Adaptive Effect
An adaptive effect enhances an organism's performance as a whole and/or its ability to withstand a challenge. An example of an adaptive effect is an increase in hepatic smooth endoplasmic reticulum, but only if hepatic metabolism reduces the chemical's toxicity.

Adverse Effect
Any biochemical change, functional impairment, or pathologic lesion which impairs performance and reduces the ability of an organism to respond to additional challenge. An adverse effect may have different degrees of severity, and should be distinguished from adaptive (beneficial) effects and compensatory (neutral) effects.

Basis  
The data used by an organization to calculate a risk value. The basis is listed on ITER's noncancer risk value tables. Examples of the basis include: No Observed Adverse Effect Level (NOAEL), No Observed Effect Level (NOEL), Lowest Observed Adverse Effect Level (LOAEL), or Lowest Observed Effect Level (LOEL). This basis is generally divided by a number of uncertainty factors to calculate the risk value (e.g., RfD, TC, MRL). 

Basis (ADJ) 
This is the NOAEL, LOAEL, or benchmark dose identified in the critical study, adjusted for continuous exposure, that was administered in a laboratory animal experiment, or to which humans were exposed occupationally or in controlled studies. For example, for a gavage study in which the animals were administered the compound 5 days/week, the administered dose would be multiplied by 5/7 to obtain a continuous dose. Similarly, for an inhalation study carried out 6 hours/day, the administered concentration would be adjusted by a factor of 6/24 to obtain a continuous dose. 

Basis (EXP) 
This is the NOAEL, LOAEL, or benchmark dose identified in the critical study. It is expressed as the actual dose or concentration that was administered in a laboratory animal experiment, or to which humans were exposed occupationally or in controlled studies. This dose/concentration has not been adjusted for continuous exposure.

 Biomonitoring Equivalent (BE) 
A BE is the concentration or range of concentrations of a chemical in a biological medium (blood, urine, or other medium) that is consistent with an existing health-based exposure guideline. BE values are most appropriately used as screening values to evaluate biomonitoring data in the context of existing risk assessments rather than for assessing data from individuals. BE values are derived through integration of available data on toxicokinetics with the toxicity data underlying the exposure guidelines. 

CAS Number 
The Chemical Abstract Services unique number for each chemical. It can be used to search for a specific chemical regardless of the choice of chemical name. 

CR(inhal) 
The cancer risk from inhalation exposure, CR(inhal) is the 1 in 10,000 (E-4) lifetime excess cancer risk following exposure by inhalation (expressed in microgram/cu.m), as derived by RIVM. For comparison purposes on ITER, this value has been converted to a 1 in 100,000 (E-5) risk level, and has also been converted to milligrams/cu.m. 

CR(oral) 
The cancer risk from oral exposure, CR(oral) is the 1 in 10,000 (E-4) lifetime excess cancer risk following oral exposure (expressed in microgram/kg bw-day), as derived by RIVM. For comparison purposes onITER, this value has been converted to a 1 in 100,000 (E-5) risk level, and has also been converted to milligrams/kg-day. 

Carcinogenesis 
The formation of tumors caused by chemical exposures. (Very likely a series of steps). The carcinogenic event modifies the genome and/or other molecular control mechanisms in the target cells such that these can give rise to a population of altered cells. The formation of benign and malignant tumors (i.e., cancers) is often considered together in determining a dose-response relationship and estimating a risk value for this endpoint. These effects are often considered not to have a threshold in response. 

Chemical 
The risk value is developed for the named chemical, or for a compound of the chemical. In the latter case, the risk value generally reflects the molecular weight of the chemical and not the compound. Please see individual descriptions for exceptions. 

Classification 
The organizations listed on ITER use a specific approach to classifying the human potential for carcinogenicity from exposure to a chemical. While most of these organizations are based on information from all routes of exposure and are not route-specific, EPA assessments completed after approximately 1996 may have route-specific classifications, depending on the available data and the chemical's mode of action. 

