Physiologically Based Pharmacokinetic modeling of the temperature-dependent dermal absorption of chloroform by humans following bath water exposures

Journal Article · Fri Jan 14 04:00:00 EST 2000 · Toxicological Sciences

DOI:https://doi.org/10.1093/toxsci/53.1.13· OSTI ID:15002319

Corley, Rick A ^[1]; Gordon, Syd M ^[2]; Wallace, Lance A ^[3]

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1. BATTELLE (PACIFIC NW LAB)
2. Battelle Memorial Institute
3. U.S. Environmental Protection Agency

The kinetics of chloroform in the exhaled breath of human volunteers exposed skin-only via bath water (concentrations < 100 ppb) were analyzed using a physiologically based pharmacokinetic (PBPK) model. Significant increases in exhaled chloroform (and thus bioavailability) were observed as exposure temperatures were increased from 30 to 40?C. The blood flows to the skin and effective skin permeability coefficients (Kp) were both varied to reflect the temperature-dependent changes in physiology and exhalation kinetics. At 40?C, no differences were observed between males and females. Therefore, Kp?s were determined ({approx}0.06 cm/hr) at a skin blood flow rate of 18% of the cardiac output. At 30 and 35?C, males exhaled more chloroform than females resulting in lower effective Kp?s calculated for females. At these lower temperatures, the blood flow to the skin was also reduced. Total amounts of chloroform absorbed averaged 41.9 and 43.6 mg for males and 11.5 and 39.9 mg for females exposed at 35 and 40?C, respectively. At 30?C, only 2/5 males and 1/5 females had detectable concentrations of chloroform in their exhaled breath. For perspective, the total intake of chloroform would have ranged from 79 - 194 mg if the volunteers had consumed 2 L of water orally at the concentrations used in this study. Thus, the relative contribution of dermal uptake of chloroform to the total body burdens associated with bathing for 30 min and drinking 2 L of water (ignoring contributions from inhalation exposures) was predicted to range from 1-28% depending on the temperature of the bath.

• Research Organization: Pacific Northwest National Lab., Richland, WA (US)
• Sponsoring Organization: US Department of Energy (US)
• DOE Contract Number: AC06-76RL01830
• OSTI ID: 15002319
• Report Number(s): PNWD-SA-5055
• Journal Information: Toxicological Sciences, Journal Name: Toxicological Sciences Journal Issue: 1 Vol. 53; ISSN 1096-6080; ISSN TOSCF2
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ABSORPTION
BLOOD CIRCULATION
BLOOD FLOW
BODY BURDEN
BREATH
CHLOROFORM
DERMAL BIOAVIALABILITY
EXHALATION
FEMALES
INHALATION
KINETICS
MALES
PBPK MODELING
PERMEABILITY
PHYSIOLOGY
WATER