Ricinoleyl monomaleate triglyceride

Toxicity to reproduction

Administrative data

Endpoint:

fertility, other

Remarks:

based on test type (migrated information)

Type of information:

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

Adequacy of study:

key study

Study period:

April to July 1988

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Studies performed and report issued and peer-reviewed as part of the National Toxicology Program under auspicion of U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health.

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1992

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Examination of fertility parameters in 90-d repeated toxicity tests.

GLP compliance:

yes

Limit test:

no

Test material

Reference

Name:

Unnamed

Type:

Constituent

Details on test material:

Castor Oil

Test animals

Species:

other: rat and mouse

Strain:

other: F344/N rats; B6C3F1 mice

Sex:

male/female

Details on test animals or test system and environmental conditions:

Test Animals:
Source: Simonsen Laboratories, Gilroy, CA
Method of Animal Distribution: Animals weight-randomized into groups by sex, assigned to cages, and cages assigned to dose groups.
Diet: NIH 07; available ad libitum
Size of Study Groups: 10 males and 10 females of each species. Rats were housed 5 per cage, and mice were individually caged.
Time Held Before Study: Rats 14 d, mice 15 d
Age When Placed on Study: 6 wk
Type and Frequency of Observation: Observed 2 X d, weighed initially and 1 x wk thereafter.
Age When Killed: 19 wk
Animal Room Environment:
Temperature: 68-76°F;
Relative humidity: 42-72%;
Fluorescent light 12 h/d;
Air-changes: 10 room air changes/h

Administration / exposure

Route of administration:

oral: feed

Details on analytical verification of doses or concentrations:

The stability of the study material during the toxicology studies was monitored by determination of peroxide content and by high performance liquid chromatography. The homogeneity of castor oil in feed at 10% (100 mg/g) was determined by gravimetric analysis, and blends at 0.5% (5 mg/g) were determined by HPLC analysis. Periodic analysis of the castor oil-formulated diets was conducted by HPLC at the study and analytical chemistry laboratories. Three complete sets of formulated diet mixtures were analyzed by either the study laboratory or the analytical laboratory during the 13-week studies.

Duration of treatment / exposure:

13 weeks

Frequency of treatment:

Daily

Details on study schedule:

Sperm motility and morphology were evaluated at necropsy, and vaginal cytology was evaluated on core-study animals during the week just preceding necropsy. Females were subject to vaginal lavage with saline 12 days prior to termination. Sperm motility was evaluated at necropsy. After sperm sampling for motility evaluation, the cauda was placed in phosphate buffered saline (PBS), and gently chopped with a razor blade. The solution was mixed gently and heat-fixed at 65°C. Sperm density was then determined using a hemocytometer. The left testis was frozen and stored for counting of homogenization spermatid nuclei at a later date.

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 0.62, 1.25, 2.5, 5.0, and 10.0% in feed
Basis:
nominal in diet

No. of animals per sex per dose:

10

Control animals:

yes, plain diet

Examinations

Parental animals: Observations and examinations:

Observed twice per day, weighed initially and once per week thereafter.

Oestrous cyclicity (parental animals):

The aspirated cells gained from the vaginal lavage were air-dried onto slides, stained with Toluidine Blue O, and coverslipped. The relative preponderance of leukocytes, nucleated epithelial cells, and large squamous epithelial cells were used to identify the stages of the estrual cycle.

Sperm parameters (parental animals):

The left epididymis was removed and quickly weighed; the cauda epididymis was removed at the junction of the vas deferens and the corpus epididymis, then weighed. A small cut was made in the distal cauda epididymis. The sperm removed from the epididymis were dispersed and the number of moving and non-moving sperm were counted in 5 fields of 30 sperm or less on each slide. After thawing of the left testis, testicular spermatid head count was determined by removing the tunica albuginea and homogenizing the testis in PBS containing 10% DMSO. Homogenization spermatid nuclei were enumerated using a hemocytometer; the data were expressed as spermatid heads per total testis and per gram of testis.

Litter observations:

Not included.

Postmortem examinations (parental animals):

Necropsy and Histologic Examinations:
The following tissues were routinely processed for preparation of histologic sections and microscopic examination: adrenal glands, brain, cecum, colon, duodenum, epididymis/seminal vesicles/prostate/testes or ovaries/uterus, esophagus, eyes (if grossly abnormal), femur (including marrow), heart, ileum, jejunum, kidneys, liver, lungs and mainstem bronchi, mammary gland, mandibular and mesenteric lymph nodes, nasal cavity and turbinates, pancreas, parathyroid glands, pituitary gland, preputial or clitoral glands, rectum, salivary glands, skin, spinal cord and sciatic nerve (if neurologic signs present), spleen, forestomach and glandular stomach, thymus, thyroid gland, trachea, urinary bladder, zymbal glands, and all gross lesions and tissue masses including regional lymph nodes.
A complete histopathologic examination was conducted on all rats and mice from the control and 10% dose groups. Liver was examined from male rats in all other dose groups, and histologic sections of gross lesions were examined from all rats.

Postmortem examinations (offspring):

Not included.

Statistics:

Not applcable fro the reproductive parameters.

Reproductive indices:

Sperm mobility and quantity.
Staging of the estrual cycle.

Offspring viability indices:

Not included.

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:

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 adverse effects of castor oil administration were noted in these studies.

Effect levels (P0)

1

Dose descriptor:

NOAEL

Effect level:

5 800 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male

Remarks on result:

other: Generation: young sexually mature rats (migrated information)

2

Dose descriptor:

NOAEL

Effect level:

5 725 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

female

Remarks on result:

other: Generation: young sexually mature rats (migrated information)

3

Dose descriptor:

NOAEL

Effect level:

15 000 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male

Remarks on result:

other: Generation: adolescent to adult mice (migrated information)

4

Dose descriptor:

NOAEL

Effect level:

16 800 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

female

Remarks on result:

other: Generation: adolescent to adult mice (migrated information)

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 included in the study.

Overall reproductive toxicity

Reproductive effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

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 estrous cycles of rats or mice given diets containing castor oil. Thus, no significant adverse effects of castor oil administration were noted in these studies.