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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
sub-chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study
Cross-reference
Reason / purpose:
reference to same study

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1998
Reference Type:
publication
Title:
Comparative gavage suchronic toxicity studies of o-chloroaniline and m-chloroaniline in F344 rats and B6C3F1 mice
Author:
Hejtmancik MR, Trela BA, Kurtz PJ, Persing RL, Ryan MJ, Yarrington JT, Chhabra RS
Year:
2002
Bibliographic source:
Toxicol Sci 69, 234-243 (2002)

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity in Rodents)
Principles of method if other than guideline:
Groups of 10 male and 10 female F344/N rats were administered 0, 10, 20, 40, 80, or 160 mg m-chloroaniline per kilogram body weight in dilute hydrochloric acid by gavage 5 days a week for 13 weeks. Animals were evaluated for hematology, clinical chemistry, histopathology, and reproductive system effects.
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: liquid
Details on test material:
m-chloroaniline, a pale yellow liquid, was identified by infrared spectroscopy; each spectrum was consistent with a literature reference (Aldrich Library of FT-IR Spectra, 1985) and with that expected for the chemical structure. Gas chromatography indicated a purity greater than 99%.
Boiling Point: 230.5°C
Density at 22°C: 1.210
Vapor pressure: <0.1 mmg Hg at 30°C
Solubility: practically insoluble in water, soluble in organic solvents

Test animals

Species:
rat
Strain:
Fischer 344
Sex:
male/female

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: 1 M hydrochloric acid
Analytical verification of doses or concentrations:
yes
Duration of treatment / exposure:
13 weeks
Frequency of treatment:
5 days a week for 13 weeks
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 10, 20, 40, 80, or 160 mg m-chloroaniline per kilogram body weight
Basis:
actual ingested
No. of animals per sex per dose:
10 male and 10 female rats/dose
Control animals:
yes, concurrent vehicle

Results and discussion

Effect levels

Dose descriptor:
LOAEL
Effect level:
10 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: Hematotoxicity

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

The hematopoietic system was the target of m-chloroaniline in rats. One female rat in the 160 mg/kg m-chloroaniline group during week 12, possibly secondary to methemoglobinemia. The final mean body weights and weight gains of male rats in the highest dose group were significantly less than those of the respective controls. Clinical findings of toxicity included a transient bluish discoloration of the genital and footpad regions in rats administered m-chloroaniline; these effects occurred primarily in the 80 and 160 mg/kg groups. Methemoglobin concentrations were increased in dosed rats and resulted in a secondary anemia; the severity of the anemia increased with increasing dose. Microscopic lesions considered related to chemical administration in included hemosiderin pigmentation in the bone marrow, kidney, liver, and spleen; hematopoiesis in the liver and spleen; and erythroid cell hyperplasia in the bone marrow. These lesions reflected the response to hemolytic anemia and methemoglobinemia induced by chloroanilines.

Applicant's summary and conclusion

Executive summary:

Groups of 10 male and 10 female F344/N rats were administered 0, 10, 20, 40, 80, or 160 mg m-chloroaniline per kilogram body weight in dilute hydrochloric acid by gavage 5 days a week for 13 weeks. Animals were evaluated for hematology, clinical chemistry, histopathology, and reproductive system effects.

The hematopoietic system was the target of m-chloroaniline in rats. One female rat in the 160 mg/kg m-chloroaniline group during week 12, possibly secondary to methemoglobinemia. The final mean body weights and weight gains of male rats in the highest dose group were significantly less than those of the respective controls. Clinical findings of toxicity included a transient bluish discoloration of the genital and footpad regions in rats administered m-chloroaniline; these effects occurred primarily in the 80 and 160 mg/kg groups. Methemoglobin concentrations were increased in dosed rats and resulted in a secondary anemia; the severity of the anemia increased with increasing dose. Microscopic lesions considered related to chemical administration in included hemosiderin pigmentation in the bone marrow, kidney, liver, and spleen; hematopoiesis in the liver and spleen; and erythroid cell hyperplasia in the bone marrow. These lesions reflected the response to hemolytic anemia and methemoglobinemia induced by chloroanilines.

The LOAEL is 10 mg/kg bw in this study.