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REACH PRS 143825
ECHA list of pre-registered substances
On 19 December 2008, ECHA published a list of about 150,000 substances which had been pre-registered by 65,000 companies in the EU between 1 June and 1 December 2008. Last updated 10 May 2016
Reach Registrations
Chemicals registered under REACH.
Source: European Chemicals Agency. Last updated 02.05.2018
Candidate List of Substances of Very High Concern
This list contains the substances under the REACH procedure that have been identified as Substances of Very High Concern and have been included in the Candidate List. This inclusion is the first step of the authorisation procedure. Companies may have immediate legal obligations following such inclusion which are linked to the listed substance on its own, in preparations and articles. Further documentation or more detailed information on the identification process of substances of very high concern can be found on the web pages of ECHA

EU Research Projects
SEURAT-1 Gold Compounds
Mechanism-Based Selection of Reference Compounds for Toxicity Testing Procedures for the SEURAT-1 research cluster. The SEURAT-1 cluster is addressing hepatic, cardiac, renal, neuronal, muscle, and skin toxicities. The compound selection strategy to date has been developed only for hepatic and cardiac toxicities, and will be expanded with time to other tissues. By agreement across the cluster, carcinogenicity and mutagenicity are excluded from consideration.
Reference chemicals used in the PREDICT-IV FP 7IP to evaluate drug-induced toxicity using non animal-based approach integrating toxicodynamics and biokinetics
The chemicals are relevant for three organs toxicity testing: liver, kidney and central nervous system
Compound selection for in vitro modeling of developmental neurotoxicity
The list is serving the development of a test battery analysing different critical windows during prenatal neural cell differentiation
ACuteTox 124
Reference chemicals used in the FP6 Integrated Project ACuteTox
The main goal of this integrated project funded by EU 6FP, was to develop, optimise and prevalidate a simple and robust non-animal testing strategy for predicting human acute oral toxicity and for classification and labelling of chemicals into the four EU CLP acute oral toxicity categories and the non-classified. The project was set up in two phases and 124 reference chemicals were tested.
DG ENV EDS Database
DG-ENV ED DB containes compounds that corresponds to the priority list of chemicals developed within the EU-Strategy for Endocrine Disruptors. The DB contains in vitro, in vivo and human toxicological data, for both human health and the environment, published until the 2007
FP6 ReProTect 133
Test chemicals used for the development of in vitro tests within the FP6 project .ReProTect
The list was created for test developers participating in the FP 6 project ReProTect. This list contains more than 130 reproductive toxicants covering different target cells and toxicological mechanisms. The substances have been selected according to predefined criteria and were independently peer reviewed.
CarcinoGENOMICS 34
Test chemicals used for the development of in vitro carcinogenicity tests during the FP6 project carcinoGENOMICS.
This chemical list includes three chemical classes: genotoxic carcinogens, non-genotoxic carcinogens and non-carcinogens. The chemicals have been selected according to predefined criteria. In the selection of these chemicals, target organ carcinogenicity was also considered.

International Research Projects
DNT list 71
A database of developmental neurotoxicants
Chemicals on this list were derived from published reports or regulatory data from humans, non-human primates, or laboratory mammals. Findings were deemed to be suggestive of adverse neurological outcomes following developmental exposure. To be included on the list there must be positive results from more than one laboratory (Mundy et al., 2009).
Compound Cytotoxicity Profiling Using Quantitative High-Throughput Screening
The National Toxicology Program and the National Institutes of Health Chemical Genomics Center are collaborating to identify a battery of cell-based screens to prioritize compounds for further toxicologic evaluation. A collection of 1,408 compounds previously tested in one or more traditional toxicologic assays were profiled for cytotoxicity using quantitative high-throughput screening (qHTS) in 13 human and rodent cell types derived from six common targets of xenobiotic toxicity (liver, blood, kidney, nerve, lung, skin). Selected cytotoxicants were further tested to define response kinetics.
