Squalene-rich fraction obtained from vegetable oil deodorizer distillate by transesterification, crystallisation and vacuum distillation

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1972

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

publication

Title:

Effects of fresh and used hydrogenated soybean oil on reproduction and teratology in rats

Author:

Nolen GA

Year:

1972

Bibliographic source:

J. Am. Oil Chem. Soc. 49:688-693

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Developmental toxicity/teratogenicity potential was observed in a two generation reproductive toxicity study after dietary administration of the constituent 15% partially hydrogenated soybean oil in Sprague Dawley rats.

Groups of 25 pairs of two generations of male and female rats were fed diets containing 15% of fresh partially hydrogenated soybean oil. F0 generation was exposed to the test material from weaning and F1 generation from conception. The first two litters of each generation were
permitted to be born naturally. During the third pregnancy of each generation, one-half of the females were sacrificed on Day 13 of gestation and inspected for early embryonic death. The remaining females were sacrificed on Day 21 of gestation, and the fetuses were examined for either skeletal or soft tissue abnormalities.

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:

266-948-4

Test animals

Species:

rat

Strain:

Sprague-Dawley

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Diet: Semipurified rat diet, ad libitum

Administration / exposure

Route of administration:

oral: feed

Vehicle:

unchanged (no vehicle)

Details on exposure:

DIET PREPARATION
- Rate of preparation of diet (frequency): Weekly
- Mixing appropriate amounts with (Type of food): Semipurified rat diet
- Storage temperature of food: Under refrigeration

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

Not applicable

Details on mating procedure:

- Proof of pregnancy: Cornified cells and spermatozoa in vaginal smear; referred to as Day 0 of pregnancy

Duration of treatment / exposure:

F0 generation: From weaning and F1 generation: From conception

Frequency of treatment:

Daily ad libitum in diet

Duration of test:

Up to Day 13/21 of gestation or up to weaning of offsprings (see further details on study design for explanation)

Doses / concentrations

Remarks:

Doses / Concentrations:
15%
Basis:
nominal in diet

No. of animals per sex per dose:

25 animals/sex

Control animals:

no

Details on study design:

The first two litters of F0 and F1 generations (i.e. F1a, F1b, F2a and F2b) were permitted to be born naturally. All F1a, F2a and F2b litters were discarded at weaning. F1b rats were allowed to grow for further mating. During the third pregnancy of each generation (i.e. F1c and F2c), one-half of the females were sacrificed on Day 13 of gestation and inspected for early embryonic death. The remaining females were sacrificed on Day 21 of gestation, and the fetuses were examined for either skeletal or soft tissue abnormalities.

Examinations

Maternal examinations:

BODY WEIGHT: Weekly during the first 8 wks (after weaning)


FOOD CONSUMPTION: Weekly during the first 8 wks (after weaning)


POST-MORTEM EXAMINATIONS: Yes
- Organs examined: Heart, lung, stomach, liver, kidney, adrenals, small and large intestine, spleen, gonads, bladder, pancreas and mesenteric lymph nodes

Ovaries and uterine content:

The uterine content was examined after termination: Yes
Examinations included:
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of resorptions: Yes

Fetal examinations:

- Soft tissue examinations: Yes
- Skeletal examinations: Yes

Statistics:

The data were analyzed statistically by the Analysis of Variance and Chi-square method

Indices:

None

Historical control data:

No data

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:

Maternal toxic effects:no effects

Details on maternal toxic effects:
No evidence of maternal toxicity in both F0 and F1 generation

Effect levels (maternal animals)

Key result

Dose descriptor:

NOAEL

Effect level:

15 other: % in diet

Basis for effect level:

other: no treatment-related effects

Results (fetuses)

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
No dead fetuses or any evidence of teratogenic effects

Effect levels (fetuses)

Key result

Dose descriptor:

NOAEL

Effect level:

15 other: %

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: no treatment-related effects on development of the fetuses

Fetal abnormalities

Key result

Abnormalities:

no effects observed

Overall developmental toxicity

Key result

Developmental effects observed:

no

Any other information on results incl. tables

Table 1. Effect of partially hydrogenated soybean oil on development of rat fetus

 

Generation	F1c	F2c
No. of fetuses examined for soft-tissue defects	65	75
Fetuses with soft-tissue defects	0	0
No. of fetuses examined for skeletal defects	30	37
Fetuses with skeletal defects	0	1

Applicant's summary and conclusion

Conclusions:

Under the conditions of this study, the NOAEL for maternal and developmental toxicity was considered to be 15% of the substance in diet.

Executive summary:

A study was conducted to evaluate the developmental toxicity/teratogenicity potential of the constituent 15% ‘glycerides, C8 -18 and C18 -unsatd.’ (as partially hydrogenated soybean oil) in Sprague Dawley rats. Groups of 25 pairs of two generations of male and female rats were fed diets containing 15% of the substance. The F0 generation was exposed to the substance from weaning and the F1 generation from conception. The first two litters of each generation were allowed to be born naturally. During the third pregnancy of each generation, one-half of the females were sacrificed on Day 13 of gestation and inspected for early embryonic death. The remaining females were sacrificed on Day 21 of gestation and fetuses were examined for either skeletal or soft tissue abnormalities. No evidence of any maternal or developmental toxicity (including teratogenicity) was observed in any of the generations. Under the conditions of this study, the NOAEL for maternal and developmental toxicity was considered to be 15% of the substance in diet (Nolen, 1972).