Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route
Dose descriptor:
NOAEL
2 000 mg/kg bw/day
Additional information

The main constituent of the registered substance, i.e. octandecan-1-ol, has been tested according to OECD test guideline 422 (Combined Repeat dose and Reproductive/Developmental Toxicity Screening Test) under GLP (Hansen, 1992). As octadecan-1-ol is the constituent with the shortest C-chain, it is regarded as a conservative representative regarding the toxicological effects of all alcohol-based constituents. This study is, therefore, considered as a key study. The substance was administered to rats in doses of 0, 100, 500, and 2000 mg/kg bw/day via the diet over 14 days. Reproductive parameters examined were pregnancy rate, length of gestation period, findings of corporea luteae, implantations, resorptions and number of fetuses at birth, number of pups per litter, weight, sex distribution, dead foetuses from day 1-5 and macroscopy. No indication for effects of the test substance on any of these parameters were found. Consequently, the NOAEL of 1-Octadecanol for reproductive/developmental toxicity was determined to be 2000 mg/kg bw. This NOAEL is read-across to the registered substance.

This NOAEL is supported by an OECD SIDS on long-chain alcohols (OECD, 2006). The information presented confirms the absence of a potential for reproductive toxicity for the category of the linear and essentially linear alcohols. In particular, no effects on fertility and reproduction of behenyl alcohol was observed for doses of 1000 mg/kg bw or higher in rats (Iglesias G. et al. (2002). The toxicity of behenyl alcohol: II. Reproduction studies in rats and rabbits. Regulatory Tox. and Pharm. 36, 80-85.).

The only further relevant constituents group are wax esters. Such esters constitute the main part of natural plant- and insect-based waxes, such as beewax, candelilla and carnauba wax. As these waxes have been authorised as food additives, it can be assumed that they will not have any fertility effects. This is supported by a statement of the Scientific Committe on Food of the European Commission on carnauba wax (SCF/CS/ADD/MsAd/194 Final; 2001: Opinion of the Scientific Committee on Food on carnauba wax), which states 'In a reproduction and subchronic feeding study 25 male and 25 female Wistar rats (F0) were fed 0,

0.1, 0.3, or 1.0% (w/w) of carnauba wax in the diet for 4 weeks prior to mating and throughout the reminder of the study including gestation and lactation (F0). Their progeny (F1) continued on the respective diets for 13 consecutive weeks after weaning. No treatment related adverse effects were recorded in this study (Parent RA, Re, TA, Babish, JG, Cox, GE, Voss, GE and Becci PJ (1983b). Reproduction and subchronic feeding study of carnauba wax in rats. Food and Chemical Toxicology 21: 89-93.).'


Short description of key information:
The main constituent of the registered substance has been tested in a OECD test guideline 422 (Combined Repeat dose and Reproductive/Developmental Toxicity Screening Test). As no reproductive effects were observed, the NOAEL was determined to be 2000 mg/kg bw. This NOAEL is read-across to the registered substance.

Effects on developmental toxicity

Description of key information
The main constituent of the registered substance has been tested in a OECD test guideline 422 (Combined Repeat dose and Reproductive/Developmental Toxicity Screening Test). As no developemental effects were observed, the NOAEL was determined to be 2000 mg/kg bw. This NOAEL is read-across to the registered substance.
In addition, a branched wax ester (Fatty acids, C16-18, 2-ethylhexyl esters) has been tested in a study according to OECD test guideline 414 in rats under GLP. No maternal toxicity, embryotoxicity nor teratogenicity were observed. Therefore, the respective NOAEL are considered to be 1000 mg/kg bw.
his NOAEL is read-across to the registered substance.
Effect on developmental toxicity: via oral route
Dose descriptor:
NOAEL
1 000 mg/kg bw/day
Additional information

The main constituent of the registered substance, i.e. octandecan-1-ol, has been tested according to OECD test guideline 422 (Combined Repeat dose and Reproductive/Developmental Toxicity Screening Test) under GLP (Hansen, 1992). As octadecan-1-ol is the constituent with the shortest C-chain, it is regarded as a conservative representative regarding the toxicological effects of all alcohol-based constituents. This study is, therefore, considered as a key study. The substance was administered to rats in doses of 0, 100, 500, and 2000 mg/kg bw/day via the diet over 14 days. Developmental parameters examined were external and head examinations, as well as organ formations.No indication for effects of the test substance on any of these parameters were found. Consequently, the NOAEL of 1-Octadecanol for reproductive/developmental toxicity was determined to be 2000 mg/kg bw.

