3-chlorophthalic anhydride

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2004

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2004

Report date:

2004

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

1987

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Version / remarks:

1998

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

3-chlorophthalic anhydride

EC Number:

204-179-8

EC Name:

3-chlorophthalic anhydride

Cas Number:

117-21-5

Molecular formula:

C8H3ClO3

IUPAC Name:

4-chloro-1,3-dihydro-2-benzofuran-1,3-dione

Test animals

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

Male and female New Zealand White rabbits were received from Millbrook Breeding Labs, Amherst, MA. The animals weighed 2.14-2.64 kg and were 12-15 weeks old. They were individually housed upon arrival in stainless steel suspended cages. The animals were acclimated for at least 5 days prior to dosing. Water and feed were provided ad libitum. The temperature and humidity were maintained at 68±5°F and 30-70%, respectively. Room lights were on a 12-hour light/dark cycle.

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

The application site, not less than 10% of the body surface, was prepared approximately 24 hours prior to dosing by clipping the skin of the trunk free of hair. 3 CLPA was dosed as received from the Sponsor. In the limit test, 3-CLPA was dosed at 2000 mg/kg. 3-CLPA was moistened slightly (1 g 3-CLPA with 0.5 mL USP water) and introduced under gauze patches (two single layers thick) directly to the skin of 10 animals. The animals were immobilized and the patches were secured in place by wrapping the entire trunk of the animal with an impervious bandage. Test sites were secured to prevent the animals from ingesting the test substance. After the completion of the 24-hour exposure period, the wrapping was removed and the skin was gently wiped and rinsed with USP water to remove any test substance still remaining.

Duration of exposure:

24 hours

Doses:

2000 mg/kg

No. of animals per sex per dose:

5/sex

Control animals:

no

Details on study design:

Five animals/sex were dosed at 2000 mg/kg. All animals survived at this dose. Therefore, the main test was not conducted. The animals were observed frequently during the first day and then a careful clinical examination was made at least once a day through 14 days. The test site of each animal was also observed for signs of erythema and edema after the exposure period according to the Draize Scale for Scoring Skin Reactions. Animals were weighed at Day 0 (prior to dose administration), Day 7 and Day 14. Changes in body weights were calculated and recorded. At the end of the study, all animals were sacrificed by an injectable barbiturate and subjected to a gross necropsy.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No animals died over the course of this study.

Clinical signs:

other: No overt signs of toxicity were observed during the course of the study.

Gross pathology:

There were no abnormalities or lesions observed at necropsy.

Other findings:

No irritation was observed at any dose site over the course of the study.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The acute dermal LD50 was determined to be >2000 mg/kg body weight.

Executive summary:

Dermal toxicity was determined in a study performed according to OECD 402 and in compliance with GLP criteria. In this study, 5 male and 5 female New Zealand White rabbits were exposed to a test concentration of 2000 mg/kg on the skin. The test substance was slightly moistened and introduced under gauze patches directly to the skin, where it was held for 24 hours under semi-occlusive conditions. After the exposure period the test substance was removed and the skin was gently wiped and rinsed with USP water. The animals were observed frequently during the first day and then a careful clinical examination was made at least once a day through 14 days. The test site of each animal was also observed for signs of erythema and edema after the exposure period according to the Draize Scale for Scoring Skin Reactions. Additionally, body weight was recorded on day 0, 7 and 14. At the end of the study gross necropsy was performed. No mortality was observed during the study period and no overt signs of toxicity were observed. Also, no irritation was noted during the study and all animals gained weight. No abnormalities or lesions were seen at necropsy. Based on these results, the LD50 was determined to be >2000 mg/kg body weight.