Updated weight of evidence for an association between adverse reproductive and developmental effects and exposure to disinfection by-products

Regul Toxicol Pharmacol. 2006 Jul;45(2):185-205. doi: 10.1016/j.yrtph.2006.03.001. Epub 2006 Apr 19.


Disinfection by-products (DBP) are produced when water is treated with chemical disinfectants. Some toxicological and epidemiological studies suggest an association between DBP exposure and adverse reproductive and developmental effects. In a previous critical review, [Graves, C.G., Matanoski, G.M., Tardiff, R.G., 2001. Weight of evidence for an association between adverse reproductive and developmental effects and exposure to disinfection by-products: a critical review. Regul. Toxicol. Pharmacol. 34, (2) 103-124] evaluated the weight of evidence for this exposure and these effects. This investigation updates the previous evaluation and considers all toxicological and epidemiological evidence since the earlier review and reassesses the weight-of-evidence for all of the data on the various effects, outcome by outcome. The updated toxicity weight of evidence found little indication of previously unreported reproductive or developmental toxicity. In particular, the recently published findings of an exceptionally well conducted cohort study of broad scope found no impact of chlorination by-products on the highly controversial outcome of spontaneous abortion, unlike predecessor studies of more limited methodology, leading the authors to recommend no further epidemiologic pursuit for this hypothesis since the cohort was scrutinized very closely and dispelled any concern of such an association. The updated epidemiologic weight of evidence demonstrated that no association with DBP exposure exists for over a dozen outcomes including low and very low birth weight, preterm delivery, some specific congenital anomalies, and neonatal death. The analysis found inconsistent or very weak results for all congenital anomalies/birth defects, all central nervous system anomalies, neural tube defects, and spontaneous abortion. As in the previous article, the updated weight of evidence suggested a positive association with DBP exposure and some measure of growth retardation such as intrauterine growth retardation, small for gestational age, term low birth weight, and small body length or head circumference. Exposure assessment in most epidemiological studies remains inadequate to definitively demonstrate any association of small magnitude.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Birth Weight
  • Disinfectants / metabolism*
  • Disinfectants / toxicity
  • Fetal Growth Retardation / chemically induced
  • Growth and Development / drug effects*
  • Humans
  • Reproduction / drug effects*
  • Water Pollutants, Chemical / toxicity*
  • Water Purification*


  • Disinfectants
  • Water Pollutants, Chemical