Tissue residue

Last updated

Tissue residue is the concentration of a chemical or compound in an organism's tissue or in a portion of an organism's tissue. [1] Tissue residue is used in aquatic toxicology to help determine the fate of chemicals in aquatic systems, bioaccumulation of a substance, or bioavailability of a substance, account for multiple routes of exposure (ingestion, absorption, inhalation), and address an organism's exposure to chemical mixtures. [2] A tissue residue approach to toxicity testing is considered a more direct and less variable measure of chemical exposure and is less dependent on external environmental factors than measuring the concentration of a chemical in the exposure media. [3]


In general, tissue residue approaches are used for chemicals that bioaccumulate or for bioaccumulative chemicals. [2] The majority of these substances are organic compounds that are not easily metabolized by organisms and have long environmental persistence. Examples of these chemicals include polychlorinated dibenzodioxins, furans, biphenyls, DDT and its metabolites, and dieldrin. [2]

The use of tissue residues in assessing toxicity and bioaccumulation may also be referred to as the tissue residue-effects approach (TRA), critical body residue (CBR), or tissue residue-based toxicity tests. [1] [4]


Historically, aquatic toxicology toxicity tests have focused on water-based approaches where concentration of a toxicant is determined by its concentration in the water. [2] Although tissue residue use and concepts have existed for over 100 years due to interest in narcosis and anesthesia, it was not widely used in toxicology. [5] The first known study of tissue residue in environmental toxicology was reported in 1912 by White and Thomas who investigated the effects of copper exposure to fish using whole-body copper concentrations. [5]

Since the 1980s, there has been rapid growth in the tissue residue approach to toxicology. [5] The water-based approach has been re-evaluated due to challenges in assessing the toxicity of bioaccumulating chemicals. [2] Water-based approaches are not always an accurate estimation of the concentration of a bioaccumulating chemical in an organism, nor does the water-based approach incorporate the multiple routes of exposure of an organism to a toxicant and the additive effects across these routes. [2]


The use of tissue residue allows an investigator to: account for multiple routes of exposure, account for toxicokinetic differences between species, account for factors that alter bioavailability and potentially address exposure of an organism to a chemical mixture. [1] [4] [5] [6] [7] Tissue residue also has the ability to represent temporal and spatial exposure or an organism, [4] [8] as well as clarify the cause-effect relationship of chemicals. These relationships are often distorted by uncertainty in chemical bioavailability. [4] The mechanism of action for a chemical depends on the internal tissue concentration, thus tissue residue gives researchers a more direct estimate of the residue-effect (dose-response) relationship. [3] [9] Tissue residue is also less variable than other measures of chemical exposure. [2] [8]

In addition to the aforementioned advantages of tissue residue use, the U.S. EPA also states that this approach explicitly considers exposure through diet, will support identification and investigation of a chemical's mode of action, incorporate the effects of an organism's metabolism on accumulation and allow for experimental verification between lab and field studies. [6]


The majority of issues with tissue residue arise in the interpretation of tissue residue data. [1] [3] Interpretation complication can be caused by choice of endpoints, species choice, life stage sensitivity, data quality, and toxicity data extrapolation. [3] Choice of tissue for tissue residue analysis can also be difficult and has an effect on tissue residue data. When choosing tissue, a scientist needs to consider: mode and mechanism of action of chemical being tested, site of toxic action for the chemical and species combination being studied and strength of the tissue residue-response relationship. There is also a lack of reliable tissue residue relationships available for comparison. [3] [5]

Although use of tissue residue can account for multiple routes of exposure, it cannot identify the routes of exposure. Tissue residue also cannot account for biotransformation of organic chemicals. [3] [5] If a chemical is biotransformed, the concentration of the parent chemical is lower, but the metabolites may still be toxic. [3] Tissue residue approaches are not as useful for chemicals with short half-lives because an organism will only be sporadically exposed. [1] Overall, tissue residue is meant to complement data from water-based approaches, not replace them. [4]

Use in regulation

North America

The U.S. Environmental Protection Agency (USEPA) has incorporated tissue residue through the development of the Biotic Ligand Model as well as water quality standards for copper. USEPA has also recently published draft aquatic life criteria for selenium using a tissue-based approach. USEPA is currently working on incorporating tissue residue into standards for bioaccumulating chemicals, which are usually hydrophobic with a log octanol-water partition coefficient greater than 5 (log Kow>5). [2] Canada uses tissue residue formally in guidelines called tissue residue guidelines (TRGs), which are primarily used for protecting wildlife that consume aquatic life. [10] [11]


There is a lack of formal use of tissue residue in Europe.

