Glycerides, C16-18

Endpoint summary

Key value for chemical safety assessment

Toxic effect type:

dose-dependent

Effects on fertility

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

7 500 mg/kg bw/day

Study duration:

subacute

Species:

rat

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 two generation reproductive toxicity study was conducted in Mongolian gerbils to assess the effect of ‘glycerides, C8-18 and C18-unsatd.’ (as palm kernel oil). Adult Mongolian gerbils (highly resistant to atherosclerosis) and their sucklings (first generation) were randomly assigned to two groups of 5 couples each (group 1: basal diet; group 2: 8.75% test substance in diet). Four months after starting the diets, four adult animals of each dietary group of the first generation were sacrificed and histopathological changes in liver and spleen were observed along with liver and serum cholesterol levels. In the second generation parameters such as frequency of litters, number of pups, mean litter size, mean weight, postnatal mortality were also observed. Both in the first and second generations, no significant differences of body weight were observed compared to controls. The liver and spleen of the animals of the first generation also had a normal histology. However, a slightly elevated serum cholesterol level was observed in the test substance fed group. No significant effect on frequency of litters, mean litter size, total no. of newborns, and no suckling death were found in the second generation of the test substance fed group compared to the basal dietary group. Hence, under the test conditions, the substance did not exhibit any significant reproductive toxicity at 8.57% in diet (Temmerman, 1988).

A three-generation study was conducted with groups of 12 male and 12 female rats fed 10% of either groundnut oil (controls), ‘glycerides, C16 -18 and C18 -unsatd.’ (as red palm oil), refined, bleached and deodorized palm olein or hydrogenated vegetable oil containing mahua oil through diet. Reproduction parameters including percentage conception, birth, weight, litter size, weanling weight, sex ratio at birth and weaning, preweaning mortality and number of days from introduction to mating, were recorded. Behavioural and reflexological tests were conducted on preweaning animals. No significant differences were recorded in any of the reproductive or toxicological parameters observed between the treated and control groups. In this multigeneration study no adverse effects were observed on the reproductive or toxicological parameters studied. According to the author, these results indicate that the substance can be safely used as an edible oil (Manorama, 1993).

A combined repeated and reproductive screening study was conducted to determine the effect of ‘glycerides, C16-18 and C18-unsatd.’ (as crude palm oil) on rats when administered for 13 weeks at 15% in diet. Results were compared to those obtained with heated palm oil, crude/heated soy oil, crude/heated peanut oil, or crude/heated sunflower oil at the same concentration. Clinical signs and bodyweight were recorded throughout the study. After 13 weeks, hematology, clinical chemistry and urinalysis parameters were assessed, as well as gross and microscopic pathology. After 10 weeks of treatment, 10 males and 20 females were mated for 18 d. Maternal bodyweight and reproductive parameters were recorded. At 5 weeks of age, the young were sacrificed. Liver and kidneys weights were recorded and these organs were examined microscopically. The substance did not show any adverse effects on male and female rats compared to other crude or heated vegetable oils when administered for 13 weeks at 15% in diet. Furthermore, no signs of toxicity were observed on maternal rats or pups in the follow-up reproductive screening trial. Under the conditions of this study, the NOAEL of the substance can be considered to be 15% in diet as no significant toxicity were observed on maternal rats and pups (Coquet, 1977).

A combined repeated and reproductive screening study was conducted to determine the effect of crude soy oil on rats when administered for 13 weeks at 15% in diet. Results were compared to those obtained with heated palm oil, crude/heated soy oil, crude/heated peanut oil, or crude/heated sunflower oil at the same concentration. Clinical signs and bodyweight were recorded throughout the study. After 13 weeks, hematology, clinical chemistry and urinalysis parameters were assessed, as well as gross and microscopic pathology. After 10 weeks of treatment, 10 males and 20 females were mated for 18 days. Maternal bodyweight and reproductive parameters were recorded. At 5 weeks of age, the young were sacrificed. Liver and kidneys weights were recorded, and these organs were examined microscopically. Test substance did not show any adverse effects on male and female rats compared to other crude or heated vegetable oils when administered for 13 weeks at 15% in diet. Furthermore, no signs of toxicity were observed on maternal rats or pups in the follow-up reproductive screening trial. Under the conditions of this study, the NOAEL of the substance can be considered to be 15% in diet as no significant toxicity were observed on maternal rats and pups (Coquet, 1977).

