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EC number: 931-082-4
CAS number: -
The reproductive toxicity of NExBTL
renewable diesel (a UVCB substance of similar composition to the substance:
see analogue approach justification document) 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. Due to compositional similarities, the same overall NOAEL is
considered to apply to the substance also.
Short description of key information:
No biologically or toxicologically relevant effects on fertility or reproduction in a GLP-compliant guideline study on NExBTL renewable diesel (a UVCB substance of similar composition to the substance) up to an oral limit dose of 1000 mg/kg bwt/d
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
No classification required under Directive 67/548/EEC
or Regulation EC 1272/2008 for effects on fertility, reproduction or
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