Acute to chronic ratio

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The acute to chronic ratio (ACR) uses acute toxicity data to gauge the chronic toxicity (MATC) of a chemical of interest to an organism. The science behind determining a safe concentration to the environment is imperfect, statistically limited, and resource intensive. There is an unfilled demand for the rapid assessment of different chemical toxicity to many different organisms. The ACR is a proposed solution to this demand.

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While empirical methods are crucial to making scientific conclusions and informed decisions, best personal judgement is often the best tool to the regulator in allowing or prohibiting potentially toxic chemicals from entering the environment. This means taking into consideration information about chemical structure, physical and chemical properties including fate and transport in the environment, and most importantly toxicological data. [1]

The ACR is mathematically the inverse of the application factor (AF), which was first proposed by Mount and Stephan (1967). [2] It provides no new information, it simply converts AF values into whole integer numbers that are more easily comparable for researchers visually.

Calculation

The ACR is the inverse of the application factor (AF). This makes it easier for regulators to visualize data as whole numbers rather than decimals. The AF is calculated by dividing the Maximum Acceptable Toxicant Concentration (MATC) by the Lethal Concentration that kills 50% of test organisms in an acute toxicity test (LC50).

The Maximum Allowable Toxicity Concentration (MATC) is determined by taking the square root of the No Effects Concentration (NOEC) multiplied by the Low effect concentration (LOEC).

The Application Factor (AF) is determined by dividing the MATC by the LC50

or

The ACR is then the inverse of the AF.

Regulatory use

There are thousands of new and different chemicals that are designed and synthesized by private chemical manufacturers every year. The public demands that all of these chemicals go through testing and be approved for use by the EPA under the TSCA. Part of that testing requirement is determining the toxicity of chemicals to organisms in the environment. [3]

Law

Section 5 of the TSCA states that the EPA must respond to pre-manufacturing notices (PMN) 90 –180 days after submission by the manufacturer. The EPA is responsible for identifying the substance, its proposed use, amount made, byproducts, exposure levels, and all existing environmental and health data necessary to prevent significant harm to the environment. [4] Additionally there are no PMN test requirements so there is often a minimal amount of data presented. This may be discussed as a fault of the TSCA. [5] New chemical PMNs are submitted early in the chemical's development so they rarely contain information about chronic toxicity - yet the EPA must respond within the 90-180 day time period after submission of the PMN. This essentially puts a huge burden on the EPA because chemical effects to the environment are extremely hard to predict simply based on single species toxicity tests (SST). [6] The limited time period that the TSCA gives the EPA for making this decision requires the EPA to make decisions with a high amount of uncertainty. This ultimately makes the goal of protecting the environment from significant adverse effects difficult.

The results of acute and chronic toxicity testing form the basis of knowledge that regulators draw from in performing work related to ecological risk assessment and designing policy that defines how much of a chemical of interest should be allowed in certain environments. While this sounds simple enough to the layperson, it is extremely difficult in practice due to a large number of modifying factors inextricably tied to toxicity tests and statistical analysis. [7] Different toxic effects can be observed from the same chemical through different types of environmental exposures and parameters, and thus toxicity results from acute and chronic tests must be jointly considered in decision making. Additionally, chronic toxicity tests tend to require significantly more attention and resources than acute tests which makes them much less feasible for basing decisions off of in a timely manner. The need for development of more advanced statistical methods, and uniformity in using these methods by regulators has been made apparent in literature. [8]

Scientific methods for determining acute and chronic toxicity to organisms are inherently imperfect and non-uniform throughout the field of research, and the most useful tool for decision making by officials is more often than not best personal judgement. [9]

A popular new method for ecological risk assessment is the acute to chronic estimation (ACE). This method uses computer software to estimate chronic toxicity, which provides similar information with much less effort and expense to the researcher.

