Percutaneous absorption of trihalomethanes, haloacetic acids, and haloketones.

Bathing in chlorinated drinking water causes significant exposure to potentially toxic disinfection by-products (DBPs). In the present studies, we measured the permeation coefficients (K(p)) of three important classes of DBPs, trihalomethanes (THMs), haloketones (HKs), and haloacetic acids (HAAs), in aqueous solution across human skin using in vitro diffusion chambers. Linear mixed-effects model was utilized to calculate the steady-state permeability coefficients. The permeability coefficients of THMs ranged from 0.16 to 0.21 cm/h when the donor solution was at 25 degrees C. Bromoform had the highest K(p) value, while chloroform was the least permeable through the skin. THMs were approximately 10 times more permeable than HKs, while the permeability of HAAs through the skin was very low (1 to 3 x 10(-3) cm/h, pH 7). The permeability of HKs tripled as the temperature was increased from room temperature (20 degrees C) to bathing temperature (40 degrees C). A direct relationship was found between the permeability of THMs, but not HKs and HAAs, and their octanol/water partition coefficients. The dermal dose from daily bathing activities was approximated for an average adult using U.S. EPA recommended methods and found to be 40-70% of the daily ingestion dose for the THMs, 10% of the ingestion dose for HKs, and an insignificant percentage of the ingestion dose for the HAAs. In addition to ingestion, dermal absorption is an important route of exposure to THMs and HKs and must be considered in models of risk assessment.

[1]  J. Konz,et al.  Exposure factors handbook , 1989 .

[2]  G. Flynn,et al.  Transdermal Delivery of Narcotic Analgesics: pH, Anatomical, and Subject Influences on Cutaneous Permeability of Fentanyl and Sufentanil , 1990, Pharmaceutical Research.

[3]  A. E. Greenberg,et al.  Standard methods for the examination of water and wastewater : supplement to the sixteenth edition , 1988 .

[4]  J D Pleil,et al.  Alveolar breath sampling and analysis to assess trihalomethane exposures during competitive swimming training. , 1997, Environmental health perspectives.

[5]  T. Franz,et al.  Percutaneous Penetration of N-Nitrosodiethanolamine through Human Skin (in Vitro): Comparison of Finite and Infinite Dose Applications from Cosmetic Vehicles , 1993 .

[6]  M. R. Simon,et al.  Methods for in vitro percutaneous absorption studies. VII: Use of excised human skin. , 1986, Journal of pharmaceutical sciences.

[7]  I Chu,et al.  Penetration of chloroform, trichloroethylene, and tetrachloroethylene through human skin. , 1999, Journal of toxicology and environmental health. Part A.

[8]  Nancy L. Patania,et al.  The occurrence of disinfection by-products in U , 1989 .

[9]  R. Barnes,et al.  Determination of the aqueous chlorination products of humic substances by gas chromatography with microwave plasma emission detection , 1980 .

[10]  W. Meylan,et al.  Atom/fragment contribution method for estimating octanol-water partition coefficients. , 1995, Journal of pharmaceutical sciences.

[11]  McKone Te,et al.  Linking a PBPK model for chloroform with measured breath concentrations in showers: implications for dermal exposure models. , 1993 .

[12]  A. Leo,et al.  Partition coefficients and their uses , 1971 .

[13]  Y. Kalia,et al.  Passive skin penetration enhancement and its quantification in vitro. , 2001, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[14]  P. J. Callahan,et al.  Effect of water temperature on dermal exposure to chloroform. , 1998, Environmental health perspectives.

[15]  J. Rook Formation of Haloforms during Chlorination of natural Waters , 1974 .

[16]  C. Hansch,et al.  A NEW SUBSTITUENT CONSTANT, PI, DERIVED FROM PARTITION COEFFICIENTS , 1964 .

[17]  B. E. Stewart,et al.  Activity of 1,1,1- and 1,1,3-trichloroacetones in a chromosomal aberration assay in CHO cells and the micronucleus and spermhead abnormality assays in mice. , 1988, Mutation research.

[18]  P. Lioy,et al.  Chloroform exposure and the health risk associated with multiple uses of chlorinated tap water. , 1990, Risk analysis : an official publication of the Society for Risk Analysis.

[19]  R. Warner,et al.  Water disrupts stratum corneum lipid lamellae: damage is similar to surfactants. , 1999, The Journal of investigative dermatology.

[20]  A. Bunge,et al.  A New Method for Estimating Dermal Absorption from Chemical Exposure. 1. General Approach , 1993, Pharmaceutical Research.

[21]  C. Weisel,et al.  DERMAL ABSORPTION OF DICHLORO-AND TRICHLOROACETIC ACIDS FROM CHLORINATED WATER , 1999 .

[22]  R H Guy,et al.  Homogeneous transport in a heterogeneous membrane: water diffusion across human stratum corneum in vivo. , 1996, Biophysical journal.

[23]  R. F. Christman,et al.  Identity and yields of major halogenated products of aquatic fulvic acid chlorination. , 1983, Environmental science & technology.

[24]  H. Gorchev,et al.  Water chlorination : environmental impact and health effects , 1978 .

[25]  R A Corley,et al.  Physiologically based pharmacokinetic modeling of the temperature-dependent dermal absorption of chloroform by humans following bath water exposures. , 2000, Toxicological sciences : an official journal of the Society of Toxicology.

[26]  John Aurie Dean,et al.  Lange's Handbook of Chemistry , 1978 .

[27]  R L Chinery,et al.  A compartmental model for the prediction of breath concentration and absorbed dose of chloroform after exposure while showering. , 1993, Risk analysis : an official publication of the Society for Risk Analysis.

[28]  S. Curry,et al.  Disposition and pharmacodynamics of dichloroacetate (DCA) and oxalate following oral DCA doses , 1991, Biopharmaceutics & drug disposition.

[29]  G. Aggazzotti,et al.  Plasma chloroform concentrations in swimmers using indoor swimming pools. , 1990, Archives of environmental health.

[30]  B. Merrick,et al.  Chemical reactivity, cytotoxicity, and mutagenicity of chloropropanones. , 1987, Toxicology and applied pharmacology.