Ethylene chlorohydrin




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Chlorohydrin special considerations

Time:2015/9/24 7:15:05

Chlorohydrin Metabolism and Disposition

There is no information on the metabolism and disposition of chlorohydrin following inhalation exposure. In Wistar rats, up to 80% of an orally administered radiolabeled

dose was excreted in the urine although none of the radioactivity represented the parent compound (Grunow and Altmann, 1982). Radioactivity in the blood declined by 50% after hours. The major urinary metabolites were thiodiacetic acid and thionyldiacetic acid. Carbon dioxide was also detected in expired air. Johnson (1965) hypothesized that ethylene

chlorohydrin toxicity may, in part, be a function of increased chloroacetaldehyde resulting from saturation of glutathione conjugation. Results of in vitro and in vivo metabolism studies showed formation of S-carboxymethyl-GSH in livers of rats given chlorohydrin (Johnson(1967).

Chlorohydrin Mechanism of Toxicity

The precise mode of action of chlorohydrin is not known. Bush et al.,(1949) reported autopsy findings of severe liver and brain damage as well as involvement of other organs in an occupational accident. Signs and symptoms in nonfatal exposures suggested multi-organ involvement including gastrointestinal disorders, nervous system effects, and respiratory tract irritation. In animals, Goldblatt (1944) stated that although inhalation exposure to ethylene chlorohydrin appeared to have a depressant effect on the central nervous system and would induce immobility, a typical narcosis was not observed. Additionally, necropsy results from the Goldblatt (1944) experiments did not reveal significant evidence of respiratory tract tissue damage but did suggest renal involvement. Goldblatt (1944) reported that inhalation exposure of rats (chamber exposure or via a tracheal cannula) produced neither respiratory disturbances nor effects on blood pressure.

Chlorohydrin Structure-Activity Relationships

There are no structure activity data with which to develop AEGL values for ethylene chlorohydrin. It has been hypothesized that chloroacetaldehyde is a metabolite of ethylene

chlorohydrin. AEGL values for chlorohydrin and chloroacetaldehyde vary by less than 2-fold; 10-minute and 30-minute values for chlorohydrin are somewhat lower than those for chloroacetaldehyde while for 1-, 4-, and 8-hours, chlorohydrin values are slightly greater.chlorohydrin (2-CHLOROETHANOL) Page 16 of 37 INTERIM 05/2008

Chlorohydrin Species Variability

Data are insufficient with which to accurately assess species variability in the toxic response to inhalation exposure to chlorohydrin.

Chlorohydrin Concurrent Exposure Issues

There are no concurrent exposure issues unique to chlorohydrin that would be instrumental in developing the AEGL values.