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Key value for chemical safety assessment

Effects on fertility

Description of key information

Based on the available information of the constituents, reproductive toxicity is not expected.

Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Additional information

Experimental data for the reaction product is not available. The endpoint is assessed based on the data obtained with the constituents and further considerations.

Sucrose Stearate:

Sucrose Esters are authorised food additives (E473). Based on the toxicokinetic information as well as several long-term toxicity studies (eg 2 years carcinogenicity study) and the current human intake, there is no concern regarding reproductive toxicity.

Fatty acids, C16 -18, Methyl Ester:

The substance methyl dodecanoate (CAS 111-82-0) was studied for oral toxicity in rats in an OECD 422 combined repeat dose and reproductive/developmental toxicity screening test under GLP conditions (JECDB 2000). 12 male and female Crj:CD (SD) rats per dose were administered doses of 0, 250, 500 and 1000 mg/kg/day by gavage. The animals were mated. The test material was administered to females from 14 days before mating until day 3 of lactation and to males for 45 days. Terminal kill was on day 45 for males and on day 4 of lactation for females. There were no effects of the test substance on the estrous cycle, copulation index, fertility index, gestation length, number of corpora lutea or implantations, implantation index, delivery index or parturition. The NO(A)ELs for reproductive performance of males and females, as well as pup development are considered to be 1000 mg/kg/day in each case.

A 90-day oral feeding study (Bookstaff, 2004) was performed with ethyl oleate (CAS 111-62-6) according to the 1993 FDA draft "Redbook II" guidelines (Toxicological Principles for the Safety Assessment of Direct Food Additives and Color Additives Used in Food). The study was performed equivalent to OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity in Rodents) with additional assessment of oestrus cycle and sperm parameters. The purpose of the study was to determine the safety of ethyl oleate (EO) in a 91-day feeding study in Sprague-Dawley rats. EO was mixed into AIN-93G purified diet at levels of approx. 0, 1900, 3800 and 6000 mg/kg bw/day. All diets were calorie- and fat-matched using high oleic safflower oil (HOSO) as the control fat. There were 20 male and 20 female rats per group. EO in the diet was well-tolerated and there were no toxicologically significant findings in any of the measured parameters (clinical observations, body weight gains, appearance of the faeces, ophthalmic examinations, haematology, clinical chemistry, urinalysis, organ weights, histopathology, or male and female reproductive assessments). Based on the absence of abnormalities concerning oestrus cycle, sperm characterization and histopathologic evaluations the subchronic 90-day oral NOAEL for fertility in rats for ethyl oleate was found to be approx. 6000 mg/kg bw/day.

Fatty Acids, C16-18 Methyl Ester and the test substances belong to the short chain methyl esters category (SCAE Me). A detailed justification for the grouping and read-across is provided in the Justification document (see Section 13).

Fatty Acids, C16 -18:

15% oleic acid (C18) in the diet [approximately 7.5 g/kg bw/day] (the only dose tested) for 10 to 16 weeks did not affect the fertility of male rats but appeared to impair reproductive capacity in the females by interfering with parturition and mammary gland development. Mortality in the offspring was increased. No other information is available (BIBRA, 1986).

Hendrichet al.(1993) conducted a study in which three generations of CBA/2 and C57Bl/6 mice were reared on semipurified diets containing 8.6% crudeCupheaoil. TheCupheaoil contained 76% capric acid (C10 fatty acid). Males of each generation were housed individually and fed for 13-weeks. Food intakes and body weights were measured weekly. Some males of each generation were fed for 5-12 months. BecauseCupheaoil was in short supply, the F1 generation of the C57B1/6 strain were fed for 10 months, the F2 generation was fed for 8 months and the F3 generation was fed for 5 months; whereas in the CBA/2 strain, the F1 generation was fed for 11-12 months, the F2 generation was fed for 9-11 months and the F3 generation was fed for 6-8 months. The diet containingCupheaoil did not impair reproductive parameters or cause any pathology in the mouse tissues examined.Cupheaoil moderately suppressed body weights and food intakes of mice in some groups between 4 and 13-weeks of age, but had no long-term effects on body weight, food intake or cholesterol status.

Again, the long history of safe use of these acids and their related glycerides and food oils, as well as the GRAS status for several of the fatty acids and their salts, indicate the low potential for reproductive toxicity of these chemicals.

Also, it is worth bearing in mind when considering the reproductive toxicity of fatty acids and their salts, that due to their innocuous nature, fats and oils are commonly used as controls and as vehicles in animal toxicity studies. For example, OECD Guideline 408 (repeated dose 90-day oral toxicity study in rodents) recommends the use of “a solution/emulsion in oil (e.g. corn oil)” as a vehicle where an aqueous vehicle is not suitable (OECD, 1993).

 

BIBRA (1986) Toxicity Profile. Oleic acid. The British Industrial Biological Research Association.Surrey, UK.

 

Hendrich, S. Lii, C.K. Myers, R. and Dupont, J. (1993) Effects of feedingCupheaoil to three generations of CBA/2 and C57B1/6 mice.JAOCS,70(8): 797-802.

 

OECD (1993) OECD Guidelines for the Testing of Chemicals. Volume 2, Organisation for Economic Co-Operation and Development, Paris.

Justification for classification or non-classification