Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Additional information

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 cyclus, sperm characterization and histopathologic evaluation of oestrus cyclus in females, sperm characterization in males and histologic examinations (incl. Epididymides, Mammary gland, Ovaries, Prostate, Seminal vesicles, Testes, Thyroid with parathyroid, Uterus with uterine horns and Vagina) the subchronic 90-day oral NOAEL for fertility in rats for ethyl oleate was found to be approx. 6000 mg/kg bw/d.

 

A reproduction/developmental toxicity screening test was performed with butyl stearate (CAS# 123-95-5) similar to OECD Guideline 421 (Smith, 1953; summarized by Elder, 1985). 20 male and female Sprague-Dawley rats received butyl stearate at a concentration of 6.25% of the diet, corresponding to approx. 6000 mg/kg bw/day for a period of 10 weeks. 12 male and female negative control animals were fed with basal diet concurrently. After 10 weeks animals were mated. Successfully mated pregnant female were housed individually in breeding cages. The date of parturition and the number of young in each litter were recorded. Litters were weaned 21 days postpartum and the weights of the weanling determined. From each of the three groups of weanling (those on the test material and the controls), 24 males and 24 females were chosen at random and for the next 21 days, these young were fed the same 6.25% diet as had been ingested by their parents. Diet intake and body weights were recorded daily; 21 days after weaning, the rats were sacrificed and necropsies were performed.

Based on reproduction, fertility index, litter size, survival index/viability index of offspring and necropsy at day 21 after weaning the NOAEL for parental fertility as well as for offspring development was found to be 6000 mg butyl stearate /kg bw/d.


Short description of key information:
Studies on reproduction toxicity/fertility were available for the following category members (CAS#): 111-62-6 and 123-95-5.
For both, ethyl oleate and butyl stearate a 90-day subchronic NOAEL for fertility was found to be 6000 mg/kg bw/d in rats.

Effects on developmental toxicity

Description of key information
The NOAEL for maternal and developmental toxicity for 2-ethylhexylstearate (CAS# 91031-48-0) was found to be 1000 mg/kg bw/d.
The NOAEL for maternal and developmental toxicity for butyl stearate (CAS# 123-95-5) was found to be 6000 mg/kg bw/d.
Additional information

A Prenatal Developmental Toxicity Study was performed with 2-ethylhexylstearate (assigned as CAS# 91031-48-0) according to OECD Guideline 414 (Pittermann, 1994). Groups of 24 female Sprague-Dawley rats received daily oral gavage doses of the test substance in arachidis oil at concentrations of 0, 100, 300 and 1000 mg/kg bw/d during gestational days 6 to 15. On day 20 of gestation the animals were euthanized and examined for maternal and foetal parameters.

Based on the number of implantations, number of total litter losses by resorption, mortality, clinical signs, body weight, gross pathology and organ weights of maternal animals the NOAEL for maternal toxicity was found to be 1000 mg/kg bw/d. Examination of foetus litter size and weights, offspring viability (number alive and number dead), sex ratio, grossly visible abnormalities, external, soft tissue and skeletal abnormalities and head examinations showed no abnormalities and no indication for teratogenic effects. Therefore, the NOAEL for embryo-/foetotoxicity and teratogenicity in rats for 2-ethylhexylstearate was found to be 1000 mg/kg bw/d.

A reproduction/developmental toxicity screening test was performed with butyl stearate (CAS# 123-95-5) similar to OECD Guideline 421 (Smith, 1953; summarized by Elder, 1985). 20 male and female Sprague-Dawley rats received butyl stearate at a concentration of 6.25% of the diet, corresponding to ca. 6000 mg/kg bw/day for a period of 10 weeks. 12 male and female negative control animals were fed with basal diet concurrently. After 10 weeks animals were mated. The date of parturition and the number of young in each litter were recorded. Litters were weaned 21 days postpartum and the weights of the weanling determined. From each of the three groups of weanling (those on the test material and the controls), 24 males and 24 females were chosen at random and for the next 21 days, these young were fed the same 6.25% diet as had been ingested by their parents. Diet intake and body weights were recorded daily; 21 days after weaning, the rats were sacrificed and necropsies were performed. No gross pathologic changes were found among the young rats during necropsy at the end of the 21-day post-weaning period. Based on the study results a developmental NOAEL for butyl stearate of 6000 mg/kg bw/d could be determined.

Justification for classification or non-classification

The available studies within the Category were judged to be sufficient for risk assessment, considering the similarity of toxicological characteristics upon systemic uptake of the category members. Accounting for animal welfare, further animal testing would not be reasonable.

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

Additional information