In vitro and in vivo assessments of the genotoxic potential of 3‐chloroallyl alcohol

Abstract

3‐Chloroallyl alcohol (3‐CAA) can be found in the environment following the application of plant protection products. 3‐CAA is formed in groundwater following the injection of 1,3‐dichloropropene, a fumigant used to control nematodes. 3‐CAA is also formed, in leafy crops, as a glycoside conjugate following application of the herbicide, clethodim. Human exposure may occur from groundwater used as drinking water or through dietary consumption. To characterize 3‐CAA's potential to cause genotoxicity in mammals, in vitro and in vivo studies were conducted. 3‐CAA was negative in an Ames test and positive in a mouse lymphoma forward mutation assay. 3‐CAA was negative in an acute in vivo CD‐1 mouse bone marrow micronucleus assay when administered up to a dose level of 125 mg/kg/day for two consecutive days. In a combined gene mutation assay and erythrocyte micronucleus assay, using transgenic Big Blue® Fischer 344 rats, 3‐CAA was administered via drinking water at targeted dose levels of 0, 10, 30, and 100 mg/kg/day for 29 days. Peripheral blood samples, collected at the end of treatment, were analyzed for micronucleus induction in reticulocytes using flow cytometry. Liver and bone marrow samples, collected 2 days after the termination of the treatment, were analyzed for the induction of mutations at the cII locus. 3‐CAA did not induce an increase in mutant frequency or micronuclei under the experimental conditions. In conclusion, the mutagenic response observed in the in vitro mouse lymphoma assay is not confirmed in the whole animal. 3‐CAA is not considered to pose a mutagenic risk.