Structure-Based Thresholds of Toxicological Concern (TTC): Guidance for Application to Substances Present at Low Levels in the Diet

Kroes, R.

doi:10.1080/01926230490462101

Cited by 41 publications

(145 citation statements)

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“…Considering the fact that there are few or no relevant toxicity data on Alternaria toxins, and that the chemical structure of several of them is known, the CONTAM Panel considered it appropriate to use the threshold of toxicological concern (TTC) approach to assess the relative level of concern of these mycotoxins (Kroes et al, 2004;EFSA 2011c). Because it is essential for the application of the TTC approach to have suitably conservative exposure estimates, which take into account the high exposure scenarios, the CONTAM Panel based the assessment on the mean and 95 th percentile chronic dietary exposure to AOH, AME, TeA and TEN for adult population using LB and UB.…”

Section: Human Health Risk Assessmentmentioning

confidence: 99%

“…Regarding TeA and TEN, for which there is no evidence of genotoxicity in bacteria or clear structural alerts 11 that raise concern for potential genotoxicity, the level defined by the TTC decision tree is 1500 ng/kg b.w. per day (90 µg/person per day) for compounds in Cramer structural class III (Kroes et al, 2004). For TEN, the mean chronic dietary exposure ranged from 36 to 141 ng/kg b.w.…”

Section: Human Health Risk Assessmentmentioning

confidence: 99%

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Scientific Opinion on the risks for animal and public health related to the presence ofAlternariatoxins in feed and food

2011

EFSA Journal

410

188

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The European Commission asked the European Food Safety Authority to review the safety of Alternaria toxins in food and feed. In addition to causing plant diseases on many crops such as cereals, oilseeds, tomatoes, apples and olives, some of these toxins are genotoxic in vitro and/or fetotoxic in rats. This opinion deals with alternariol, alternariol monomethyl ether, tenuazonic acid, iso-tenuazonic acid, altertoxins, tentoxin, altenuene and AAL-toxins (Alternaria alternata f. sp. lycopersici toxins). Two Member States provided 11,730 occurrence results in food and also data published in the scientific literature were considered. Generally these toxins were found in grains and grain-based products, tomato and tomato products, sunflower seeds and sunflower oil, fruits and fruit products, and beer and wine. The feed occurrence data (1150 results) were collected from the literature only. The knowledge on toxic effects of Alternaria toxins on farm and companion animals and occurrence data in feed were insufficient to assess the health risk for different species. For chicken there are indications that alternariol represents a health risk but it cannot be excluded that tenuazonic acid could also be of concern. Considering: (1) there are few or no relevant toxicity data on Alternaria toxins, (2) the chemical structure of several of them is known, (3) dietary exposure data exist for some of them, the Panel on Contaminants in the food chain used the threshold of toxicological concern (TTC) approach to assess the relative level of concern for dietary exposure of humans to these mycotoxins. For the genotoxic Alternaria toxins, alternariol and alternariol monomethyl ether, the estimated chronic dietary exposure exceeded the relevant TTC value indicating a need for additional toxicity data. The dietary exposure estimates for nongenotoxic tentoxin and tenuazonic acid are lower than the relevant TTC value and are considered unlikely to be a human health concern. SUMMARYAlternaria toxins are mycotoxins produced by Alternaria species that cause plant diseases on many crops. They are the principal contaminating fungi in wheat, sorghum and barley, and have also been reported to occur in oilseeds such as sunflower and rapeseed, tomato, apples, citrus fruits, olives and several other fruits and vegetables. Alternaria alternata is the most common Alternaria species in harvested fruits and vegetables, and is the most important mycotoxin-producing species. Due to their growth even at low temperature, Alternaria species are also responsible for spoilage of these commodities during refrigerated transport and storage.Alternaria species produce more than 70 phytotoxins, but a small proportion of them have been chemically characterised and reported to act as mycotoxins to humans and animals. Some toxins such as alternariol (AOH), alternariol monomethyl ether (AME), tenuazonic acid (TeA) and altertoxins (ATX) are described to induce harmful effects in animals, including fetotoxic and teratogenic effects. Culture extracts of A. altern...