IARC cancer classification groups and detailed descriptions of these groups can be found in the Preamble to each monograph and at https://monographs.iarc.fr/wp-content/uploads/2018/06/CurrentPreamble.pdf. Briefly, these are Group 1 - carcinogenic to humans, Group 2A - probably carcinogenic to humans, Group 2B - possibly carcinogenic to humans, Group 3 - not classifiable as to carcinogenicity, and Group 4 - probably not carcinogenic to humans. The IARC evaluation considers the evidence of carcinogenicity in humans, the evidence of carcinogenicity in experimental animals, and other data relevant to the evaluation of carcinogenicity and its mechanisms. 

Health Canada classifies chemicals into six groups on criteria modified from those of the International Agency for Research on Cancer (IARC): I-Carcinogenic to Humans; II-Probably Carcinogenic to Humans; III-Possibly Carcinogenic to Humans; IV-Unlikely to be Carcinogenic to Humans; V-Probably Not Carcinogenic to Humans; and VI-Unclassifiable with Respect to Carcinogenicity in Humans.

More information regarding Health Canada's classification scheme can be found in Meek ME, Newhook R, Liteplo RG, Armstrong VC. 1994. Approach to assessment of risk to human health for Priority Substances under the Canadian Environmental Protection Act. In: Environmental Carcinogenesis and Ecotoxicology Review, Part C of Journal of Environmental Science and Health. C12(2):105-134. 

Beginning in 1996, EPA has been revising its carcinogen risk assessment guidelines to focus on mode of action and a weight of evidence narrative summarizing the chemical's carcinogenic potential. From 1996 to 1999, the following major narrative descriptors were used, with sub-descriptors in each group: "Known/likely;" "cannot be determined;" and "not likely." Beginning in approximately 1999, EPA has used the following standard hazard descriptors: "carcinogenic to humans," "likely to be carcinogenic to humans," "suggestive evidence of carcinogenic potential," "inadequate information to assess carcinogenic potential," and "not likely to be carcinogenic to humans." Depending on the chemical's mode of action, different descriptors may apply for different routes or under different exposure conditions (e.g., different doses, different co-exposures). These descriptors were finalized in the 2005 guidelines. For further information regarding the 2005 guidelines, please see: U.S. EPA. (2005) Guidelines for Carcinogen Risk Assessment. Washington, DC, National Center for Environmental Assessment. EPA/630/P-03/001b. NCEA-F-0644b. . This document is available online at http://cfpub.epa.gov/ncea/CFM/nceaQFind.cfm?keyword=Cancer%20Guidelines.  

Documents prepared by NSF International use the most recent version of the U.S. EPA guidelines for carcinogen risk assessment in classifying the human carcinogenic potential of a chemical. This is currently the U. S. EPA (2005) final guidelines, but previous risk assessments have used the U.S. EPA (1999) draft, U.S. EPA (1996) proposed, or U.S. EPA (1986) final guidelines for carcinogen risk assessment. If another agency has classified the carcinogenic potential of the chemical, that classification is noted in the risk comparisons and conclusions section of the NSF International document, with discussion if there are differences in classification. 

Compensatory Effect 
This effect maintains overall function without enhancement or significant cost. Increased respiration due to metabolic acidosis is an example of a compensatory effect. 

Critical Effect  
The first adverse effect, or its known precursor, that occurs as the dose rate increases. There is an assumption that for some toxic responses, there is a level (threshold) below which adverse effects will not occur. The critical effect is often the basis of noncancer risk values, on the assumption that if the critical effect is prevented, then all subsequent adverse effects are prevented. 

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GPL 
General Population Limit (GPL): The maximum concentration to which members of the general population may be continually exposed 24 hours per day, 7 days per week. The GPL is intended for application to the entire general population, including all ages and medical conditions (e.g., infants, elderly, infirm, and healthy). Expressed as mg/cu.m. Used by the Centers for Disease Control and Prevention (CDC) and the U.S. Army. 

Human Equivalent Concentration 
Abbreviated as HEC, EPA defines this as the exposure concentration for humans that has been adjusted for dosimetric differences between experimental animal species and humans to be equivalent to the exposure concentration associated with observed effects in the experimental animal species. If occupational human exposures are used for extrapolation, the human equivalent concentration represents the equivalent human exposure concentration adjusted to a continuous basis. 

In Prep 
In preparation indicates that the information is pending preparation and loading by TERA staff. 

