. No with. + reactions: 0.0. Total no. in groups: 10.0.

Results 4

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. No with. + reactions: 0.0. Total no. in groups: 10.0.

Results 5

Reading:

1st reading

Hours after challenge:

24

Group:

other: sham control

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. No with. + reactions: 0.0. Total no. in groups: 10.0.

Results 6

Reading:

2nd reading

Hours after challenge:

48

Group:

other: sham control

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. No with. + reactions: 0.0. Total no. in groups: 10.0.

Any other information on results incl. tables

Summation of individual erythema scores and statistical analyses of isophthalic acid.

	Time of scoring after challenge Dose.
	24 hours					48 hours
	Erythema score					Erythema score
Group	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

The results show a relatively high incidence of reactions in the treated group following challenge with isophthalic acid, however similar incidences of reactions were seen in the vehicle control and sham control groups.

Applicant's summary and conclusion

Interpretation of results:

not sensitising

Remarks:

Migrated information

Conclusions:

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 dermal sensitization was not induced in guinea pigs following repeated dermal application of isophthalic acid.

Executive summary:

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 dermal sensitization was not induced in guinea pigs following repeated dermal application of isophthalic acid.