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

“ 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. ”

“ 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. ”

“ A biological monitoring analytical result is a determination of the level of the biomarker in the biological matrix from which the sample was taken, at the time it was taken. Extrapolation from that datum to insight on the exposure of the worker requires knowledge of how the human body responds to the agent. ”

“ 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 ”

“ 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. ”

“ Among the factors affecting the rate of creatinine excretion are the muscularity of the subject, physical activity, urine flow, time of day, diet, pregnancy, and disease [27] .
Quality Assurance. Good data require the utilization of an effective quality assurance program. In 1992, regulations implementing the Clinical Laboratory Improvement Amendments (CLIA) of 1988 were published by the Health Care Finance Administration and the Public Health Service to ensure that analysis of human specimens was done accurately and under good quality control procedures [29] . ”

“ An important consideration in blood monitoring is that obtaining blood specimens requires an invasive procedure and should be performed only by trained persons.
3. Urine is more suitable for monitoring hydrophilic chemicals, metals, and metabolites than for monitoring chemicals poorly soluble in water. The concentration of the biomarker in urine usually is correlated to its mean plasma level during the period the urine dwells in the bladder [5] . ”

“ Some chemicals, while not immunogenic in their own right because of small size and other limitations, may bind to constitutive polymers (such as host proteins) and become immunogenic, causing the production of specific antibodies. ”

“ Some persons are genetically predisposed to excrete primarily free aniline; while others, primarily, acetanilide.
6. Concurrent exposure to several agents that compete for the same biotransformation sites in the body. This may lead to altered metabolism and excretion, which would change the relationship between exposure or health effect and the level of the biomarker [8] .
7. Concurrent exposure to several agents, which are metabolized to the same biomarker. This frustrates the interpretation of the biological monitoring data. ”

“ Any analysis of human specimens that can be used by a health care practitioner to assess the health of the individual or used in the diagnosis, prevention, or treatment of disease or impairment falls under the CLIA guidelines. ”

“ The method should have a sufficiently low limit of detection to differentiate exposed from nonexposed workers. A method developed when biological monitoring reference levels were higher may be inadequate for measuring exposures at and below the current guidelines.
4. Limitations of the sample matrix and its affect on the analysis need to be assessed. In general, blood serum and urine specimens require different sample preparations and may require separate methodologies to eliminate matrix effects. ”