Registration Dossier

Administrative data

Link to relevant study record(s)

Description of key information

Data clearly demonstrated that the substance was not topically or systemically toxic at dose levels that could be considered in excess of a maximum tolerated dose.

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential

Additional information

Introduction

No specific toxicokinetic (TK) investigations, or studies on potential metabolites, were available at the time of this review. However, physical chemical and mammalian toxicity data were available for evaluation from which a reasoned scientific opinion on the TK or ADME parameters of this substance may be predicted. Most of the data were generated on a research substance with some data available on the manufactured product. An on-line literature search did not reveal any further useful data.

Key physico-chemical data

The research material was miscible in water (20 °C) and had a partition coefficient (Log10 Pow) of ≤ -3.75, indicating a lipophobic substance. Further, the surface tension (21°C) was 72.5 ± 0.5 mN/m and the substance was therefore not considered to be surface active. The physio-chemical data demonstrated that this substance had a vapour pressure (at 25°C) of 1.87 Pa (research material) or 23.7 Pa (manufactured product). The latter suggests a relatively high value (higher volatility) in comparison to the research material.

Mammalian toxicity data

Acute toxicity by the oral or dermal routes was very low with an LD50 of 3390 mg/kg bw. The substance was not irritating to the skin or eyes and was not a skin sensitiser. The genotoxicity studies employed for the substance demonstrated overall no toxicity (e.g. mouse lymphoma assay at 4 hours) and no genotoxic potential. However, some toxicity was seen in the mouse lymphoma assay at 24 hours as reductions in the relative suspension growth, e.g. at 2000µg/mL. In an OECD 422 study, where the highest dose tested was 1000 mg/kg bw/day, no parental systemic or reproductive toxicity, no developmental or neonatal toxicity was evident. The data clearly demonstrated that the substance was not topically or systemically toxic at dose levels that could be considered in excess of a maximum tolerated dose.

Absorbtion and distribution

The relative lipophobicity, and miscibility in water, indicates that the substance may be not be rapidly absorbed (systemic availability), compared to a more lipophilic substance, after either oral or dermal exposure. The data from the acute toxicity studies provide further evidence of this where no toxicity was seen at the highest dosages tested. However, it is likely that some absorption did occur, particularly following repeated oral exposure (in arachis oil), but that distribution and bioaccumulation would be expected to be limited. The data also suggest that dermal absorption would most likely be low, for example as no systemic toxicity was seen in either the acute dermal toxicity or LLNA. Despite the vapour pressure of the manufactured product, it is considered unlikely that inhalation toxicity would present significant toxicity considering the very low toxicity evident in the studies previously undertaken.

Metabolism

It is judged that metabolism would be primarily via the liver; the very low toxicity seen after repeated oral exposure further suggests that potential metabolites would also be of limited toxicity in the animal models used. The data from the genotoxicity studies (with S9-mix, i.e. induced metabolic activation) support this opinion.

Excretion

Given the physical chemical properties of the substance and possible limited bioavailability it is likely that excretion would be mostly via the urine and faeces.