Bromoacetic acid

Endpoint summary

Description of key information

The weight of evidence of the available information indicates that the substance is likely to be readily absorbed via the oral, dermal and inhalation route. Thereafter rapid metabolism occurs and the substance is not detctable in the blood, neither after i.v. nor after oral administration. It has been shown that it is rapidly removed from the blood and a rapid excretion of metabolites can be expected from the available information.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Absorption rate - oral (%):

100

Absorption rate - dermal (%):

100

Absorption rate - inhalation (%):

100

Additional information

Absorption

 Oral

No specific study to determine the oral absorption of bromoacetic acid by measuring the amount of bromoacetic acid absorbed from the gut has been performed. Several studies, dosing bromoacetic acid via drinking water or by gavage, show some effect at the high dose demonstrating absorption after oral application.

For oral application of bromoacetic acid 100% absorption can therefore be assumed.

 Dermal

Anin-vitroskin permeation study (Maas,A6.2.2/01)shows that bromoacetic acid is absorbed through intact skin. The preliminary study part, targeted on skin integrity showed that above a bromoacetic acid concentration of 1.33% the flux increases significantly both with rat and human skin. At a concentration of 5% the skin barrier did not function properly. The observed lag-time is 2-4 hours.

In the main study mean recovery of bromoacetic acid in human skin was > 91.0%, in rat skin >91.3%. Mean penetration into the receptor fluid was 83.9% (dose 4.98%), 55.7% (dose 1.32%) and 44.4% (dose 0.76%, similar to in use concentration of the biocidal product). For the rat skin the mean penetration was 43.1% (dose 5.0%), 14.4% (dose 1.33%) and 12.7% (dose 0.77%). Additional investigations show that the applied small volume 10mL/cm²may have resulted in local higher amounts and concentration of bromoacetic acid on the skin and some impairment of the skin barrier resulting in higher absorption due to skin damage. This is based on as additional experiments with an applied dose of 50mL/cm²that showed a longer lag-time of 2-4 hours similar to what is found in the preliminary study. Nevertheless, in a realistic worst-case situation absorption of bromoacetic acid through skin must be assumed.

For the purpose of risk assessment in this dossier conservative 100% absorption of bromoacetic acid through the skin will be applied.

 

Metabolism and distribution

No specific metabolism and distribution study has been performed as literature data (Saghir and Schultz, A6.2.1/01) show that the elimination of bromoacetic acid after iv or oral dosing is very rapid, in most samples it could not detected in the first sample after 3 min resp. 1 min.

From the molecular structure of bromoacetic acid it can be deduced that the acetate ion or hydroxy acetic acid and bromine ion could be metabolites. Acetate ions and hydroxy acetic acid are normal body constituents of no concern and are further metabolised to CO₂. Therefore they do not need a further evaluation. A second metabolic pathway leading to detoxification is the conjugation with glutathione and further excretion in urine as mercapturic acid derivatives. To get additional insight into metabolism a study on the stability of bromoacetic acid in blood was performed(Maas,A6.2.3/01). The results of this investigation show fast and almost complete removal of bromoacetic acid from plasma and in particular whole blood. No unexpected metabolites are found; the observed conjugation with glutathione is a normal detoxification route and an observed strong binding to cellular proteins in erythrocytes in the in vitro study that is probably related to the GSH conjugation, which removes bromoacetic acid from circulation. It can be concluded that the reported results of Saghir et al. 2005 are realistic and the observed short time to render bromoacetic acid undetectable are in line with the results of the stability of bromoacetic acid in blood study.