Australia and New Zealand

Australia and New Zealand both use tissue residue-based approaches for biomonitoring programs for mussels and oysters.

Available databases

There are two comprehensive aquatic toxicology databasesAquatic Toxicology Databases available for tissue residue in the United States. The first is the Toxicity Residue Database maintained by the USEPA. [3] The second is the Environmental residue-effects database (ERED) maintained by the U.S. Army Corps of Engineers. [3] Currently, the majority of the data available is derived from acute lethal response studies. [3]



Tissue residue of metals in invertebrate prey organisms may reduce uncertainty in estimating exposure from multiple routes. [8] This may be especially important in early life stages of an organism or for species listed under the Endangered Species Act (ESA). [8] However, it is challenging to develop a suitable approach to assessing metal toxicity through tissue residue because water quality can have a large influence on metal toxicity. With the exception of organometallic compounds, no generalized approaches have been created for analyzing metals in tissue residue, although site-specific and species-specific approaches have been successfully developed and used, especially for invertebrates. [12] A recent paper examined tissue-residue toxicity for copper and cadmium in fish and found low variability among species for both metals compared to aqueous-exposure toxicity metrics. [13] These results indicate that whole-body concentrations of metals in fish may be useful for Environmental Quality Guidelines, forensic evaluation, and ecological risk assessment. An additional benefit includes the potential to characterize a contaminated ecosystem based on elevated whole-body metal concentrations resulting from acclimation.

PAHs (Polycyclic aromatic hydrocarbons)

Fish are able to quickly metabolize and eliminate PAHs, therefore tissue residue of parent PAH compounds will not provide adequate information on exposure to the organism. [8] PAH exposure in fish has been associated with reproductive impairment, immune deficiency, and liver lesions as well as other health problems. [8] In contrast, invertebrates do not metabolize and excrete PAHs as efficiently as fish, therefore an investigator can better understand location and temporal patterns of bioavailable PAHs through tissue residue of these invertebrates. [8]

PCBs (Polychlorinated biphenyls)

Unlike PAHs, tissue residue of PCBs for fish can provide reliable information on exposure and toxicity. [8] The tissue residue of PCBs in fish can provide vital information in an exposure assessment because fish generally receive PCBs through exposure via the food web. There are currently two screening approaches for PCBs in fish based on PCB body burdens. [8]


Both the United States and United Kingdom have mussel watch monitoring programs. Although these programs differ in many ways, both use tissue residues to establish biological effects, such as survival and body condition, of chemicals present. In contrast to the passive nature of the mussel watch monitoring programs, tissue residue has also been applied in in-situ bioassays in the United States, United Kingdom and Canada.

Superfund sites

Tissue residue guidelines were developed for tributyltin (TBT) for the Harbor Island Superfund site, Lower Duwamish Superfund site and the Portland Harbor Superfund site. At the Harbor Island Superfund site, tissue trigger levels were developed to provide guidance on remediation action. [14] Tissue residue toxicity reference value (TRV) was developed for TBT regarding mortality and growth at the Lower Duwamish Superfund site. Tissue residue TRVs were also developed for TBT, as well as many other chemicals, for use in the Portland Harbor Superfund site work. [14]

Ecological risk assessment

Ecological risk assessment aims to source of contamination to exposure to a toxicity endpoint. [5] [8] [14] This requires a risk assessor to identify and estimate exposure pathways. [8] Tissue residue is the only approach that inherently accounts for toxicity due to multiple exposure pathways. [1] [5] [6] [7] There is also a need in risk assessment to understand the bioaccumulation of chemicals4, as well as a direct estimation of bioavailability. [8] Modeling food web exposure is difficult in risk assessment and requires many assumptions but this uncertainty can be reduced through tissue residue. [8] Tissue residue may also allow provide a link between ecological risk assessment and human health risk assessment. [5] [14]

The issues with using tissue residue in risk assessment are similar to the disadvantages listed above. [14]

Related Research Articles

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

Polychlorinated biphenyls (PCBs) are highly carcinogenic chemical compounds, formerly used in industrial and consumer products, whose production was banned in the United States by the Toxic Substances Control Act in 1979 and internationally by the Stockholm Convention on Persistent Organic Pollutants in 2001. They are organic chlorine compounds with the formula C12H10−xClx; they were once widely used in the manufacture of carbonless copy paper, as heat transfer fluids, and as dielectric and coolant fluids for electrical equipment.

