Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route
Dose descriptor:
NOAEL
1 000 mg/kg bw/day
Additional information

The reproductive toxicity of NExBTL renewable diesel was examined in the rat following oral gavage administration over two consecutive generations at dose levels of 50, 250 and 1000 mg/kg/day. The study, which was GLP-compliant and included a sub-chronic reproductive toxicity phase, followed OECD guideline 416. Clinical signs were limited to salivation following dosing in the high and intermediate treatment groups which also showed increased water intake; both findings were considered secondary to the unpleasant taste of the test substance formulations. Oestrus cycle, mating cycle and pre-coital intervals were comparable in control and parental animals although a non-significant increase in non-pregnant females was observed in the P-generation at 1000 mg/kg/d and 250 mg/kg/d. The study was therefore extended to include a second generation which showed a non-significant increase in fertility (all treated groups) when compared to controls. It was therefore concluded that the finding from the first generation was not indicative of an adverse effect on reproduction. There was no statistically significant or treatment related effect on number of corpora lutea, implantation sites or number of live births in either generation although mean litter size for the intermediate and high dose groups from both P and F1 generations was approx. 8-10% lower than controls; this finding was considered of negligible toxicological significance. Semen analysis for males from both generations and ovarian follicle development for F1 generation females were unremarkable. Liver and kidney weights were elevated for high and intermediate males from both generations with treatment-related effects observed microscopically. Hepatic findings consisted of generalised hepatocyte enlargement for females treated with 1000 and 250 mg/kg/day from the P generation, and for animals of either sex treated with 1000 mg/kg/day from the F1 generation. Hepatocyte enlargement is commonly observed in the rodent liver following the administration of xenobiotics and considered to be adaptive in nature. Renal changes were characterised as globular accumulations of eosinophilic material in the tubular epithelium of males treated with 1000 and 250 mg/kg/day from both the P and F1 generations. This finding appeared consistent with alpha-2-microglobulin accumulation and was confirmed by the additional staining with Mallory-Heidenhain stain. Alpha-2-microglobulin is absent from humans and the findings were therefore viewed of negligible toxicological relevance. It was concluded that oral administration of NExBTL Renewable diesel to rats throughout the reproductive cycle over two generations at dose levels of up to 1000 mg/kg/day did not result in any toxicologically significant effects with an overall NOAEL of 1000 mg/kg bwt/d for reproductive and systemic toxicity.


Short description of key information:
No biologically or toxicologically relevant effects on fertility or reproduction in a GLP-compliant guideline study up to an oral limit dose of 1000 mg/kg bwt/d

Effects on developmental toxicity

Description of key information
No biologically or toxicologically relevant effects on development in a GLP-compliant study up to an oral limit dose of 1000 mg/kg bwt/d
Effect on developmental toxicity: via oral route
Dose descriptor:
NOAEL
1 000 mg/kg bw/day
Additional information

No statistically significant or treatment related effects were found ion number of corpora lutea, implantation sites or number of live births in pregnant female rats administered NExBTL renewable diesel over 2-generations at dose levels of 50, 250 or 1000 mg/kg bwt/day. The study, which was GLP-compliant and included a sub-chronic reproductive toxicity phase, followed OECD guideline 416. An approx. 8-10% reduction in mean litter size for the intermediate and high dose groups was considered a chance finding of negligible toxicological significance an overall oral NOAEL of 1000 mg/kg bwt/d for developmental toxicity. The study was conducted to achieve compliance under chemical, safety and health regulations other than EU REACH.

Justification for classification or non-classification

No classification required under Directive 67/548/EEC or Regulation EC 1272/2008 for effects on fertility, reproduction or development.