Registration Dossier

Toxicological information

Carcinogenicity

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Administrative data

Endpoint:
carcinogenicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1978
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Short report, non-GLP, early study, one sex only;

Data source

Reference
Reference Type:
publication
Title:
Testing of twenty-one environmental aromatic amines or derivatives for long-term toxicity or carcinogenicity
Author:
Weisburger, E.K. et al.
Year:
1978
Bibliographic source:
J. Environ. Pathol. Toxicol. 2: 325-356 (1978)

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Animals were fed a diet containing the test material for 18 months. Afterwards they were observed for and additional recovery period and subsequently killed and tissues examined histopathologically.
GLP compliance:
no
Remarks:
pre-dates GLP

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
purity: 97 - 99 %, commercial sample

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River
- Age at study initiation: 4 - 6 weeks

- Food: Standard diet ad libitum
- aclimation period: 2 weeks
- housing: groups of 5

Administration / exposure

Route of administration:
oral: feed
Vehicle:
not specified
Details on exposure:
Stability in feed over 3 days was determined via extraction and chemical identification/quantification
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
18 months
Frequency of treatment:
daily
Post exposure period:
6 months
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
low
Basis:
other: 1000 ppm(diet, nominal) for 2 months; 250 for 3 months; 500 for 13 months; recovery for 6 months
Remarks:
Doses / Concentrations:
high
Basis:
other: 2000 (diet, nominal) for 2 months; 500 for 3 months; 1000 for 13 months; recovery for 6 months
No. of animals per sex per dose:
25
Control animals:
yes, plain diet
Details on study design:
The dose level was changed several times due to observed/ no-observed effects on body weight
Positive control:
not required

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: No data

DETAILED CLINICAL OBSERVATIONS: Yes / No / No data
- Time schedule:


BODY WEIGHT: Yes
- Time schedule for examinations: no data ("carefully")


FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No data
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No data


FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No data


WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data
- Time schedule for examinations:


OPHTHALMOSCOPIC EXAMINATION: No data

HAEMATOLOGY:No data

CLINICAL CHEMISTRY: No data

URINALYSIS: No data

NEUROBEHAVIOURAL EXAMINATION: No data
Sacrifice and pathology:
GROSS PATHOLOGY: Yes ; only in animals surviving > 6 months
HISTOPATHOLOGY: Yes : but no details reported

Results and discussion

Results of examinations

Clinical signs:
not specified
Mortality:
not specified
Body weight and weight changes:
effects observed, treatment-related
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
effects observed, treatment-related
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Histopathological findings: neoplastic:
effects observed, treatment-related
Details on results:
1-Chloro-2,4-dinitrobenzene was not tumorigenic in rats
Relevance of carcinogenic effects / potential:
The study provided no indication of an influence of the testmaterial on tumor incidence in male rats.

Effect levels

Dose descriptor:
NOAEL
Effect level:
ca. 1 028 ppm (nominal)
Sex:
male
Basis for effect level:
other: Although the dose level was changed due to (missing) effects on body weight, no details were reported
Remarks on result:
other: Effect type: carcinogenicity (migrated information)

Applicant's summary and conclusion

Conclusions:
1-Chloro-2,4-dinitrobenzene was not tumorigenic in rats