Registration Dossier

Administrative data

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Justification for type of information:
Peer reviewed journal research article

Data source

Reference
Reference Type:
publication
Title:
A Review: Trichloroethylene Metabolites: Potential Cardiac Teratogens
Author:
Paula D. Johnson, Brenda V. Dawson and Stanley J. Goldberg
Year:
1998
Bibliographic source:
Environmental Health Perspectives, Vol 106, Supplement 4, 995-999, August 1998.

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
other: Refer below Principle
Principles of method if other than guideline:
The developmental toxicity of test chemical was evaluated by conducting study in female rats.
GLP compliance:
no
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Trichloroacetaldehyde
EC Number:
200-911-5
EC Name:
Trichloroacetaldehyde
Cas Number:
75-87-6
Molecular formula:
C2HCl3O
IUPAC Name:
trichloroacetaldehyde
Test material form:
liquid
Details on test material:
- Name of test material (as cited in study report): Chloral
- Molecular formula: C2HCl3O
- Molecular weight: 147.3879 g/mol
- Substance type: organic
- Physical state: Liquid
- Smiles notation: C(C=O)(Cl)(Cl)Cl
- InChl: 1S/C2HCl3O/c3-2(4,5)1-6/h1H

Test animals

Species:
rat
Strain:
not specified
Details on test animals or test system and environmental conditions:
not specified

Administration / exposure

Route of administration:
oral: drinking water
Type of inhalation exposure (if applicable):
not specified
Vehicle:
water
Details on exposure:
not specified
Analytical verification of doses or concentrations:
no
Details on mating procedure:
not specified
Duration of treatment / exposure:
Approx. 21 days (During Pregnancy)
Frequency of treatment:
Daily
Duration of test:
not specified
Doses / concentrations
Remarks:
0 and 151 mg/kg bw/day
No. of animals per sex per dose:
not specified
Control animals:
yes, concurrent vehicle
Details on study design:
not specified

Examinations

Maternal examinations:
Survival, Clinical sign, Weight gain, pregnancy complications and uterine complication were examined.
Ovaries and uterine content:
implantation sites and resorption site were examined.
Fetal examinations:
Live and dead fetuses. Fetal weight, placental weight, crown-rump length, and external morphology were studied.
Congenital cardiac malformations: Like Abnormal looping, Aortic hypoplasia, Pulmonary artery hypoplasia, Atrial septal defects, Mitral valve defects, Tricuspid valve defects ,Pulmonary valve defects, Atrioventricular septal defects,etc were examined.

Statistics:
Fisher exact analysis were used.
Indices:
not specified
Historical control data:
not specified

Results and discussion

Results: maternal animals

General toxicity (maternal animals)

Clinical signs:
no effects observed
Description (incidence and severity):
No evidence of toxicity was observed in treated female rats at 151 mg/kg bw as compared to contorl.
Dermal irritation (if dermal study):
not specified
Mortality:
no mortality observed
Description (incidence):
No mortality was observed in treated female rats at 151 mg/kg bw as compared to contorl.
Body weight and weight changes:
no effects observed
Description (incidence and severity):
No change in body weight gain was observed in treated female rats at 151 mg/kg bw as compared to contorl.
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
Immunological findings:
not specified
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
no effects observed
Description (incidence and severity):
No gross pathological changes were observed in treated female rats at 151 mg/kg bw as compared to contorl.
Neuropathological findings:
not examined
Histopathological findings: non-neoplastic:
not examined
Histopathological findings: neoplastic:
not examined

Maternal developmental toxicity

Number of abortions:
no effects observed
Pre- and post-implantation loss:
no effects observed
Description (incidence and severity):
No effect on implantation sites were observed
Total litter losses by resorption:
no effects observed
Description (incidence and severity):
No effect on resorption sites were observed
Early or late resorptions:
no effects observed
Description (incidence and severity):
No effect on resorption sites were observed
Dead fetuses:
no effects observed
Description (incidence and severity):
No effect on live and dead fetuses were observed in treated female rats at 151 mg/kg bw as compared to contorl.
Changes in pregnancy duration:
no effects observed
Changes in number of pregnant:
not specified
Other effects:
not specified
Details on maternal toxic effects:
There was no complications in pregnancy were observed, steady weight gain was observed. All uterine and ovarian morphologic examinations were normal.

Effect levels (maternal animals)

Dose descriptor:
NOAEL
Effect level:
151 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
other: Congenital cardiac malformations

Maternal abnormalities

Abnormalities:
not specified
Localisation:
not specified

Results (fetuses)

Fetal body weight changes:
no effects observed
Description (incidence and severity):
No effect on fetal weight were observed.
Reduction in number of live offspring:
no effects observed
Description (incidence and severity):
No efect on numbers of live or dead fetuses were observed.
Changes in sex ratio:
not specified
Changes in litter size and weights:
not specified
Changes in postnatal survival:
not specified
External malformations:
no effects observed
Description (incidence and severity):
No effect on external morphology were observed.
Skeletal malformations:
not specified
Visceral malformations:
not specified
Other effects:
no effects observed
Description (incidence and severity):
No effect on placental weight were observed.
No effect on crown-rump length and noncardiac internal organ congenital abnormalities were observed.

Effect levels (fetuses)

Dose descriptor:
NOAEL
Effect level:
151 mg/kg bw/day
Based on:
test mat.
Sex:
female
Basis for effect level:
reduction in number of live offspring
fetal/pup body weight changes
external malformations
other: Placental weight, Crown-rump length.

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

Any other information on results incl. tables

Table: Congenital cardiac Malformations

 

 

Group

Heart abnormalities

Trichloroacetaldehyde p.

(151 mg/kg bw/day)

Abnormal looping

-

Aortic hypoplasia

-

Pulmonary artery hypoplasia

-

Atrial septal defects

2

Mitral valve defects,

Hypoplasia or ectasia

2

Tricuspid valve defects,

Hypoplasia or ectasia

-

Ventricular septal defects,

Perimembranousa

Mascular

 

3

-

Atrioventricular

Septal defects

-

Pulmonary valve defects

1

Aortic valve defects

-

Situs inversus

-

Total

Abnormal Hearts

Fetuses with abnormal hearts

Fetuses

 

8

8

248


aSubaortic

Applicant's summary and conclusion

Conclusions:
NOAEL was considered to be 151 mg/kg/day P and F1 generation when female rats were treated with test chemical orally in water.

Executive summary:

The developmental toxicity of test chemical was evaluated by conducting experiment in female rats. Test chemical was administered orally in drinking water. Chemical was given to rats during organogenesis. Test chemical dose 0 and 151 mg/kg bw/day. No reproductive effects were observed on health, weight gain, and pregnancy, uterine and ovarian morphologic examinations. Similarly, no effect on implantation sites, resorption sites were observed as compared to control. In addition, no deveplmental effect such as live and dead fetuses, fetal weight, placental weight, crown-rump length, gross external or noncardiac internal organ congenital abnormalities were observed in fetus of treated female rats. Therefore, NOAEL was considered to be 151 mg/kg/day P and F1 generation when female rats were treated with test chemical orally in water.