The test chemical selection procedure of the European Centre for the Validation of Alternative Methods for the EU Project ReProTect

Pazos, Patricia; Pellizzer, Cristian; Stummann, Tina C.; Hareng, Lars; Bremer, Susanne

doi:10.1016/j.reprotox.2010.04.001

Cited by 12 publications

(12 citation statements)

References 327 publications

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“…The current translational safety biomarkers for early screening of testicular toxicity are limited (Pazos et al, 2010). To enhance the efficiency and success in pharmaceutical development, while ensuring patient safety, many efforts have focused on finding translational safety biomarkers (Sistare and DeGeorge, 2011).…”

Section: Introductionmentioning

confidence: 99%

Inhibin B Response to Testicular Toxicants Hexachlorophene, Ethane Dimethane Sulfonate, Di‐(n‐butyl)‐phthalate, Nitrofurazone, DL‐Ethionine, 17‐alpha Ethinylestradiol, 2,5‐Hexanedione, or Carbendazim Following Short‐Term Dosing in Male Rats

Erdős

Pearson

Goedken

et al. 2013

Birth Defects Research Pt B

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Section: Introductionmentioning

confidence: 99%

Inhibin B Response to Testicular Toxicants Hexachlorophene, Ethane Dimethane Sulfonate, Di‐(n‐butyl)‐phthalate, Nitrofurazone, DL‐Ethionine, 17‐alpha Ethinylestradiol, 2,5‐Hexanedione, or Carbendazim Following Short‐Term Dosing in Male Rats

Erdős

Pearson

Goedken

et al. 2013

Birth Defects Research Pt B

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“…Generally, fewer chemicals were selected (<50%) for the chemical classes that contained a large number of chemicals and low structural diversity (e.g., aliphatic linear and cyclic hydrocarbons, benzenes, ethers, phenols, and nitrobenzenes) than for more diverse chemical groups with a fewer number of chemicals (e.g., organophosphates, amides, and heterocyclic compounds; Table 3). The selection covers chemicals used in a range of industrial applications such as 1) intermediates in the production of pharmaceuticals (91, 123), cosmetic and fragrances (192), plastics (46, 225), detergents (36); 2) pesticides including insecticides (35,38,221,227,248,250,261), nematocides (13,98), fungicides (262), and herbicides (222); 3) dyes (251-255); and 4) industrial solvents (14,21,229,234). Of the selected compounds, naphthalene (88), pentachlorophenol (151), and nonylphenol (154) should be considered of high environmental relevance because of their multiple industrial applications.…”

Section: Tier Iii: Refinement Of Chemical Domainmentioning

confidence: 99%

Development of a list of reference chemicals for evaluating alternative methods to in vivo fish bioaccumulation tests

