Toxicological considerations occupational 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. 

There is considerably less information available on the toxicology of HDl after oral exposure compared to the data available on the inhalation toxicology of HDl discussed in the previous section of this profile. Clearly, inhalation is the major route of occupational exposure to HDl however, given exposure routes such as the lung mucocilliary clearance pathways, a very small amoimt of HDl could eventually enter the gastrointestinal tract and be presented for absorption, with possible systemic effects. Most of the information available on the oral absorption of HDl is about relatively large doses of HDl administered to laboratory animals, with no information located on the health effects of HDl in humans after oral exposure. 

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. 

Professional literature should be reviewed. Manuals of analytical methods ( 1,2) describe various sampling scenarios and considerations. Overview references (3) discussing processes similar to the one proposed for study may also be available. Professional publications e.g., The Journal of the American Industrial Hygiene Association, Journal of Occupational Medicine, may outline specific aspects of the process to be studied. Toxicological texts (4,.5,.6 7) provide information about potentially hazardous agents. These sources can provide information about the character of exposure, and their relative expected concentration or intensity, and methods previously used for detection, sampling and analysis. 

The book provides a short, authoritative overview of the information available on the occupational toxicology of many important chemical exposures. Consideration of reproductive and developmental toxicology is limited. 

From both operational and occupational perspectives there is a requirement to study the effects of RCAs initially by short-term repeated exposures in order to determine the potential for cumulative toxicity. The need for subchronic and combined chronic/oncogenicity studies depends on a broad spectrum of considerations with decisions made on a case-by-case basis (Ballantyne, 1999c). The wide range of factors includes exposure patterns, nature and biological reactivity of the RCA, genetic toxicology, suspect biological activity and sociopolitical demands. 

If an excess number of deaths due to cancer are observed, a detailed review of medical and occupational records is undertaken for each individual whose death was ascribed to cancer in an attempt to investigate a possible association between these deaths and exposure to the product. We take into consideration the employment history prior to joining the company, the interval between exposure and death, cumulative exposure to the product and length of exposure, the toxicology of the other substances in the workplace and the nature of the illness. 

The neurotoxicological and neuromechanistic evidence for adverse effects in adult human populations is considerably less complete and more fragmentary than for children. This comparative status of adults versus children exists despite adult exposures, mainly in occupational settings, having been the first area of interest for health science investigators. The reasons are many and understandable. These are the objective comparative toxicological and... 

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