Sorbitan monostearate, ethoxylated

Developmental toxicity / teratogenicity

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:

Data is from publication.

Data source

Reference

Reference Type:

publication

Title:

TERATOLOGY STUDY OF TEST CHEMICAL IN RATS

Author:

Ema, M. et al

Year:

1988

Bibliographic source:

Drug Chem. Toxicol. (1977) 1988, 11(3), 249-260

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:

To examine the teratogenic potential of test chemical given to pregnant rats during the organogenetic period.

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Sorbitan monostearate, ethoxylated

EC Number:

500-020-4

EC Name:

Sorbitan monostearate, ethoxylated

Cas Number:

9005-67-8

Molecular formula:

C64-H126-O26 Unspecified

IUPAC Name:

Sorbitan monostearate, ethoxylated

Details on test material:

- Name of test material (as cited in study report): Sorbitan monostearate, ethoxylated
- Substance type: Organic
- Physical state: Liquid

Specific details on test material used for the study:

- Substance type: Organic
- Physical state: Liquid

Test animals

Species:

rat

Strain:

Wistar

Details on test animals or test system and environmental conditions:

Details on test animals and env. conditions
TEST ANIMALS
- Source: No Data Available
- Age at study initiation: 12 weeks of age
- Weight at study initiation: (P) No Data
- Fasting period before study: No Data Available
- Housing: No Data Available
- Use of restrainers for preventing ingestion (if dermal): No
- Diet (e.g. ad libitum): basal diet (CE-2, Drug Clea Japan Inc., Tokyo) and tap water ad libitum.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 24+/- 1 oC
- Humidity (%): 55+/- 5 %.
- Air changes (per hr): No data Available
- Photoperiod (hrs dark / hrs light): No Data Available

Administration / exposure

Route of administration:

oral: feed

Vehicle:

other: feed

Details on exposure:

Pregnant rats were given test chemical at a dose of 0, 0.1 (99 mg/kg), 1.0 (960 mg/kg) or 10% (7693 mg/kg)of test chemical in the diet from day 7 to day 14 of pregnancy.

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

No data available

Details on mating procedure:

Virgin female rats of about 12 weeks of age were mated for 15 hours with male rats of same strain. The day when the spermatozoa in the vagina was detected was considered to be day 0 of pregnancy.

Duration of treatment / exposure:

Days 7-14 of gestation

Frequency of treatment:

Daily

Duration of test:

No data

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 0.1, 1.0 or 10%
Basis:
0.1% (99 mg/kg), 1.0% (960 mg/kg) or 10% (7693 mg/kg)

No. of animals per sex per dose:

No data

Control animals:

yes, plain diet

Details on study design:

No data available

Examinations

Maternal examinations:

The pregnant rats were observed for evidence of clinical signs of toxicity and weighed daily.

Ovaries and uterine content:

The peritoneal cavity and uterus were opened, and the numbers and positions of live and dead fetuses and resorptions were recorded.23

Fetal examinations:

The live fetuses removed from the uterus by cesarean section were sexed, weighed and inspected for external anomalies and anomalies within
the oral cavity.

About half of the fetuses in each litter were fixed in alcohol, cleared in KOH solution, stained with Alizarin Red S14 and examined for skeletal anomalies.

The remaining half of the fetuses in each litter were fixed in Bouin's solution, sectioned with a razor blade and examined for internal anomalies

Statistics:

Statistical analysis of the data was carried out using the litter as a unit.Student's t-test, Wilcoxon's rank sum test, chi-square test with Yates' correction or Fisher's exact probability test was used. The level of significance chosen was p < 0.05.

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:

not specified

Body weight and weight changes:

no effects observed

Description (incidence and severity):

No significant difference was noted in the maternal body weight gain during the treatment period between the treated and control groups.

Food consumption and compound intake (if feeding study):

no effects observed

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

Maternal developmental toxicity

Number of abortions:

effects observed, non-treatment-related

Description (incidence and severity):

The incidences of intrauterine death in the 1.0 % (960mg/kg) group were significantly higher than that of the control group

Pre- and post-implantation loss:

effects observed, non-treatment-related

Description (incidence and severity):

In the 99 mg/kg group, the number of implantations per litter was significantly higher than that of the control group.

Total litter losses by resorption:

effects observed, non-treatment-related

Description (incidence and severity):

The incidences of resorptions in the 1.0 % (960mg/kg) group were significantly higher than that of the control group. No significant effect on number of resorptions were observed in treated and control animals.

