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Description of key information

There is no reliable and relevant information source in which the toxicokinetic properties (absorption, distribution, metabolism, elimination) of CHIMEXANE NB 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.

Key value for chemical safety assessment

Additional information

There is no reliable and relevant information source in which the toxicokinetic properties (absorption, distribution, metabolism, elimination) of CHIMEXANE NB 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 NB is a substance composed of constituents having a molecular weight of 343, 416 and 490. It is a yellow viscous liquid with estimated water solubility at 3.80 mg/L, above this concentration micelle formation occurs (micellular solubilisation). Vapour pressure was calculated to be about 0.00082 Pa at 20 °C and it has high lipophilic properties (for the three main constituents, log Kow > 4, log Kow= 5.5 for the multiconstituent substance CHIMEXANE NB).The surface tension is 29.63 mN/m.Detailed information can be found in section 4 of CHIMEXANE NB IUCLID dossier.

Absorption:

In acute toxicity studies, either by oral or dermal route, no systemic toxic effects were observed. Only local effects such as moderate-severe erythema associated with slight to moderate oedema, showing skin irritancy 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 substancewere transient reduced body weight gain and food consumption, reduced total cholesterol concentration in both males and females, and lower mean glucose level and mean creatinine valuesin females. These observations indicate partial bioavailability of CHIMEXANE NBviaoral route.

Although no signs of toxicity were observed in an acute dermal toxicity study, CHIMEXANE NB has a molecular weight < 500 and is a high lipophilic substance (main constituents with log Kow > 4) therefore dermal absorption is expected.

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

Distribution:

The physico-chemical information (molecular weights < 500, lipophilicity and low water solubility) indicates that CHIMEXANE NB 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 NB may be metabolized by hepatic microsomal fractions.

Excretion:

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

Accumulative potential:

Based on some toxicological studies that provide indications on CHIMEXANE NB absorption and metabolism (repeated dose toxicity study and genotoxicity studies) and on physico-chemical information (molecular weights < 500 and log Kow >4), it is concluded that CHIMEXANE NB is partially bioavailable, it is also likely to be metabolized by hepatic enzymes and excreted. Therefore, the potential for bioaccumulation is expected to be low.