Adjusting exposure limits for long and short exposure periods using a physiological pharmacokinetic model

Journal Article · Wed Apr 01 04:00:00 EST 1987 · Am. Ind. Hyg. Assoc. J.; (United States)

DOI:https://doi.org/10.1080/15298668791384850· OSTI ID:6514435

Andersen, M E; MacNaughton, M G; Clewell, III, H J; Paustenbach, D J

This paper advocates use of a physiologically-based pharmacokinetic (PB-PK) model for determining adjustment factors for unusual exposure schedules. The PB-PK model requires data on the blood:air and tissue:blood partition coefficients, the rate of metabolism of the chemical, organ volumes, organ blood flows and ventilation rates in humans. Laboratory data on two industrially important chemicals - styrene and methylene chloride - were used to illustrate the PB-PK approach. At inhaled concentrations near their respective 8-hr Threshold Limit Value - Time-weighted averages both of these chemicals are primarily eliminated from the body by metabolism. For these two chemicals, the appropriate risk indexing parameters are integrated tissue dose or total amount of parent chemical metabolized. These examples also illustrate how the model can be used to calculate risk based on various other measures of delivered dose. For the majority of volatile chemicals, the parameter most closely associated with risk is the integrated tissue dose. This analysis suggests that when pharmacokinetic data are not available, a simple inverse formula may be sufficient for adjustment in most instances and application of complex kinetic models unnecessary. At present, this PB-PK approach is recommended only for exposure periods of 4 to 16 hr/day, because the mechanisms of toxicity for some chemicals may vary for very short- or very long-term exposures. For these altered schedules, more biological information on recovery in rest periods and changing mechanisms of toxicity are necessary before any adjustment is attempted.

• Research Organization: Harry G. Armstrong Aerospace Medical Research Lab., Wright-Patterson Air Force Base, OH
• OSTI ID: 6514435
• Journal Information: Am. Ind. Hyg. Assoc. J.; (United States), Journal Name: Am. Ind. Hyg. Assoc. J.; (United States) Vol. 48:4; ISSN AIHAA
• Country of Publication: United States
• Language: English

Related Subjects

560300* -- Chemicals Metabolism & Toxicology
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ALKYLATED AROMATICS
ANIMALS
AROMATICS
BIOCHEMICAL REACTION KINETICS
HYDROCARBONS
KINETICS
MAMMALS
MAN
MATHEMATICAL MODELS
MAXIMUM PERMISSIBLE EXPOSURE
METABOLISM
METHYLENE CHLORIDE
OCCUPATIONAL EXPOSURE
ORGANIC CHLORINE COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
PRIMATES
REACTION KINETICS
RISK ASSESSMENT
SAFETY STANDARDS
STANDARDS
STYRENE
VERTEBRATES