Occupational toxicology

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Occupational toxicology is the application of toxicology to chemical hazards in the workplace. It focuses on substances and conditions that people may be exposed to in workplaces, including inhalation and dermal exposures, which are most prevalent when discussing occupational toxicology. These environmental and individual exposures can impact health, and there is a focus on identifying early adverse affects that are more subtle than those presented in clinical medicine.

Contents

Occupational toxicology interfaces heavily with other subfields of occupational safety and health. Occupational epidemiology studies may inspire toxicological study of causative agents, and toxicological investigations are important in establishing biomarkers for workplace health surveillance. Occupational toxicology studies may suggest or evaluate hazard controls used by industrial hygienists. Toxicological studies are also an important input for performing occupational risk assessment, and establishing standards and regulation such as occupational exposure limits.

Background

As of 1983, around 60,000 chemical compounds were considered to be of occupational consequence. [1] Certain sectors have an increased potential for exposure to chemical and biological agents, including manufacturing, construction, mining, logging, and agriculture, as well as service sector workplaces such as in automobile repair, gasoline stations, pipelines, truck and rail transportation, waste management and remediation, and botanical gardens. [2] These sectors contain an increased risk of exposure largely due to the fact that they are working with heavy machinery that can emit potentially harmful fumes when being operated. [3] Additionally, these sectors involve directly handling various substances that can possibly contain harmful chemical compounds.

Toxicological studies are experimental laboratory studies on the response of organisms and biological pathways to a substance, and can generate data that are used for other occupational safety and health activities. [4] These studies can range anywhere from 2 weeks to 2 years and primarily focus on determining whether or not the compound is toxic/carcinogenic and how toxic it is if so. [5] To discover if a compound is toxic/carcinogenic, toxicologists expose mice to the compound being studied and examine them over a given amount of time. These toxicologists then look for any patterns in the mice that may suggest toxicity or carcinogenicity and draw a conclusion from this data.

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Goals

Occupational toxicology generates data that is used to identify hazards and their physiological effects, and quantify dose–response relationships. [4] 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. [2] Toxicologists have a large role in determining what biomarkers may be used for biomonitoring during exposure assessment and workplace health surveillance activities. [4]

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. [1] [2] 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. [2]

Toxicological studies have the benefit over epidemiology that they can study new substances before there is exposure in commerce, [2] or when epidemiological data are not available. [4] 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. [4]

Occupational toxicology studies may also suggest or evaluate hazard controls used by industrial hygienists. [1]

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. [6]

Challenges

Occupational toxicology has the challenge of performing studies that mimic actual workplace conditions, for which inhalation exposure and dermal exposure are most important, [1] [2] although in medical industries, injection exposure through needlestick injuries is a hazard. [4] 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. [2] 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. [4]

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. [4] 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. [2] Workers may be exposed to toxic substances at higher levels than the general public, who are mainly exposed through consumer products and the environment. [7] 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. [2]

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. [2]

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. [2]

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. [8] 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. [4]

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. [9]

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. [8]

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A carcinogen is any substance, radionuclide, or radiation that promotes carcinogenesis. This may be due to the ability to damage the genome or to the disruption of cellular metabolic processes. Several radioactive substances are considered carcinogens, but their carcinogenic activity is attributed to the radiation, for example gamma rays and alpha particles, which they emit. Common examples of non-radioactive carcinogens are inhaled asbestos, certain dioxins, and tobacco smoke. Although the public generally associates carcinogenicity with synthetic chemicals, it is equally likely to arise from both natural and synthetic substances. Carcinogens are not necessarily immediately toxic; thus, their effect can be insidious.

<span class="mw-page-title-main">Toxicology</span> Study of substances harmful to living organisms

Toxicology is a scientific discipline, overlapping with biology, chemistry, pharmacology, and medicine, that involves the study of the adverse effects of chemical substances on living organisms and the practice of diagnosing and treating exposures to toxins and toxicants. The relationship between dose and its effects on the exposed organism is of high significance in toxicology. Factors that influence chemical toxicity include the dosage, duration of exposure, route of exposure, species, age, sex, and environment. Toxicologists are experts on poisons and poisoning. There is a movement for evidence-based toxicology as part of the larger movement towards evidence-based practices. Toxicology is currently contributing to the field of cancer research, since some toxins can be used as drugs for killing tumor cells. One prime example of this is ribosome-inactivating proteins, tested in the treatment of leukemia.

