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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:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data

Data source

Reference
Reference Type:
publication
Title:
Teratogenic effects of Polyethylene Glycol 200 in the Mouse but not In the Rat.
Author:
VANNIER, B., R. BREMAUD, M. BENICOURT and P. JULIEN
Year:
1989
Bibliographic source:
TERATOLOGY; EUROPEAN TERATOLOGY SOCIETY; 40:267-304 (1989)

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
Principles of method if other than guideline:
In developmental toxicity test the teratogenic effects of the test chemical to female rat by oral route were assessed in a one generation in an overall estimation of 6-14 or 11-16 days of gestation.
GLP compliance:
not specified
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Poly(oxy-1,2-ethanediyl),α-hydro-ω-hydroxy- Ethane-1,2-diol, ethoxylated
EC Number:
500-038-2
EC Name:
Poly(oxy-1,2-ethanediyl),α-hydro-ω-hydroxy- Ethane-1,2-diol, ethoxylated
Cas Number:
25322-68-3
Molecular formula:
(C2-H4-O)mult-H2-O
IUPAC Name:
Poly(oxy-1,2-ethanediyl),α-hydro-ω-hydroxy- Ethane-1,2-diol, ethoxylated
Details on test material:
- Name of test material (as cited in study report):Polyethylene Glycol 200
- Molecular weight (if other than submission substance):200
Specific details on test material used for the study:
- Molecular weight (if other than submission substance): 200 daltons

Test animals

Species:
rat
Strain:
Sprague-Dawley
Details on test animals or test system and environmental conditions:
No Data Available

Administration / exposure

Route of administration:
oral: unspecified
Vehicle:
unchanged (no vehicle)
Details on exposure:
Rats were orally dosed on gestation days 6-14 or 11-16 with 1.5 to 5 ml/animal/day.
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
No Data Available
Details on mating procedure:
Time Mated females were used in the study.
Duration of treatment / exposure:
6-14 or 11-16 days of gestation
Frequency of treatment:
Daily
Duration of test:
20 days
Doses / concentrations
Remarks:
Doses / Concentrations:
1.5 - 5 mg/animal/day
Basis:

No. of animals per sex per dose:
No Data Available
Control animals:
not specified
Details on study design:
No Data Available

Examinations

Maternal examinations:
Maternal animals were observed for any mortality.
Ovaries and uterine content:
No Data Available
Fetal examinations:
Body weight and Fetal loss were examined.
Statistics:
No Data Available
Indices:
No Data Available
Historical control data:
No Data Available

Results and discussion

Results: maternal animals

General toxicity (maternal animals)

Clinical signs:
not specified
Dermal irritation (if dermal study):
not specified
Mortality:
mortality observed, treatment-related
Description (incidence):
Maternal death were observed at administered doses.
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
Details on results:
No Data Available

Maternal developmental toxicity

Number of abortions:
not specified
Pre- and post-implantation loss:
not specified
Total litter losses by resorption:
not specified
Early or late resorptions:
not specified
Dead fetuses:
not specified
Changes in pregnancy duration:
not specified
Changes in number of pregnant:
not specified
Other effects:
not specified
Details on maternal toxic effects:
Maternal toxic effects:yes

Details on maternal toxic effects:
Maternal deaths occured at mentioned dosages.

Effect levels (maternal animals)

Remarks on result:
not measured/tested

Maternal abnormalities

Abnormalities:
not specified

Results (fetuses)

Fetal body weight changes:
effects observed, non-treatment-related
Description (incidence and severity):
-Foetal loss and foetal bodyweight remained within normal limits.
Reduction in number of live offspring:
effects observed, non-treatment-related
Description (incidence and severity):
-Foetal loss and foetal bodyweight remained within normal limits.
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
Skeletal malformations:
no effects observed
Visceral malformations:
no effects observed
Other effects:
not specified
Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
-Foetal loss and foetal bodyweight remained within normal limits.
- No malformations were observed.

Effect levels (fetuses)

Dose descriptor:
NOAEL
Effect level:
1 500 - 5 000 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
other: teratogenicity

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified
Treatment related:
not specified

Applicant's summary and conclusion

Conclusions:
The negative teratogenic effects on foetal body weight,foetal loss and malformation by the test chemical was observed at dose concentration 1.5 - 5 ml/animal/day (equivalent to 1500 -5000 mg/kg bw/d) in 6-14 or 11-16 days of gestation period. Thus, LOAEL (No observed adversed effect level) for teratogenicity study is considered to be 1.5 - 5 ml/animal/day (equivalent to 1500 -5000 ng/kg bw/d).
Executive summary:

A teratogenic study was conducted to evaluate the foetal body weight,foetal loss and any kind of malformation by the test chemical to female rats orally dosed on gestational days 6-14 or 11-16 with 1.5 -5 ml/animal/day (equivalent to 1500 -5000 ng/kg bw/d). The test chemical was shown to have negative teratogenic effects as Foetal loss and foetal body weight remained within normal limits and no malformations were observed in rats after administration of dosage 1.5 -5 ml/animal/day (equivalent to 1500 -5000 mg/kg bw/d) of the test chemical. Since LOAEL (Low observed adversed effect level) is 1.5 -5 ml/animal/day (equivalent to 1500 -5000 mg/kg bw), it is regarded that there is no teratogenic effectsin the fetuses at concentrations 1.5 -5ml/animal/day (equivalent to 1500 -5000 mg/kg bw/d) when administered orally.