Registration Dossier

Administrative data

Link to relevant study record(s)

Description of key information

Introduction

No specific toxicokinetic or ADME investigations, or studies on potential metabolites, were available at the time of the review. However, physical chemical and mammalian toxicity data were available for evaluation from which a reasoned scientific opinion on the ADME parameters of this substance may be predicted. The data were generated specifically on the registered substance inGLP and regulatory compliant studies.An on-line literature (primarily PubChem, TOXNET, ChemIDplus) search did not reveal any further data that might aid in this prediction.

Available data

The test material was very poorly soluble in water (1.61 x 10E-02 gTOC/L) and had a partition coefficient (Log10 Pow) of 4.15 (anionic components) and 4.94 (cationic components), indicating a lipophilic substance. The flash point (143 ± 2 °C), boiling point (partial boiling, approximately 75%, from about 227 °C) and pour point (-9 ± 3 °C) would not suggest that this substance would present a risk of inhalation exposure under ambient environmental conditions. Moreover, the surface tension was 48.1 mN/m, and the substance was considered to be surface active.

Adsorption

The lipophilicity of the test material indicates that it would be readily absorbed across the lipid bilayers of cell membranes, after oral exposure and this may have been aided using the vehicle for oral gavage dosing. The lack of toxicity seen in the either the acute oral or dermal studies does not preclude acute oral or dermal absorption. The systemic toxicity observed in the 28-day repeat oral toxicity reproductive/developmental toxicity screening study clearly demonstrated the oral absorption and bioavailability of test item.

Distribution

The substance would be expected to be widely distributed particularly in the liver and kidneys as revealed by the liver and kidney effects after repeated oral dosing.  The data overall would not suggest significant bioaccumulation as illustrated by the recovery phase in the repeat dose study. The physical nature of the test item and physical chemistry data suggest that it is unlikely that acute inhalation exposure (not expected to present an exposure risk) would result in toxicity considering the very low toxicity evident in the acute studies presented.

Metabolism

It is expected, from the both the physical chemistry and toxicity data, that metabolism would be primarily via the liver and secondarily the kidneys. At 500 mg/kg bw/day in the repeat dose toxicity study, particularly in the male rats, the liver weights were increased, which is a sensitive indication of hepatocellular microsomal enzyme induction. Therefore, the substance is likely to be extensively metabolised in the liver. In the genotoxicity studies no genotoxicity was seen either with or without the addition of metabolic activation (+/- liver S9-mix), this support the view that potential metabolites that may be of limited mammalian toxicity.

Excretion

Given the physical chemical properties of the substance, the nature of the effects seen in the repeat dose toxicity study (increased liver and kidney weight; enhanced hepatic metabolism) and possibly limited bioaccumulation, it is predicted that excretion would be primarily via the urine and faeces.

Conclusion

The physical chemical characteristics of the registered substance plus data from the repeat dose toxicity study clearly suggest and demonstrate that the test item is likely to be rapidly absorbed, distributed and excreted with limited bioaccumulation. The substance was not acutely toxic via oral and dermal routes and not a sensitiser, although causing serious damage to eyes and irritating to skin. The data suggest that the liver is a target organ and that enhanced metabolism is likely to occur, although the toxicity of metabolites is likely to be limited as in the genotoxicity studies metabolic activation was without demonstrable effect. Considering these attributes, the most likely route of excretion would be primarily via the urine and secondarily the faeces.

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential

Additional information