Linseed oil, ester with pentaerythritol

Toxicity to reproduction

Administrative data

Endpoint:

screening for reproductive / developmental toxicity

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1977

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The study is well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

publication

Title:

Etude sur les huiles chauffées. II: Etude toxicologique et nutritionelle chez le rat des huiles d'arachide, palme, soja et tournesol

Author:

Coquet B, Guyot D, Fouillet X and Rouard JL

Year:

1977

Bibliographic source:

Revue Française des Corps Gras 10:483-488

Materials and methods

Principles of method if other than guideline:

A 13 week (90 d) oral combined repeated dose and reproduction / developmental screening study was conducted in Sprague Dawley rat to evaluate the reproductive parameters. After 10 weeks of treatment with 15% crude palm oil, 10 males and 20 females (15 - 16 weeks of age) were mated for 18 days. The females were then allowed to produce young. Maternal bodyweight and reproductive parameters (e.g. % implantation, % surviving young, % embryo loss, ...) were recorded. At 5 weeks of age, the young were sacrificed. One male and 2 females of each litter was autopsied. Liver and kidneys were weighed. For 5 males and 5 females selected randomly, these organs were examined microscopically.

GLP compliance:

no

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Glycerides, C16-18 and C18-unsatd.

EC Number:

266-948-4

EC Name:

Glycerides, C16-18 and C18-unsatd.

Cas Number:

67701-30-8

IUPAC Name:

Glycerides, C16-18 and C18-unsatd.

Details on test material:

- Name of test material (as cited in study report): Crude palm oil (Cas N° 8002-75-3, EC N° 232-316-1). Under the SDA nomenclature, the name of this substance is ‘Glycerides, C16-18 and C18-unsatd.’
- Substance type: Triglycerides of vegetable origin

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Own breeding
- Age at study initiation: ca. 6 weeks
- Weight at study initiation: 150 g
- Housing: 5 per sex per cage
- Diet (e.g. ad libitum): 40% wheat, 20% maize, 12% fish meal, 7% blood powder, 15% oil and 6%vitamin/minerals complement
- Water (e.g. ad libitum): yes

Administration / exposure

Route of administration:

oral: feed

Vehicle:

unchanged (no vehicle)

Details on exposure:

PREPARATION OF DOSING SOLUTIONS:

DIET PREPARATION
- Rate of preparation of diet (frequency): every 4 - 5 days
- Storage temperature of food: 4°C

Details on mating procedure:

After 10 weeks of treatment, 10 males and 20 females (15 - 16 weeks of age) were mated for 18 days. The females were then allowed to produce young.

Analytical verification of doses or concentrations:

no

Details on analytical verification of doses or concentrations:

Not applicable

Duration of treatment / exposure:

90 d

Frequency of treatment:

Daily

Doses / concentrations

Remarks:

Doses / Concentrations:
15%
Basis:
nominal in diet

No. of animals per sex per dose:

10 males, 20 females for the reproduction screening

Details on study design:

No data

Positive control:

No data

Examinations

Parental animals: Observations and examinations:

See section 7.5.1 for details on 13 WEEK FEEDING STUDY

REPRODUCTION SCREENING:
Maternal bodyweight and reproductive parameters (e.g. % implantation, %surviving young, % embryo loss, ...) were recorded. At 5 weeks of age, the young were sacrificed. One male and 2 females of each litter was autopsied. Liver and kidneys were weighed. For 5 males and 5 females selected randomly, these organs were examined microscopically.

Postmortem examinations (offspring):

Microscopic pathology of liver and kidney of young rats were performed from the reproduction screening at 35 days of age.

Statistics:

No data

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:

no effects observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

no effects observed

Organ weight findings including organ / body weight ratios:

no effects observed

Histopathological findings: non-neoplastic:

not examined

Other effects:

not examined

Reproductive function / performance (P0)

Reproductive performance:

no effects observed

Details on results (P0)

During the reproductive screening study, no effects on maternal bodyweight evolution, reproductive parameters, pup liver and kidney weights, and pup liver and kidney histopathology

Effect levels (P0)

Key result

Dose descriptor:

NOAEL

Effect level:

> 15 other: % in diet equivalent to 17 - 7 g/kg bw/day

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: No significant toxicity on maternal rats or pups

Target system / organ toxicity (P0)

Key result

Critical effects observed:

not specified

Results: P1 (second parental generation)

General toxicity (P1)

Clinical signs:

not specified

Target system / organ toxicity (P1)

Key result

Critical effects observed:

not specified

Results: F1 generation

General toxicity (F1)

Clinical signs:

not specified

Details on results (F1)

During the reproductive screening study, no effects on maternal bodyweight evolution, reproductive parameters, pup liver and kidney weights, and pup liver and kidney histopathology

Effect levels (F1)

Key result

Dose descriptor:

NOAEL

Generation:

F1

Effect level:

> 15 other: % in diet equivalent to 7000 - 17000 mg/kg bw/day

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: No effects on maternal and pups

Target system / organ toxicity (F1)

Key result

Critical effects observed:

not specified

Results: F2 generation

General toxicity (F2)

Clinical signs:

not specified

Target system / organ toxicity (F2)

Key result

Critical effects observed:

not specified

Overall reproductive toxicity

Key result

Reproductive effects observed:

not specified

Any other information on results incl. tables

None

Applicant's summary and conclusion

Conclusions:

Under the study conditions, the NOAEL was considered to be 15% in diet, equivalent to 7000 - 17000 mg/kg bw/day, as no significant toxicity were observed on maternal rats and pups.

Executive summary:

A combined repeated and reproductive screening study was conducted to determine the effect of glycerides, C16-18 and C18-unsatd. (in the form of crude palm oil) on rats when administered for 13 weeks at 15% in diet. Results were compared to those obtained with heated palm oil, crude/heated soy oil, crude/heated peanut oil or crude/heated sunflower oil at the same concentration. Clinical signs and bodyweight were recorded throughout the study. After 13 weeks, hematology, clinical chemistry and urinalysis parameters were assessed, as well as gross and microscopic pathology. After 10 weeks of treatment, 10 males and 20 females were mated for 18 days. Maternal bodyweight and reproductive parameters were recorded. At 5 weeks of age, the young were sacrificed. Liver and kidneys weights were recorded and these organs were examined microscopically. The test substance did not show any adverse effects on male and female rats compared to other crude or heated vegetable oils. Furthermore, no signs of toxicity were observed on maternal rats or pups in the follow-up reproductive screening trial. Under the study conditions, the NOAEL was considered to be 15% in diet, equivalent to 7000 - 17000 mg/kg bw/day, as no significant toxicity were observed on maternal rats and pups (Coquet, 1977).