Registration Dossier

Administrative data

Endpoint:
short-term repeated dose toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: secondary literature

Data source

Reference
Reference Type:
secondary source
Title:
Unnamed
Year:
1982

Materials and methods

Principles of method if other than guideline:
Groups of 16 mal Crl:CD rats were exposed head-only, 6 hrs/day, 5 days/week, for 2 weeks to either 6, 30 or 50 ppm( = ca. 31.8, 159 or 265 mg/m³) m-chloroaniline. A control group was simultaneously exposed to air only. Animals were evaluated for clinical and histopathological lesions following 10 exposures and after a 14-day recovery period.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: liquid
Details on test material:
no data

Test animals

Species:
rat
Strain:
Crj: CD(SD)
Sex:
male

Administration / exposure

Route of administration:
other: vapour/aerosol
Type of inhalation exposure:
head only
Vehicle:
air
Remarks on MMAD:
MMAD / GSD: no data
Analytical verification of doses or concentrations:
yes
Duration of treatment / exposure:
2 weeks
Frequency of treatment:
6 hrs/day, 5 days/week, for 2 weeks
Doses / concentrations
Remarks:
Doses / Concentrations:
6, 30 or 50 ppm( = ca. 31.8, 159 or 265 mg/m³) m-chloroaniline
Basis:
nominal conc.
No. of animals per sex per dose:
16 animals/dose
Control animals:
yes, concurrent vehicle

Results and discussion

Effect levels

Dose descriptor:
LOAEC
Effect level:
32 mg/L air (nominal)
Based on:
test mat.
Sex:
male
Basis for effect level:
other: extramedullary hematopoesis, hemosiderin deposits in spleen, methemoglobinemia

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

During and immediately following exposure, rats in the 30 and 50 ppm dose groups were slight to moderately cyanotic. Slight increase in body weights were observed in all test groups during exposure and recovery.

Clinical pathological examinations revealed a dose-dependent effect of m-chloroaniline on several hematologic parameters. Decrease in erythrocyte count, hemoglobin content, and hematocrit and increase in leucocytes, immature erythrocytes, mean cell volume and mean cell hemoglobin resulted from 10 exposures to all exposure levels.

Pathologic examinations revealed dose-dependent microscopic changes in hematopoetic tissues consistent with the development of hemolytic anemia and subsequent extramodullary hematopoesis.

Applicant's summary and conclusion

Executive summary:

Groups of 16 mal Crl:CD rats were exposed head-only, 6 hrs/day, 5 days/week, for 2 weeks to either 6, 30 or 50 ppm( = ca. 31.8, 159 or 265 mg/m³) m-chloroaniline. A control group was simultaneously exposed to air only. animals were evaluated for clinical and histopathological lesions following 10 exposures and after a 14-day recovery period.

During and immediately following exposure, rats in the 30 and 50 ppm dose groups were slight to moderately cyanotic. Slight increase in body weights were observed in all test groups during exposure and recovery.

Clinical pathological examinations revealed a dose-dependent effect of m-chloroaniline on several hematologic parameters. Decrease in erythrocyte count, hemoglobin content, and hematocrit and increase in leucocytes, immature erythrocytes, mean cell volume and mean cell hemoglobin resulted from 10 exposures to all exposure levels.

Pathologic examinations revealed dose-dependent microscopic changes in hematopoetic tissues consistent with the development of hemolytic anemia and subsequent extramodullary hematopoesis.