Early or late resorptions:

effects observed, non-treatment-related

Description (incidence and severity):

The incidences of resorptions in the 1.0 % (960mg/kg) group were significantly higher than that of the control group. No significant effect on number of resorptions were observed in treated and control animals.

Dead fetuses:

no effects observed

Description (incidence and severity):

No significant effect were observed in live and dead fetuses per litter in treated and control animals.

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:no effects

Effect levels (maternal animals)

Dose descriptor:

NOAEL

Effect level:

960 mg/kg bw/day

Based on:

test mat.

Basis for effect level:

body weight and weight gain

dead fetuses

early or late resorptions

effects on pregnancy duration

food consumption and compound intake

maternal abnormalities

number of abortions

organ weights and organ / body weight ratios

pre and post implantation loss

total litter losses by resorption

Remarks on result:

other: Not Specified

Maternal abnormalities

Abnormalities:

not specified

Results (fetuses)

Fetal body weight changes:

no effects observed

Description (incidence and severity):

No change in the fetal body weight of both sexes were seen in any group at 99, 960 and 7693mg/kg

Reduction in number of live offspring:

not specified

Changes in sex ratio:

no effects observed

Description (incidence and severity):

No change in the sex ratio of live fetuses of both sexes in any group at 99, 960 and 7693mg/kg

Changes in litter size and weights:

not specified

Changes in postnatal survival:

not specified

External malformations:

no effects observed

Description (incidence and severity):

Neither external anomalies were found in any group at 99, 960 and 7693mg/kg

Skeletal malformations:

no effects observed

Description (incidence and severity):

Neither skeletal anomalies were found in any group at 99, 960 and 7693mg/kg

Visceral malformations:

no effects observed

Description (incidence and severity):

No visceral abnirmalities were seen in any group at 99, 960 and 7693mg/kg

Other effects:

not specified

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:no effects

Effect levels (fetuses)

Dose descriptor:

NOAEL

Effect level:

7 693 mg/kg bw/day

Based on:

test mat.

Sex:

female

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:

Based on the observations the NOAEL for the test chemical was considered to be 7693mg/kg in Wistar rats

Executive summary:

The present study aimed, to examine the teratogenic potential of test chemical given to pregnant rats during the organogenetic period. The mating was done by using Virgin female rats of about 12 weeks of age were mated for 15 hours with male rats of same strain. The day when the spermatozoa in the vagina was detected was considered to be day 0 of pregnancy. In this study the pregnant Wistar rats were given test chemical at a dose of 0, 0.1 (99 mg/kg), 1.0 (960 mg/kg) or 10% (7693 mg/kg) in the diet from day 7 to day 14 of pregnancy. The treated female rats observed for evidence of clinical signs of toxicity and weighed daily. On day 20 of pregnancy, the pregnant rats in each group were killed by cervical dislocation. The peritoneal cavity and uterus were opened, and the numbers and positions of live and dead fetuses and resorptions were recorded. The live fetuses removed from the uterus by cesarean section were sexed, weighed and inspected for external anomalies and anomalies within the oral cavity. About half of the fetuses in each litter were fixed in alcohol, cleared in KOH solution, stained with Alizarin Red S14 and examined for skeletal anomalies. The remaining half of the fetuses in each litter were fixed in Bouin's solution, sectioned with razor blade and examined for internal anomalies.The results of the study revealed, No significant difference in the maternal body weight gain during the treatment period between the treated and control groups. The maternal developmental toxicity results revealed, the incidences of intrauterine death in the 1.0 % (960mg/kg) group were significantly higher than that of the control group however no such effects were seen in treated group at 96 and 7693mg/kg. In the 99mg/kg group, the number of implantations per litter was significantly higher than that of the control group. The incidences of resorptions in the 1.0 % (960mg/kg) group were significantly higher than that of the control group. No significant effect on number of resorptions were observed in treated and control animals. No significant effect were observed in live and dead fetuses per litter in  treated and control animals. No change in the sex ratio of live fetuses and the fetal body weight of both sexes. No other maternal toxicty effects were observed. When the fetuses toxicity examined no change in the sex ratio of live fetuses and the fetal body weight of both sexes weight were observed. Neither external, skeletal and vesceral anomalies were observed in any treated groups at 99, 960 and 7693mg/kg. Thus, based on the observations and results of the study, the NOAEL for the test chemical was considered to be 7693mg/kg in Wistar rats.