Glycerides, C16-18

Endpoint summary

Key value for chemical safety assessment

Toxic effect type:

dose-dependent

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

3 750 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Repeated dose toxicity (Oral):

A subchronic toxicity study was conducted in rats to investigate the effect of 'glycerides, C16-18' (as fully hydrogenated soybean oil) in diet. Diets containing 7.5% of the substance (plus 11.5% soybean oil as normal fat source) were fed to 20 Sprague-Dawley rats/sex for 91 d. A control group was fed with 19% soybean oil for same duration. There was no indication of any systemic toxicity (including body weight gain, organ weights, urinalysis, clinical chemistry, haematology, gross and histopathology). Only observable effect was slightly increased feed consumption (and thus increased caloric efficiency) in treatment group after 4 wks which was attributed to the lower absorbability of the substance. Hence, under the conditions of this study, the NOAEL of the substance in rats was determined to be 7.5% in diet (Nolen, 1981).

A chronic study was conducted in LAFJ and C3H1HeJ mice to determine the repeated dose toxicity potential of ‘glycerides, C8-18 and C18-unsatd.’ (as fully hydrogenated coconut oil) on longevity, hepatic lipid peroxidation and hepatic fatty acid composition. 15% of the substance or sucrose was fed to 60 animals/strain/group for lifetime. Body weights were recorded at monthly intervals. When the animals were sacrificed 12 -24 h before the anticipated death, a portion of the liver was extracted to determine hepatic peroxide values and hepatic fatty acid compositions. No differences were observed in longevity, body weights, hepatic peroxide values and hepatic fatty acid compositions between the groups in both the strains. No information was provided about the general toxicological effects. Under the test conditions, the NOEAL was determined to be equivalent to 15% of the substance in the diet (Morin, 1967).

A chronic study was conducted in rats to compare the repeated dose toxicity of ‘glycerides, C8 -18 and C18 -unsatd.’ (as coconut oil) in rats according to an unspecified method. Various constituents of dietary fat (oleo oil, butter fat, corn oil and safflower oil) were included at 18.5% level in diets of 15 wistar rats/sex/group for 47 weeks. Additional 2.5% safflower oil was included to insure adequacy of the essential fatty acids in all diets. Body weight gain and food intake were measured during the course of the study. Fecal samples were also collected daily for fat absorption analysis. At specified intervals, blood was obtained for cholesterol determination. At termination of study various organs were weighed, and liver and intestine were examined histologically. The total lipid, phospholipids and cholesterol levels were also determined in liver. No effects were observed on body weight gains and calorific efficiency in the substance group with respect to other groups. Mortality was not markedly different with respect to other groups. No effects were observed on various organ weights and histopathology of liver and intestine. The plasma cholesterol and liver lipid, phospholipids and cholesterol level were not markedly different from other groups. Under the test conditions, supplementation of 18.5% of the substance in diet for 47 weeks did not produced any significant adverse effects in rats as compared to other normal dietary fat sources (Harkins, 1968).

A 90 d oral repeated dose study was conducted in F344/N rat to evaluate the sub-chronic and reproductive toxicity of ‘glycerides, C16 and C18-unsatd. and C18-unsatd. hydroxy’ (as castor oil). Rats (10 /sex / group) were exposed for 13 weeks to 0, 0.62, 1.25, 2.5, 5.0 or 10% of the substance mixed in diet. Mortality, bodyweight, food consumption, hematology and clinical chemistry parameters were recorded throughout the study. Organ weights were determined and gross pathology and histopathology conducted at termination. Additionally, sperm motility and morphology were evaluated at necropsy, and vaginal cytology during the week preceding necropsy. Exposure to the substance at dietary concentrations as high as 10% did not affect survival or bodyweight gain. There were no biologically significant effects noted in hematologic analyses. Mild increases in total bile acids and serum alkaline phosphatase were recorded at various times in the high dose groups. Liver weights were increased in male rats at this dose and in females as of 5% in diet. However, there were no histopathologic lesions associated with these liver changes, nor were there any compound related morphologic changes in any organ. 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. Thus, no significant adverse effects of the substance were noted. Under the conditions of this study, the NOAEL of the substance in rats was determined to be 10% in diet (i.e. ca. 5,700 - 6,500 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 male and female B6C3F1 mice in order to evaluate the sub-chronic and reproductive toxicity of castor oil. Mice were exposed for 13 weeks to castor oil at 0, 0.62, 1.25, 2.5, 5.0 or 10% in the diet. Mortality, bodyweight and food consumption were recorded throughout the study. Organ weights were determined, and gross pathology as well as histopathology conducted at termination. Sperm motility, morphology and vaginal cytology were evaluated at various time intervals. Exposure to castor oil at dietary concentrations as high as 10% did not affect survival or body weight gains. Liver weights were increased in male and female mice as of 5% castor oil in the diet. However, there were no histopathological lesions associated with these liver changes, nor were there any compound-related morphologic changes in any organ. 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 the female estrous cycles. Thus, no significant adverse effects of castor oil were noted. Under the conditions of this study, the NOAEL of the substance in mice was determied to be 10% in diet (i.e. ca. 16000 mg/kg bw/day based on actual feed consumption and body weight data) (Irwin, 1992).

