Tissue residue is the concentration of a chemical or compound in an organism's tissue or in a portion of an organism's tissue.McCarty, L. and D. MacKay. 1993. Enhancing ecotoxicological modeling and assessment. Environmental Science and Technology 27 (9): 1719-1728. Tissue residue is used in

aquatic toxicology 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 commu ...

to help determine the fate of chemicals in aquatic systems,

bioaccumulation Bioaccumulation is the gradual accumulation of substances, such as pesticides or other chemicals, in an organism. Bioaccumulation occurs when an organism absorbs a substance faster than it can be lost or eliminated by catabolism and excretion. T ...

of a substance, or

bioavailability In pharmacology, bioavailability is a subcategory of absorption and is the fraction (%) of an administered drug that reaches the systemic circulation. By definition, when a medication is administered intravenously, its bioavailability is 100%. H ...

of a substance, account for multiple routes of exposure (ingestion, absorption, inhalation), and address an organism's exposure to chemical mixtures.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 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.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. In general, tissue residue approaches are used for chemicals that bioaccumulate or for bioaccumulative chemicals. The majority of these substances are

organic compounds Some chemical authorities define an organic compound as a chemical compound that contains a carbon–hydrogen or carbon–carbon bond; others consider an organic compound to be any chemical compound that contains carbon. For example, carbon-co ...

that are not easily metabolized by organisms and have long environmental persistence. Examples of these chemicals include

polychlorinated dibenzodioxins Polychlorinated dibenzodioxins (PCDDs), or simply dioxins, are a group of long-lived polyhalogenated organic compounds that are primarily anthropogenic, and contribute toxic, persistent organic pollution in the environment. They are commonly ...

furans Furan is a heterocyclic organic compound, consisting of a five-membered aromatic ring with four carbon atoms and one oxygen atom. Chemical compounds containing such rings are also referred to as furans. Furan is a colorless, flammable, highly ...

biphenyl Biphenyl (also known as diphenyl, phenylbenzene, 1,1′-biphenyl, lemonene or BP) is an organic compound that forms colorless crystals. Particularly in older literature, compounds containing the functional group consisting of biphenyl less one ...

DDT Dichlorodiphenyltrichloroethane, commonly known as DDT, is a colorless, tasteless, and almost odorless crystalline chemical compound, an organochloride. Originally developed as an insecticide, it became infamous for its environmental impacts. ...

and its

metabolites In biochemistry, a metabolite is an intermediate or end product of metabolism. The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, c ...

, and

dieldrin Dieldrin is an organochlorine compound originally produced in 1948 by J. Hyman & Co, Denver, as an insecticide. Dieldrin is closely related to aldrin, which reacts further to form dieldrin. Aldrin is not toxic to insects; it is oxidized in the i ...

. 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.

History

Historically,

toxicity tests have focused on water-based approaches where concentration of a

toxicant A toxicant is any toxic substance, whether artificial or naturally occurring. By contrast, a toxin is a poison produced naturally by an organism (e.g. plant, animal, insect, bacterium). The different types of toxicants can be found in the air, so ...

is determined by its concentration in the water. 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. 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.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 Since the 1980s, there has been rapid growth in the tissue residue approach to toxicology. The water-based approach has been re-evaluated due to challenges in assessing the

toxicity 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, bacteria, bacterium, or plant, as well as the effect o ...

of bioaccumulating chemicals. 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.

Advantages

The use of tissue residue allows an investigator to: account for multiple routes of exposure, account for

toxicokinetic Toxicokinetics (often abbreviated as 'TK') is the description of both what rate a chemical will enter the body and what occurs to excrete and metabolize the compound once it is in the body. Relation to pharmacokinetics It is an application of pha ...

differences between species, account for factors that alter bioavailability and potentially address exposure of an organism to a chemical mixture.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)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) Tissue residue also has the ability to represent temporal and spatial exposure or an organism,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) as well as clarify the cause-effect relationship of chemicals. These relationships are often distorted by uncertainty in chemical bioavailability. 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.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. Tissue residue is also less variable than other measures of chemical exposure. 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.

Disadvantages

The majority of issues with tissue residue arise in the interpretation of tissue residue data. Interpretation complication can be caused by choice of endpoints, species choice, life stage sensitivity, data quality, and toxicity data extrapolation. 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. 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 Biotransformation is the biochemical modification of one chemical compound or a mixture of chemical compounds. Biotransformations can be conducted with whole cells, their lysates, or purified enzymes. Increasingly, biotransformations are effected ...

of organic chemicals. If a chemical is biotransformed, the concentration of the parent chemical is lower, but the

may still be toxic. Tissue residue approaches are not as useful for chemicals with short half-lives because an organism will only be sporadically exposed. Overall, tissue residue is meant to complement data from water-based approaches, not replace them.

