Risk assessment dermal absorption estimates

How Dermal Absorption Estimates Are Used in Risk Assessment... 

HOW DERMAL ABSORPTION ESTIMATES ARE USED IN RISK ASSESSMENT... 

Generally, the main pathways of exposure considered in tliis step are atmospheric surface and groundwater transport, ingestion of toxic materials that luu c passed tlu-ough the aquatic and tcncstrial food chain, and dermal absorption. Once an exposure assessment determines the quantity of a chemical with which human populations nniy come in contact, the information can be combined with toxicity data (from the hazard identification process) to estimate potential health risks." The primary purpose of an exposure assessment is to... 

Risk assessment and epidemiology could be successfully combined to analyze environmental health risks. Exposure assessments estimate concentrations of toxic chemicals in the environment that could be transferred to humans by ingestion, inhalation, or dermal absorption. In the future, there will be a greater need for agreement on how best to simultaneously assess societal risks involved with damage to both ecosystems and the human population (Ruttenber, 1993). 

Until very recently the risks associated with different types of chemicals such as food additives, pesticides, environmental contaminants and natural constituents of food were assessed and managed separately. However, a particular substance might fall into two or more of these categories and so the opportunity for simultaneous exposure might be overlooked. Furthermore, exposure to a chemical could occur through diet, drinking water, air pollution or dermal absorption. Aggregate exposure assessment aims to take all of the possible sources and routes of exposure into account in a realistic manner and thereby obtain a better overall estimate of risk. Initiatives have been set up in both the... 

This model has a straightforward structure aud is simple to use. It is based on exposure studies carried out for registration purposes. In addition, it has relatively small databases for two out of three formulations and for downward applications with tractor-mounted equipment. It covers the full range of the risk assessment process, i.e. dermal absorption and a comparison of estimated exposure and tolerable exposure. Exposure reduction coefficients are presented for several important exposure reduction measures. 

The route of exposure is another aspect of exposure in which health-relevance must be considered. In Section One of this book, there is a detailed discussion of exposure assessment methodologies, including the importance of identification of the most prevalent route of exposure (dermal, inhalation or oral) and the necessity of knowing the absorption of the pesticide to allow calculation of the absorbed dose for risk assessment. For epidemiological purposes, exposure-assessment smdies are usually limited to assessing contact exposure levels. Since dermal absorption is not known for many pesticides or complex mixtures, uptake through the dermal route can often not be estimated and contact exposure data are a poor proxy of internal exposure (absorbed dose) (Schneider et al., 1999). 

In order to assess risk to individuals following dermal exposure to a pesticide, dermal absorption data are often required to convert dermal deposition data to estimates of systemic exposure. These estimates of systemic exposure are then compared with the No Observed Adverse Effect Levels (NOAELs) from oral toxicity studies or limit values (for instance. Acceptable Operator Exposure Levels (AOELs)) derived from these oral data (Bos et at., 1998 Rennen et al 1999). As noted in the introduction, oral studies are generally used because the toxicology database is typically focused on the oral route of exposure. 

An oral ADME (absorption, distribution, metabolism, excretion, following oral administration of the pesticide) study may also be of utility in refining the risk assessment. If a default value for dermal absorption of 100 % is applicable based on the physico-chemical properties of a substance and an appropriate oral ADME study is available, the results of this study may be used to refine the default value for dermal absorption. It is required that the oral absorption is determined at low dose levels in experimental animals, in order to obtain an accurate estimate of the oral absorption. Based on theoretical grounds and supported by a comparison of oral and dermal absorption data available for twelve pesticides, it is assumed that dermal absorption will not exceed oral absorption (Hakkert et al unpublished data). 

Because risk is principally a function of usage or exposure, any form of assessment should only be based on experimental protocols that reproduce demographic use of the product in question. In dermal risk assessment, it is important that any estimation of skin absorption take into consideration the likely amount, extent, and duration of exposure that would occur in use (see, for example, Barlow et al., 2001). These parameters are readily controlled during in vitro experiments, and certainly the amount of product applied has been the subject of considerable guidance. There are several published recommendations on both the expression of dose levels and the specific quantities involved. The FDA/AAPS guidelines (Skelly etal., 1987)... 

These exposure estimates are not sufficient of themselves to define the amount of chemical Inhaled, absorbed or Ingested by the worker. The dose received by the worker Is also dependent on Intake and absorption factors such as breathing rate and dermal absorption rate. All of these factors must be considered for comparison of the estimated dose to the toxicity data In a risk assessment. Although these factors are often chemical specific, the exposure value, as we have defined It, Is not. We are therefore limiting our proposal to Include only worker exposure values which are free of chemical specific biases. 

Recently some emphasis has been placed on obtaining exposure data on each Individual compound under consideration. These studies can be costly In both time and money. In some cases they are not even a major factor In the judgement of risk simply because the toxicity and/or dermal absorption values are very low. In other cases the uncertainty of using exposure estimates from small sample groups compromises the risk assessment. Addressing these problems requires some form of data management. 

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