p-toluidine

Repeated dose toxicity: oral

Administrative data

Endpoint:

chronic toxicity: oral

Type of information:

experimental study

Adequacy of study:

other information

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study with acceptable restrictions

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference 1

Reference Type:

publication

Title:

Testing of twenty-one environmental aromatic amines or derivatives for long-term toxicity or carcinogenicity

Author:

Weisburger EK, Russfield AB, Homburger F, Bogner E, Van Dongen CG, Chu KC (1978). Testing of twenty-one environmental aromatic amines or derivatives for long-term toxicity or carcinogenicity. J. Environm. Pathol. Toxicol. 2, 325-356.

Year:

1978

Bibliographic source:

J Environm Pathol Toxicol 2: 325-356.

Reference 2

Reference Type:

secondary source

Title:

p-Toluidine - CAS No: 106-49-0 - SIDS Initial Assessment Report.

Author:

OECD

Year:

2005

Bibliographic source:

UNEP Publications

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 452 (Chronic Toxicity Studies)

Deviations:

yes

Remarks:

Analytical purity not reported. Animals housing and enviromental conditons were not reported. Only two doses tested

GLP compliance:

no

Remarks:

GLP compliance was not mandatory at the time of the study

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

p-toluidine

EC Number:

203-403-1

EC Name:

p-toluidine

Cas Number:

106-49-0

Molecular formula:

C7H9N

IUPAC Name:

4-methylaniline

Details on test material:

- Name of test material (as cited in study report): p-toluidine
- Analytical purity: no data

Test animals

Species:

rat

Strain:

other: CD

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles Riveres laboratories, USA
- Diet (e.g. ad libitum): animals were held on basal diet of Purina laboratory chow for two weeks before grouping for the toxicity or feeding studies
- Age at study initiation: 4-6 week-old animals
- Acclimation period: 2 weeks


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23±2°C

Administration / exposure

Route of administration:

oral: feed

Vehicle:

unchanged (no vehicle)

Analytical verification of doses or concentrations:

no

Duration of treatment / exposure:

18 months

Frequency of treatment:

daily

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 1000, 2000 ppm (approx. 0,. 75, 150 mg/kg bw)
Basis:
nominal in diet

No. of animals per sex per dose:

25

Control animals:

yes, concurrent no treatment

Details on study design:

Post-exposure period: 6 months

Examinations

Sacrifice and pathology:

GROSS PATHOLOGY: Yes. A complete gross was done on all animals which died after 6 months on test or were killed at the end of the experimental period of approximately 24 months
HISTOPATHOLOGY: Yes. Histopathological examinations were done on all grossly abnormal organs, tumor masses, lung, liver, spleen, kidney, adrenal, heart, bladder, stomach, intestines, reproductive organs, and pituitaries.

Statistics:

Statistical analysis of tumors found was performed using the Fisher exact test with Bonferroni correction.

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

not examined

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

not examined

Ophthalmological findings:

not examined

Haematological findings:

not examined

Clinical biochemistry findings:

not examined

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

not examined

Gross pathological findings:

not specified

Histopathological findings: non-neoplastic:

not specified

Histopathological findings: neoplastic:

no effects observed

Effect levels

Dose descriptor:

NOAEL

Effect level:

ca. 2 000 ppm

Sex:

male

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

no mortality and no signs of toxicity are reported. Body weight  development seems to correspond to the respective control group because  body weight gain in the treated rats 10 % below that of  the respective  controls should result in a reduction of the dosage. No gross and no  histopathological findings are reported. 
Thus, under the condition of this investigation, the NOAEL(systemic  toxicity) is 2000 ppm (approximately 150 mg/kg bw/day)
Results on carcinogenicity: see endpoint studys 7.7

Applicant's summary and conclusion

Executive summary:

Weisburger EK (1978):

25 male CD rats per group received doses of 0, 1000 and 2000 ppm p-toluidine in the diet for 18 months (corresponding to 0, 75 and 150 mg/kg bw/day) followed by a 6 months recovery period. A control group of 25 male rats received diet only. Doses were chosen due to preliminary 30-day feeding study followed by a 2-week recovery period (no details given). No mortality and no signs of toxicity are reported.

Body weight development seems to correspond to the respective control group because body weight gain in the treated rats 10 % below that of the respective controls should have resulted in a reduction of the dosage. No gross and no histopathological changes were discovered. Other examined parameters were not reported. Thus, under the conditions of this investigation, the

NOAEL (systemic toxicity) is 2000 ppm (approximately 150 mg/kg bw/day).