US EPA ToxCast list - phase I
The US EPA's ToxCast program aims to address concerns over animal use and the thousands of environmental chemicals lacking toxicity data by screening and prioritizing chemicals for potential human toxicity using in vitro assays and in silico approaches. During Phase I, 309 environmental chemicals (mostly pesticides were screened) using 500 in vitro assays
US EPA ToxCast list - phase II
The US EPA's ToxCast program aims to address concerns over animal use and the thousands of environmental chemicals lacking toxicity data by screening and prioritizing chemicals for potential human toxicity using in vitro assays and in silico approaches. During Phase II, 700 additional chemicals are being screened, including drugs, green chemicals, and chemicals in consumer products.
TOX21 LIST1 8198
Tox21 Chemical Inventory for High-Throughput Screening
Tox21 is a collaboration among multiple federal Agencies -- EPA's National Center for Computational Toxicology, the National Institutes of Environmental Health Sciences (NIEHS)/National Toxicology Program (NTP), the National Institutes of Health/National Human Genome Research Institute/NIH Chemical Genomics Center (NCGC), and the U.S. Food and Drug Administration (FDA) - working together to develop, validate and translate innovative, high-throughput screening (HTS) chemical testing methods to characterize key steps in toxicity pathways. The goals of the .Tox21 Community. are to investigate the use of these new tools to prioritize substances for further in-depth toxicological evaluation, identify mechanisms of action for further investigation, and develop predictive models for in vivo biological response. The full Tox21 chemical inventory is currently undergoing screening (as of Nov 2011) at the NCGC's Tox21 HTS Robotics Facility . All HTS assay results are to be publicly released after quality review through various public database venues (EPA ACToR, NIEHS CEBS, NCGC Tox21 Browser, and PubChem). In addition, all parent Tox21 solution plates are undergoing analytical QC (LC MS and follow-up GC MS) in association with testing to assess compound sample purity, identity, concentration, and stability. The Tox21 effort represents the largest and most comprehensive evaluation of the interaction of a wide range of environmental and commercial chemicals with putative and known toxicity pathways. The effort is helping to pave the way for the use of HTS tools in hazard identification, chemical prioritization, and risk assessment. For further information on the Tox21 HTS testing program, see Source Websites.
The Virtual Liver Project: Modeling Tissue Response To Chemicals Through Multiscale Simul
The Virtual Liver Pilot Chemical list consist of matrix of chemicals spanning ToxCast Phase I from two categorizations: a) the in vitro assay results for the 309 chemicals in ToxCast. Phase I can be grouped into seven broad clusters of human nuclear receptor activity, spanning from promiscuous, highly active compounds to compounds with minimal or no activity among any assay and b) a subset of these chemicals can be organized by observed hepatic lesions in chronic rodent toxicity studies (ToxRefDB), with some compounds showing progression toward lesions in both rats and mice, some being species specific, and some having no observed effect in either. To these chemicals EPA add a list of 7 well-known hepatic toxicants, including paracetamol and phenobarbital, for a total of 29 compounds
Japanese TGx project 132
TG-GATEs (Genomics-Assisted Toxicity Evaluation System developed by the Toxicogenomics Project in Japan)
The Toxicogenomics Project (TGP) has established a large-scale toxicogenomics database known as TG-GATEs The primary goal of the TGP was to create a gene expression database by using the Affymetrix GeneChips of 150 chemicals, mainly medical drugs and the main target organ was the liver. The TGP was completed in 2007. The entire system consists of a database, an analysis system, and a prediction system and is named as TG-Genomics-Assisted Toxicity Evaluation System.

Method Validation
Reference chemicals used in the NICEATM/ECVAM validation study of the Neutral Red Uptake (NRU) basal cytotoxicity assay
The NICEATM/ECVAM Validation Study of the Neutral Red Uptake (NRU) basal cytotoxicity assay assessed the accuracy of the standardised in vitro cytotoxicity test methods for estimating rodent oral LD50 values across the five United Nations Globally Harmonized System of Classification and Labelling of Chemicals categories of acute oral systemic toxicity, as well as unclassified toxicities. 72 chemicals were tested in three laboratories using two standard cell systems: a human cell system (normal human keratinocytes, NHK) and a rodent fibroblast cell line (BALB/3T3).
