Environmental risk assessments necessitate determining the risks for physiologically diverse individuals exposed to various air and water pollutants. A safe human dose/concentration (SHD/SHC) can be calculated in risk assessment evaluation to estimate the threshold dose/concentration. The SHD/SHC is referred to differently by different national and health agencies. The US Environmental Protection Agency (EPA), for example, refers to this safe dose as a reference dose (RfD) or reference concentration (RFC) in the form of a quantity in food or water, the amount of chemical in contact with the skin, or chemical concentration in air. The US Food and Drug Administration uses the term allowable daily intake. The term acceptable daily intake is used by the World Health Organization. Because a chemical can have multiple toxic effects, the first step in these assessments is determining the adverse impact at the lowest dose. The second step is to choose a threshold dose or the dose below which no adverse effects are expected. The threshold dose is the lowest observed negative effect level (LOAEL), the lowest amount tested that caused an adverse effect. However, the no practical adverse effect level (NOAEL) is the highest exposure level at which no statistically or biologically significant increases in the frequency or severity of adverse effects are observed between the exposed population and its appropriate control population and is desired for risk assessment purposes. A benchmark dose (BMD) or benchmark dose lower limit is an alternative to the NOAEL (BMDL). Deriving a BMDL, for example, according to the US EPA, entails selecting a predetermined change in the response rate of an adverse effect (called the benchmark response), typically in the range of 1-10%, depending on the power of a toxicity study). The BMDL is a statistically lower confidence limit on the dose that produces the selected response.
For many of the most toxic chemicals, such as pollutants in the air, food, or water, the US EPA has calculated toxicity factors or values (RFDS, RfCs, and cancer slope factors). The EPA’s online Integrated Risk Information System provides discounts for several of these chemicals. These profiles contain low-risk levels but are frequently based on critical studies or derived using various uncertainty factors (UFs).
RfD/RFC as BMD is a quantitative dose-response assessment of noncancer toxicity for ingested or inhaled chemicals. Noncancer toxicity refers to adverse health effects not caused by cancer or gene mutations. These effects include those on the tissue or organ where the chemical enters the body, such as the gastrointestinal tract, respiratory tract, or skin, as well as those that result from the toxicant’s absorption and distribution to a site distant from its entry point. Acute RfD or RFC estimates continuous ingestion or inhalation exposure for a short period (24 hours or less). In contrast, chronic RfD or RFC estimates daily ingestion or contact with a pollutant or continuous inhalation exposure for an extended period (up to a lifetime) to the human population (including sensitive subgroups). RfD or RFC is the ingestion dose (or amount in skin contact) or air exposure concentration above which chronic exposure may cause disease.