Toxicology

Toxicology is the study of the deleterious effects of chemical compounds on biological systems and the evaluation of the probability of their occurrence. It is a multidisciplinary science that uses concepts and knowledge from many disciplines such as biochemistry, ecology, genetics, pathology, and epidemiology. More specifically, the branch of environmental toxicology examines how environmental exposures to chemical pollutants may present risk to biological systems. As toxicants are omnipresent in our lives, understanding the nature of these chemicals and the adverse effects that they may cause, is vital. Furthermore, understanding the biologic significance of these adverse health effects is critical to assessing the health risks associated with environmental exposure, for developing safety standards, and for developing cost-effective risk management strategies.

Factors that affect responses to a toxic chemical include route of entry into the body, dose of the chemical received, duration of exposure, interactions that transpire among multiple chemicals, and individual sensitivity to the chemical. Other factors include age, gender, reproductive status, overall health and nutrition, genetics, lifestyle factors, and previous sensitization. Route of entry into the body affects the toxicity of chemicals differently. Toxicants can be ingested by mouth, inhaled by nose, absorbed through the skin, or injected intravenously, intramuscularly, intraperitoneally, or subcutaneously. The toxicity of each chemical can vary depending upon the route of exposure. The dose of chemical that is received also affects the toxic response of a chemical. Generally, the magnitude of the response is due to the amount of the dose that was received by the body. As a chemical is administered, only a portion of that chemical is biologically available for absorption into the bloodstream. Multiple chemical interactions can also affect the toxicity of a chemical.  Exposure to more than one chemical

simultaneously can produce the following effects: additive, in which is when two chemicals combined produce an effect that is equal to their individual effects, synergistic, in which the effects of both chemicals combined magnifies the toxicity; potentiation, in which one chemical has a non-toxic effect, however, when combined with another, their effects are far greater than the sum of either; and antagonistic, in which is when two chemicals are administered together causing interference. Individual sensitivity to a chemical is another important factor affecting the toxicity of a chemical. Chemical allergies or idiosyncrasies may occur on an individual basis.  Additionally, the duration of exposure to a chemical is another factor affecting toxicity. The severity of adverse health effects associated with exposure to toxicants generally depends upon the duration of exposure; acute, subacute, sub-chronic, or chronic. More often, the reaction from chronic exposure to toxic chemicals is most severe, however, depending upon the chemical, some chemicals, known as acute toxins, can elicit health complications with acute exposure. Acute toxicity describes the adverse effects of a substance that result either from a single exposure or from multiple exposures between 24 to 96 hours. To be categorized as acute, the adverse effects should occur within 14 days of the administration of the substance. Acute toxicity differs from chronic toxicity, which describes the adverse health effects from repeated, lower concentrations of exposures to a substance over an extended period of time.

In essence, the toxicity of a chemical refers to the degree to which a substance can damage an organism. Toxicity can refer to the effect on a whole biological organism, such as an animal or plant, substructure of the organism, such as a cell, an organ, such as the kidneys, or an organ system (such as the cardiovascular system). The toxicity of a chemical is usually determined by computing the lethal dose or LD50. The LD50 is the amount of a toxicant that is sufficient to kill 50 percent of a population of animals usually within a certain time; a lower LD50 is indicative of increased toxicity.

Paracelsus was a medieval alchemist who was coined, the Father of Toxicology. He stated that “All substances are poisons; there is none which is not a poison. The right dose differentiates a poison from a remedy.”  This statement implies that a substance can produce the harmful effect associated with its toxic properties only if it reaches a susceptible biological system within your body at a sufficient or high enough dose. The toxicity of a substance increases as the dose increases. For all chemicals, there is a dose response curve, or a range of doses that result in a graded effect between the extremes of no effect and a full, 100% toxic effect.  All chemical substances will exhibit a toxic effect given a large enough dose, no matter the chemical; at very low doses, even the most toxic chemicals known will cause no discernable effect on humans, while at very high doses, even essential substances like oxygen and water will harm or kill.  The toxic potency of a chemical is thus ultimately defined by the amount of the chemical that will produce a specific response in a specific biological system.

In the process of exposure assessment, quantitative measures of exposure are used: in risk assessment, together with inputs from toxicology, to determine risk from substances released to the environment, to establish protective standards, in epidemiology, to distinguish between exposed and control groups, and to protect workers from occupational hazards. Exposure assessment identifies populations exposed to the toxicant, describes their composition and size, and examines the roots, magnitudes, frequencies, and durations of such exposures. Exposure assessment provides answers to the following questions:  Who or what biological organism or system is being exposed? (humans, animals, plants, terrestrial geosystems, aquatic ecosystems, etc), What is the route of exposure? (ingestion, inhalation, dermal contact, etc.), What is the frequency and duration of exposure? (How often and how long does this exposure occur?). The concentration of the chemical and the extent of the contact are important components of exposure assessment. The results of an exposure assessment are often considered with a hazard assessment of the chemical. A hazard assessment provides an understanding of the potential for the chemical to cause adverse effects to humans and plant and animal life. Together, the exposure assessment and the hazard assessment can be combined into a risk assessment, which reaches conclusions about the likelihood of adverse effects in the exposed population. (EPA, 2015) Exposure assessments estimate concentrations and exposures in the environment using models and monitoring data. Exposure can be quantified by direct measurement, scenario modeling, and biomonitoring. Direct measurement quantifies the exposures to pollutants by directly sampling and monitoring pollutant concentration in the environment. The scenario modeling approach focuses on the pollutant concentrations within microenvironments or activities rather than the concentrations directly reaching the respondents. The measured concentrations are correlated to large-scale activity pattern data. Biomonitoring is another approach to measuring exposure. This measures the amount of a pollutant within the body by examining samples of hair, blood, breath, adipose tissue, bone, or urine (Lioy, 1990). However, since biological monitoring measures the body burden of a pollutant but not the source from, whence it came, a combination of biomonitoring, scenario monitoring, and direct measurement serves as the most effective strategy for exposure assessment.