Isophthaloyl dichloride

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference 1

Reference Type:

publication

Title:

Range-finding toxicity data: List VIII

Author:

Carpenter CP, Weil CS, and Smyth HF. Jr.

Year:

1974

Bibliographic source:

Toxicol. Appl. Pharmacol., 28:313-319

Reference 2

Reference Type:

publication

Title:

Rangefinding toxicity data: List VI

Author:

Smyth HF Jr., Carpenter CP, Weil CS, Pozzani UC, and Striegel JA

Year:

1962

Bibliographic source:

Amer. Ind. Hyg. J., 23:95-107.

Materials and methods

Principles of method if other than guideline:

Penetration of rabbit skin was estimated by a technique similar to the one-day cuff method of Draize and associates (Draize, J. H., G. Woodard, and H. O. Calvery (1944). "Methods for study of irritation and toxicity of substances applied topically to the skin and mucous membranes" J. Pharmacol. Exp. Therap., 82:377).

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Isophthaloyl dichloride

EC Number:

202-774-7

EC Name:

Isophthaloyl dichloride

Cas Number:

99-63-8

Molecular formula:

C8H4Cl2O2

IUPAC Name:

benzene-1,3-dicarbonyl dichloride

Details on test material:

Isophthaloyl chloride, purity not reported

Test animals

Species:

rabbit

Strain:

New Zealand White

Sex:

male

Administration / exposure

Type of coverage:

occlusive

Details on dermal exposure:

TEST SITE
- Area of exposure: entire trunk
- Type of wrap if used: impervious plastic film

REMOVAL OF TEST SUBSTANCE
- Time after start of exposure: 24-hr contact period under film, then film is removed and animals are observed for 14 days

TEST MATERIAL
- Concentration (if solution): <20 mL/kg

Duration of exposure:

24-hr contact period under film, then film is removed and animals are observed for 14 days

No. of animals per sex per dose:

4

Control animals:

not specified

Details on study design:

Penetration of rabbit skin was estimated by a technique similar to the one-day cuff method of Draize and associates (Draize, J. H., G. Woodard, and H. O. Calvery (1944). "Methods for study of irritation and toxicity of substances applied topically to the skin and mucous membranes" J. Pharmacol. Exp. Therap., 82:377). Groups of 4 male albino rabbits weighing 2.5 to 3.5 kg were used. The fur was clipped from the entire trunk and the dose of the test substance was retained beneath an impervious plastic film. The rabbits were immobilized during the 24-hour exposure period, after which the film was removed and the rabbits were caged for the subsequent 14-day observation period. The LD50 value and its fiducial range were estimated by the method of Thompson (Thompson, W. R. (1947). "Use of moving averages and interpolation to estimate median effective dose" Bacteriol. Rev., 11:115) using the Tables of Weil (Weil, C. S. (1952). "Tables for the convenient calculation of median effective dose and instructions for their use" Biometrics, 8:249).

Results and discussion

Effect levels

Sex:

male

Dose descriptor:

LD50

Effect level:

1 410 mg/kg bw

95% CL:

>= 870 - <= 2 310

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The dermal LD50 was calculated to be 1.41 mL/kg (1410 mg/kg bodyweight) with confidence limits of 870 - 2310 mg/kg bodyweight).

Executive summary:

Penetration of rabbit skin by the test substance was estimated by a technique similar to the one-day cuff method of Draize and associates (Draize, J. H., G. Woodard, and H. O. Calvery (1944). "Methods for study of irritation and toxicity of substances applied topically to the skin and mucous membranes" J. Pharmacol. Exp. Therap., 82:377). Groups of 4 male albino rabbits weighing 2.5 to 3.5 kg were used. The fur was clipped from the entire trunk and the dose of the test substance was retained beneath an impervious plastic film. The rabbits were immobilized during the 24-hour exposure period, after which the film was removed and the rabbits were caged for the subsequent 14-day observation period. The LD50 value and its fiducial range were estimated by the method of Thompson (Thompson, W. R. (1947). "Use of moving averages and interpolation to estimate median effective dose" Bacteriol. Rev., 11:115) using the Tables of Weil (Weil, C. S. (1952). "Tables for the convenient calculation of median effective dose and instructions for their use" Biometrics, 8:249). The dermal LD50 was calculated to be 1.41 mL/kg (1410 mg/kg bodyweight) with confidence limits of 870 - 2310 mg/kg bodyweight).