3-chloro-o-toluidine

Repeated dose toxicity: oral

Administrative data

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

experimental study

Adequacy of study:

other information

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: Only secondary literature available

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference 1

Reference Type:

secondary source

Title:

Chlortoluidine (3-Chlor-2-methylanilin, 5-Chlor-2-methylanilin, 3-Chlor-4-methylanilin)

Author:

Gesellschaft Deutscher Chemiker

Year:

1990

Bibliographic source:

Beratergremium für umweltrelevante Altstoffe (BUA), BUA-Stoffbericht 55

Reference 2

Reference Type:

study report

Title:

Unnamed

Year:

1978

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Subacute pre-study for carcinogenicity study.

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

5-chloro-o-toluidine

EC Number:

202-452-6

EC Name:

5-chloro-o-toluidine

Cas Number:

95-79-4

Molecular formula:

C7H8ClN

IUPAC Name:

5-chloro-2-methylaniline

Test animals

Species:

rat

Strain:

Fischer 344

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: A. R. Schmidt, Madison, Wisconsin; Laboratory Supply Company, Inc., Indianapolis, Indiana; and Charles River Breeding Laboratories, Inc., Wilmington, Massachusetts.
- Age at study initiation: approximately 6 weeks
- Housing: 4 per cage
- Diet: The basal laboratory diet for both dosed and control animals consisted of Wayne Lab-Blox® meal (Allied Mills, Inc., Chicago, Illinois) ad libitum.
- Water: Acidulated water (pH 2.5) ad libitum.
- Acclimation period: two weeks

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 - 26
- Humidity (%): 45 - 55
- Air changes (per hr): 12 - 15
- Photoperiod (hrs dark / hrs light): 16/8

Administration / exposure

Route of administration:

oral: feed

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

DIET PREPARATION
- Rate of preparation of diet (frequency): once weekly
- Mixing appropriate amounts with (Type of food): Wayne Lab-Blox® meal
- Storage temperature of food: in the dark at 4°C

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

four weeks

Frequency of treatment:

daily

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
315, 680, 1465, 3155 and 6800 mg/kg food
Basis:
nominal in diet

Doses / concentrations 2

Remarks:

Doses / Concentrations:
31.5, 68.0, 146.5, 315.5, and 680 mg/kg bw/day
Basis:
actual ingested

No. of animals per sex per dose:

5

Control animals:

yes, plain diet

Details on study design:

- Post-exposure recovery period in satellite groups: all animals for two weeks

Examinations

Observations and examinations performed and frequency:

BODY WEIGHT: Yes
- Time schedule for examinations: Individual body weights were recorded twice weekly throughout the study.

MORTALITY AND CLINICAL SYMPTOMS: Yes

Sacrifice and pathology:

Upon termination of the study all survivors were euthanized and necropsied.

Statistics:

Probabilities of survival were estimated by the product-limit procedure of Kaplan and Meier (1958). Animals were statistically censored as of the time that they died of other than natural causes or were found to be missing; animals dying from natural causes were not statistically censored. Statistical analyses for a possible dose-related effect on survival used the method of Cox (1972) when testing two groups for equality and used Tarone's (1975) extensions of Cox's methods when testing a dose-related trend. One-tailed P-values have been reported for all tests except the departure from linearity test, which is only reported when its two-tailed P-value is less than 0.05.

Results and discussion

Results of examinations

Details on results:

MORTALITY: All animals survived.

BODY WEIGHT AND WEIGHT GAIN: At the highest dose all animals showed a reduced weight gain.

HISTOPATHOLOGY: All animals even in the lowest dose had mottled livers. In male rats additonally spotted kidneys were observed.

Effect levels

Dose descriptor:

LOAEL

Effect level:

31.5 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: lowest dose tested, mottled livers

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

Study results:

	Mean Body weight Gain (%)^a		Survival^b		Observation of Abnormal Signs^b
ppm	Males	Females	Males	Females	Males	Females
5800	- 35	- 21	5/5	5/5	5/5^c,d	5/5^c
3155	+ 23	- 3	5/5	5/5	5/5^c,d	5/5^c
1465	- 19	+ 3	5/5	5/5	5/5^c,d	5/5^c
680	+ 8	+ 5	5/5	5/5	5/5^c,d	5/5^c
315	+ 18	+ 4	5/5	5/5	5/5^c,d	5/5^c
0	--	--	5/5	5/5	0/5	0/5

a+ is indicative of mean body weight gain greater than that of controls.

a- is indicative of mean body weight gain less than that of controls.

b Number of animals observed/number of animals originally in group.

c These rats had mottled livers.

d These rats had spotted kidneys.