A study was conducted to evaluate the nutritional effects and repeated dose toxicity effects of ‘glycerides, C16 -18 and C18 -unsatd.’ (as palm oil) in rat.

The substance was administered through the diet to groups of fifteen male and female rats for up to 90 d at dose levels of 10%. No adverse effects compared to controls were observed as judged by growth rate, feed efficiency ratio, protein efficiency ratio, net protein utilization, digestibility, fat absorption, nitrogen balance, phosphorous and calculi retention, serum enzymes and hematology. There was also no difference in lipid concentrations compared to controls. Under the study conditions, the substance showed adequate nutritional value compared to groundnut and palm olein oil. A NOAEL of 10% for the plam oil in diet was established (Manorama and Rukmini, 1991).

A 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 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. The 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 (Coquet, 1977).

A study was conducted to determine the subchronic oral toxicity of ‘glycerides, C16-18 and C18 -unsatd.’ (as pine nut oil) in rats according to OECD Guideline 408 and GLP. The substance was administered through the diet to three groups, each of ten male and ten female Wistar Crl:Wi(Han) strain rats, for up to 98 and 100 d, at dose levels of 0, 1, 5 and 15%. In Week 12, a functional observation test was carried out. At Week 13 ophthalmoscopic examinations were carried out. Clinical signs, bodyweight development, food intake and mortality/viability were monitored during the study. Haematology and blood chemistry were evaluated for all animals at the end of the treatment period. All animals were subjected to gross necropsy and macroscopic examination and a complete histopathological examination was performed. No toxicologically significant changes were observed at any of the dietary levels. Under the study conditions, the substance is considered to have a NOAEL of 15% in diet, i.e. 8,866 and 10,242 mg/kg bw/d for male and female rats, respectively (Speijers, 2009).

A study was conducted to determine the repeated dose toxicity of ‘glycerides, C16-18 and C18-unsatd.’ (as soybean oil) as control in a subchronic toxicity study through diet. Diet containing 7.5% of the substance (plus 11.5% soybean oil as normal fat source) was fed to 20 Sprague-Dawley rats/sex for 91 d. The control group was fed with 19% soybean oil for same duration. There was no indication of any systemic toxicity (including body weight gain, food consumption, organ weights, urinalysis, clinical chemistry, haematology, gross and histopathology) in the treated group. Hence, under the conditions of this study, the NOAEL of the substance in rats was found to be 19% in diet (Nolen, 1981).

A study was conducted to determine the effect of ‘glycerides, C16 -18 and C18 -unsatd.’ (as crude soy oil) in 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 offsprings were sacrificed. Liver and kidneys weights were recorded and these organs were examined microscopically. The substance did not show any adverse effects in 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 study conditions, the NOAEL of the substance can be considered to be 15% in diet (Coquet, 1977).

Justification for classification or non-classification

A large number of repeated dose oral toxicity studies have been conducted with ‘glycerides, C16-18 (SDA Reporting Number: 19-001-00)’ and other substances of the category. These studies are usually conducted in the form of various vegetable oils at different degrees of hydrogenation, particularly in the context of nutritional research as well as in toxicological investigations. As defined in the present Chemical Safety Report (see Section 1.2),‘glycerides, C16-18 (SDA Reporting Number: 19-001-00)’ is a components of normal diets. Although differences may be observed on bodyweight gain, food consumption and certain measured parameters depending on the chain length distribution of the fatty acids associated to the glycerides and their degree of unsaturation, research overall indicates that, when consumed at nutritionally relevant concentrations (i.e. up to the equivalent of ca. 35% of total calorie intake, there are no adverse effects on health and longevity. Similar results were obtained for the other substances of the same read-across category.

Across all studies, tested doses ranged from 7.5 to 19% in diet. No significant toxicity was seen at any of the tested dose rates.

‘Glycerides, C16-18 (SDA Reporting Number: 19-001-00)’ and other substances from the same read-across categorypresent low systemic toxicity upon repeated dose oral exposure for which absorption is higher than via the dermal route, so that repeated dose dermal toxicity is also expected to be minimal.

Finally,based on its physical state (solid at ambient temperature) and low vapour pressure (< 1.33 x 10^-8Pa 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 in powder form, sprayed or otherwise finely dispersed in the air, the use of respiratory protection (filter mask) is recommended at workplace.Thus, repeated inhalation exposure is not expected to pose an issue for human health.

Based on the above information, the substance does not qualify for repeated dose toxicity classification according to EU CLP Regulation (EC) No. 1272/2008.