Toxicological considerations chemical substances, exposure

Galer, D. M., Leung, H.-W., Sussman, R.G. and Trzos, R.J. (1989). Scientific and practical considerations for developing occupational exposure limits for chemical substances. Presentation to the Second Annual Occupational Toxicology Roundtable, November 21, 1989, Rahway, New Jersey. 

Tiered approaches to dermal exposure and risk assessment have been developed (OECD, 1997 de Heer et al, 1999 Harney, 2000 EC, 2002). Although the number of tiers differ depending on the specific approach, common to all approaches is the sequential refinement of the value used for dermal absorption in the risk assessment. For example, in a Tier 1 risk assessment, a conservative value of 100 % dermal absorption is often used. If required, a more refined default may be justifiable, based on a number of considerations such as the physico-chemical properties of the substance and the toxicological database. Use of dermal absorption data would be the third tier. Biological monitoring data would be a potential fourth tier, if required. 

The hazard assessments for SCCPs and MCCPs have shown that these structurally very similar substances also have very similar hazard profiles. Both substances have a similar potency (i.e. NOAELs of the same order of magnitude) (see EU RARs on SCCPs and MCCPs) target organs in mammals include the liver, kidney and thyroid. Reth et al. [52] have measured MCCPs in two arctic bird species at concentrations somewhat exceeding the ones of SCCPs. As noted in Annex E, the risk profile can include consideration of toxicological interactions involving multiple chemicals , which in this case would be to consider the combined risk from exposure to both SCCPs and MCCPs. Therefore, the present risk profile could underestimate the risks from SCCPs in the presence of MCCPs. 

The term binding occupational exposure limit value (BOELV) was introduced in article 3,4 of the chemical agents directive 98/24/EC. This type of Hmit is established in accordance to J 118 a of the European Treaty and is Hsted in the annex of this directive. According to the procedure for incorporation of limit values into national laws, the EU member states are required to adopt a national occupational exposure limit, which may be equal to or below the Hmit, but not higher than the BOELV. The procedure for establishing BOELV is quite complicated. Besides the toxicological properties, feasibility plays an important role. This includes technical aspects as well as considerations of the excess risk at estimated exposure levels. The acceptable-risk approach for genotoxic substances requires intense discussions on socio-economic factors between aU interested parties. 

An important aspect of toxicological chonistry that relates chemical structure to toxic effects is the QSAR. Increasingly, sophisticated computerized calculations of QSAR are leading to predictions of the effects of toxic substances and can play an important role in determining the avoidance of exposure to toxic substances in the practice of green chemistry. The following are chemical features of substances that may be indicative of toxic effects and that may be taken into consideration in doing QSAR calculations ... 

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