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Toxicological information

Toxicity to reproduction

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Administrative data

Endpoint:
fertility, other
Remarks:
Cardiac teratogenesis
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:
Data from peer reviewed journal.

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:
Reproductive toxicity effect of test chemical was evaluated by conducting experiment on rat.
GLP compliance:
no
Limit test:
no
Justification for study design:
No data

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
Sex:
female
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
Remarks:
drinking
Details on exposure:
PREPARATION OF DOSING SOLUTIONS: Test chemical was dissolve in drinking Water.

VEHICLE
- Justification for use and choice of vehicle (if other than water): drinking water
- Concentration in vehicle: 0 and 151 mg/kg bw
- Amount of vehicle (if gavage): 42 ml/day
- Lot/batch no. (if required): No data
- Purity: No data
Details on mating procedure:
not specified
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
approx 21 days (During pregnancy)
Frequency of treatment:
Daily
Details on study schedule:
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
Positive control:
not specified

Examinations

Parental animals: Observations and examinations:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: No data
- Cage side observations checked in table [No.?] were included: Rats were observed for mortality.

DETAILED CLINICAL OBSERVATIONS: Rats were observed for sign of toxicity.

- Time schedule: No data

BODY WEIGHT: Rats were observed for body weight.
- Time schedule for examinations: No data

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): No data
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No data
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No data

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data
- Time schedule for examinations: No data

OTHER:
Oestrous cyclicity (parental animals):
Pregnancy complications, implantation sites, were observed
Sperm parameters (parental animals):
not specified
Litter observations:
Numbers of live or dead fetuses, fetal weight and crown-rump length were observed
Postmortem examinations (parental animals):
uterine and ovarian morphologic were examinations.
Postmortem examinations (offspring):
placental weight, no gross external or noncardiac internal organ congenital abnormalitieswere examined.
Statistics:
Using Fisher exact analysis, mean number of implantation site and resorption site for treated group and control group was estimated.
Reproductive indices:
not specified
Offspring viability indices:
not specified

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

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:
not specified
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not specified
Other effects:
not specified

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:
no effects observed
Description (incidence and severity):
No effect on implantation sites and resorption sites were observed in treated female rats at 151 mg/kg bw as compared to contorl.
Reproductive function: sperm measures:
not specified
Reproductive performance:
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.

Effect levels (P0)

Dose descriptor:
NOAEL
Effect level:
151 mg/kg bw/day
Based on:
test mat.
Sex:
female
Basis for effect level:
clinical signs
mortality
body weight and weight gain
gross pathology
reproductive function (oestrous cycle)
reproductive performance
Remarks on result:
other: No effects were noted

Target system / organ toxicity (P0)

Critical effects observed:
not specified
System:
other: Not specified
Organ:
not specified

Results: P1 (second parental generation)

General toxicity (P1)

Clinical signs:
not specified
Dermal irritation (if dermal study):
not specified
Mortality:
not specified
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:
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:
not specified
Gross pathological findings:
not specified
Neuropathological findings:
not specified
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not specified
Other effects:
not specified

Reproductive function / performance (P1)

Reproductive function: oestrous cycle:
not specified
Reproductive function: sperm measures:
not specified
Reproductive performance:
not specified

Effect levels (P1)

Based on:
not specified
Sex:
not specified
Basis for effect level:
other: not specified
Remarks on result:
other: not specified

Target system / organ toxicity (P1)

Critical effects observed:
not specified
System:
other: Not specified
Organ:
not specified

Results: F1 generation

General toxicity (F1)

Clinical signs:
not specified
Dermal irritation (if dermal study):
not specified
Mortality / viability:
no mortality observed
Description (incidence and severity):
No efect on numbers of live or dead fetuses were observed.
Body weight and weight changes:
no effects observed
Description (incidence and severity):
No effect on fetal weight were observed.
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
Sexual maturation:
not specified
Organ weight findings including organ / body weight ratios:
no effects observed
Description (incidence and severity):
No effect on placental weight were observed.
Gross pathological findings:
no effects observed
Description (incidence and severity):
No effect on external morphology were observed.
Histopathological findings:
not specified
Other effects:
no effects observed
Description (incidence and severity):
No effect on crown-rump length and noncardiac internal organ congenital abnormalities were observed.

Developmental neurotoxicity (F1)

Behaviour (functional findings):
not specified

Developmental immunotoxicity (F1)

Developmental immunotoxicity:
not specified

Effect levels (F1)

Dose descriptor:
NOAEL
Generation:
F1
Effect level:
151 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
viability
mortality
body weight and weight gain
organ weights and organ / body weight ratios
gross pathology
other: cardiac defects

Target system / organ toxicity (F1)

Critical effects observed:
no
System:
cardiovascular
Organ:
heart

Results: F2 generation

General toxicity (F2)

Clinical signs:
not specified
Dermal irritation (if dermal study):
not specified
Mortality / viability:
not specified
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:
not specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Sexual maturation:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Histopathological findings:
not specified
Other effects:
not specified

Developmental neurotoxicity (F2)

Behaviour (functional findings):
not specified

Developmental immunotoxicity (F2)

Developmental immunotoxicity:
not specified

Effect levels (F2)

Based on:
not specified
Sex:
not specified
Basis for effect level:
other: not specified
Remarks on result:
other: not specified

Target system / organ toxicity (F2)

Critical effects observed:
not specified
System:
other: not specified
Organ:
other: not specified

Overall reproductive toxicity

Reproductive 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 for P and F1 generation when female rats were treated with test chemical orally in water.
Executive summary:

The reproductive 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 at the concentration of 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 developmental effect such as live and dead fetuses, fetal weight, placental weight, crown-rump length, gross external or no cardiac 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.

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