Benzene, ethenyl-, ar-bromo derivs.

Endpoint summary

Additional information

Basic Toxicokinetics

Physicochemical properties of Ethenylbenzene Ar-Bromo Derivs can give light to a number of factors important when assessing several areas of toxicological importance. As the substance is a liquid at room temperature and atmospheric pressure, it is not necessary to assess the inhalation hazard of the substance in terms of particle size. Furthermore, assessment of the vapour pressure revealed that the substance is not volatile. Overall, exposure via inhalation is considered unlikely.

Assessing the physical properties of the substance against the criteria set out in Lipinski’s rule of five (for drug likeness), the substance does not breach the five rules; this implies that the substance is orally active. From the partition coefficient, it can be seen that the substance is lipophilic, in addition, the substance is known to be only slightly soluble.

No data were available concerning human exposure; furthermore, there were no specific studies on the substance specifically investigating toxicokinetics in animal models. Therefore the assessment of the substance is based on the physicochemical properties of the substance and the available toxicity.

 

Dermal absorption:

From the submitted acute dermal toxicity studies, no evidence of systemic toxicity is observed. Irritation of the test site was noted, which is anticipated with this substance. Local irritation can facilitate dermal absorption by disruption of the integrity of the dermal barrier. Furthermore, the molecular weight of the substance (261.94 Da) is considerably below the size of exclusion for dermal penetration (500 Da). The partition coefficient of the substance indicates that the substance is lipophilic (log Pow 4.43), the substance will have a tendency to penetrate lipid rich layers, however a degree of hydrophilicity is required to achieve full absorption. Optimal absorption generally requires a log Pow between 1 and 2.

 

Inhalation:

One study was available, however the study submitted was not suitable to base classification and labelling as the highest dose was not high enough to determine whether the toxicity of the substance was outside the limits for the lowest classification. During the study, signs of respiratory irritation was observed. No signs of systemic toxicity was observed in any of the animals tested. Absorption via inhalation is anticipated to be slow, if at all. The substance is highly lipophilic, diffusion into the blood would be very limited. Furthermore as the substance is a liquid, with a vapour pressure of 12 Pa, the substance does not present a significant risk as an inhalation hazard.

 

Oral:

The oral route is the most likely route of exposure, optimum absorption occurs between 0 and 4, the substance falls just outside of this optimal range, indicating the substance absorbs preferentially in lipid rich environments and would be absorbed slowly via the oral route. This is apparent in the available toxicity studies, in which effects are noted at concentrations below the maximum tested in the repeated dose studies (though no sufficient to trigger a classification), however not at the maximum dose in the acute toxicity studies. In repeated dose studies, the level of test material ingested is maintained at a fairly constant level, however in the acute toxicity study, as the substance is absorbed relatively slowly, the substance is excreted from the system before a significant systemic dose is absorbed. This is apparent in the available sub-chronic, 90 day oral toxicity study, in which elevated bromine levels were noted in the serum, and a slight increase in bromine levels were noted in tissues.

 

Metabolism:

Very little data is available addressing the metabolism of the substance, however the substance is known to be hydrolytically stable, not-readily biodegradable, and there is no indication of toxic or mutagenic metabolites in the in vitro genotoxicity studies presented. As bromine levels were elevated in tissues and serum during the observations of the 90 day sub-chronic oral toxicity study, some debromination is expected to occur in the body.