Page:NIOSH Manual of Analytical Methods - Chapter F.pdf/1

 F.

by Alexander W. Teass, Ph.D., Raymond E. Biagini, Ph.D., D. Gayle DeBord, Ph.D., NIOSH/DBBS, and R. DeLon Hull, Ph.D., NIOSH/DSHEFS

1. INTRODUCTION

Biological monitoring is the assessment of worker exposure to a hazardous agent through the measurement of a biomarker which results from contact with the agent. The biomarker typically is the agent or its metabolite in a biological specimen derived from the worker; examples are styrene in expired air, styrene in blood, and mandelic and phenylglyoxylic acids (metabolites of styrene) in urine. The biomarker also can be an effect of the agent, such as elevated levels of zinc protoporphyrin in blood, caused by exposure to lead.

Industrial hygiene professionals use biological monitoring to assess the risk to workers from exposure hazards and to demonstrate the adequacy of control technologies and intervention strategies. This chapter provides an overview of the effective and appropriate application of the biological monitoring analytical methods published herein. The analytical results should be interpreted in light of what is known about the uptake, metabolism, and excretion of the agent and the effect of the agent on the body. This chapter introduces these areas, provides other considerations, and gives references to sources of more comprehensive information on specific agents and situations. Additional resources on biological monitoring include reviews [1-10], books [11-17], and methods and quality assurance manuals [18-22].

2. GENERAL CONSIDERATIONS

A worker exposed to a chemical receives a dose of that chemical only if it is absorbed into the body. Absorption can occur after dermal contact, inhalation, ingestion, or from a combination of those routes. The extent of absorption from an exposure and the rate of absorption depend on the properties of the chemical (especially its solubility in lipids and water) and the route of exposure. Once absorbed, a chemical is distributed and partitions into various tissues due to tissue variations in pH, permeability, etc. Highly water-soluble chemicals may be distributed throughout the total body water, while more lipophilic substances may concentrate in the body fat or other lipidrich tissues, such as the brain. The loss of chemical from the body can loosely be defined as elimination, which depends on metabolism and excretion. Chemicals may be eliminated by numerous routes, including fecal, urinary, exhalation, perspiration, and lactation. A chemical can be excreted from the body without metabolism, in which case the parent compounds may be detectable in the urine, breath, or fecal material. In other cases, the chemical may be metabolized through oxidation, reduction, hydrolysis, or a combination of these processes, often followed by conjugation with an endogenous substrate. Conjugation of a chemical or metabolite is a pathway for excretion. The more important conjugation reactions include glucuronidation, amino acid conjugation, acetylation, sulfate conjugation, and methylation. Metabolism and excretion and the rates of metabolism and excretion can be affected by age, diet, general health status, race, and other factors. In general, the metabolic products will be more water soluble than the parent chemical. Where metabolism yields more than one product, the relative amounts of each and the parent-metabolite ratios are affected by an individual's general health status, diet, genetic makeup, degree of hydration, time after exposure, and other factors. The kidney is the major organ of excretion and is the primary route for water-soluble substances. These substances enter the urine by either glomerular filtration, tubular secretion, or sometimes both mechanisms.

Biological monitoring has the potential to assess worker exposure to industrial chemicals by all routes, including inhalation, skin absorption, and ingestion. Selection of an appropriate biomarker for an exposure requires knowledge of the distribution, metabolism, and excretion of the toxicant sufficient for selection of the proper compound to be determined, biological medium to be sampled, and time for obtaining a specimen. Often, most of the toxicological and pharmacological information available is from experimental animals and, thus, not always directly applicable to humans. 1/15/98 Manual of Analytical Methods