Alachlor not estrogenic.

We read with interest the article "Developmental Effects of Endocrine-Disrupting Chemicals in Wildlife and Humans," by Colborn et al. (EHP 101: 378-384). This paper reviews the important issue of potential long-term consequences resulting from exposure to endocrine-disrupting chemicals during early life. In this article, the authors primarily discuss agents that interfere with the functioning of endogeneous estrogen. We would like to bring to your attention an important factural error in this paper. Alachlor is listed in Table 1 of that review as a chemical "reported to have reproductive and endocrine-disrupting effects." This assessment is not supported by the extensive toxicological database on alachlor and has created the incorrect impression among some readers that alachlor has estrogenic activity. Given the importance of this issue in public health, scientific, regulatory , and legislative arenas, it is necessary to clarify the scientific facts regarding alachlor and endocrine disruption. Neither of the references cited by Colborn et al. (1,2) for alachlor discusses any data suggesting that it has estrogenic properties or interferes with reproductive activity. Both references noted that EPA concluded that minor kidney changes observed in some high-dose rats in a reproduction study were indicative of a treatment related effect. This conclusion was contrary to that of the scientists involved in the study. Nevertheless, such changes would not represent reproductive toxicity. The EPA document (2) mentions the occurrence of adrenal tumors in high-dose female rats, but a more detailed analysis by the agency subsequently concluded that these tumors were spontaneous and not treatment related (3). The only data discussed in either reference that could be misinterpreted as a direct effect on any endocrine system is the occurrence of thyroid neoplasia in rats fed alachlor throughout their lifetime at a dose that exceeded the maximum tolerated dose (MTD). It should be noted that this dose is more than 1 million times higher than EPA's estimate of dietary human exposure (4). The thyroid tumors in rats appear to be secondary to a hepatic effect rather than a primary effect of the chemical on the thyroid. Results from mechanistic studies have provided strong evidence indicating that chronic high-dose alachlor exposure results in increased thyroid hormone clearance via induction of hepatic uridine diphosphate glucuronyl transferase activity, thereby causing a compensatory increase in circulating thyroid-stimulating hormone levels followed by hyperplasia and ultimately neoplasia (5). The vast body of scientific literature surrounding this general nongenotoxic mechanism has been evaluated …