Glycerides, C8-18 and C18-unsatd.

Toxicity to reproduction

Administrative data

Endpoint:

multi-generation reproductive toxicity

Remarks:

based on test type (migrated information)

Type of information:

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

Adequacy of study:

weight of evidence

Study period:

Not available

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The study is adequately documented. Not run according to GLP.

Justification for data waiving:

other:

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1993

Materials and methods

Principles of method if other than guideline:

Multigeneration breeding studies in rats were conducted according to the protocol used in earlier studies on unconventional oils (Rukmini, 1988 and 1990) according to the guidelines of the FDA/WHO/DGHS safety evaluation protocol (FDA, 1970).

Groups of 24 (12 male and 12 female) inbred weanling albino rats were given a 20% protein diet, adequate in all nutrients and containing 10% of either groundnut oil (GNO; controls), red palm oil (RPO), refined, bleached, deodorized palm olein oil (RBDPO), or hydrogenated vegetable oil (HVPO) with 30% mahua oil.

Bodyweight and food intake were recorded weekly for 15 weeks (100 - 120 days).

Propagation of the three generations was conducted as follows: F0 rats were mated twice to produce F1a and F1B litters. F1b rats were mated twice to produce F2a and F2b litters, and two matings of the F2b rats produced the F3a and F3b litters. The parameters recorded included fertility index or conception rate, sex ratio, mean weaning weight, pre-weaning mortality, number of days from introduction of mating, behaviour of pups and adults.

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): Red 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.'

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

The rats were kept in galvanized aluminium cages at a constant temperature of 25 °C, with 50-60% relative humidity and a 12 h light/dark cycle. The rats were given a 20%-protein diet adequate in all nutrients. Food and water were given ad libitum.

Administration / exposure

Route of administration:

oral: feed

Vehicle:

unchanged (no vehicle)

Details on exposure:

Group 1 (control): 10% groundnut oil
Group 2: 10% red palm oil
Group 3: 10% bleached and deodorized palmoilein
Group 4: 10% hydrogenated oil containing 30% of mahua oil

The test substances were mixed in the diet.

Details on mating procedure:

12 males and 12 females in each group were mated after 100-120 days. The mated animals were allowed to be together for a period of 18-20 days. Mating behaviour was checked in the morning by looking for the capulatory plug in the bottom tray to confirm for pregnancy. After further confirmation by palpation and periodic checking for the increase in body weight in females, the mated animals were separated and housed in individual plastic cages.

Analytical verification of doses or concentrations:

no

Details on analytical verification of doses or concentrations:

None

Duration of treatment / exposure:

3 generations

Frequency of treatment:

Daily

Details on study schedule:

The F0 rats were mated twice to produce the F1a and F1b litters. The F1b rats were mated twice to produce the F2a and F2b litters, and two matings of the F2b rats produced the F3a and F3b litters.

Once the female delivered, the litters were counted, sexed and weighted and return to the mother where they staid for the lactation period of 21 days. After the 21 days they were taken from the mothers, the number of female and males were recorded and their weight. Six male and six female pups of the F1a generation were killed after weaning. Gross pathology and organ weights were recorded. The mothers got to rest for 1 week and then again housed with the same males. This second mating produced F1b pups. After weaning the F1b pups were fed for 90 days, allowed to mature and bred to produce a second generation (F2b rats).

Doses / concentrations

Remarks:

Doses / Concentrations:
10%
Basis:
nominal in diet

No. of animals per sex per dose:

12

Control animals:

yes

Details on study design:

The toxic or non-toxic responses from the reproduction studies were expressed in terms of indices that considered all stages from conception to weaning (as developed by Mirone L., Panzarella F. P. and Cerecodo L. R., 1948 A new method of reporting data on reproduction and lactation in the mouse. Scince 108, 139).

Positive control:

None

Examinations

Parental animals: Observations and examinations:

Bodyweight and food consumption, recorded weekly

Oestrous cyclicity (parental animals):

No data

Sperm parameters (parental animals):

No data

Litter observations:

The sex ratio, mean weaning weight, preweaning mortality and behaviour such as righting reflex (tested on day 2 after birth), negative geotaxis (tested on day 5 after birth), cliff drop aversion (tested on day 5 after birth) and auditory startle response (tested on day 12 after birth).