<span class="mw-page-title-main">Toxicity</span> Degree of harmfulness of substances

Toxicity is the degree to which a chemical substance or a particular mixture of substances can damage an organism. Toxicity can refer to the effect on a whole organism, such as an animal, bacterium, or plant, as well as the effect on a substructure of the organism, such as a cell (cytotoxicity) or an organ such as the liver (hepatotoxicity). By extension, the word may be metaphorically used to describe toxic effects on larger and more complex groups, such as the family unit or society at large. Sometimes the word is more or less synonymous with poisoning in everyday usage.

<span class="mw-page-title-main">Piperonyl butoxide</span> Chemical compound

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<span class="mw-page-title-main">Chlorfenvinphos</span> Chemical compound

Chlorfenvinphos is the common name of an organophosphorus compound that was widely used as an insecticide and an acaricide. The molecule itself can be described as an enol ester derived from dichloroacetophenone and diethylphosphonic acid. Chlorfenvinphos has been included in many products since its first use in 1963. However, because of its toxic effect as a cholinesterase inhibitor it has been banned in several countries, including the United States and the European Union. Its use in the United States was cancelled in 1991.

<span class="mw-page-title-main">Occupational hygiene</span> Management of workplace health hazards

Occupational hygiene is the anticipation, recognition, evaluation, control, and confirmation (ARECC) of protection from risks associated with exposures to hazards in, or arising from, the workplace that may result in injury, illness, impairment, or affect the well-being of workers and members of the community. These hazards or stressors are typically divided into the categories biological, chemical, physical, ergonomic and psychosocial. The risk of a health effect from a given stressor is a function of the hazard multiplied by the exposure to the individual or group. For chemicals, the hazard can be understood by the dose response profile most often based on toxicological studies or models. Occupational hygienists work closely with toxicologists for understanding chemical hazards, physicists for physical hazards, and physicians and microbiologists for biological hazards. Environmental and occupational hygienists are considered experts in exposure science and exposure risk management. Depending on an individual's type of job, a hygienist will apply their exposure science expertise for the protection of workers, consumers and/or communities.

<span class="mw-page-title-main">Chemical hazard</span> Non-biological hazards of hazardous materials

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<span class="mw-page-title-main">Environmental hazard</span> Harmful substance, a condition or an event

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References

  1. 1 2 3 4 Johnson, Barry L. (January 1983). "Occupational Toxicology: NIOSH Perspective". Journal of the American College of Toxicology. 2 (1): 43–50. doi: 10.3109/10915818309140666 . ISSN   0730-0913. S2CID   84847131.
  2. 1 2 3 4 5 6 7 8 9 10 11 Thorne, Peter S. (2019). "Occupational Toxicology". In Klaassen, Curtis D. (ed.). Casarett & Doull's Toxicology: The Basic Science of Poisons (9 ed.). McGraw Hill Medical. Retrieved 2021-03-13.
  3. ↑ Occupational Safety and Health Administration. (1970). Occupational safety and health standards: Toxic Industrial Chemicals (TICs) Guide. Retrieved 2023-11-13.
  4. 1 2 3 4 5 6 7 8 9 Wattenberg, E.V. (2014), "Occupational Toxicology", Encyclopedia of Toxicology, Elsevier, pp. 643–647, doi:10.1016/b978-0-12-386454-3.00045-2, ISBN   978-0-12-386455-0 , retrieved 2021-03-17
  5. 1 2 "Toxicology/Carcinogenicity". National Toxicology Program. Retrieved 2023-11-13.
  6. ↑ Mutti, A (1999-09-05). "Biological monitoring in occupational and environmental toxicology". Toxicology Letters. 108 (2–3): 77–89. doi:10.1016/S0378-4274(99)00076-4. PMID   10511249.
  7. ↑ "Occupational toxicology". British Toxicology Society. Retrieved 2021-03-12.
  8. 1 2 Vainio, Harri (December 1998). "Use of biomarkers — new frontiers in occupational toxicology and epidemiology". Toxicology Letters. 102–103: 581–589. doi:10.1016/S0378-4274(98)00252-5. PMID   10022317.
  9. ↑ Carter, J.T. (September 1988). "Occupational Toxicology". Human Toxicology. 7 (5): 429–432. doi:10.1177/096032718800700508. ISSN   0144-5952. PMID   3056838. S2CID   208606729.
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