Limitations

The ACR is derived from data generated by SSTs, as so falls victim to the same errors and limitations. These limitations are described in detail in literature [10]

Using point estimates such as NOECs/LOECs reduces a data set containing many values down to an isometric, removing the rich visual information that allows the researcher to assess the reliability and variability in the data. Information such as the slope of the dose-response curve, from which NOECs are LOECs are derived, is lost. [11] However, without NOECs and LOECs regulatory decisions are much harder to make. While ACR has drawbacks due to the uncertainty of the point estimates it uses to define it, it is still widely valued as a regulatory tool in making environmental assessments and policy decisions.

ACRs are based on tests with a number of different methodologies, which means that there can be significant variance among ACRs.

Related Research Articles

<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.

Chronic toxicity, the development of adverse effects as a result of long term exposure to a contaminant or other stressor, is an important aspect of aquatic toxicology. Adverse effects associated with chronic toxicity can be directly lethal but are more commonly sublethal, including changes in growth, reproduction, or behavior. Chronic toxicity is in contrast to acute toxicity, which occurs over a shorter period of time to higher concentrations. Various toxicity tests can be performed to assess the chronic toxicity of different contaminants, and usually last at least 10% of an organism's lifespan. Results of aquatic chronic toxicity tests can be used to determine water quality guidelines and regulations for protection of aquatic organisms.

<span class="mw-page-title-main">Aquatic toxicology</span>

Aquatic toxicology is the study of the effects of manufactured chemicals and other anthropogenic and natural materials and activities on aquatic organisms at various levels of organization, from subcellular through individual organisms to communities and ecosystems. Aquatic toxicology is a multidisciplinary field which integrates toxicology, aquatic ecology and aquatic chemistry.

Acute toxicity describes the adverse effects of a substance that result either from a single exposure or from multiple exposures in a short period of time. To be described as acute toxicity, the adverse effects should occur within 14 days of the administration of the substance.

<span class="mw-page-title-main">Toxic Substances Control Act of 1976</span> United States federal law

The Toxic Substances Control Act (TSCA) is a United States law, passed by the 94th United States Congress in 1976 and administered by the United States Environmental Protection Agency (EPA), that regulates chemicals not regulated by other U.S. federal statutes, including chemicals already in commerce and the introduction of new chemicals. When the TSCA was put into place, all existing chemicals were considered to be safe for use and subsequently grandfathered in. Its three main objectives are to assess and regulate new commercial chemicals before they enter the market, to regulate chemicals already existing in 1976 that posed an "unreasonable risk of injury to health or the environment", as for example PCBs, lead, mercury and radon, and to regulate these chemicals' distribution and use.

<span class="mw-page-title-main">Ecotoxicology</span>

Ecotoxicology is the study of the effects of toxic chemicals on biological organisms, especially at the population, community, ecosystem, and biosphere levels. Ecotoxicology is a multidisciplinary field, which integrates toxicology and ecology.

Measures of pollutant concentration are used to determine risk assessment in public health.

Exposure assessment is a branch of environmental science and occupational hygiene that focuses on the processes that take place at the interface between the environment containing the contaminant of interest and the organism being considered. These are the final steps in the path to release an environmental contaminant, through transport to its effect in a biological system. It tries to measure how much of a contaminant can be absorbed by an exposed target organism, in what form, at what rate and how much of the absorbed amount is actually available to produce a biological effect. Although the same general concepts apply to other organisms, the overwhelming majority of applications of exposure assessment are concerned with human health, making it an important tool in public health.

High production volume chemicals are produced or imported into the United States in quantities of 1 million pounds or 500 tons per year. In OECD countries, HPV chemicals are defined as being produced at levels greater than 1,000 metric tons per producer/importer per year in at least one member country/region. A list of HPV chemicals serves as an overall priority list, from which chemicals are selected to gather data for a screening information dataset (SIDS), for testing and for initial hazard assessment.

