3-chloroaniline

Repeated dose toxicity: oral

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 for cross-reference:

reference to same study

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1998

Reference 2

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

Guideline:

OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study 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

Test material information

Constituent 1

Reference substance name:

3-chloroaniline

EC Number:

203-581-0

EC Name:

3-chloroaniline

Cas Number:

108-42-9

Molecular formula:

C6H6ClN

IUPAC Name:

3-chloroaniline

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.