Plant Sterols

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

migrated information: read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study was conducted according to current OECD guideline and in compliance with GLP.

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1999

Report date:

1999

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 414 (Prenatal Developmental Toxicity Study)

GLP compliance:

yes

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Stanol fatty acid esters

IUPAC Name:

Stanol fatty acid esters

Details on test material:

The sample identified as Sito – 70 stanol ester contained 57.08% total stanols/100g fat (68% sitostanol, 30% campestanol, 2% unsaturated sterol), 41.96% fatty acids and 2% unsaturated sterols and unknowns.

Approximately 93.4% of the esterified groups was C-18 fatty acids, with 3.6% C-16, 2.1% C-20 and 0.9% other fatty acid esters.



Note: Rapeseed oil was used to top-up the diets in the developmental toxicity study. Although the literature reports sterol concentrations in the order of a few hundred mg/100 g, this is unlikely to negate the validity of the study, since there were no findings of adverse effects on developmental parameters.

Test animals

Species:

rat

Strain:

Wistar

Administration / exposure

Route of administration:

oral: feed

Vehicle:

unchanged (no vehicle)

Duration of treatment / exposure:

From day 0 to 21 of gestation. The diets contained 0, 1, 2 or 5% total stanols (corresponding to 0, 1.75, 4.38 and 8.76% of the stanol ester test material).

Frequency of treatment:

From day 0 to 21 of gestation, daily

Duration of test:

21 days

Doses / concentrations

Remarks:

Doses / Concentrations:
The diets contained 0, 1, 2 or 5% total stanols (corresponding to 0, 1.75, 4.38 and 8.76% of the stanol ester test material).
Basis:
nominal in diet

No. of animals per sex per dose:

28 mated females

Control animals:

yes, concurrent no treatment

Results and discussion

Results: maternal animals

Effect levels (maternal animals)

Dose descriptor:

NOAEL

Effect level:

> 2 400 mg/kg bw/day

Based on:

test mat.

Basis for effect level:

other: developmental toxicity

Results (fetuses)

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:no effects

Fetal abnormalities

Abnormalities:

not specified

Overall developmental toxicity

Developmental effects observed:

not specified

Any other information on results incl. tables

Food consumption

The effect of PE on the food consumption was inconsistent, but significantly different compared to the control group; both increasing and decreasing during different phases of the study.

Water consumption

No information.

 

Clinical signs

None noted that could be attributed to the test compound.

 

Effects on developmental performance

None noted that could be attributed to the test compound.

 

Body weight

Body weight gains were not significantly different from control values for any group throughout gestation except for a small but statistically significant decrease at days 0 -7 for the high dose group. This is believed to be due to a decrease in calorific content of the diet from the levels of unabsorbable stanols at the highest dose.

 

Organ weights

No statistically significant changes in organ weights in comparison to the control group.

 

Haematology

No specific information provided.

 

Clinical Chemistry

No specific information provided.

 

Urinalysis

No specific information provided.

 

Macroscopic examination

No findings noted at necropsy.

 

Histopathology

No specific information provided.

Applicant's summary and conclusion

Conclusions:

The test sample was given in the diet of rats (SPF Wistar) from day 0 to 21 of gestation after which time they were sacrificed and examined. The diets contained 0, 1, 2 or 5% total stanols (corresponding to 0, 1.75, 4.38 and 8.76% of the stanol ester test material). No adverse treatment-related maternal or foetal developmental effects were produced following ingestion of a diet containing up to 8.76% plant stanol fatty acid esters. This diet provided up to 5% of total dietary stanols equivalent to 2.4-3.5 g stanols/kg bw/day.

Executive summary:

No adverse treatment-related maternal or foetal developmental effects were produced following ingestion of a diet containing up to 8.76% plant stanol fatty acid esters. This diet provided up to 5% of total dietary stanols equivalent to 2.4-3.5 g stanols/kg bw/day depending on the (days 0 -7: 3.5 g total stanols/kg bw/day, days 7 -14: 3.6 g total stanols/kg/bw/day, days 14 -21: 2.4g total stanols/kg/bw/day)

 

No significant differences were seen in reproductive performance, maternal and foetal body weights, sex distribution, or visceral or skeletal malformations, anomalies, and variations. Vegetable oil-derived stanol fatty acid esters are concluded not to be developmental toxicants and did not produce any embryotoxic, foetotoxic, or teratogenic effects in Wistar rats under the conditions of the study.