IRIS 
The Integrated Risk Information System (IRIS) is a database of the U.S. EPA containing human health risk values for over 500 chemicals. The values represent the consensus of the U.S. EPA. IRIS can be accessed online at www.epa.gov/iris. For additional information, contact the U.S. EPA Risk Information Hotline at (301) 345-2870 or at Hotline.IRIS@epamail.epa.gov. 

ITER 
The International Toxicity Estimates for Risk (ITER) is a database of international risk values, managed by Toxicology Excellence for Risk Assessment (TERA). ITER provides risk values from health organizations, government agencies and independent groups worldwide in a side-by-side format with a synopsis to explain any differences in values across organizations. ITER also provides a link to each organization for more detailed information. ITER is available at https://iter.tera.org 

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LOAEL 
The Lowest-Observed-Adverse-Effect-Level (LOAEL) is the lowest exposure level at which there are statistically or biologically significant increases in frequency or severity of adverse effects between the exposed population and its appropriate control group. 

LOEL 
The Lowest-Observed-Effect-Level (LOEL) is the lowest exposure level at which there are statistically or biologically significant increases in frequency or severity of an effect between the exposed population and its appropriate control group. 

MPR 
The Maximum Permissible Risk (MPR) is the general term used by RIVM to indicate the limit value(s), including TDI, TCA, CR(oral), and CR(inhal). 

MRL  
Chronic MRL  Chronic Minimal Risk Level (MRL): An estimate of daily human exposure to a dose of a chemical that is likely to be without an appreciable risk of adverse noncancerous effects over a lifetime of exposure (based on studies of 365 or more days). Expressed in mg/kg/day. Used by ATSDR. 

Intermediate MRL  
Intermediate Minimal Risk Level: An estimate of the daily human exposure to a dose of a chemical that is likely to be without an appreciable risk of adverse noncancerous effects over less than a lifetime of exposure (based on studies of 15-364 days). Expressed in mg/kg/day. Used by ATSDR. 

NOTE: Information about an intermediate MRL derived by ATSDR is only included on ITER (and only in the synopsis) if ATSDR has not derived a chronic MRL and no other organization has derived a risk value for that chemical. 

N/A or NA 
Not applicable. 

NOAEL 
The No-Observed-Adverse-Effect Level (NOAEL) is an exposure level at which there are no statistically or biologically significant increases in the frequency or severity of adverse effects between the exposed population and its appropriate control; some effects may be produced at this level, but they are not considered as adverse, nor precursors to adverse effects. In an experiment with several NOAELs, the regulatory focus is primarily on the highest one, leading to the common usage of the term NOAEL as the highest exposure without adverse effect. 

NOEL 
The No-Observed-Effect Level (NOEL) is an exposure level at which there are no statistically or biologically significant increases in the frequency or severity of any effect between the exposed population and its appropriate control. 

NSF/ANSI Standard 60 
NSF/ANSI Standard 60 is the nationally recognized health effects standard for chemicals which are used to treat drinking water. The NSF International Water Distribution Systems Program (http://www.nsf.org/business/water_distribution/index.asp?program=WaterDistributionSys) is responsible for the Certification of drinking water treatment chemicals to ensure that these products do not contribute contaminants to drinking water that could cause adverse health effects. These drinking water treatment chemicals are certified under NSF/ANSI Standard 60, entitled Drinking Water Treatment Chemicals -- Health Effects ( https://www.techstreet.com/standards/nsf-60-2019?product_id=2092251.  

NSF/ANSI Standard 61 
NSF/ANSI Standard 61 is the nationally recognized health effects standard for all devices, components and materials which contact drinking water. The NSF Water Distribution Systems Program (http://www.nsf.org/business/water_distribution/index.asp?program=WaterDistributionSys) is responsible for the Certification of drinking water system components to ensure that these products do not contribute contaminants to drinking water that could cause adverse health effects. These drinking water system components are certified under NSF/ANSI Standard 61, entitled Drinking Water System Components -- Health Effects ( http://www.techstreet.com/cgi-bin/detail?product_id=1598705). 

Noncancer Toxicity  
Local and systemic effects caused by chemical exposures that are not cancer. These effects are generally considered to have a threshold in response. 