Rodríguez-Sánchez

Cronin

Lillicrap

et al. 2014

Enviro Toxic and Chemistry

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44The desire to reduce the number of animals used in experiments has highlighted the need to 45 standardise and validate in vitro methods as alternatives to bioaccumulation studies using fish. 46The present work details a process based on five criteria to develop a list of reference 47 compounds to evaluate alternative test methods to standard assays using rainbow trout 48 (Oncorhynchus mykiss). The approach was based on: 1) inclusion of relevant chemical classes 49for bioaccumulation and supported by data on bioconcentration factor (BCF), whole body 50 biotransformation rate (Kmet) and metabolic pathways (criteria 1-2); 2) cover a broad range of 51 bioconcentration potencies, logarithmof octanol-water coefficient (Log Kow), metabolic 52 susceptibility, molecular weight and maximum molecular diameter (criteria 3-4); and 3) 53 identification of chemicals that are unsuitable for in vitro testing according to cut-off values for 54 hydrolysis, volatility in solution and lipophilicity (criterion 5). In silico techniques were 55 employed to predict maximal log BCF, Kmet and the metabolic pathway for those chemicals for 56 which in vivo data for some of these properties were not available. Of the 139 compounds 57 considered as reference compounds, 51 were supported by high quality in vivo BCF, 22 58 compounds were supported by either in vivo Kmet or metabolic biotransformation data and ten 59 chemicals did not pass volatility and lipophilicity cut-off values. The list of reference 60 compounds is anticipated to provide a transparent basis for future experimental assessment of 61 the applicability of alternative methods for bioaccumulation assessment within the larger 62 scientific community. The potential of a compound to bioaccumulate is one of many hazardous properties that needs 67 to be evaluated in risk assessment procedures. Although bioaccumulation refers to the 68 accumulation of a substance in an organism from all routes of exposure (from the environment 69 and diet), the bioaccumulation of chemicals is usually expressed by the bioconcentration factor 70 (BCF) that refers only to its accumulation from the environment in a waterborne exposure. In 71 aquatic risk assessments, BCFs have been measured in fish according to the Organisation for 72Economic Cooperation and Development (OECD) Test Guideline305 [1][2]. 73In vivo test systems for bioaccumulation are demanding in terms of resources and the use of 74 large number of animals per test substance. Coupled with this, compliance with legislation such 75 as the European Union REACH (Registration, Evaluation, Authorisation and restriction of 76 Chemicals) regulation [3] has the potential to increase the demand for animal testing to assess 77 bioaccumulation for a large number of chemicals. Other methods such as in silico (computer-78 based) and in vitro techniques have been proposed as alternatives to in vivo testing since they 79 comply better with the principles of the 3Rs (reduction, refinement and replacement) for animal 80 testing [4]. 81In silic...

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“…While not much structured information is available on targeted compound selection for DNT, some literature is available on principles of compound selection itself. For instance, several EU-funded research consortia describe their procedure of compound selection in the area of carcinogenesis or reproductive toxicology (101,102). These compilations are based mainly on information available from animal studies.…”

Section: "Gold Standards" Vs "Mechanistic Tool Compounds"mentioning

confidence: 99%

Compound selection for in vitro modeling of developmental neurotoxicity

Kadereit

Zimmer²,

Thriel³

et al. 2012

Front Biosci

100

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Development of in vitro systems, such as those based on embryonic stem cell differentiation, depends on the selection of adequate test and training compounds. We recommend the use of two classes of positive controls, the "gold standard compounds" for which developmental neurotoxicity (DNT) has been proven in man, and the "pathway compounds" that are known to disrupt signalling pathways and key processes relevant for neuronal differentiation. We introduce the concept of toxicity endophenotypes (TEP) as changes in neuronal connectivity resulting from exposure to developmental toxicants. Thus, TEPs provide the scientific rationale for modeling DNT with simple in vitro models of key neurodevelopmental events. In this context, we discuss scientific and technical aspects of the test compound selection process. We suggest to include compounds with unspecific toxicity, besides negative control compounds, and we recommend tandem approaches to determine relative toxicities instead of absolute measures. Finally, we discuss how to avoid pitfalls by distinguishing between unspecific forms of cytotoxicity and specific developmental neurotoxicity. A compilation of compound lists corresponding to the above-discussed principles supplement this review.

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The test chemical selection procedure of the European Centre for the Validation of Alternative Methods for the EU Project ReProTect

Cited by 12 publications

References 327 publications

Inhibin B Response to Testicular Toxicants Hexachlorophene, Ethane Dimethane Sulfonate, Di‐(n‐butyl)‐phthalate, Nitrofurazone, DL‐Ethionine, 17‐alpha Ethinylestradiol, 2,5‐Hexanedione, or Carbendazim Following Short‐Term Dosing in Male Rats

Inhibin B Response to Testicular Toxicants Hexachlorophene, Ethane Dimethane Sulfonate, Di‐(n‐butyl)‐phthalate, Nitrofurazone, DL‐Ethionine, 17‐alpha Ethinylestradiol, 2,5‐Hexanedione, or Carbendazim Following Short‐Term Dosing in Male Rats

Development of a list of reference chemicals for evaluating alternative methods to in vivo fish bioaccumulation tests

Compound selection for in vitro modeling of developmental neurotoxicity

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