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Toxicological information

Developmental toxicity / teratogenicity

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Administrative data

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
4 (not assignable)

Data source

Reference
Reference Type:
other: study report
Title:
Unnamed
Year:
2008

Materials and methods

Principles of method if other than guideline:
The study was designed to investigate the teratogenic effects of 3,4-Dichloroaniline in Charles River CrI:CD BR rats by oral (gavage) route.
GLP compliance:
not specified
Limit test:
no

Test material

Constituent 1
Reference substance name:
3,4-dichloroaniline
EC Number:
202-448-4
EC Name:
3,4-dichloroaniline
Cas Number:
95-76-1
IUPAC Name:
3,4-dichloroaniline
Details on test material:
- Name of test material :3,4-dichloroaniline
- Molecular formula :C6H5Cl2N
- Molecular weight :162.01
- Substance type:organic

Test animals

Species:
rat
Strain:
other: Charles River CrI:CD BR

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
Days 6 through 15 of gestation.
Frequency of treatment:
daily
Duration of test:
15 days of gestation
Doses / concentrations
Remarks:
Doses / Concentrations:
0,5, 25 and 125 mg/kg
Basis:

Control animals:
yes

Examinations

Maternal examinations:
BODY WEIGHT: Yes

FOOD CONSUMPTION : Yes
Ovaries and uterine content:
The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Number of implantations: Yes
- Number of absorption: Yes
Fetal examinations:
- External examinations: Yes
- Skeletal examinations: Yes

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:
Maternal toxic effects:no effects

Details on maternal toxic effects:
No statistically significant or toxicologically relevant adverse effects on any of the maternal reproductive parameters studied were observed in the 5 and 25 mg/kg dose groups.The test article did, however, produce a slight (though not statistically,,significant)increase in absorptions and consequently in post-implantation loss at 125 mg/kg.

Effect levels (maternal animals)

Dose descriptor:
NOAEL
Effect level:
25 other: mg/kg
Based on:
test mat.
Basis for effect level:
other: maternal toxicity
Remarks on result:
other: not specified

Maternal abnormalities

Abnormalities:
not specified
Localisation:
not specified
Description (incidence and severity):
not specified

Results (fetuses)

Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects:yes

Details on embryotoxic / teratogenic effects:
*No statistically significant or toxicologically relevant adverse effects on any of the embryotoxicity parameters studied were observed in the 5 and 25 mg/kg dose groups.
*A statistically significant reduction was recorded in the average body weight gains and food consumption in both the 25 and 125 mg/kg groups.
No other clinical signs of test article-related toxicity were observed for the parameters evaluated in any of the dose groups during the course of the treatment.
*There was also a significant delay in ossification of a few skeletal elements of the fetuses in this high-dose group when compared to controls.



Effect levels (fetuses)

Dose descriptor:
LOAEL
Effect level:
125 other: mg/kg bw
Based on:
test mat.
Sex:
not specified
Basis for effect level:
other: teratogenicity
Remarks on result:
other: not specified

Fetal abnormalities

Abnormalities:
not specified
Localisation:
other: not specified
Description (incidence and severity):
not specified

Overall developmental toxicity

Developmental effects observed:
not specified
Treatment related:
not specified

Applicant's summary and conclusion

Conclusions:
NOAEL for maternal toxicity study was considered to be 25 mg/kg whereas LOAEL for teratogenicity study was considered to be 125 mg/kg in Charles River CrI:CD BR rats when 3,4-dichloroaniline was administered orally by gavage.

Executive summary:

In this study, 3,4-dichloroaniline (CASRN 95-76-1) was administered orally by gavage at three doses - 5, 25 and 125 mg/kg - to groups of pregnant Charles River CrI:CD BR rats to assess its potential to promote embryotoxicity, fetotoxicity and/or teratogenicity.No statistically significant or toxicologically relevant adverse effects on any of the maternal reproductive parameters studied were observed in the 5 and 25 mg/kg dose groups.The test article did, however, produce a slight increase in absorptions and consequently in post-implantation loss at 125 mg/kg.No statistically significant or toxicologically relevant adverse effects on any of the embryotoxicity parameters studied were observed in the 5 and 25 mg/kg dose groups.A statistically significant reduction was recorded in the average body weight gains and food consumption in both the 25 and 125 mg/kg groups.No other clinical signs of test article-related toxicity were observed for the parameters evaluated in any of the dose groups during the course of the treatment.There was also a significant delay in ossification of a few skeletal elements of the fetuses in this high-dose group when compared to controls.Hence, NOAEL for maternal toxicity study was considered to be 25 mg/kg whereas LOAEL for teratogenicity study was considered to be 125 mg/kg in Charles River CrI:CD BR rats when 3,4-dichloroaniline was administered orally by gavage.