Reaction products resulting from the esterification of C18 unsaturated fatty acid with glycerol and glycerol oligomers

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

1950-MM-DD to 1960-MM-DD

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Sound scientific publication. This study was conducted during the late 1950s/early1960s and the methods represented the state of the art which existed during this period. They nevertheless allow an adequate assessment of the potential reproductive and chronic toxicity of PGPR.

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1998

Report date:

1998

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: This study was conducted during the late 1950s/early1960s and the methods represented the state of the art which existed during this period. They nevertheless allow an adequate assessment of the potential reproductive and chronic toxicity of PGPR.

Principles of method if other than guideline:

A three-generation reproduction study was conducted on PGPR to investigate the potential adverse effects on reproduction. Breeding was conducted using a continuous breeding protocol in which pairs of animals were maintained until each female had produced five litters (or it became evident that breeding had ceased) and this was conducted over three generations. The main focus of the study design was to observe any effect on breeding. Parameters measured in each of the three generations included number of litters per dam, average litter size, average weaning weights of males and females, litters per group showing 100% survival and total survival (%) at day 21.

GLP compliance:

no

Remarks:

Studies were performed prior to implementation of GLP

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Polyglycerol polyricinoleate

IUPAC Name:

Polyglycerol polyricinoleate

Constituent 2

Reference substance name:

29894-35-7

EC Number:

608-428-5

Cas Number:

29894-35-7

IUPAC Name:

29894-35-7

Constituent 3

Reference substance name:

PGPR

IUPAC Name:

PGPR

Test material form:

not specified

Details on test material:

ADMUL WOL, a brand of polyglycerol polyricinoleate (PGPR). PGPR is a very powerful emulsifier which was primarily developed for the production of water-in-oil emulsions for tin-greasing in the baking trade. However, its main use is in chocolate where in addition to its action as an emulsifier, it also has valuable properties as a viscosity modifier and thus improves the moulding properties of the molten chocolate.

Specific details on test material used for the study:

ADMUL WOL tradename/brand of polyglycerol polyricinoleate (PGPR)

Test animals

Species:

rat

Strain:

Wistar

Details on test animals or test system and environmental conditions:

Colworth Wistar rats (obtained from the breeding facility at the Unilever Colworth Laboratory, Sharnbrook, Bedford, UK) were used in these stu-
dies.
TEST ANIMALS
- Source: Colworth Wistar rats (obtained from the breeding facility at the Unilever Colworth Laboratory, Sharnbrook, Bedford, UK) were used in these studies.
- Housing: Each pair occupied a single cage. Breeding was conducted using a continuous breeding protocol in which pairs of animals were maintained until each female had produced five litters (or it became evident that breeding had ceased) and this was conducted over three generations.)
- Diet (e.g. ad libitum): yes
- Water (e.g. ad libitum): yes
- Acclimation period: n.a.

ENVIRONMENTAL CONDITIONS
no inforamtion

IN-LIFE DATES: during late 1950's/early 1960's

Administration / exposure

Route of administration:

oral: feed

Details on exposure:

DIET PREPARATION
- Rate of preparation of diet (frequency): Fresh mixes were prepared each week, and PGPR was incorporated into the ground diet first by hand,
then well mixed in a mechanical mixer.
- Mixing appropriate amounts with (Type of food): commercial pelleted stock diet (Spital)
- Storage temperature of food: n.a.

VEHICLE
none

Analytical verification of doses or concentrations:

not specified

Details on mating procedure:

The first-generation parents were selected from five litters which were assigned randomly into two groups: a control (11 males and 17 females) and a treatment group fed 1.5% PGPR (six males and 13females). The dietary level of 1.5% PGPR was chosen to provide an intake by the pregnant and lactating rat which was in excess of 150 times the intake of a person consuming 5 mg PGPR/kg body weight/day.