Bioaccumulation is the gradual accumulation of substances, such as pesticides or other chemicals, in an organism. Bioaccumulation occurs when an organism absorbs a substance at a rate faster than that at which the substance is lost or eliminated by catabolism and excretion. Thus, the longer the biological half-life of a toxic substance, the greater the risk of chronic poisoning, even if environmental levels of the toxin are not very high. Bioaccumulation, for example in fish, can be predicted by models. Hypothesis for molecular size cutoff criteria for use as bioaccumulation potential indicators are not supported by data. Biotransformation can strongly modify bioaccumulation of chemicals in an organism.

<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.

<span class="mw-page-title-main">Persistent organic pollutant</span> Organic compounds that are resistant to environmental degradation

Persistent organic pollutants (POPs) are organic compounds that are resistant to degradation through chemical, biological, and photolytic processes. They are toxic chemicals that adversely affect human health and the environment around the world. Because they can be transported by wind and water, most POPs generated in one country can and do affect people and wildlife far from where they are used and released.

<span class="mw-page-title-main">Biomagnification</span> Process of progressive accumulation in food chain

Biomagnification, also known as bioamplification or biological magnification, is the increase in concentration of a substance, e.g a pesticide, in the tissues of organisms at successively higher levels in a food chain. This increase can occur as a result of:

<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">Environmental toxicology</span>

Environmental toxicology is a multidisciplinary field of science concerned with the study of the harmful effects of various chemical, biological and physical agents on living organisms. Ecotoxicology is a subdiscipline of environmental toxicology concerned with studying the harmful effects of toxicants at the population and ecosystem levels.

Toxic equivalency factor (TEF) expresses the toxicity of dioxins, furans and PCBs in terms of the most toxic form of dioxin, 2,3,7,8-TCDD. The toxicity of the individual congeners may vary by orders of magnitude.

In aquatic toxicology, bioconcentration is the accumulation of a water-borne chemical substance in an organism exposed to the water.

In environmental toxicology, effects range low (ERL) and effects range median (ERM) are measures of toxicity in marine sediment. They are used by public agencies in the United States in formulating guidelines in assessing toxicity hazards, in particular from trace metals or organic contaminants.

Persistent, bioaccumulative and toxic substances (PBTs) are a class of compounds that have high resistance to degradation from abiotic and biotic factors, high mobility in the environment and high toxicity. Because of these factors PBTs have been observed to have a high order of bioaccumulation and biomagnification, very long retention times in various media, and widespread distribution across the globe. Most PBTs in the environment are either created through industry or are unintentional byproducts.

A mode of toxic action is a common set of physiological and behavioral signs that characterize a type of adverse biological response. A mode of action should not be confused with mechanism of action, which refer to the biochemical processes underlying a given mode of action. Modes of toxic action are important, widely used tools in ecotoxicology and aquatic toxicology because they classify toxicants or pollutants according to their type of toxic action. There are two major types of modes of toxic action: non-specific acting toxicants and specific acting toxicants. Non-specific acting toxicants are those that produce narcosis, while specific acting toxicants are those that are non-narcotic and that produce a specific action at a specific target site.

Toxicodynamics, termed pharmacodynamics in pharmacology, describes the dynamic interactions of a toxicant with a biological target and its biological effects. A biological target, also known as the site of action, can be binding proteins, ion channels, DNA, or a variety of other receptors. When a toxicant enters an organism, it can interact with these receptors and produce structural or functional alterations. The mechanism of action of the toxicant, as determined by a toxicant’s chemical properties, will determine what receptors are targeted and the overall toxic effect at the cellular level and organismal level.

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).

Simultaneously extracted metals/Acid-volatile sulfide (SEM-AVS) is an approach used in the field of aquatic toxicology to assess the potential for metal ions found in sediment to cause toxic effects in organisms dwelling in the sediment. In this approach, the amounts of several heavy metals in a sediment sample are measured in a laboratory; at the same time, the amount of acid-volatile sulfide is determined. Based on the chemical interactions between heavy metals (SEM) and acid-volatile sulfide (AVS), the concentrations of these two components can be used to assess the potential for toxicity to sediment-dwelling organisms.

