Substance Evaluation

Select Committee on GRAS Substances, Evaluation of the Health Mspects of Certain Silicates as Food Ingredients, SCOGS-61, NTIS Pb 301-402/MS, Federation of American Societies for Experimental Biology, Springfield, Va., 1979, p. 26. 

In spite of the great effort and advances made on in vitro testing, we are still far to have alternative methods robust enough to cover developmental, neurotoxic, reproductive, or carcinogenic potential for the substances evaluated. However the use of some distinct approaches may cover a great part of the potential toxic effects of some environmental pollutants. 

The instrumentation of REACH is differentiated and targeted to this complex regulatory field. And the waste phase, as shown, is explicitly subject to exposure scenario building, which in turn is the basis for substance evaluation and the resulting management measures to be derived. 

Environment Canada (2007) Existing substances evaluation. Substance profile for the challenge. Decamethylcyclopentasiloxane (D5). Chemical Abstracts Service Registry Number 541-02-6. http //www.ec.gc.ca/substances/ese/eng/challenge/batch2/batch2 541-02-6.cfm... 

The fom basic instruments for substance evaluation and hazard information can be... 

Evaluation is undertaken by the ECHA (see below) to evaluate testing proposals made by industry or to check compliance with the registration requirements. The ECHA will also coordinate substance evaluation by the authorities to investigate chemicals with perceived risks. This assessment may be used later to prepare proposals for restrictions or authorization. Substances with properties of very high concern will be made subject to authorization the ECHA will publish a list containing such candidate substances. Applicants will have to demonstrate that risks associated with uses of these substances are adequately controlled or that the socioeconomic benefits of their use outweigh the risks and there are no suitable alternative substitute substances or technologies. 

Stepanchikova AV, Lagunin AA, Filimonov DA, Poroikov W. (2003) Prediction of biological activity spectra for substances Evaluation on the diverse sets of drug-like structures. Curr. Med. Chem. 10 225-233. 

In Siemiatycki s (1991) population-based case-control study of cancer in Montreal, Canada (see monograph on dichloromethane in this volume), phenol was one of the substances evaluated 1% of the entire study population had been exposed to it at some time. Among the main occupations to which phenol exposure was attributed in this study were electric motor repairmen and foundry workers. The publication reported an association between phenol and pancreatic cancer (odds ratio, 4.8 90% CI, 1.8-12.7 n = 4) for no other site was cancer risk associated with phenol exposure. [The Working Group noted that detailed results for other sites were not provided, because they were based on small numbers, and that workers typically had multiple exposures.]... 

In the Montreal case-control study carried out by Siemiatycki (1991) (for details, see the monograph on dichloromethane in this volume), the investigators estimated the associations between 293 workplace substances and several types of cancer. 1,1,1-Tri-chloroethane was one of the substances evaluated. About 1% of the study subjects had ever been exposed to 1,1,1-trichloroethane. Among the main occupations to which... 

Drug discovery requires a host of inputs, new ideas, design and synthesis of substances, evaluation of preclinical toxicity tests in animals, clinical studies in human volunteers, permission to market the drug, postmarketing studies of safety, and comparison with other medicines. Drug development is highly technical and enormously expensive, with a success rate of 1 in 10,000 compounds. 

The substances evaluated for risk assessment were selected on the basis of potential concerns, areas of use, and volumes sold. Four priority lists were established.42 The risk assessments looked at the environmental and human health aspects of a chemical s use under a variety of scenarios. For each scenario, one of the following three conclusions was drawn 43... 

ECHA coordinates substance evaluations by the authorities to investigate chemicals with perceived risks. This assessment may be used later to prepare proposals for restrictions or authorization... 

In the substance evaluation, further information from industry may be requested to clarify suspicions of risks to human health or the environment, at the request of the Agency in coordination with the Competent Authorities of Member States. The Agency will develop guidance on the prioritization of substances for further evaluation. The Agency will publish information on its Web site to identify which Member States will carry out the evaluation on each priority substance. 

Leisewitz, A., et al., Chapter V, Summarized Substance Evaluation 2. Tetrabromobisphenol A (TBBPA), UBA Report 204 08 542, Substituting Environmentally Relevant Flame Retardants Assessment Fundamentals, Oko-Recherche, Frankfurt am Main, Germany, 2001. 

End November 2006, the number of ICCA substances evaluated and accepted by OECD the Screening information Data Set (SIDS) Initial Assessment Meetings (SIAMs) was 465 but in November 2007 it was close to 600. As the EU s new chemicals legislation, Registration, Evaluation, Authorisation and Restriction of Chemical substances (REACH) entered into force in June 2007, there is some concern about competition at European level with REACH requirements but it seems now that the data collected within the HPV programme would be recognised under REACH. 

The training dose of the comparator and saline are tested initially to confirm adequate stimulus control for testing. Thereafter, 4 different doses of the test substance are studied using a Latin Square design. On concluding test substance evaluation, the comparator and vehicle are tested again. 

Finally, CA and RA both apply algorithms that combine the results of single substance evaluations to produce an estimate of the mixture risk. The uncertainty in the estimate is a combination of the uncertainties in the individual components. Calculation rules for evaluating the overall uncertainty based on the uncertainties in the individual components are provided in Appendix 1. 

The Substance Evaluation process, in turn, rests on a near identical institutional configuration as the one formerly supporting existing substances prioritisation and... 

ECHA, in cooperation with EU Member State authorities, may request further information from industry on particular substances, when there are suspicions of risks for humans and animals. The costs for these procedures should be shared among registrants of the substance. Substance evaluation will be prioritized on the basis of risk following guidance developed by the ECHA. 

The complete list of agents and chemical substances evaluated by the I ARC and their classifications is available in lARC Monographs, volumes 1-98. ... 

Complementary Medicines Evaluation Committee (CMEC). The CMEC was established in 1997 a Traditional Medicines Evaluation Committee (TMEC) had been established by the Minister to provide expertise for the evaluation of non-prescription traditional medicines and advice on their registration. Whereas ADEC and MEC had a long history prior to the enactment of the Therapeutic Goods Act, 1989, there was no committee to handle traditional and alternative medicines which came under regulation for the first time with this Act. Although the TMEC was not a statutory committee, its role was to advise on quality and manufacture of traditional and alternative medicines, their pharmacognosy and toxicology and their clinical use. In practice, the committee formed a broad advisory role rather than a substance-by-substance evaluation role. 

No induction observed The substance evaluated is not an enzyme inducer if P450 inhibitory and cytotoxic potential are eliminated as confounding factors. 

Induction observed The substance evaluated is observed to cause dose-dependent and physiologically significant induction (e.g., induced activity over twofold of negative control activity). If the doses found to be positive are within clinical plasma concentrations (e.g., within lOx of plasma Cmax), in vivo studies may be needed to further define the test article s in vivo enzyme induction and the subsequent drug-drug interaction potential. 

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