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Section: Human Health Risk Assessmentmentioning

confidence: 99%

Section: Human Health Risk Assessmentmentioning

confidence: 99%

Scientific Opinion on the risks for animal and public health related to the presence ofAlternariatoxins in feed and food

2011

EFSA Journal

410

188

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“…The threshold for toxicological concern (TTC) is a pragmatic nontesting approach that establishes exposure levels for chemicals below which no appreciable risk to human health or the environment is expected based on a de minimis value for toxicity identified for many chemicals (US Food and Drug Administration 1993; Kroes et al 2004). The TTC can then be compared to an estimate of the likely exposure to a chemical to complete a screening-level safety assessment for a given route of exposure or environmental compartment/species of concern.…”

Section: Introductionmentioning

confidence: 99%

Creation of a Curated Aquatic Toxicology Database: EnviroTox

Connors

Beasley

Barron

et al. 2019

Enviro Toxic and Chemistry

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Flexible, rapid, and predictive approaches that do not require the use of large numbers of vertebrate test animals are needed because the chemical universe remains largely untested for potential hazards. Development of robust new approach methodologies and nontesting approaches requires the use of existing information via curated, integrated data sets. The ecological threshold of toxicological concern (ecoTTC) represents one such new approach methodology that can predict a conservative de minimis toxicity value for chemicals with little or no information available. For the creation of an ecoTTC tool, a large, diverse environmental data set was developed from multiple sources, with harmonization, characterization, and information quality assessment steps to ensure that the information could be effectively organized and mined. The resulting EnviroTox database contains 91 217 aquatic toxicity records representing 1563 species and 4016 unique Chemical Abstracts Service numbers and is a robust, curated database containing high‐quality aquatic toxicity studies that are traceable to the original information source. Chemical‐specific information is also linked to each record and includes physico‐chemical information, chemical descriptors, and mode of action classifications. Toxicity data are associated with the physico‐chemical data, mode of action classifications, and curated taxonomic information for the organisms tested. The EnviroTox platform also includes 3 analysis tools: a predicted‐no‐effect concentration calculator, an ecoTTC distribution tool, and a chemical toxicity distribution tool. Although the EnviroTox database and tools were originally developed to support ecoTTC analysis and development, they have broader applicability to the field of ecological risk assessment. Environ Toxicol Chem 2019;9999:1–12. © 2019 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC.

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“…This level can then be compared with an estimate of the likely exposure to a chemical to complete a screening-level safety assessment for a given route of exposure or environmental compartment/species of concern. The TTC concept is well established for assessing human safety of indirect food-contact substances [2] and has been reapplied for a variety of endpoints, including carcinogenicity, teratogenicity, and reproductive toxicity, albeit with different databases for each endpoint, with endpointspecific TTC values as the result [3]. Thresholds for toxicological concern have benefits for screening-level risk assessments, including the potential for rapid decision-making, fully utilizing existing knowledge, reasonable conservativeness for chemicals used in lower volumes, and reduction or elimination of unnecessary animal tests.…”

Section: Introductionmentioning

confidence: 99%

It is time to develop ecological thresholds of toxicological concern to assist environmental hazard assessment

Belanger

Sanderson

Embry

et al. 2015

Enviro Toxic and Chemistry

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The threshold of toxicological concern (TTC) concept is well established for assessing human safety of food-contact substances and has been reapplied for a variety of endpoints, including carcinogenicity, teratogenicity, and reproductive toxicity. The TTC establishes an exposure level for chemicals below which no appreciable risk to human health or the environment is expected, based on a de minimis value for toxicity identified for many chemicals. Threshold of toxicological concern approaches have benefits for screening-level risk assessments, including the potential for rapid decision-making, fully utilizing existing knowledge, reasonable conservativeness for chemicals used in lower volumes (low production volume chemicals (e.g., < 1 t/yr), and reduction or elimination of unnecessary animal tests. Higher production volume chemicals (>1 t/yr) would in principle always require specific information because of the presumed higher exposure potential. The TTC approach has found particular favor in the assessment of chemicals used in cosmetics and personal care products, as well as other chemicals traditionally used in low volumes. Use of the TTC in environmental safety is just beginning, and initial attempts are being published. Key questions focus on hazard extrapolation of diverse taxa across trophic levels, importance of mode of action, and whether safe concentrations for ecosystems estimated from acute or chronic toxicity data are equally useful and in what contexts. The present study provides an overview of the theoretical basis for developing an ecological (eco)-TTC, with an initial exploration of chemical assessment and boundary conditions for use. An international collaboration under the International Life Sciences Institute Health and Environmental Sciences Institute has been established to address challenges related to developing and applying useful eco-TTC concepts. Environ Toxicol Chem 2015;34:2864-2869. # 2015 SETAC

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Structure-Based Thresholds of Toxicological Concern (TTC): Guidance for Application to Substances Present at Low Levels in the Diet

Cited by 41 publications

References 0 publications

Scientific Opinion on the risks for animal and public health related to the presence ofAlternariatoxins in feed and food

Scientific Opinion on the risks for animal and public health related to the presence ofAlternariatoxins in feed and food

Creation of a Curated Aquatic Toxicology Database: EnviroTox

It is time to develop ecological thresholds of toxicological concern to assist environmental hazard assessment

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