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 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.

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.


  1. 1 2 3 4 5 6 McCarty, L. and D. MacKay. 1993. Enhancing ecotoxicological modeling and assessment. Environmental Science and Technology 27 (9): 1719-1728.
  2. 1 2 3 4 5 6 7 8 Tissue-Based Criteria for “Bioaccumulative” Chemicals.http://www.epa.gov/scipoly/sap/meetings/2008/october/aquatic_life_criteria_guidelines_tissue_08_26_05.pdf U.S. Environmental Protection Agency (EPA), 2005
  3. 1 2 3 4 5 6 7 8 9 10 McElroy, A.E., M.G. Barron, N. Beckvar, S.B. K. Driscoll, J.P. Meador, T.F. Parkerton, T.G. Preuss, and J.A. Steevens. 2011. A review of the tissue residue approach for organic and organometallic compounds in aquatic organisms. Integrated environmental assessment and management 7 (1): 50-74.http://onlinelibrary.wiley.com/doi/10.1002/ieam.132/abstract.
  4. 1 2 3 4 5 Meador, J.P.; et al. (2011). "The Tissue Residue Approach for Toxicity Assessment: Findings and Critical Reviews from a Society of Environmental Toxicology and Chemistry Pellston Workshop". Integrated Environmental Assessment and Management. 7 (1): 2–6. doi:10.1002/ieam.133. PMID   21184566. S2CID   34615756.
  5. 1 2 3 4 5 6 7 8 9 McCarty, L.S., P.F. Landrum, S.N. Luoma, J.P. Meador, A.A. Merten, B.K. Shephard and A.P. van Wezel. 2011. Advancing environmental toxicology through chemical dosimetry: External exposures versus tissue residues. Integrated Environmental Assessment and Management 7 (1): 7-27.http://onlinelibrary.wiley.com/doi/10.1002/ieam.98/abstract
  6. 1 2 3 Jarvinen, A.W., D.R. Mount and G.T. Ankley. Development of Tissue Residue Threshold Valueshttp://water.epa.gov/polwaste/sediments/cs/upload/mount.pdf U.S. Environmental Protection Agency (EPA)
  7. 1 2 McCarty, L.S. Comments on the Significance and Use of Tissue Residues in Sediment Toxicology and Risk Assessment.http://water.epa.gov/polwaste/sediments/cs/upload/mccarty.pdf U.S. Environmental Protection Agency (EPA)
  8. 1 2 3 4 5 6 7 8 9 10 11 12 13 Field, L.J. Use of Tissue Residue Data in Exposure and Effects Assessments for Aquatic Organisms.http://water.epa.gov/polwaste/sediments/cs/upload/field.pdf U.S. Environmental Protection Agency (EPA)
  9. Dyer, S., St J. Warne, J.S. Meyer, H. A. Leslie, and B.I. Escher. 2011. Tissue residue approach for chemical mixtures. Integrated environmental assessment and management 7 (1): 99-115.
  10. Canada Environmental Quality Guidelines. 1998. http://ceqg-rcqe.ccme.ca/download/en/290/
  11. Canada Environmental Quality Guidelines. 1999. http://ceqg-rcqe.ccme.ca/download/en/314/
  12. Adams, W. J., R. Blust, U. Borgmann, K. V. Brix, D. K. DeForest, A. S. Green, J. S. Meyer, J. C. McGeer, P. R. Paquin, P. S. Rainbow and C. M. Wood. 2010. Utility of tissue residues for predicting effects of metals on aquatic organisms. Integrated environmental assessment and management 7 (1): 75-98.
  13. Meador, J.P. (2015). "Tissue concentrations as the dose metric to assess potential toxic effects of metals in field-collected fish: Copper and cadmium". Environmental Toxicology and Chemistry. 34 (6): 1309–1319. doi:10.1002/etc.2910. PMID   25939475. S2CID   33163106.
  14. 1 2 3 4 5 Sappington, K.G.; et al. (2011). "Application of the tissue residue approach in ecological risk assessment". Integrated Environmental Assessment and Management. 7 (1): 116–140. doi:10.1002/ieam.116. PMID   21184572. S2CID   14413684.