Organizations  
ITER contains risk values and/or cancer classifications from 6 organizations:

1. U.S. Agency for Toxic Substances and Disease Registry (ATSDR) 
2. Health Canada 
3. International Agency for Research on Cancer (IARC) 
4. Independent parties whose risk values have undergone peer review through a process outside TERA's ITER Peer Review process (listed under the IPRV column) 
5. Independent parties whose risk values have undergone peer review through TERA's ITER Peer Review process (listed under the ITER PR column) 
6. NSF International (NSF Intl) 
7. The National Institute of Public Health & Environmental Protection (RIVM) (the Netherlands) and, 
8. U.S. Environmental Protection Agency (U.S. EPA) 

Risk values derived by independent groups will be accepted for inclusion on ITER after undergoing independent peer review and after approval by Toxicology Excellence for Risk Assessment (TERA). We anticipate adding data from the International Programme on Chemical Safety (IPCS), a part of the World Health Organization, in the future.

ATSDR 
Health Canada 
IARC 
IPRV 
IPCS 
ITER PR 
NSF Intl 
RIVM 
U.S. EPA 

ATSDR 
Agency for Toxic Substances and Disease Registry of the Centers for Disease Control of the United States. Information from ATSDR is based on the Toxicological Profiles that ATSDR publishes for each chemical. Copies of Toxicological Profiles can be obtained from ATSDR by calling 1-888-42-ATSDR (1-888-422-8737). A list of available Profiles can be found at https://www.atsdr.cdc.gov/toxguides/index.asp. 

Health Canada 
Health Canada information on ITER is compiled from several sources. Each chemical will identify the source of information in its For Further Information section on ITER. The sources of information include: Environmental Carcinogenesis and Ecotoxicology Review, Part C of Journal of Environmental Science and Health. C12(2). 559 p.; and Environment Canada, Health Canada. 2000 Priority substances list assessment reports <by chemical>. Ottawa. Ministry of Public Works and Government Services. Available at http://www.hc-sc.gc.ca/ewh-semt/pubs/contaminants/index_e.html or at the Inquiry Center at 1-800-668-6767 (in Canada) or 819-997-2800 (outside Canada). 

IARC 
International Agency for Research on Cancer (IARC), a part of the World Health Organization (WHO). Cancer classifications from IARC are provided in the IARC Monographs, which are available at http://monographs.iarc.fr

IPCS 
International Programme on Chemical Safety (IPCS), a part of the World Health Organization (WHO). Information on chemical assessments from IPCS will be added to ITER in the future. In the meantime, IPCS documents are available at http://www.inchem.org/pages/about.html. 

IPRV  
The Independently Peer Reviewed Values (IPRV) column contains risk values derived by independent parties whose risk values have undergone peer review through a process outside TERA's ITER Peer Review process.

ITER PR 
The ITER Peer Review (ITER PR) column contains risk values derived by independent parties whose risk values have undergone peer review through TERA's ITER Peer Review process. These risk values are typically found only on ITER. 

NSF Intl 
NSF International, an independent, not-for-profit organization, prepares compound specific oral risk assessment documents based on the requirements of Annex A of NSF International/American National Standards 60 "Drinking water treatment chemicals - Health effects" and 61 "Drinking water system components - Health effects". Oral RfDs or cancer risk levels are derived using U.S. EPA risk assessment guidelines. NSF/ANSI standards and oral risk assessment documents prepared by NSF are available on-line at the NSF Bookstore. NSF/ANSI Standards 60 or 61, which include Annex A, are available at: https://www.techstreet.com/standards/nsf-60-2019?product_id=2092251. Compound specific oral risk assessment documents prepared by NSF International are available at: http://www.techstreet.com/cgi-bin/browsePublisher?publisher_id=133&subgroup_id=13180. 

