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Description of key information

Short description of key information on bioaccumulation potential result: 
An assessment of the toxicokinetics behaviour of this material and also that of a close structural analogue of the substance has been conducted to the extent that can be derived from relevant available information.

Key value for chemical safety assessment

Bioaccumulation potential:
low bioaccumulation potential

Additional information

JUSTIFICATION FOR USE OF READ-ACROSS DATA

While the target material has test data which can be used for toxicokinetics assessment, comparison of overall physico-chemical and toxicity profiles for a similar analogue material with a larger dataset indicates it is appropriate to also consider and apply read-across data from the structural analogue when discussing basic toxicokinetics (see read-across matrix, attached).

TEST MATERIAL(S)

The test material is magnesium alkyl salicylate salt. It is a brown sticky solid which is made commercially available in liquid form with a refined mineral oil. The test substance analogue comprises calcium alkyl salicylate, which is a purple flaky solid but again is made commercially available in liquid form with a refined mineral oil. Therefore the substances were both administered as a solution in the availablein vivostudies.

The low vapour pressure value of the neat substance (in both cases) shows that it is not volatile and therefore inhalation is not a significant route of exposure. The neat substance is not expected to undergo hydrolysis under physiological conditions. As a result, exposure to hydrolysis products, following oral ingestion, is not expected.

The test substance (and analogue) has a relatively high molecular weight (747g/moL - for main % component), which suggests absorption across biological membranes is unlikely. However, based on a moderately high octanol/water partition coefficient (5.64± 0.15 at 40 degrees Centigrade), the substance could theoretically partition across biological membranes. The available physicochemical data on the neat substance and toxicological data on the preparation of neat substance and carrier oil were reviewed and, although the presence of carrier oil in the studies was taken into account, the assessment of toxicokinetic behaviour was based solely on the neat substance. 

ABSORPTION

While there are little data on the test material for repeat dose toxicity, the repeated dose oral toxicity study in rats for the closely related analogue material showed that the substance is absorbed via the gastrointestinal tract. The moderately high log octanol/water partition coefficient will also favour absorption of the substance from the gut. Publically available absorption, distribution, metabolism and excretion (ADME) data for the carrier oil shows very poor permeability across the dermal membrane. However, signs of absorption are seen in the skin sensitisation test in guinea pigs. This may be explained by the mild skin irritation produced by the substance since damage to the skin surface may enhance penetration of the substance through the skin to some extent. Low volatility of the substance suggests that the test material would not be available for inhalation. The target material is expected to behave similarly.

DISTRIBUTION

There is no evidence to suggest that the target substance is distributed systemically in oral studies, however there is some limited evidence of this occurring with the analogue material in a positive response in a skin sensitisation study in the guinea pig which suggests that the test material binds to carrier proteins in the circulatory system. The relatively high log octanol/water partition coefficient suggests that the substance may distribute into the adipose tissue and accumulate in body fat.

METABOLISM

The test substance is hydrolytically stable under physiological conditions and is likely to undergo further metabolism prior to excretion. The results of the long-term oral toxicity studies in the analogue material show evidence of an adaptive response in the livers of rats, which is normally associated with enhanced metabolism. The results of thein vitro genotoxicity assays in both materials, however, do not show any evidence that addition of the S9 metabolising system enhances or diminishes the activity of the substance.

EXCRETION

There is no evidence to indicate the route of excretion for this material but poorly water soluble products with high molecular weight are not likely to undergo urinary excretion, therefore biliary excretion may well be a significant route for this material. Any test material that is not absorbed will most likely be excreted in the faeces.