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Description of key information

Based on two acute toxicity studies in rat (oral and dermal), 28 day oral study in rats and oral (daily) Study of Fertility and Early Embryonic Development (rat).  Also consideration of the substances water solubility, partition coefficient, molecular mass and particle size. The substance is a substituted valine of molecular weight that does not preclude absorption. The substance is stable to hydrolysis so exposure to degradation products is not relevant.

Oral: evidence presented by the subacute oral toxicity study indicates that the substance is slightly absorbed following at the high dose. Additionally, no toxicologically significant effects were observed on reproductive or developmental parameters in the exposed animals.

Inhalation: It is a non-volatile powder with a proportion of particles in the respirable size range so inhalation exposure is possible. Evidence presented by the acute inhalation study indicate some systemic absorption but only at high doses: lethargy, hunched posture, and piloerection were observed in the animals. Laboured respiration and ptosis were seen for the males and watery discharge and chromodacryorrhoea was seen for the females. However, these effects were reversible after 6 days.

Dermal absorption: The low Log Kow (0.832) and the high water solubility (26.4g/L) would indicate that absorption to the lipophilic stratum corneum would be low. No effects were detected in an acute dermal study up to a limit value of 2000mg/kg and no effects seen in in-vivo irritation studies.

Distribution: No specific distribution studies have been conducted the low log Pow value indicates that wide distribution and bioaccumulation would not be expected. However it is conceivable based on limited evidence from the 28 Day study at the higher dose concentrations (1000mg/kg) that some distribution may occur.

Macroscopic findings including small spleen, gaseous distension of the intestines and stomach and thinning/sloughing of the non-glandular gastric epithelium and microscopic examination of tissues revealed an increased incidence and severity of agglomeration of secretion and goblet cell hyperplasia in the stomach indicates that some there is some distribution throughout the body at high doses. The substance is not a contact sensitiser and may, therefore, not become bound to proteins.

Metabolism: there is no evidence to suggest metabolism; it is possible, if possible, that the substance could be metabolised as an amino acid by transamination, deamination or decarboxylation reactions.

Excretion: No specific excretion studies have been conducted however the physical characteristics (MW, water solubility and partition coefficient), would suggest that the substance is excreted by the kidneys. Amino acid catabolism could occur resulting in production of urea. The parent substance is non-volatile so elimination via the lungs, in expired air, would not be expected.

Key value for chemical safety assessment

Bioaccumulation potential:
low bioaccumulation potential
Absorption rate - oral (%):
100
Absorption rate - dermal (%):
50

Additional information

Based upon the results of repeat dose toxicity testing and the physical properties of the substance, it can be predicted that absorption and distribution can be expected by the oral and inhalation routes. Uptake is unlikely by the dermal route, a default value of 10% is assigned based upon the physical properties of the substance.