Isophthalic acid

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1990-04-19 to 1990-05-04

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: It was not indicated in the study that the experiment was conducted according to any guidelines or if was GLP compliant. However, the methodology of the study is similar to OECD guideline 402.

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1990

Report date:

1990

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

yes

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
- Physical state: White powder
- Lot/batch No.: 10820-59-A
- Storage condition of test material: Stored at room temperature (approximately 22°C)

Test animals

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

The animals were male and female New Zealand albino rabbits. They were purchased from Johnson Rabbit Ranch (IN), were 1.5 to 3 months of age and weighed 1.61 - 2.33 kg on arrival. They were held in quarantine for approximately 9 weeks, and examined for ensure their health and suitability as test subjects. Individuals were identified by metal ear tags.
Each rabbit was provided with ca 150 g of Purina Lab Rabbit Chow #5326 daily. Reverse osmosis-purified water was supplied ad libitum.
The rabbits were housed individually in stainless steel cages with stainless steel mesh floors. The animal room was maintained at an average temperature and relative humidity of 23.7°C and 32%, respectively. Fluorescent lighting was provided on a 12 hour light/dark cycle.
In life dates: April 19th 1990 to May 5th 1990.

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

The test article was applied undiluted, individual doses were dispensed in glass vials. The shaved application site was pre-moistened with water immediately prior to test article administration, and the test article was covered with a 12.8x23.0 cm surgical dressing. The dressing was covered by a plastic film and secured by lint free cloth and Elastoplast. The wrappings were removed after 24 hours and the skin was wiped gently with gauze and 0.9% saline to remove residual test article.
All rabbits were weighed immediately prior to dosing and the weights used for dosage calculations.

Duration of exposure:

24 hours

Doses:

2 g/kg bodyweight test article applied as a single application.

No. of animals per sex per dose:

10 animals in the dose group, 5 per sex.

Control animals:

no

Details on study design:

Rabbits used in the study were selected at random.
All rabbits were observed approximately 1, 3.5, 4.5, and 5.5 hours after dosing, and at least once per day for 14 days after dressing removal. All rabbits were weighed immediately prior to dosing. The rabbits were also weighed 7 days following test article application and at study termination.
All rabbits were euthanised at the end of the observation period and a limited gross necropsy was performed.

Statistics:

A formal statistical analysis was not required.

Results and discussion

Preliminary study:

No preliminary results.

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No mortality at the limit dose

Mortality:

No deaths occurred during the study.

Clinical signs:

other: Minor signs of dermal irritation (erythema) were observed within the application site of 4 male rabbits immediately following unwrapping. The application site of most test animals was partially or completely masked by hair regrowth during the observation

Gross pathology:

Gross necropsy findings were within normal limits in 8/10 rabbits, One female had a distended (clear fluid) uterus and another had multiple mesenteric abscesses. These lesions were not considered to be related to treatment.

Other findings:

No other findings reported.

Any other information on results incl. tables

The application site of most test animals was partially or completely masked by hair regrowth throughout the observation period, possibly preventing detection of signs of irritation.

Summary of body weights:

	Mean Body Weight (kg)±SD
Time	Males	Females
Pre-dosing	3.28± 0.24	3.15±0.16
Day 7	3.40±0.30	3.28±0.17
Day 15	3.38±0.16	3.29±0.18
Weight Change (Day 15 – pre-dosing)	0.10	0.14

Summary of Clinical Observations:

	Incidence
Observation	Males	Females
Skin (application site):
Erythema	4	0
Masked by hair growth	3	5

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Based on the results of this study, the median acute lethal dermal dose (LD50) for isophthalic acid was estimated to be greater than 2000 mg/kg of bodyweight.

Executive summary:

Isophthalic acid was applied at a dose level of 2000 mg/kg bodyweight to the shaved backs of 5 male and 5 female New Zealand rabbits in a single application. The test article remained on the skin for 24 hours under an occlusive dressing and was then washed off. During the 24 hour exposure period, the test animals were observed at 1, 3.5, 4.5 and 5.5 hours after dosing and at least once per day for 14 days after treatment. No deaths occurred during the study. Mild erythema was observed within the application site of 4 animals immediately after unwrapping. Mean body weights increased during the study. No gross pathological lesions attributable to treatment were evident in any of the rabbits at necropsy.

Based on the results of this study, the median acute lethal dermal dose (LD50) was estimated to be greater than 2000 mg/kg bodyweight.