Use in regulation

North America

The U.S. Environmental Protection Agency (USEPA) has incorporated tissue residue through the development of the

Biotic Ligand Model Biotics describe living or once living components of a community; for example organisms, such as animals and plants. Biotic may refer to: *Life, the condition of living organisms *Biology, the study of life *Biotic material, which is derived from ...

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 The ''n''-octanol-water partition coefficient, ''K''ow is a partition coefficient for the two-phase system consisting of ''n''-octanol and water. ''K''ow is also frequently referred to by the symbol P, especially in the English literature. It is a ...

greater than 5 (log Kow>5). Canada uses tissue residue formally in guidelines called tissue residue guidelines (TRGs), which are primarily used for protecting wildlife that consume aquatic life.Canada Environmental Quality Guidelines. 1998. http://ceqg-rcqe.ccme.ca/download/en/290/Canada Environmental Quality Guidelines. 1999. http://ceqg-rcqe.ccme.ca/download/en/314/

Europe

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 In analytical chemistry, biomonitoring is the measurement of the body burden of toxic chemical compounds, elements, or their metabolites, in biological substances. Often, these measurements are done in blood and urine. Biomonitoring is performe ...

programs for mussels and oysters.

Available databases

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

Applications

Metals

Tissue residue of metals in invertebrate prey organisms may reduce uncertainty in estimating exposure from multiple routes. This may be especially important in early life stages of an organism or for species listed under the

Endangered Species Act The Endangered Species Act of 1973 (ESA; 16 U.S.C. § 1531 et seq.) is the primary law in the United States for protecting and conserving imperiled species. Designed to protect critically imperiled species from extinction as a "consequence of e ...

(ESA). 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 Organometallic chemistry is the study of organometallic compounds, chemical compounds containing at least one chemical bond between a carbon atom of an organic molecule and a metal, including alkali, alkaline earth, and transition metals, an ...

, 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.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. 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. 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 A Polycyclic aromatic hydrocarbon (PAH) is any member of a class of organic compounds that is composed of multiple fused aromatic rings. Most are produced by the incomplete combustion of organic matter— by engine exhaust fumes, tobacco, inciner ...

, therefore tissue residue of parent PAH compounds will not provide adequate information on exposure to the organism. PAH exposure in fish has been associated with reproductive impairment, immune deficiency, and liver lesions as well as other health problems. 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.

PCBs (Polychlorinated biphenyls)

Unlike PAHs, tissue residue of

PCBs Polychlorinated biphenyls (PCBs) are organochlorine compounds with the formula C12 H10−''x'' Cl''x''; they were once widely used in the manufacture of carbonless copy paper, as heat transfer fluids, and as dielectric and coolant fluids f ...

for fish can provide reliable information on exposure and toxicity. The tissue residue of PCBs in fish can provide vital information in an

exposure assessment Exposure assessment is a branch of environmental science, toxicology, epidemiology, environmental engineering, and occupational hygiene that focuses on the processes that take place at the interface between the environment containing the contam ...

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.

In-situ

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 is a Latin phrase meaning 'in place' or 'on site', derived from ' ('in') and ' ( ablative of ''situs'', ). The term typically refers to the examination or occurrence of a process within its original context, without relocation. The term is use ...

bioassays in the United States, United Kingdom and Canada.

Superfund sites

Tissue residue guidelines were developed for

tributyltin Tributyltin (TBT) is an umbrella term for a class of organotin compounds which contain the group, with a prominent example being tributyltin oxide. For 40 years TBT was used as a biocide in anti-fouling paint, commonly known as bottom paint, ...

(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. 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.

Ecological risk assessment

Ecological

risk assessment Risk assessment is a process for identifying hazards, potential (future) events which may negatively impact on individuals, assets, and/or the environment because of those hazards, their likelihood and consequences, and actions which can mitigate ...

aims to source of contamination to exposure to a toxicity endpoint. This requires a risk assessor to identify and estimate exposure pathways. Tissue residue is the only approach that inherently accounts for toxicity due to multiple exposure pathways. There is also a need in risk assessment to understand the

of chemicals4, as well as a direct estimation of

. Modeling food web exposure is difficult in risk assessment and requires many assumptions but this uncertainty can be reduced through tissue residue. Tissue residue may also allow provide a link between ecological risk assessment and human health risk assessment. The issues with using tissue residue in risk assessment are similar to the disadvantages listed above.

References

{{Reflist Toxicology