ToxTermsTerminology Reference

The four processes describing the fate of a substance in the body: uptake into the systemic circulation, transport to tissues, biotransformation, and elimination.

The amount of a substance (typically a food additive, pesticide residue or veterinary drug) that can be ingested daily over a lifetime without appreciable health risk, derived from the point of departure divided by uncertainty factors.

The amount of a substance that can be ingested over a short period (typically one meal or one day) without appreciable health risk to the consumer.

The integral of the concentration–time curve of a substance in plasma or blood, representing the total systemic exposure over a defined period.

The term used under REACH and in ecotoxicology for the factors applied to a POD to account for uncertainties such as inter- and intra-species variation, exposure duration and data completeness. Conceptually equivalent to an uncertainty factor.

A dose that produces a predetermined change in response (the benchmark response, e.g. a 10% increase in effect incidence), estimated by fitting a mathematical model to the entire dose–response dataset.

The lower one-sided confidence bound (commonly 95%) on the benchmark dose, accounting for statistical uncertainty in the estimate of the BMD.

The predefined level of change in the measured effect (e.g. 5% or 10% extra risk, or one standard deviation for continuous data) used to define the benchmark dose.

The progressive build-up of a substance in an organism when the rate of uptake exceeds the rate of elimination, often expressed via the bioconcentration factor (BCF).

The fraction of an administered dose that reaches the systemic circulation in an unchanged, active form, and the rate at which this occurs.

The ratio of the concentration of a substance in an organism to its concentration in the surrounding medium (typically water) at steady state, resulting from uptake via that medium.

The ability of a substance to cause cancer or increase its incidence, either through a genotoxic (DNA-reactive) or a non-genotoxic (threshold-based) mode of action.

The volume of plasma or blood cleared of a substance per unit time, quantifying the body's efficiency at eliminating it.

A range of values, computed from the data, that is expected to contain the true parameter with a stated probability (commonly 95%) over repeated sampling.

Under REACH, the level of exposure to a substance above which humans should not be exposed, derived from the POD and assessment factors for a specified route, duration and population.

The relationship between the magnitude of exposure to a substance (dose) and the magnitude or frequency of a resulting effect (response) in an exposed population.

The time required for the concentration of a substance in the body (or plasma) to fall by one half.

The capacity of a substance to damage genetic material (DNA or chromosomes), through mechanisms such as gene mutation, chromosomal aberration or DNA strand breakage.

A formal quality system covering the organisational process and conditions under which non-clinical safety studies are planned, performed, monitored, recorded, archived and reported.

The concentration of a substance that produces 50% of its maximal effect (or affects 50% of the population) for a specified, typically non-lethal, endpoint.

The concentration of a substance required to inhibit a specific biological or biochemical process (e.g. enzyme activity, cell viability) by 50%.

The sum of hazard quotients for multiple substances or exposure routes that act on the same target organ or by the same mechanism, used to assess combined (cumulative) risk.

The ratio of an estimated exposure to a substance to its reference value (e.g. RfD or ADI). A value at or below 1 suggests exposure is within the acceptable range.

The lowest tested dose or exposure level at which a statistically or biologically significant adverse effect is observed compared with the control group.

The lowest tested dose at which any effect — adverse or non-adverse — is observed compared with controls.

The ratio of a point of departure (e.g. a BMDL) to the estimated human exposure. A larger MOE indicates a lower level of health concern.

The ratio between a no-effect level (e.g. NOAEL) and the estimated or actual level of human exposure, used to judge whether exposure is acceptably far below the level causing effects.

The highest concentration of a substance reached in plasma or blood after administration.

The highest dose that produces toxicity without causing death or severe suffering, and without unduly compromising the animals' ability to reveal a carcinogenic or toxic response.

The concentration of a substance in air or water, estimated statistically, that is lethal to 50% of an exposed test population over a defined exposure period.

The single dose of a substance, estimated statistically, that is expected to cause death in 50% of an exposed test population.

The ability of an agent to induce permanent, transmissible changes (mutations) in the amount or structure of the genetic material of a cell or organism.

The highest tested dose or exposure level at which no statistically or biologically significant increase in the frequency or severity of an adverse effect is observed in the exposed population compared with controls.

The highest tested dose at which no effect of any kind — adverse or non-adverse — is observed relative to controls.

Internationally agreed, standardized methods for testing the safety of chemicals, adopted by the OECD to ensure studies are reproducible and their data mutually accepted across member countries.

The probability of observing data at least as extreme as those obtained, assuming the null hypothesis (no effect) is true. Small values are taken as evidence against the null hypothesis.

The maximum acceptable intake of a substance (e.g. a residual solvent or elemental impurity in a pharmaceutical) per day, derived from a POD and a series of adjustment factors.

The dose–response point taken from the critical study (a NOAEL, LOAEL or BMDL) that serves as the starting point for extrapolation to a health-based guidance value or a margin of exposure.

The concentration of a substance below which adverse effects on the environment (e.g. aquatic organisms) are not expected to occur, derived by applying assessment factors to ecotoxicity data.

A tolerable intake expressed on a weekly basis, used for contaminants that accumulate in the body so that day-to-day variation is less important than the longer-term average. 'Provisional' reflects data limitations.

A computational (in silico) model that predicts a substance's biological activity or property from its chemical structure and physicochemical descriptors.

A data-gap-filling technique that predicts a property or effect for a target substance using data from one or more similar (analogue) substances, justified by structural and mechanistic similarity.

The inhalation analogue of the reference dose: an estimate of a continuous inhalation exposure likely to be without appreciable risk of deleterious effects over a lifetime.

An estimate of a daily oral exposure to the human population (including sensitive subgroups) that is likely to be without appreciable risk of deleterious effects over a lifetime. The US EPA equivalent of the ADI/TDI.

Adverse effects on sexual function and fertility in adults, or on the development of offspring, resulting from exposure to a substance.

The capacity of an agent to cause structural or functional abnormalities in a developing embryo or fetus, or other adverse effects on development following exposure during pregnancy.

The dose or exposure level below which no adverse effect is expected to occur; a central assumption for most non-genotoxic effects.

A generic human exposure threshold, based on chemical structural class, below which the risk to human health is considered negligible even in the absence of substance-specific toxicity data.

The estimated amount of a contaminant that can be ingested daily over a lifetime without appreciable health risk. Analogous to the ADI but used for unavoidable or non-intentional substances.

The study of the time course of absorption, distribution, metabolism and excretion of a substance at toxicologically relevant doses, quantifying internal exposure.

A numerical factor (commonly a default of 10 each for interspecies and intraspecies variability) applied to divide a point of departure when deriving a health-based guidance value, to account for extrapolation uncertainties.

A structured approach that integrates and weighs all available lines of evidence — considering quality, relevance and consistency — to reach an overall conclusion about a hazard or property.