RIVM 
Rijksinstituut voor Volksgezondheid en Milieu (RIVM; National Institute of Public Health and the Environment, the Netherlands). Information from RIVM is based on chemical assessments that are compiled in the framework of the Dutch governmental programme on risks in relation to soil quality, quantifying the human-toxicological risk limits (MPRs) for a number of rather widespread chemicals. These MPR values are published in the form of RIVM reports.   The data on ITER is obtained from the following report from RIVM: Baars AJ et al. 2001. Re-evaluation of human-toxicological maximum permissible risk levels. RIVM report no. 711701025, National Institute of Public Health and the Environment, Bilthoven, The Netherlands, March 2001. Available athttp://www.rivm.nl/bibliotheek/rapporten/711701025.pdf or at http://www.rivm.nl/en/ (click on Search, type "711701025", then click on document). 

U.S. EPA  
United States Environmental Protection Agency. U.S. EPA information on ITER is compiled from EPA's Integrated Risk Information System (IRIS). IRIS can be accessed online at www.epa.gov/iris. For additional information, contact the U.S. EPA Risk Information Hotline at (301) 345-2870 or at Hotline.IRIS@epamail.epa.gov 

Peer Review 
This section of ITER lists what internal and external reviews the organization's toxicity value received prior to public release. 

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RfC  
Reference Concentration (RfC): An estimate (with uncertainty spanning perhaps an order of magnitude) of a continuous inhalation exposure to the human population (including sensitive subgroups) that is likely to be without an appreciable risk of deleterious noncancer effects during a lifetime. RfCs are based on non-carcinogenic effects and are usually calculated by applying uncertainty factors to a NOAEL or LOAEL. Expressed in units of mg/cu.m. Used by the U.S. EPA. 

RfD 
Reference Dose (RfD): An estimate (with uncertainty spanning perhaps an order of magnitude) of a daily exposure to the human population (including sensitive subgroups) that is likely to be without an appreciable risk of deleterious effects during a lifetime. RfDs are based on non-carcinogenic effects and are usually calculated by applying uncertainty factors to a NOAEL or LOAEL. Expressed as mg/kg-day. Used by the U.S. EPA, NSF International, and the US Army. 

Risk 
The probability of injury, disease, or death under specific circumstances. In quantitative terms, risk is expressed in values ranging from zero (representing the certainty that harm will not occur) to one (representing the certainty that harm will occur). 

Risk Assessment 
The determination of the kind and degree of hazard posed by a chemical, the extent to which a particular group of people has been or may be exposed to the chemical, and the present or potential health risk that exists due to the chemical. 

RSC 
Risk Specific Concentration (RSC). The risk value of a chemical in mg/cu.m that is associated with a specified excess lifetime cancer risk, usually an upper 95% confidence limit. In ITER, all RSCs are calculated byTERA from the organization's unit risk or TC05 and represent the risk at a 1 in 100,000 (E-5) level. 

RSD  Risk Specific Dose (RSD).
The risk value of a chemical in mg/kg-day that is associated with a specified excess lifetime cancer risk, usually an upper 95% confidence limit. In ITER, the RSDs for the U.S. EPA and Health Canada are calculated by TERA from the organization's slope factor or TD05, respectively, and represent the 1 in 100,000 (E-5) risk level. NSF International calculates a human equivalent dose at the 10-5 risk level that is then used to calculate the TAC in drinking water. 

Risk Value Name  
CR(inhal) Cancer Risk from Inhalation Exposure  
CR(oral) Cancer Risk from Oral Exposure  
GPL General Population Limit  
MPR Maximum Permissible Risk  
MRL Minimal Risk Level  
RfC Reference Concentration  
RfD Reference Dose  
RSC Risk Specific Concentration  
RSD Risk Specific Dose  
SPAC Single Product Allowable Concentration  
STEL Short-Term Exposure Level  
TAC Total Allowable Concentration  
TC (or TCA) Tolerable Concentration (or Tolerable Concentration in Air)  
TDI (or TI) Tolerable Daily Intake (or Tolerable Intake)  
TD05 Tumourigenic Dose, 5%  
TC05 Tumourigenic Concentration, 5% 

Risk Value 
A dose in mg of chemical per kg of body weight per day (expressed as mg/kg-day), or concentration of chemical in mg of chemical per cubic meter of air (expressed as mg/cu.m) that for noncancer toxicity is generally considered to be without adverse effects in populations of humans (including sensitive subpopulations) for the duration of exposure specified. Examples of noncancer risk values include: GPL, MRL, RfD, RfC, TC, TDI. For cancer toxicity, this dose or concentration is usually associated with a specified lifetime cancer risk from exposure to the chemical. Examples of cancer risk values include: CR(inhal), CR(oral), RSC, RSD, TD05, TC05. NOTE: A "p" listed before a risk value indicates that it is a provisional value. 

