Genotoxicity and Carcinogenicity of Disinfection By-products in Drinking Water. Outline. Health Effects of Chlorinated Drinking Water Review of 30 years of DBP research on occurrence, genotoxicity, and carcinogenicity Dermal/inhalation exposure, genotype, and health risks Research needs.
Genotoxicity and Carcinogenicity of Disinfection By-products in Drinking Water
Occurrence, Genotoxicity, and Carcinogenicity of Regulated and Emerging Disinfection By-products in Drinking Water: A Review and Roadmap for ResearchSD Richardson, MJ Plewa, ED Wagner,R Schoeny, DM DeMariniMutation Research 636:178-242, 2007
aIARC 2B = possible/EPA B2 = probable human carcinogen.
4 Other halo-acids
9 Iodo- & other THMs
12 MX compounds
Projecte d’Investigació Sobre Compostos Irritants en Natació
Research Project on Irritants in Swimming Pools
[DeMarini et al., Environ Mol Mutagen 26:270, 1995]
Activation of Halomethanes,but Not Chloroform, to Mutagens by GSTT1-1RA Pegram et al.Toxicol Appl Pharmacol 144:183, 1997
Disposition of Bromodichloromethane in Humans Following Oral and
TL Leavens et al., Toxicol Sci 99:432, 2007
Subject’s arm was in water for 1 h with bromodichloromethane(~50 ppm or 50 ng/kg), or subject drank water giving 50 ng/kg exposure. BDCM was metabolized much faster by the oral route than dermal route of exposure.
Bladder Cancer and Exposure to Water Disinfection By-products Through Ingestion, Bathing, Showering and Swimming in Pools
[CM Villanueva et al.
Am J Epidemiol 165:148, 2007]
Activated by GSTT1-1
in kidney & intestine
Human Mol Epi
↑ Bladder cancer
↓ Bladder cancer
expression of only
2 genes and no
pathways in common
● 6 regulated DBPs still have significant
genotoxicity data gaps, and 1 has never
been tested for carcinogenicity.
● 14 unregulated DBPs have no
genotoxicity toxicology data, but 2 are
● 29 unregulated DBPs at μg/L levels are
● ~70 DBPs studied systematically and quantitatively for DNA damage (comet assay) in CHO cells (M. Plewa, U. of IL)
● ~20 DBPs studied similarly in Salmonella (D. DeMarini, EPA)
3. Studies on route of exposure & genotype
● Rodent studies (dermal-bladder/colon)
● Human studies (experimental & epi)
● >50% of total organic halide (TOX) and assimilable organic carbon (AOC) have not been identified as specific compounds. Savitz et al. (2006) epi study on chloraminated water showed correlation between TOX and pregnancy loss.
● Additional analytical studies should be conducted in concert with toxicological studies.
● chloramine, ozone, and chlorine dioxide
● UV and membrane technologies
● Salmonella assay used already in a region of Brazil for source-water assessment and regulation
● Salmonella assay literature on drinking water mutagenicity is extensive but not linked well to chemical analysis.
● >600 identified DBPs, many are toxic, exposed via oral, dermal, and inhalation.
● This complexity is not reflected in any of the toxicology studies of individual DBPs.
● Need for bioassay-directed fractionation of water extracts for genotoxicity, from different source waters and treatment methods.
● Merge with current review to permit a sound, scientific assessment of current regulations and directions for future research.
The collective enterprise of creative thinking and skeptical thinking, working together, keeps the field on track.
Carl Sagan, 1996