OECD validation study of the zebrafish embryo acute toxicity test
These 20 chemicals were used to assess the reproducibility of the zebrafish embryo acute toxicity test.
Reference chemicals used in NICEATM BG1Luc Estrogen Receptor Transactivation Assay validation study
This list proposes chemicals for validation studies for estrogen and androgen binding and transactivation assays. It has been compiled by NICEATM in 2003 and revised in 2006.
Reference chemicals used in the ECVAM validation study of the 3T3 NRU basal cytotoxicity assay to identify non-classified chemicals on the basis of the 2000 mg/kg b.w. threshold.
The aim of this ECVAM Validation Study was to assess the capacity of the 3T3 Neutral Red Uptake (3T3 NRU) basal cytotoxicity assay to identify substances not requiring classification for acute oral systemic toxicity according to the EU Classification, Labelling and Packaging system (CLP) (i.e. oral LD50 > 2000 mg/kg). 56 chemicals were tested
CTA Carcinogenicity 8
ECVAM prevalidation study on cell transformation assays for carcinogenicity
Chemicals selected in the ECVAM study on three cell transformation assays (CTAs) using Syrian Hamster Embryo Cells (SHE) and the BALB/c 3T3 Mouse Fibroblast Cell Line for In Vitro Carcinogenicity Testing
In vitro genotoxicity 71
Updated recommended lists of genotoxic and non-genotoxic chemicals for assessment of the performance of new or improved genotoxicity tests
This list has been first established following a recommendation made at the ECVAM workshop on ways to reduce the frequency of irrelevant positive results in mammalian cell genotoxicity tests1. It was considered important to identify chemicals that could be used in the evaluation of modified or new assays. In light of newly available data, the JRC's European Union Reference Laboratory for Alternatives to Animal Testing (EURL ECVAM), together with a group of experts, has revised its recommended list2 of genotoxic and non-genotoxic chemicals for assessing the performance of new or improved in vitro genotoxicity test methods. Recommendations were made to fit three different sets of characteristics: Group 1: chemicals that should be detected as positive in in vitro mammalian cell genotoxicity tests; Group2: chemicals that should give negative results in in vitro genotoxicity tests and routinely do give negative results in existing in vitro mammalian cell genotoxicity tests; Group 3: chemicals that should give negative results in in vitro mammalian cell genotoxicity tests, but have been reported to induce chromosomal aberrations or tk mutations in mouse lymphoma cells, often at high concentrations or at high levels of cytotoxicity.
Prospective validation study on RhE test methods (EpiSkinTM, EpiDermTM SIT and SkinEthicTM RHE) for skin irritation
"The selected chemicals had been taken from one of four different source databases, the New Chemical Database (NCD) of the European Chemicals Bureau (ECB), the ECETOC database for skin irritation (ECETOC, 1995; Bagley et al., 1996), the TSCA (Toxic Substances Control Act) database and the Cosmetics Ingredients Review (CIR) compendium." "Forty-two of the chemicals had been tested repeatedly in one laboratory per in vitro test in the optimisation phase (Kandarova et al., 2005; Cotovio et al., 2005). The remaining 58 chemicals were tested blind in a multi-laboratory (three laboratories per test) design in the ECVAM Validation Study for Skin Irritation (Spielmann et al., 2007; Eskes et al., 2007)."
Chemicals for the Development and Evaluation of In Vitro Methods for Skin Sensitisation Testing
This list of chemicals is the result of a collaborative effort between ECVAM and Colipa (now Cosmetics Europe) aimed to define a set of core reference substances to be used for the development/optimisation of in vitro methods for skin sensitisation. Inclusion of chemicals into the list was based on predefined criteria. The list consists of 8 sensitisers, 4 chemicals requiring activation to act as sensitisers, 4 negative chemicals.

JRC Projects
JRC Acute Systemic Toxicity 180
The use of computational and in vitro methods for acute systemic toxicity prediction
Information on the acute mammalian toxicity of chemicals, referring to the adverse effects caused by either a single exposure to a chemical substance or multiple exposures within 24 hours, is required under multiple pieces of EU legislation aimed at protecting consumers and workers. Presently all regulatory methods for determining acute oral toxicity are based on animal tests.