Severity  
This is the degree to which an effect changes and impairs the functional capacity of an organ system. 

Slope Factor 
EPA defines slope factor on IRIS as the slope of the dose-response curve in the low-dose region. An upper bound (i.e., the 95% upper confidence limit) on this slope is used instead of the slope itself because it is a statistically more stable number. The units of the slope factor are usually expressed as 1/(mg/kg-day). 

SPAC 
The Single Product Allowable Concentration (SPAC) is the maximum concentration (generally in mg/L) of a contaminant that a single product is allowed to contribute to a public drinking water supply as defined by Annex A of NSF/ANSI 60 and 61, consensus standards developed by a consortium including NSF International. Used by NSF International. 

Species  
The experimental animal species from which the toxicity data are derived and on which the risk value is based. Sometimes, humans are tested in clinical studies at doses or concentrations that are unlikely to cause adverse effects in order to establish no-effect levels. Sometimes human case studies and epidemiology studies are used to estimate risk values. 

STEL  
The Short-Term Exposure Level (STEL) is the maximum concentration of a contaminant (generally in mg/L) that is permitted in drinking water for an acute exposure period, calculated and applied in accordance with Annex A of NSF/ANSI 61. The drinking water concentration is required to decay to a level at or below the TAC or SPAC within 90 days. Used by NSF International. 

Study 
The study from which the toxicity data are analyzed to estimate the risk value. Occasionally, more than one study is used. 

Synopsis 
A brief description of the available risk values describing differences when appropriate. 

Systemic Effects 
Systemic effects are those that require absorption and distribution of the toxicant to a site distant from its entry point, at which point effects are produced. Most chemicals that produce systemic toxicity do not cause a similar degree of toxicity in all organs, but usually demonstrate major toxicity to one or two organs. These are referred to as the target organs of toxicity for that chemical. 

TAC 
The Total Allowable Concentration (TAC) is the maximum concentration (generally in mg/L) of a non-regulated contaminant permitted in a public drinking water supply as defined by Annex A of NSF/ANSI 61, a consensus standard developed by a consortium including NSF International. Used by NSF International. 

Target Organ  
The organ or system of the body that is generally affected first as the dose of the chemical is increased from zero. For noncancer toxicity, the critical effect occurs in the primary target organ. Often, multiple organs or systems are impacted by a chemical at its lowest effective dose or concentration. 

TC05 
The Tumourigenic Concentration (05) is the concentration in air (expressed in mg/cu.m) associated with a 5% increase in incidence or mortality due to tumours. The TC05 is not based on the confidence limit but rather, is computed directly from the curve. Health Canada calculates TC05s for compounds classified in Groups I and II basing these values on tumours observed in epidemiological studies (generally) in occupationally exposed human populations, or those considered relevant to humans as observed in bioassays in experimental animals. The estimates of potency are generally restricted to effects for which there has been a statistically significant increase in incidence and a dose-response relationship, characterized by appropriate mathematical models (e.g. multistage). The Health Canada TC05 can be divided by a suitable margin, to provide a benchmark against which the adequacy of intake can be judged, with respect to potential carcinogenicity.   

TC or TCA 
The Tolerable Concentration (or Tolerable Concentration in Air), generally expressed in mg/cu.m, is an airborne concentration to which it is believed that a person can be exposed continuously over a lifetime without deleterious effect. The TCs (or TCAs) are based on non-carcinogenic effects and are usually calculated by applying uncertainty factors to a NOAEL or LOAEL. Absolute values of maximum intakes per day for various age groups can be developed by multiplying the TC (or TCA) by the average ventilation rate and dividing by the average body weight of the age group under consideration. It should be noted, however, that exceedence of such a calculated intake by a particular age group for a small proportion of the lifespan does not necessarily imply that exposure constitutes an undue risk to health. Used by Health Canada and RIVM. 

