Registration Dossier

Administrative data

Endpoint:
sub-chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)

Data source

Reference
Reference Type:
secondary source
Title:
No information
Author:
National Library of Medicine HSDB Database
Year:
2002
Bibliographic source:
[Hejtmancik MR et al; Toxicol Sci 69 (1): 234-43 (2002)] **PEER REVIEWED**

Materials and methods

Principles of method if other than guideline:
Method not published.
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
other: rat and mouse
Strain:
not specified
Sex:
male/female

Administration / exposure

Route of administration:
other: deionized water
Duration of treatment / exposure:
13 weeks
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 10, 20, 40, 80, and 160 mg/kg
Basis:

No. of animals per sex per dose:
10 animals/sex/species

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
not specified
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:
effects observed, treatment-related
Clinical biochemistry findings:
effects observed, treatment-related
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

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

No mortalities occurred that could be directly attributed to treatment.

Transient clinical signs of toxicity observed after dosing included cyanosis in rats and ataxia and tremors in mice. Methemoglobin formation was directly related to dosage (rats and mice) and duration of treatment (rats). At study termination, Heinz body formation in erythrocytes in association with decreased hemoglobin, hematocrit, and red blood cell count was a prominent treatment-related effect. Enlarged spleens (gross necropsy observation) and increased spleen weight were treatment effects of each chemical in both species. Microscopic lesions typical of increased red blood cell production were found in hematopoietic tissues (bone marrow, spleen, and liver), while lesions due to increased red cell destruction were found in these tissues and also the kidneys (rats). Microscopic changes were more frequently seen and severe, and involved more body organs, in rats than mice, and in m-CA-treated animals than o-CA-treated animals. Sex differences in lesion incidence/severity were not evident.

Applicant's summary and conclusion

Conclusions:
Subchronic or Prechronic Exposure/ ... o-Chloroaniline (o-CA) or m-Chloroaniline (m-CA) was administered to 10 animals/sex/species in deionized water at dosages of 0, 10, 20, 40, 80, and 160 mg/kg for 13 weeks. Blood samples for clinical pathology were collected after 3 and 23 days in rats and at study termination (Day 93) in rats and mice. No mortalities occurred that could be directly attributed to treatment. Transient clinical signs of toxicity observed after dosing included cyanosis in rats and ataxia and tremors in mice. Methemoglobin formation was directly related to dosage (rats and mice) and duration of treatment (rats). At study termination, Heinz body formation in erythrocytes in association with decreased
hemoglobin, hematocrit, and red blood cell count was a prominent treatment-related effect. Enlarged spleens (gross necropsy observation) and increased spleen weight were treatment effects of each chemical in both species. Microscopic lesions typical of increased red blood cell production were found in hematopoietic tissues (bone marrow, spleen, and liver), while lesions due to increased red cell destruction were found in these tissues and also the kidneys (rats). Microscopic changes were more frequently seen and severe, and involved more body organs, in rats than mice, and in m-CA-treated animals than o-CA-treated animals.
Sex differences in lesion incidence/severity were not evident.