Occupational toxicology

Goals

Occupational toxicology generates data that is used to identify hazards and their physiological effects, and quantify dose–response relationships. A major use of this data is for establishing standards and regulation. These may take the form of occupational exposure limits, which are based on ambient concentration levels of toxicants. They also include biological exposure indices, which are based on biomonitoring of a toxicant, its metabolites, or other biomarkers. Toxicologists have a large role in determining what biomarkers may be used for biomonitoring during exposure assessment and workplace health surveillance activities.

Occupational toxicology is complementary to occupational epidemiology, to a greater degree than toxicology and epidemiology in general. For example, outbreaks identified through epidemiological studies such as exposure assessment case studies or workplace health surveillance may inspire toxicological study of suspected or confirmed causative agents. Conversely, the results of toxicological investigation are important in establishing biomarkers for workplace health surveillance to identify overexposure and to test the validity of occupational exposure limits. These biomarkers are intended to aid in prevention by identifying early adverse affects, unlike diagnostics for clinical medicine that are designed to reveal advanced pathological states.

Toxicological studies have the benefit over epidemiology that they can study new substances before there is exposure in commerce, or when epidemiological data are not available. Toxicology also has the advantage of elucidating not only overt health outcomes, but intermediate biochemical steps such as biotransformation processes, as well as early cellular changes. These can aid in developing measures to prevent or treat toxicity.

Occupational toxicology studies may also suggest or evaluate hazard controls used by industrial hygienists. Occupational toxicology differs from environmental toxicology in that the former has smaller number of exposed individuals, but with a wider range of exposure levels. Environmental toxicology tends to focus on situations with low exposure levels for larger numbers of people, where adverse effects may be concentrated in people who are especially susceptible to a given toxicant due to genetic or other factors.

Challenges

Occupational toxicology has the challenge of performing studies that mimic actual workplace conditions, for which inhalation exposure and dermal exposure are most important, although in medical industries, injection exposure through needlestick injuries is a hazard. In particular, experimental inhalation exposure studies require more complex methodology and equipment than for oral administration experiments. For example, measurement and control of particle size distribution is important, and the degree and location of particle retention within the respiratory tract. Inhalation and injection exposure are often more dangerous than dermal exposure, where a major function of skin is to provide a barrier to outside toxins, and ingestion exposure, where toxins may be broken down by the gastrointestinal tract and liver.

There is often exposure to mixtures of chemicals, whose effects may not be simply additive, as different toxins may interact in a way that enhances or reduces their toxicity relative to each toxin alone. Mixtures may include undesired contaminants in a product, or products that deviate from manufacturer specifications. Exposures are not always acute, but may be at low levels prolonged over decades. Workers may be exposed to toxic substances at higher levels than the general public, who are mainly exposed through consumer products and the environment. Establishing a causal relationship between a worker's illness and work conditions is often difficult because work-related illnesses are often indistinguishable from those with other causes, and there may be a long interval between the exposure and the onset of disease.

While the dose of a toxicant is a strong predictor of health outcomes, occupational diseases are often influenced or confounded by other environmental factors, or personal host factors such as preexisting health conditions, host genetics, or patterns of worker behavior. These affect the relationship between the concentration, duration, and frequency of the exposure, and the actual toxicant dose that reaches a target tissue and interacts with metabolic processes. For example, the ultimate dose from inhalation exposure depends on respiratory rate and breathing volume, and the dose from dermal exposure depends on the absorption rate through the skin, which is influenced by the chemical properties of the chemical, the thickness of the skin at the exposed location on the body, and whether the skin is intact.

Methods

Occupational toxicology uses methods common to other forms of toxicology. Animal testing is used to identify adverse effects and establish acceptable exposure levels, as well as studying the mechanism of action and dose–response relationship. There are a number of in vitro alternatives to animal testing in a number of specific cases such as predicting skin sensitizers and potential for eye injuries, as well as quantitative structure–activity relationship models. Sometimes, controlled human challenge studies are performed in cases where the risk for volunteers is negligible; these are used to verify whether results from animal studies translate to humans.

Many types of measurements may be made in occupational toxicology. These include external measurements of exposure, the internal dose measured via tissues and bodily fluids, the "biologically effective dose" measuring the compound that has actually interacted with host biomolecules such as DNA and proteins, and measuring downstream effects of mutations, cytogenetic effects, and aberrant gene expression. Experimentation may focus on the operation and regulation of biotransformation processes that may detoxify or activate toxins. These processes are subject to difference between individuals, which is studied through the field of toxicogenomics.

History

While the health hazards of substances used in the workplace have been recognized since antiquity, the first experimental studies of hazardous substances came in the late 19th and early 20th centuries, including the work of John Scott Haldane on mine gases, Karl Bernhard Lehmann on organic substances, and Ernest Kennaway on occupational skin cancer.

Biomarkers began to be used in occupational toxicology and epidemiology in the 1970s, and the 1990s showed increasing focus on molecular mechanisms such as identifying specific enzymes that interact with toxicants and studying their variation across individuals.