All rats were weaned at 23 days and mated at 121 days.
Breeding was continuous and the males were only separated from the females when it was apparent that the female was pregnant. Each pair occupied a single cage and they were maintained until the female had produced five litters or until such time as it became evident that breeding had ceased.
In all instances the first litters were discarded after weaning and second-generation breeders were randomly selected (two males and two females)
from each of the second and fourth litters. By selecting from two first-generation litters the number of animals was increased to 52 of each sex in
the control and 32 of each sex in the PGPR group. The third-generation breeders were selected in a similar manner, by which the control and the PGPR groups were increased to 92 and 44 rats of each sex, respectively. The large control groups were considered necessary to get an indication of
the variations in breeding results that occur within a normal breeding colony. The control rats were fed a pelleted stock diet and the PGPR group were given the same diet ground with 1.5% PGPR.
The main focus of the study design was to observe any effect on breeding. Parameters measured in each of the three generations included number of litters per dam, average litter size, average weaning weights of males and females, litters per group showing 100% survival and total survival
(%) at day 21.

Frequency of treatment:

daily

No. of animals per sex per dose:

1st generation parents (P) were selected from five litters which were assigned randomly into two groups
Treatment group: 6 males and 13 females
Control: 11 males and 17 females
In all instances the first litters were discarded after weaning and second-generation breeders were randomly selected (two males and two females) from each of the second and fourth litters. By selecting from two first-generation litters the number of animals was increased to 52 of each sex in the control and 32 of each sex in the PGPR group. The third-generation breeders were selected in a similar manner, by which the control and the PGPR groups were increased to 92 and 44 rats of each sex, respectively

Control animals:

yes, plain diet

Examinations

Statistics:

A Student's t-test was conducted in which the two groups were compared

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:

Maternal toxic effects:no effects

Effect levels (maternal animals)

1

Key result

Dose descriptor:

NOAEL

Effect level:

> 2 000 mg/kg bw/day (nominal)

Based on:

test mat.

Basis for effect level:

other: maternal toxicity

2

Key result

Dose descriptor:

NOAEL

Effect level:

> 2 000 mg/kg bw/day (nominal)

Based on:

test mat.

Basis for effect level:

other: developmental toxicity

Results (fetuses)

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:no data

Effect levels (fetuses)

Key result

Remarks on result:

other: The parameters measured in each of the three generations included number of litters per dam, average litter size, average weaning weights, litters per group showing 100% survival and total survival (%) at day 21. No adverse effects were observed.

Fetal abnormalities

Key result

Abnormalities:

not specified

Overall developmental toxicity

Key result

Developmental effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

No adverse effects were observed during a three generation study. The average weight of weanling males and females was comparable to respective control weanlings throughout the three generation study. The growth of rats from weaning to mating was comparable in each generation to the respective controls.

Executive summary:

A publication is available where a series of toxicology studies were conducted in the 1950s and 1960s to investigate the toxicity of ADMUL WOL, a brand of polyglycerol polyricinoleate (PGPR). Included as part of these investigations was a three-generation reproduction study in rats. The control rats received a commercial pelleted stock diet and the treated rats were given the same diet ground with 1.5% (w/w) PGPR. A continuous breeding protocol was adopted, in which the breeding pairs were maintained until the female had produced five litters or when it became evident that breeding had ceased. The main focus of the study design was to observe any effect on breeding. The parameters measured in each of the three generations included number of litters per dam, average litter size, average weaning weights of males and females, litters per group showing 100% survival and total survival (%) at day 21.

Growth was comparable to controls throughout the three generations and there were no deaths or clinical signs associated with the consumption of PGPR. No adverse effects were observed during a three generation study. The average weight of weanling males and females was comparable to respective control weanlings throughout the three generation study. The growth of rats from weaning to mating was comparable in each generation to the respective controls.

In conclusion, rats fed 1.5 % (w/w) PGPR showed no evidence of a cumulative effect on breeding performance over three generations.