<span class="mw-page-title-main">Ecotoxicity</span>

Ecotoxicity, the subject of study in the field of ecotoxicology, refers to the biological, chemical or physical stressors that affect ecosystems. Such stressors could occur in the natural environment at densities, concentrations, or levels high enough to disrupt natural biochemical and physiological behavior and interactions. This ultimately affects all living organisms that comprise an ecosystem.

<span class="mw-page-title-main">2,6-Dichlorobenzonitrile</span> Chemical compound

2,6-Dichlorobenzonitrile (DCBN or dichlobenil) is an organic compound with the chemical formula C6H3Cl2CN. It is a white solid that is soluble in organic solvents. It is widely used as an herbicide.

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

Galaxolide is a synthetic musk with a clean sweet musky floral woody odor used in fragrances. It is one of the musk components that perfume and cologne manufacturers use to add a musk odor to their products. Galaxolide was first synthesized in 1965, and used in the late 1960s in some fabric softeners and detergents. High concentrations were also incorporated in fine fragrances.

The maximum acceptable toxicant concentration (MATC) is a value that is calculated through aquatic toxicity tests to help set water quality regulations for the protection of aquatic life. Using the results of a partial life-cycle chronic toxicity test, the MATC is reported as the geometric mean between the No Observed Effect Concentration (NOEC) and the lowest observed effect concentration (LOEC).

An early life stage (ELS) test is a chronic toxicity test using sensitive early life stages like embryos or larvae to predict the effects of toxicants on organisms. ELS tests were developed to be quicker and more cost-efficient than full life-cycle tests, taking on average 1–5 months to complete compared to 6–12 months for a life-cycle test. They are commonly used in aquatic toxicology, particularly with fish. Growth and survival are the typically measured endpoints, for which a Maximum Acceptable Toxicant Concentration (MATC) can be estimated. ELS tests allow for the testing of fish species that otherwise could not be studied due to length of life, spawning requirements, or size. ELS tests are used as part of environmental risk assessments by regulatory agencies including the U.S. Environmental Protection Agency (EPA) and Environment Canada, as well as the Organisation for Economic Co-operation and Development (OECD).

Equilibrium partitioning Sediment Benchmarks (ESBs) are a type of Sediment Quality Guideline (SQG) derived by the US Environmental Protection Agency (EPA) for the protection of benthic organisms. ESBs are based on the bioavailable concentration of contaminants in sediments rather than the dry-weight concentration. It has been demonstrated that sediment concentrations on a dry-weight basis often do not predict biological effects. Interstitial water concentrations, however, predict biological effects much better. This is true because the chemical present in the interstitial water (or pore water) is the uncomplexed/free phase of the chemical that is bioavailable and toxic to benthic organisms. Other phases of the chemical are bound to sediment particles like organic carbon (OC) or acid volatile sulfides (AVS) and are not bioavailable. Thus the interstitial water concentration is important to consider for effects to benthic organisms.

The predicted no-effect concentration (PNEC) is the concentration of a chemical which marks the limit at which below no adverse effects of exposure in an ecosystem are measured. PNEC values are intended to be conservative and predict the concentration at which a chemical will likely have no toxic effect. They are not intended to predict the upper limit of concentration of a chemical that has a toxic effect. PNEC values are often used in environmental risk assessment as a tool in ecotoxicology. A PNEC for a chemical can be calculated with acute toxicity or chronic toxicity single-species data, Species Sensitivity Distribution (SSD) multi-species data, field data or model ecosystems data. Depending on the type of data used, an assessment factor is used to account for the confidence of the toxicity data being extrapolated to an entire ecosystem.

