Registration Dossier

Administrative data

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
other information
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP-guideline

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1990
Report Date:
1990

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
Qualifier:
according to
Guideline:
EPA OPPTS 870.3700 (Prenatal Developmental Toxicity Study)
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): 3,4-dichloroaniline
- Physical state: solid
- Analytical purity: 99.2 %
- Lot/batch No.: 597331

Test animals

Species:
rat
Strain:
other: Charles River Crl:CD BR
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles river Breeding laboratories, portage, MI
- Age at study initiation: older than 10 weeks, younger than 18 weeks (females) or 1 year (males)
- Weight at study initiation: more than 180 g (females, 250 g (males)
- Housing: individually
- Diet : ad libitum
- Water : ad libitum
- Acclimation period: minimum 5 d


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-24
- Humidity (%): 40-70
- Air changes (per hr): climate control
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: 1989-10-03 To:1989-11-03

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Details on exposure:

VEHICLE
- Justification for use and choice of vehicle (if other than water): insoluble in water
- Concentration in vehicle: 0.05, 0.25, 1,25 %
- Amount of vehicle (if gavage): 10 mL/ kg
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
HPLC
Details on mating procedure:
- Impregnation procedure: cohoused
- If cohoused:
- M/F ratio per cage: 1/2
- Length of cohabitation: over night
- Proof of pregnancy: sperm in vaginal smear referred to as day 0 of pregnancy
Duration of treatment / exposure:
from day 6 to day 15
Frequency of treatment:
daily
Duration of test:
day 0 to day 20 of gestation
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
0 mg/kg bw
Basis:
nominal conc.
Remarks:
Doses / Concentrations:
5 mg/kg bw
Basis:
nominal conc.
Remarks:
Doses / Concentrations:
25 mg/kg bw
Basis:
nominal conc.
Remarks:
Doses / Concentrations:
125 mg/kg bw
Basis:
nominal conc.
No. of animals per sex per dose:
28 dams/ dose
Control animals:
yes
Details on study design:
Sex: female
- Dose selection rationale: range finding test indicated severe maternal toxicity when dams were treated with 175, 250 or 325 mg/kg bw

Results and discussion

Results: maternal animals

Effect levels (maternal animals)

Dose descriptor:
NOEL
Effect level:
5 mg/kg bw/day
Basis for effect level:
other: maternal toxicity

Results (fetuses)

Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects:no effects

Effect levels (fetuses)

Dose descriptor:
NOEL
Effect level:
25 mg/kg bw/day
Basis for effect level:
other: fetotoxicity

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Any other information on results incl. tables

In general, 3,4 -dichloroaniline was well tolerated and there were no overt adverse clinical signs of toxicity. However, body weight gains and food consumption were significantly reduced during treatment for both the 25 and 125 mg/kg groups. Dose levels of 5 and 25 mg/kg produced no statistically significant or toxicologically relevant adverse effects on any maternal reproductive or fetal parameter studied. There was no evidence of embryotoxicity (increased resorption), fetotoxicity (reduced growth/ delayed ossification), nor any increase in either the fetal or litter incidence of malformations for these groups. Although not statistically significant, there was a slight increase in resorption and consequently, post-implantation loss for the 125 mg/kg group which is considered treatment-related. The high-dose also promoted delayed ossification of several skeletal elements.

Applicant's summary and conclusion

Executive summary:

Clemens and Hartnagel, 1990

In the teratogenicity study 3,4 -Dichloroaniline, administered to gravid rats at doses up to and including 25 mg/kg, is devoid of any toxicity, and/ or teratogenicity. Because of significantly reduced body weight gains and food consumption at dose levels of 25 and 125 mg/ kg a dose of 5 mg/kg is considered the maternal NOEL. As a result of a significant increase in delayed ossification of a few skeletal elements and an increase in the incidence of resorption and post-implantation loss at 125 mg/kg, a dose of 25 mg/kg is considered the NOEL for developmental toxicity.