Fatty acids, palm-oil, hydrogenated

Toxicity to reproduction

Administrative data

Endpoint:

toxicity to reproduction

Remarks:

other: Screening of reproductive parameters in subchronic oral toxicity study

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From Apr. to Jul. 1988

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

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:

1992

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

A 90 d oral repeated dose study was conducted in F344/N rat to evaluate the sub-chronic toxicity of castor oil in which reproductive parameters were also screened.
Rats (10 /sex / group) were exposed for 13 weeks to 0, 0.62, 1.25, 2.5, 5.0 or 10% castor oil mixed in diet. Apart from the standard sub-chronic toxicity examinations, sperm count, motility and morphology were evaluated at necropsy and vaginal cytology during the week preceding necropsy. Male and female gonadal weights were also determined with gross pathology and histopathology of reproductive organs at termination.

GLP compliance:

yes

Remarks:

FDA Good Laboratory Practices Regulations (21 CFR 58)

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Glycerides, C16 and C18-unsatd. and C18-unsatd. hydroxy

IUPAC Name:

Glycerides, C16 and C18-unsatd. and C18-unsatd. hydroxy

Details on test material:

- Name of test material (as cited in study report): Castor oil (CAS N° 8001-79-4, EC N° 232-293-8). Under the SDA nomenclature, the name of this substance is ‘Glycerides, C16 and C18-unsatd. and C18-unsatd. hydroxy'
- Physical state: Liquid
- Analytical purity: Purity and identity analyses were conducted by Midwest Research Institute (MRI) (Kansas City, MO)
- Analytical method used: Karl Fischer water analysis, thin layer and high performance liquid chromatography, and a battery of U.S. Pharmacopeia (USP) standard analyses for castor oil
- Lot/batch No.: #L-5G30-01
- Other: Source: Cas Chemical, Inc.

Test animals

Species:

rat

Strain:

Fischer 344

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Simonsen Laboratories, Gilroy, CA
- Age at study initiation: 6 wk
- Fasting period before study: No
- Housing: 5 per cage in polycarbonate cages lined with heat-treated hardwood chips and covered with polyester filter sheets. The cages were stored on stainless steel racks equipped with an automatic watering system
- Diet: NIH 07; available ad libitum
- Water: Ad libitum
- Acclimation period: 14 d
- Other: Feed hoppers in the animal cages were changed twice weekly


ENVIRONMENTAL CONDITIONS
- Temperature: 68-76 °F
- Humidity: 42-72%
- Air changes: 10 room air changes/h
- Photoperiod: 12 h dark/12 h light

Administration / exposure

Route of administration:

oral: feed

Vehicle:

unchanged (no vehicle)

Details on exposure:

DIET PREPARATION
- Method of mixing: Formulated diets were prepared by blending the appropriate amount of castor oil with a small quantity of feed to prepare a premix. The premix then was layered between the required amounts of feed in a twin-shell blender and blended for 15 minutes to achieve a uniform mix.
- Storage temperature of food: Stored for no longer than 3 weeks at 5 °C
- Stability under test conditions: 0.5% dose level is stable for at least 21 days when stored in the dark at 5 °C and for 3 days when stored open to air and light in a rodent cage.

Details on mating procedure:

No mating performed

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

Determined by HPLC at the study and analytical chemistry laboratories in duplicates. The results of the analyses for all dose mixtures given to the animals ranged from 97% to 106% of the target concentrations.

Duration of treatment / exposure:

13 wk or 90 d

Frequency of treatment:

Daily

Details on study schedule:

None

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 0.62, 1.25, 2.5, 5.0 or 10% in diet
Basis:
actual ingested

No. of animals per sex per dose:

10 rats per sex per dose

Control animals:

yes, plain diet

Details on study design:

None

Positive control:

Not applicable

Examinations

Parental animals: Observations and examinations:

All routine examinations were performed including body weight, food consumption, hematology and clinical chemistry. For details see section 7.5.1: Repeated dose toxicity-oral; Endpoint study record: Castor oil (232-293-8), Repeated dose toxicity: oral (rats), KL2, Irwin, 1992.

Oestrous cyclicity (parental animals):

Yes (at 12 wk)

Sperm parameters (parental animals):

Testis weight, epididymis weight, sperm count, motility and morphology were evaluated at necropsy (termination of study)

Litter observations:

Not examined

Postmortem examinations (parental animals):

Following reproductive organs were examined grossly and histologically apart from routine examinations:
Epididymis/seminal vesicles/prostate/testes or ovaries/uterus

- Complete histopathology examinations were conducted on all rats from the control and 10% dose groups

Postmortem examinations (offspring):

Not examined

Statistics:

Statistically analyzed within each sex by one-way Analysis of Variance tests, followed by Dunnett's t-test for pair-wise comparisons (p < 0.05)

Reproductive indices:

No data

Offspring viability indices:

Not calculated

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:

effects observed, treatment-related

Histopathological findings: non-neoplastic:

no effects observed

Other effects:

no effects observed

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:

no effects observed

Reproductive function: sperm measures:

no effects observed

Reproductive performance:

not examined

Details on results (P0)

No significant changes were noted in a screening for male reproductive endpoints, including sperm count and motility, and no changes were observed in the length of female estrous cycles. No significant changes were noted in male and female gonadal organs at necropsy except there was a slight decrease in epididymal weight (6-7%) which occurred in the middle- and high-dose groups, but this was not dose-related.

Effect levels (P0)

Dose descriptor:

NOAEC

Effect level:

> 10 other: % in diet

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: No effect on male and female reproductive screening parameters

Results: F1 generation

General toxicity (F1)

Clinical signs:

not examined

Mortality / viability:

not examined

Body weight and weight changes:

not examined

Sexual maturation:

not examined

Organ weight findings including organ / body weight ratios:

not examined

Gross pathological findings:

not examined

Histopathological findings:

not examined

Details on results (F1)

Not applicable

Overall reproductive toxicity

Reproductive effects observed:

not specified

Any other information on results incl. tables

None

Applicant's summary and conclusion

Conclusions:

Under the conditions of this study, the reproductive screening NOAEL of castor oil to rat was estimated to correspond to 10% in diet (i.e. ca. 5800 mg/kg bw/day based on actual feed consumption and body weight data).

Executive summary:

A 90 d oral repeated dose study was conducted in F344/N rat to evaluate the sub-chronic toxicity of castor oil in which reproductive parameters were also screened.

Rats (10 /sex / group) were exposed for 13 weeks to 0, 0.62, 1.25, 2.5, 5.0 or 10% castor oil mixed in diet. Apart from the standard sub-chronic toxicity examinations, sperm count, motility and morphology were evaluated at necropsy and vaginal cytology during the week preceding necropsy. Male and female gonadal weights were also determined with gross pathology and histopathology of reproductive organs at termination.

 

No significant changes were noted in a screening for male reproductive endpoints, including sperm count and motility, and no changes were observed in the length of female estrous cycles. No significant changes were noted in male and female gonadal organs at necropsy except there was a slight decrease in epididymal weight (6-7%) which occurred in the middle- and high-dose groups, but this was not dose-related.

 

Under the conditions of this study, the reproductive screening NOAEL of castor oil to rat was estimated to correspond to 10% in diet (i.e. ca. 5800 mg/kg bw/day based on actual feed consumption and body weight data).