Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Additional information

The repeated dose toxicity study from Casterton et al. (see 7.5.1) was a 90-day Wistar rat feeding study with in utero exposure of refined arachidonic acid-rich oil (RAO). RAO consists among other things of stearic acid and palmitic acid, the both main components of the fatty acid C16-18, sodium salt. The in utero phase of the study involved dietary exposure to RAO, covered four-weeks prior to mating, through mating, gestation and lacation until offspring (F1) weaning. There were no treatment-related fertility, reproductive or developmental index observations. Therefore, it is assumed that the fatty acid C16-18, sodium salt does not affect fertility. Because of the existing developmental toxicity study according OECD 414, which shows that the fatty acid has no developmental toxicity properties, an additional OECD 421 study is not justified with regard to avoid animal testing.

Effects on developmental toxicity

Description of key information
- NOAEL = 1000 mg/kg bw | rat (female) | OECD 414  | 2-ethylhexyl stearate 
- no specific teratogenicity | Mouse (female), rat (female), hamster (female) | no guideline followed | linear alkyl benzene sulfonate; cocoa fatty acids, potassium salts
Effect on developmental toxicity: via oral route
Dose descriptor:
1 000 mg/kg bw/day
Additional information

In one study 2-Ethylhexyl stearate was investigated in an embryo-/foetotoxicity and teratogenicity study on rats according to OECD guidelines for the testing of chemicals (No. 414). This study is used as read across, because the ester bond of 2 -ethylhexyl stearate will be hydrolyzed by pH or enzymatic activities in the body. Thus, the C18 fatty acid stearate acid is released leading to an identical situation as in case of an exposure to C18 sodium salt where also the C18 fatty acid stearate is released as the relevant component.

Dose levels of 0 (arachidis oil), 100, 300 and 1000 mg/kg body weight/day were administered by gavage. Dams tolerated the applied dose levels without any toxic effects. Pre- and post-implantation loss and mean numbers of resorptions were unaffected by treatment. All parameters were comparable with the animals of the control group. Skeletal and visceral investigations revealed no treatment-related malformations. For embryo-/foetotoxicity, teratogenicity and maternal toxicity a NOAEL of 1000 mg/kg was deduced.

In another study the surfactants linear alkylbenzene sulphonate (LAS) and cocoa fatty acid, potassium salt were examined for embryotoxic and teratogenic potential following percutaneous administration. Solutions containing, 0.03, 0.3 and 3% LAS were applied to shaved skin during pregnancy days 2 -13 in mice, 2 -15 in rats and 1 -16 in rabbits..

Dosages employed were 0.5 ml/rat or mouse/day and 10 ml/rabbit/day.

For comparison further groups of rats and mice were similarly treated with concentrations of 0.3, 3 and 30% of a standard soap solution (potassium salts of cocoa fatty acids consisting of carbon atoms: - C8 (4.7%) - C10 (5.7%) - C12 (47.2%) - C14 (18.5%) - C14 Fl (0.2%) - C16 (11.2%) - C18 (6.9%) - C18 Fl (4.7%) - C20 (0.9%))

Marked maternal toxicity in the form of local skin reaction, irritability, weight loss and failure to maintain or establish pregnancy was evident in mice treated with LAS 3% or cocoa fatty acid, 3 or 30%; marked local reaction and weight loss also occurred in rabbits receiving LAS 3% but the reduction in the number of pregnancies maintained was not significant. Moderate maternal toxicity was observed among mice treated with LAS, 0.3% and mild maternal toxicity in rats receiving LAS 3% or cocoa fatty acid 30% and rabbits receiving LAS 0.3%.

Effects on litter parameters were generally restricted to dosages causing marked maternal toxicity in mice, the principal effects being higher foetal loss (with consequent reduction in viable litter size) arising from an increased incidence of total litter losses. When dams showing total liter loss were excluded from the calculations, litter parameters were not unduly different from those of controls. Although LAS at 3% was considered to show marked maternal toxicity in the rabbit, the slightly higher foetal loss and lower litter size did not differ significantly from control values. The moderate maternal toxicity of LAS, 0.3% in the mouse correlated with a higher incidence of embryonic deaths and lower litter size but only the former differed significantly from the corresponding control value.

At dosages that were non-toxic or only slightly toxic to the dam, litter parameters were not adversely affected as the only significant deviations from control values were in respect of the higher mean pup weights observed in rats treated with LAS 3%, or all dosages of cocoa fatty acid and the consequent higher litter weights with cocoa fatty acid 0.3 or 30%.

Incidences of minor skeletal anomalies were unaffected by treatment with LAS, 0.03% or cocoa fatty acid 3%; higher values observed with LAS or cocoa fatty acid at 3% did not differ significantly from control values. There were no significant differences from control values in respect of the distribution of extra-ribbed fetuses.

With rats and rabbits intergroup variations in the incidence of major malformations, minor visceral and skeletal anomaly, and skeletal variants, were not statistically significant and showed no dosage related trends. The slightly higher incidence of major malformation observed in rats, 3% or cocoa fatty acid, 30% resulted from the uneven litter distribution of variable types of abnormality known to occur spontaneously in the CD strain.

The incidences of major malformations, minor visceral or skeletal anomalies, and skeletal variants provided no conclusive evidence of specific teratogenicity cocoa fatty acid, potassium salt and LAS, even at maternally toxic dosages.

Justification for classification or non-classification

A classification is not necessary because the NOAEL of 2-ethylhexyl stearate is 1000 mg/kg bodyweight. The ester bond of the
2-ethylhexyl stearate will be hydrolyzed by pH or enzymatic activities in the body. Thus, the C18 fatty acid stearate acid is released leading to an identical situation as in case of an exposure to C18 sodium salt where also the C18 fatty acid stearate is released as the relevant component. Stearate acid is a major component (ca. 50%) of the fatty acid C16 -18, sodium salt. Therefore fatty acid C16 -18, sodium salt will have a NOAEL in the same range like 2 -ethylhexyl stearate.

Additional information