A 90 d oral repeated dose study was conducted in F344/N rats to evaluate the sub-chronic toxicity of the constituent 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 NOAEL of castor oil for reproductive toxicity screening in rats was determined to be 10% in diet (i.e. 5800 mg/kg bw/day based on actual feed consumption and body weight data) (Irwin, 1992).

A 90 d oral repeated dose study was conducted in B6C3F1 mice to evaluate the sub-chronic toxicity of castor oil in which reproductive parameters were also screened. Mice (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 gonadal weights, epididymal sperm motility, density, or testicular spermatid head count and no changes were observed in the length of female estrous cycles or time spent in each phase of the cycle. No significant changes were noted in male and female gonadal organs at necropsy. Under the conditions of this study, the NOAEL of castor oil for reproductive toxicity screening in mice was determined to be 10% in diet (i.e. ca. 16000 mg/kg bw/day based on actual feed consumption and body weight data) (Irwin, 1992).

Effects on developmental toxicity

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

7 500 mg/kg bw/day

Study duration:

subacute

Species:

rat

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 study was conducted to evaluate the developmental toxicity/teratogenicity potential of ‘glycerides, C8 -18 and C18 -unsatd.’ (as partially hydrogenated soybean oil) in Sprague Dawley rats. Groups of 25 pairs of two generations of male and female rats were fed diets containing 15% of the substance. The F0 generation was exposed to the substance from weaning and the F1 generation from conception. The first two litters of each generation were allowed to be born naturally. During the third pregnancy of each generation, one-half of the females were sacrificed on Day 13 of gestation and inspected for early embryonic death. The remaining females were sacrificed on Day 21 of gestation and fetuses were examined for either skeletal or soft tissue abnormalities. No evidence of any maternal or developmental toxicity (including teratogenicity) was observed in any of the generations. Under the conditions of this study, the NOAEL for maternal and developmental toxicity was considered to be 15% of the substance in diet (Nolen, 1972).

A two generation reproductive toxicity study was conducted in Mongolian gerbils to assess the effect of ‘glycerides, C8 -18 and C18 -unsatd.’ (as palm kernel oil).

Adult Mongolian gerbils (highly resistant to atherosclerosis) and their sucklings (first generation) were randomly assigned to two groups of 5 couples each (group 1: basal diet; group 2: 8.75% w/w of the substance in diet). In the second generation parameters such as frequency of litters, number of pups, mean litter size, mean weight, postnatal mortality were observed. No significant effect on frequency of litters, mean litter size, total no. of newborns, mean body weight and no postnatal mortality were found in the second generation of the substance-treated group compared to the basal dietary group. Based on the test conditions, the NOAEL for developmental effects in rats was determined to be 8.57% w/w (Temmerman, 1988).

Justification for classification or non-classification

Based on evidence from other substances of the same read-across category, ‘glycerides, C16-18 (SDA Reporting Number: 19-001-00)’ are not expected to show reproductive/developmental toxicity after oral exposure. No reproductive toxicity is expected from dermal exposure as systemic uptake will be lower than from the oral route. Based on its physical state (solid at ambient temperature) and low vapour pressure (< 1.33 x 10^-8 Pa at 20°C), the possibility of inhalation exposure will be extremely limited. In many cases the substance is also used in industrial applications and transported and handled in liquid form (heated). If the substance is handled in powder form, sprayed or otherwise finely dispersed in the air, the use of respiratory protection (filter mask) is recommended at workplace. Thus, the reproductive toxicity as a result of respiratory exposure is considered unlikely.

Further, ‘glycerides, C16-18 (SDA Reporting Number: 19-001-00)’ and other substances of the same read-across category have a very long history of safe use in nutritional (food and feed), cosmetic and industrial applications. In the form of olive oil, corn oil, sunflower oil, etc., they are also frequently employed as vehicles in toxicity studies following international testing guidelines (e.g. OECD) for the evaluation of the repeated dose toxicity, carcinogenicity or reproductive/developmental toxicity of chemical substances, without any apparent adverse effects.

Based on the existing information, the substance does not require reproductive toxicity classification for reproductive or developmental toxicity according to EU CLP Regulation (EC) 1272/2008.