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Toxicological information

Repeated dose toxicity: oral

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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

Referenceopen allclose all

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 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

Constituent 1
Chemical structure
Reference substance name:
p-toluidine
EC Number:
203-403-1
EC Name:
p-toluidine
Cas Number:
106-49-0
Molecular formula:
C7H9N
IUPAC Name:
p-toluidine
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).