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Effects on fertility

Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
5 000 mg/kg bw/day
Study duration:
subchronic
Species:
other: rat and mouse
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

A 90 day oral feeding study with Castor oil (CAS No. 8001-79-4) was performed equivalent to OECD Guideline 408 in F344/N rats and B6C3F1 mice (Irwin, NTP report 1992). The test substance was mixed at concentrations of 0, 0.62, 1.25, 2.50, 5.00, 10.0 % (w/w) to the diet and the animals were fed ad libitum for 13 weeks. 10 animals per sex and per dose were used. The highest dose was equivalent to approx. 5.7 g/kg bw/day for rats and approx. 15 g/kg bw/day for mice. No matings were performed, but male and female fertility parameters were analyzed in rats and mice including oestrous cycle length, caudal weight, epididymal weight, testis weight, sperm count/g testis, sperm motility (%) and histopathology of organs relevant for reproduction (including adrenal glands, epididymis/seminal vesicles/prostate/testes or ovaries/uterus, mammary gland, pituitary gland, preputial or clitoral glands). A complete histopathologic examination was conducted on all rats and mice from the control and 10% dose groups.

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 oestrous cycles of rats or mice given diets containing castor oil. No histopathologic abnormalities were found in the reproductive organs.

A NOAEL of 5000 mg/kg bw/day for rats and a NOAEL of 15000 mg/kg bw/day for mice could be identified based on parental fertility parameters.

The lack of toxicity to reproduction was supported by several multi-generation studies in rat (Ambrose 1956 a,b). Three out of five 5 acetoglycerides did not impair reproductive performances through 3 generations. Two acetostearins (AG-194 and AG-31) impaired reproductive performance at 10% (Ambrose 1958a). In the follow up study (Ambrose, 1958b) this effect was attributed to Vitamin E depletion. Vitamin E supplement completely restored reproductive performance. Vitamin E depletion is a known effect of some fatty acids and not specific to fatty acid glycerides. Thus, the acetoglycerides are not considered reprotoxic under conditions of this study. Adverse effects on liver, testis, or kidneys are reported at very high doses of 20% (approx. 10.000 mg/kg bw/d). Thus, acetoglycerides are considered practically non-toxic.


Short description of key information:
For Castor oil (CAS No. 8001-79-4) a NOAEL for parental fertility of 5000 mg/kg bw/d in rats and 15000 mg/kg bw/d in mice could be identified (NTP, 1992). For acetoglycerides no substance related reproductive effects have been reported in several multi-generation studies in rats (Ambrose 1965 a,b).

Justification for selection of Effect on fertility via oral route:
No adverse effect on reproductive organs have been reported in a 90 day GLP guideline study in rat and mouse using castor oil.

Effects on developmental toxicity

Description of key information
Intravenously administered 20% lipid emulsion containing a 3:1 ratio of MCT (Medium Chain Triglycerides):LCT (Long Chain Triglycerides) revealed a NOAEL of 4280 mg/kg bw/day.
Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
4 280 mg/kg bw/day
Study duration:
subacute
Species:
other: rat and rabbit
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available
Additional information
A developmental toxicity study with rats and rabbits was conducted with a 20% lipid emulsion containing a 3:1 ratio of MCT (Medium Chain Triglycerides):LCT (Long Chain Triglycerides) (Henwood, 1997). Doses of 1000 and 4280 mg/kg bw/d were given intravenously from gestation day 6 through 15 (rats) or GD 7 through 19 (rabbits). The intravenous route of administration was used because the lipid emulsion is intended for intravenous human administration as a component of parenteral nutrition. The dose was administered daily to rats by intravenous infusion via a caudal vein and to rabbits via a marginal ear vein. In rats there were no treatment related direct teratogenic effects observed. In rabbit administration of the test material resulted in lower maternal food consumption and significant body weight loss during treatment at the highest dose level. Therefore, the observed foetal effects in the high dose group (i.e., increased resorptions, decreased fetal body weights, and increased incidence of morphological anomalies) were assumed to be the result of dietary deprivation, maternal toxicity, or both, rather than a direct teratogenic effect of the test article. The NOAEL was therefore set to be 4280 mg/kg bw /day for developmental toxicity for both, rats and rabbits.

Justification for selection of Effect on developmental toxicity: via oral route:
Study similar or equivalent to OECD 414

Justification for classification or non-classification

According to DSD (67/548/EEC) or CLP (1272/2008/EC) classification criteria for reproduction, no classification is required.

Additional information