Alternatives to animal experiments are being sought, and regulatory frameworks are providing an opportunity or obligation to use such methods. Most of these alternatives are based on in vitro test methods or computational models such as Quantitative Structure-Activity Relationships (QSARs).
A JRC study used a reference dataset of 180 compounds for which in vitro and in vivo data were already available from international validation studies in order to assess the abilities of five alternative approaches to predict acute oral toxicity.
ECVAMes Positives List 723
ECVAM Ames Positives List: EURL ECVAM Genotoxicity and Carcinogenicity Database of Ames Positive Chemicals
This list of 726 chemicals derives from the EURL ECVAM database of curated in vitro and in vivo genotoxicity and carcinogenicity data for Ames positive chemicals, that was compiled from a variety of sources: EU and international regulatory agencies, industry and scientific literature databases. The database is intended to aid in the development and evaluation of alternative approaches to animal testing. It has already been used to evaluate the predictivity of the in vitro Ames test for in vivo genotoxicity and carcinogenicity when used alone or in combination with in vitro assays based on mammalian cells, and for a better characterisation of those cases where the Ames test leads to misleading ('false positive') results (Kirkland et al., Mutation Research, Volumes 775.776, Pages 69.80, 2014).
JRC ADME - Human bioaccumulation potential and human and rat metabolic stability and metabolite identification
A comparative study of rat and human in vitro metabolising systems (microsomes versus homogenates) on a set of 55 chemical compounds has been carried. The goals of the project were to characterise, with human and rat liver homogenate or microsomal preparations, the metabolic stability (i.e. disappearance of the parent substance from incubations with human liver preparations and appropriate cofactors for metabolism) and the appearance of metabolic products and their tentative identification.
In addition, a generic PBTK model has been developed which, based on human in vitro liver metabolism data, minimal renal excretion and a chronic exposure, is able to assess the bioaccumulative potential of a chemical. The approach has been analysed using literature data on well-known bioaccumulative compounds (PCBs, DDT, PFOS), liver metabolism data from EURL ECVAM database and a subset of the ToxCast phase I chemical library - in total 94 compounds including pharmaceuticals, plant protection products and industrial chemicals.
Hepatotox list
A list of reference chemicals that we are using for in-vitro hepatotoxicity testing with HepaRG cells (HTS/HCA-Imaging). Info on physico-chemical properties and toxicity data (MoA as available)
Skin Sensitisation 269
Skin Sensitisation Dataset
The skin sensitisation dataset consists of information on 269 organic chemicals that was used by EURL ECVAM to develop a consensus model of two classification trees for skin sensitisation hazard prediction (i.e. sensitisers versus non-sensitisers) (Asturiol et al., 2016). Information reported in the dataset includes: name and SMILE of the chemicals, human skin sensitisation classification (1 to 6 categories), NOEL values (µg/cm2) (Basketter et al., 2014), human GHS derived classifications (1A, 1B, NS), the LLNA EC3 values obtained from different sources with a corresponding final call for those cases in which multiple LLNA studies were available for the same chemical, and the readouts from the in chemico (Direct Peptide Reactivity Assay) and in vitro methods (KeratinoSens™ and human Cell Line Activation Test (h-CLAT)). Binary descriptors indicating positive or negative predictions for each of the methods and the LLNA skin sensitisation hazard are also included in the dataset. In addition, the values of DRAGON and TIMES-SS descriptors used in the consensus model, a column indicating the use given to each chemical for each tree (i.e. training set, test set, or external test set), and the final consensus model predictions with the corresponding qualitative confidence measures are reported.

EDC SIN List 2.0 22
Substitute It Now List 2.0
The SIN (Substitute It Now!) List is an NGO driven project. The 2.0 version of the SIN List adds 22 new substances - all identified as Substances of Very High Concern solely due to their endocrine disrupting properties. This in accordance with REACH article 57f, the equivalent concern criteria