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Toxicological information

Acute Toxicity: dermal

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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

Referenceopen allclose all

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 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

Reference
Name:
Unnamed
Type:
Constituent
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).