In aquatic toxicology, the sediment quality triad (SQT) approach has been used as an assessment tool to evaluate the extent of sediment degradation resulting from contaminants released due to human activity present in aquatic environments. This evaluation focuses on three main components: 1.) sediment chemistry, 2.) sediment toxicity tests using aquatic organisms, and 3.) the field effects on the benthic organisms. Often used in risk assessment, the combination of three lines of evidence can lead to a comprehensive understanding of the possible effects to the aquatic community. Although the SQT approach does not provide a cause-and-effect relationship linking concentrations of individual chemicals to adverse biological effects, it does provide an assessment of sediment quality commonly used to explain sediment characteristics quantitatively. The information provided by each portion of the SQT is unique and complementary, and the combination of these portions is necessary because no single characteristic provides comprehensive information regarding a specific site

Toxicological databases are large compilations of data derived from aquatic and environmental toxicity studies. Data is aggregated from a large number of individual studies in which toxic effects upon aquatic and terrestrial organisms have been determined for different chemicals. These databases are then used by toxicologists, chemists, regulatory agencies and scientists to investigate and predict the likelihood that an organic or inorganic chemical will cause an adverse effect on exposed organisms.

Toxic units (TU) are used in the field of toxicology to quantify the interactions of toxicants in binary mixtures of chemicals. A toxic unit for a given compound is based on the concentration at which there is a 50% effect for a certain biological endpoint. One toxic unit is equal to the EC50 for a given endpoint for a specific biological effect over a given amount of time. Toxic units allow for the comparison of the individual toxicities of a binary mixture to the combined toxicity. This allows researchers to categorize mixtures as additive, synergistic or antagonistic. Synergism and antagonism are defined by mixtures that are more or less toxic than predicted by the sum of their toxic units.

References

  1. ↑ May, M.; Drost, W.; Germer, S.; Juffernholz, T.; Hahn, S. (2016). "Evaluation of acute-to-chronic ratios of fish and Daphnia to predict acceptable no-effect levels". Environmental Sciences Europe. 28 (1): 16. doi:10.1186/s12302-016-0084-7. PMC   5044967 . PMID   27752449.
  2. ↑ Mount, D. I.; C. E. Stephan (1967). "A method for establishing acceptable toxicant limits for fish malathion and the butoxyethanol ester of 2,4-D". Trans. Am. Fish. Soc. 96 (2): 185. doi:10.1577/1548-8659(1967)96[185:AMFEAT]2.0.CO;2.
  3. ↑ "Actions under TSCA Section 5 - US EPA". Epa.gov. 2014-10-24. Retrieved 7 January 2018.
  4. ↑ Kenaga, E. E. (1982). "Predictability of chronic toxicity from acute toxicity of chemicals in fish and aquatic invertebrates". Environmental Toxicology and Chemistry. 1 (4): 347–358. doi:10.1002/etc.5620010410.
  5. ↑ Office, U.S. Government Accountability (2 December 2009). "Chemical Regulation: Observations on Improving the Toxic Substances Control Act". Gao.gov (GAO-10-292T). Retrieved 7 January 2018.
  6. ↑ Maltby, L.; Clayton, S. A.; Yu, H.; McLoughlin, N.; Wood, R. M.; Yin, D. (2000). "Using single-species toxicity tests, community-level responses, and toxicity identification evaluations to investigate effluent impacts". Environmental Toxicology and Chemistry. 19: 151–157. doi: 10.1002/etc.5620190118 . S2CID   84557436.
  7. ↑ "ENVIRONMETRICS AUSTRALIA" (PDF). Environmetrics.net.au. Retrieved 7 January 2018.
  8. ↑ Fox, D. R.; Landis, W. G. (2016). "Don't be fooled—A no-observed-effect concentration is no substitute for a poor concentration–response experiment". Environ Toxicol Chem. 35 (9): 2141–2148. doi: 10.1002/etc.3459 . PMID   27089534.
  9. ↑ "About Risk Assessment - US EPA". Epa.gov. 2013-12-03. Retrieved 7 January 2018.
  10. ↑ Cairns, J. Environ Monit Assess (1984) 4: 259. doi:10.1007/BF00394145
  11. ↑ Landis, W. G.; Chapman, P. M. (2011). "Well past time to stop using NOELs and LOELs". Integr Environ Assess Manag. 7 (4): vi–viii. doi: 10.1002/ieam.249 . PMID   21932339.
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