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Toxicological information

Basic toxicokinetics

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Endpoint:
basic toxicokinetics
Adequacy of study:
other information

Data source

Materials and methods

Results and discussion

Applicant's summary and conclusion

Executive summary:

There is no reliable and relevant information source in which the toxicokinetic properties (absorption, distribution, metabolism, elimination) of CHIMEXANE NV were investigated. The expected toxicokinetic behaviour is derived from the physicochemical properties and the results from the available toxicological data following the guide given in the REACH guidance document R.7c.

CHIMEXANE NV is a substance composed of constituents having a molecular weight of 260, 334 and 409. It is a pasty solid with an estimated water solubility of 6 mg/L. Vapour pressure was determined to be about 227 Pa at 25 °C and it has lipophilic properties (for the 2 main constituents, log Kow 1 = 3.78 and Log Kow 2 = 4.25). The surface tension is 26.6 mN/m. Detailed information can be found in section 4 of CHIMEXANE NV IUCLID dossier.

Absorption:

In acute toxicity studies, either by oral or dermal route, no systemic toxic effects were observed. Only local effects such as necrosis associated with severe oedema, showing the corrosive properties of the substance, were identified. In a reproduction /developmental toxicity screening test and in a 4-week repeated dose toxicity study by oral route, the main effects elicited by the substance were transient reduced body weight gain and food consumption, particularly in the males, excessive salivation, loud breathing and half-closed eyes in both sexes. These observations indicate partial bioavailability of CHIMEXANE NV via oral route.

Although no signs of toxicity were observed in an acute dermal toxicity study, CHIMEXANE NV has a molecular weight < 500 and is a lipophilic substance (for the 2 main constituents log Kow is around 4) therefore dermal absorption is expected. However, due to its low water solubility, dermal absorption is expected to be low or moderate. But, as the substance has also corrosive properties, damage to the skin surface may enhance penetration.

 Thus, indications of oral and dermal uptake of CHIMEXANE NV are given. Therefore the bioavailability of CHIMEXANE NV can be considered to be existent but maybe limited.

Distribution:

The physico-chemical information (low molecular weight, lipophilicity and low water solubility) indicates that CHIMEXANE NV could be distributed to many tissues and, due to its lipophilicity, may have a particular affinity for fatty tissues.

Metabolism:

No data are available but, in in vitro genotoxicity studies (particularly in MLA test), differences in cytotoxicity were observed with and without metabolic activation. This indicates that CHIMEXANE NV may be metabolised by hepatic microsomal fractions.

Excretion:

As no toxic effects were observed in kidneys in repeated toxicity studies, it is difficult to determine if CHIMEXANE NV is excreted in urine. However, based on the physico-chemical information (low molecular weight and low water solubility), renal excretion of CHIMEXANE NV and/or its metabolites cannot be excluded.

Accumulative potential:

Based on the physico-chemical information (log Pow and low water solubility), it is concluded that the potential for bioaccumulation is low.