Postmortem examinations (parental animals):

The organs of all adults of each generation were weighted and the relative body weight were calculated.

Postmortem examinations (offspring):

Gross pathology and organ weight.

Statistics:

By using analyses of variance to test the difference between groups for parametric data and the Chi-square test was used for non-parametric data.

Reproductive indices:

Fertility Index (FI)
Number of days from introduction for mating (IFM)
Behaviour of adults

Offspring viability indices:

Sex ratio
Mean weaning weight
Preweaning mortality
Behaviour of pups

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:

effects observed, treatment-related

Body weight and weight changes:

effects observed, treatment-related

Food consumption and compound intake (if feeding study):

effects observed, treatment-related

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Histopathological findings: non-neoplastic:

not examined

Other effects:

not specified

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:

not specified

Reproductive function: sperm measures:

not specified

Reproductive performance:

effects observed, treatment-related

Details on results (P0)

No significant differences were found in body weight gain between groups in any of the three generations. The food consumption and weight gain of rats fed crude palm oil was similar to that of the controls and they also showed an adequate growth and development. In the first generation 100% of matings resulted in pregnancies in both the first and the second mating. In the second generation 91.6% of dams conceived in both matings, and in the third generation 100% and 91.6% conceived in the first and second matings, respectively.

No abnormal behavioural or reflexological changes in any of the animals.

No significant changes attributable red palm oil were evident in the relative weights of the liver, heart, spleen, lungs, kidney, testes/ovaries or total body weight in the F0 generation rats.

Gross pathology indicates no adverse abnormalities in the organs.

Effect levels (P0)

Dose descriptor:

NOAEL

Effect level:

10 other: % in diet

Sex:

male/female

Remarks on result:

other: Generation: all generations (migrated information)

Results: F1 generation

General toxicity (F1)

Clinical signs:

effects observed, treatment-related

Mortality / viability:

mortality observed, treatment-related

Body weight and weight changes:

effects observed, treatment-related

Sexual maturation:

not specified

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Gross pathological findings:

effects observed, treatment-related

Histopathological findings:

not examined

Details on results (F1)

Mean litter size, birth and weaning weights were comparable and were not found to be significantly different in all the three generations of all groups.

The sex ration at birth and weaning did not indicate any difference in the relative fitness of each sex with maturity. Preweaning mortality was higher in the first generation animals of both matings in all four groups, except for the second mating of the groups, which showed comparatively lower percentages. In the second generation, second mating, the group showed a comparatively high percentage, and in the second mating of the third generation, percentages were higher for all groups. These deaths may not be treatment related because the controls also had high preweaning mortality rates. Cannibalism was observed in some animals and the mortality of pups may be mainly due to this factor or to maternal neglect, rather than to the presence of any toxic substances that may have been excreted in milk or consumed by the pups.

There was no abnormality or unusual delay in conception or delivery in the groups.

No abnormal behavioural or refelxological changes in any of the animals.

No significant changes attributable red palm oil were evident in the relative weights of the liver, heart, spleen, lungs, kidney, testes/ovaries or total body weight in the F1b or Fb2 generations rats.

Gross pathology indicates no adverse abnormalities in the organs.

Overall reproductive toxicity

Reproductive effects observed:

not specified

Any other information on results incl. tables

None

Applicant's summary and conclusion

Conclusions:

In this multigeneration study no adverse effect were shown on the reproductive or toxicological parameters studied. According to the author, these results indicate that red palm oil can be safely used as an edible oil.

Executive summary:

A three-generation study was conducted with groups of 12 male and 12 female rats fed at 10% in the diet either groundnut oil (controls), red palm oil, refined, bleached and deodorized palm olein or hydrogenated vegetable oil containing mahua oil.

Reproduction parameters including percentage conception, birth, weight, litter size, weanling weight, sex ratio at birth and weaning, preweaning mortality and number of days from introduction to mating, were recorded. Behavioural and reflexological tests were conducted on preweaning animals.

No significant differences were recorded in any of the reproductive or toxicological parameters measured between groups fed palm oil and controls. According to the authors, these results indicate that red palm oil can be safely used as an edible oil.