TD05 
The Tumourigenic Dose (05) is the total intake (often expressed in mg/kg b.w./day) associated with a 5% increase in incidence or mortality due to tumours. The TD05 is not based on the confidence limit but rather, is computed directly from the curve. Health Canada calculates TD05s for compounds classified in Groups I and II basing these values on tumours observed in epidemiological studies (generally) in occupationally exposed human populations, or those considered relevant to humans as observed in bioassays in experimental animals. The estimates of potency are generally restricted to effects for which there has been a statistically significant increase in incidence and a dose-response relationship, characterized by appropriate mathematical models (e.g. multistage). The Health Canada TD05 can be divided by a suitable margin, to provide a benchmark against which the adequacy of intake can be judged, with respect to potential carcinogenicity. 

TDI or TI 
The Tolerable Daily Intake (or Tolerable Intake) expressed on a body weight basis (e.g., mg/kg b.w./day) are the total intakes by ingestion, to which it is believed that a person can be exposed daily over a lifetime without deleterious effect. The TDIs (or TIs) are based on non-carcinogenic effects and are usually calculated by applying uncertainty factors to a NOAEL or LOAEL. Absolute values of maximum intakes per day for various age groups can be developed by multiplying the TDI (or TI) by the average body weight of the age group under consideration. It should be noted, however, that exceedence of such a calculated intake by a particular age group for a small proportion of the lifespan does not necessarily imply that exposure constitutes an undue risk to health. Used by Health Canada and RIVM. 

TERA 
Toxicology Excellence for Risk Assessment (TERA) is a nonprofit research and education organization dedicated to the best use of toxicity data for risk values. TERA staff can be reached by phone: U.S. 513-542-RISK (7475); Fax: U.S. 513-488.11990; or email: tera@tera.org. 

Threshold 
The dose or exposure below which an adverse effect is not expected. Common approaches to assessing the risks associated with noncancer toxicity are generally different from that used to assess the potential risks associated with carcinogenesis. Scientists often assume that a small number of molecular events can evoke carcinogenic and/or mutagenic changes in a single cell, which can lead to self-replicating damage. Often, this is considered a nonthreshold effect since there is presumably no level of exposure that does not pose a small, but finite, probability of generating a response. It is most often assumed that noncancer effects have a threshold, that is, a dose level below which a response is unlikely, because a compensatory effect or adaptive effect in the cell protects against an adverse effect.  

This threshold concept is important in many regulatory contexts. The individual threshold hypothesis holds that some exposures can be tolerated by an organism with essentially no chance for expression of a adverse effect. Further, risk management decisions frequently focus on protecting the more sensitive members of a population. In these cases efforts are made to keep exposures below the more sensitive subpopulation threshold, although it is recognized that hypersensitivity and chemical idiosyncrasy may exist at yet lower doses. 

Uncertainty Factor 
Factors representing specific areas of uncertainty inherent in the available data. These are frequently multiples of 10, although different organizations utilize lesser factors when the data allow. The usual uncertainty factors account for: interhuman variability, interspecies variability (extrapolation from animals to humans), extrapolation from less-than-chronic to lifetime exposure, use of a LOAEL instead of a NOAEL, and perhaps an additional factor for the adequacy of the available studies. For a further discussion of the use of uncertainty factors the reader is referred to Dourson et al., 1996; Dourson, 1994; and Barnes and Dourson, 1988.  

Unit Risk  
EPA defines unit risk on IRIS as the upper-bound excess lifetime cancer risk estimated to result from continuous exposure to an agent at a concentration of 1 ug/L in water, or 1 ug/cu.m in air. 

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Year  
This is generally the year that the risk value was made public or published. For Health Canada and NSF International, however, the year specifies the cutoff date of the literature review on which the risk value is based. The date for U.S. EPA indicates when the risk value (or its latest significant revision) was first loaded on IRIS. The ATSDR date is the date of publication for the Toxicological Profile. For RIVM and the U.S. Army, this is the year of publication of the risk value. For IARC, this is the year provided on the Summary and Evaluation for a particular chemical (which may or may not coincide with the year the Monograph was published). These dates are important because they can sometimes explain the differences in risk values 

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