This NOAEL is read-across to the registered substance.

This NOAEL is supported by an OECD SIDS on long-chain alcohols (OECD, 2006). The information presented confirms the absence of a potential for developmental toxicity/teratogenicity for the category of the linear and essentially linear alcohols. In particular, no effects on embryonic development of behenyl alcohol was observed for doses of 1000 mg/kg bw or higher in rabbits (Iglesias G. et al. (2002). The toxicity of behenyl alcohol: II. Reproduction studies in rats and rabbits. Regulatory Tox. and Pharm. 36, 80-85.).

The only further relevant constituents group are wax esters.

The branched wax ester (Fatty acids, C16-18, 2-ethylhexyl esters) has been tested in a study according to OECD test guideline 414 in rats under GLP (Pittermann, 1994). The purpose of this study was to assess the effects of the test substance on embryonic and fetal development in pregnant CD-rats. The test substance was tested at dose levels of 0, 100, 300 and 1000 mg/kg body weight. Each group consisted of 24 female rats. It was administered orally by gavage once daily from day 6 to day 15 of gestation inclusive.All surviving females were sacrificed on day 20 of gestation and removed by caesarean section. At necropsy the females were examined macroscopically and live fetuses were weighed, sexed and examined for visceral and skeletal abnormalities.

The dams tolerated the applied dose levels of up to 1000 mg/kg without lethality. No compound-related symptoms were observed in all treatment groups. Maternal body weight gain were not affected by treatment. No treatment-related abnormalities were found at necropsy of the females. Apart from the high-dose group (1 dead fetus) all females had viable fetuses.

Pre-implantation loss and mean numbers of resorptions were not affected by treatment. The figures of the post-implantation loss, embryonic deaths and total fetuses showed some no dose-related deviations which were considered to be not treatment related. Mean fetal placental and uterus weights were not affected by treatment. Fetal sex ratio was comparable in all groups.

No treatment-related fetal abnormalities were found at necropsy. There were no treatment-related effects in the reproduction data. The examined fetuses showed no treatment-related malformations. The skeletal variations in both the test groups and the control group were considered to be similar. The figures of skeletal ossifications showed some deviations in the low- and high-dose groups which were noted as no treatment-related effects and considered to be within the normal range. The visceral variations in both the test groups and the control group were considered to be similar.

Therefore, the NOAEL for embryotoxicity and teratogenicits are considered to be 1000 mg/kg bw.

The tested was ester is considered as a conservtaive representative of the wax ester present in the registered substance, which mainly have longer C-chains. Consequently, the NOAEL of 1000 mg/kg bw of the above described reliable study, which is considered as a key study, is read-across.

In addition, such wax esters, as present in the registered substance, constitute the main part of natural plant- and insect-based waxes, such as beewax, candelilla and carnauba wax. As these waxes have been authorised as food additives, it can be assumed that they will not have any developmental/teratogenic effects. This is supported by a statement of the Scientific Committe on Food of the European Commission on carnauba wax (SCF/CS/ADD/MsAd/194 Final; 2001: Opinion of the Scientific Committee on Food on carnauba wax), which states ' ...no adverse effects were observed in a teratogenicity study in Wistar rats after dietary exposure to up to 1% carnauba wax ( World Health Organisation (WHO) (1993) Toxicological evaluation of certain food additives and naturally occurring toxicants. WHO Food Additive Series: 30. World Health Organisation, Geneva.).'

Justification for classification or non-classification

As in studies with the relevant constituents of the registered substance no toxicity to reproduction was observed

for doses up to 1000 - 2000 mg/kg bw, no classification of the registered susbtance is required.