Regulatory assessment of chemical

Based on the outcome of two OECD workshops (in 2003-2004), strategies concerning the future application of toxicogenomics in regulatory assessment of chemical safety are being developed by some OECD member countries (OECD 2007a). 

The use of QSARs for the regulatory assessment of chemicals is very limited, mainly because there is widespread disagreement on the possible applications of QSARs and the extent to which QSAR predictions can be relied upon. To address the credibility problem of QSARs, it will be necessary to obtain international agreement on acceptability criteria for the development and validation of QSARs, and to apply the criteria in the context of a formal framework that guarantees independence in the selection, confirmation, and validation of QSARs. 

The regulatory assessment of chemicals involves one or more of the following procedures (1) hazard assessment (which includes hazard identification and dose-response characterization), possibly leading to classification and... 

There is a continuing interest in the development of biomarker assays for use in environmental risk assessment. As discussed elsewhere (Section 16.6), there are both scientific and ethical reasons for seeking to introduce in vitro assays into protocols for the regulatory testing of chemicals. Animal welfare organizations would like to see the replacement of toxicity tests by more animal-friendly alternatives for all types of risk assessment—whether for environmental risks or for human health. 

The potential for a compound to induce carcinogenicity is a crucial consideration when establishing hazard and risk assessment of chemicals and pharmaceuticals in humans [53]. To date, the standard approach to assess carcinogenicity at a regulatory level is the 2-year bioassay in rodents. According to the recent REACH... 

During the last 10 years it has been attempted to develop in vitro methods as alternative methods in the study of effects where animal models have previously been necessary. Such effects include skin and eye irritation and specific organ damage. Validation programs have been launched, and some of the above-mentioned methods have been sufficiently validated for use in regulatory risk assessment of chemical substances and may now for certain purposes be used as stand-alone evidence. Results from nonvahdated methods can in some cases be used as supportive evidence to human and animal data. 

In Chapter 10 1 consider how assessments of chemicals for their riskiness could fit into a regulatory system. But first I turn to the ethical and political presuppositions of risk-based regulatory systems. Why is there such an insistence that regulation be risk-based ... 

Greiner, P. 1993. Ecotoxicology and environmental hazard assessment in the regulatory framework of chemical control in the EEC. In Chemical Exposure Predictions, Ed. D. Calamari, pp 205-219. Lewis, Boca Raton, FL. 

All QSARs should be associated with a clear scientific and regulatory purpose. A possible outcome of the peer-review step is the recommendation that the validated QSAR should be considered for inclusion into a regulatory framework. In such a case, the recommendation, and all of the supporting evidence, should be forwarded to the appropriate regulatory body (or bodies) for consideration. In the EU, if the QSAR is considered suitable for the assessment of chemicals, deliberations take place at a technical level by the National Coordinators for Testing Methods, and subsequently, a decision is taken at the policy level by representatives of the EU Competent Authorities for Directive 67/548/EEC. 

This section gives a nonexhaustive overview of the regulatory state of the art on human risk assessment of chemical mixtures in the United States, the European Union (EU), and other nations and (international agencies. The focus is on regulations for environmental pollution, but when available and relevant, mixture regulations from other policy areas have also been included in the overview, for example, for food quality and the workplace. The reader is referred to McCarty and Borgert (2006) and Monosson (2005) for a more extensive overview of mixture toxicity regulations related to human health. 

Ecological risk assessment of chemical mixtures thus has to deal with a variety of field phenomena, a possible range of assessment endpoints, and a variety of assessment approaches. Moreover, there exists a huge variety in the regulatory questions and problem formulations addressed in ecological risk assessment of chemical mixtures. Examples include the protection of specific species against well-defined mixtures (like PCBs and PAHs), the protection of an undefined concept like the ecosystem, and retrospective assessments for highly or diffusely contaminated systems. 

Risk assessment is performed for the purpose of risk management, and regulatory testing of chemicals is performed for the purpose of such risk assessment. Therefore, our discussion must start with risk management. We need to ask What should be the criterion for risk management decisions on the use of chemicals Only when at least a tentative answer to that question is available is it possible to determine what demands to put on risk assessment and on data acquisition for risk assessment. 

For certain types of toxic effea, notably cancer, some scientists believe that there is no threshold, and that the dose-effect graph would look like Graph A in Figure 29. As some chemicals cause cancer by reacting with the DNA molecule in cells, in theory one molecule of chemical would be enough to cause an effect. This notion probably arose from experiments with isolated cells exposed to radiation, but some regulatory authorities, in the USA for example, base their risk assessment of chemicals on this assumption. 

F. Lu, Safety Assessments of Chemicals with Thresholded Effects, Regulatory Toxicology and Pharmacology, 3, 121-132 (1985). 

As can be expected, some chemicals are data-rich while others are data-poor. Often they are data-poor, especially for chemical mixtures where the data may be adequate, barely adequate or nonexistent for a specific mixture. Thus limited methods are available for the toxicity assessment of chemical mixtures [1,9]. Even though there are various uncertainties and assumptions embedded in these methods, the following three approaches have gained acceptance by the regulatory agencies and the regulated community for risk assessment of mixtures of industrial, occupational, and environmental chemicals. The method employed is on a case-by-case basis, it depends on the exposure scenario and the quality of available data on exposure and toxicity. 

Assessment of chemical risks in the Indian context and anticipatory action for abatement by regulatory agencies have been taken up as follows ... 

According to Mercier of the IPCS The proliferation of groups undertaking toxicological evaluation and safety assessment of chemicals today is a fact that is looked upon by national regulatory authorities, as well as industry, since the point of these evaluations often diverge from one another [6]. 

As mentioned in the introduction, the first regulatory provisions which took into account the risk assessment of chemical plant protection products on bees started in 1956. They were progressively modified, leading to the publication of the July 5 1985 Decree [11], which modified the February 25 1975 Decree [12], and which is still in force. 

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