Risk assessment aggregate and cumulative

The MOE approach is often used to determine the acceptability of acute risks for single chemicals and MOEs of >100 or >10 are usually considered acceptable when derived from toxicological data from animal and human studies, respectively. The US-EPA favors this concept for performing aggregate and cumulative risk assessments (Whalan and Pettigrew 1997). 

Probabilistic Approaches to Aggregate and Cumulative Risk Assessment... 

Probabilistic risk assessment methods are used to incorporate uncertainty and variability into both aggregate and cumulative risk assessments. Herein, uncertainty refers to lack of knowledge or the limitations in the current state of knowledge. For example, the dermal permeability of a pesticide may not be known with certainty. Variability, on the other hand, refers to a value that differs from one individual to another individual in a population or from one instance to another. For example, the number of apphcations of a residential pesticide in a year may vary from one individual to another. Probabilistic methods use probability distributions to incorporate uncertainty and variability into both aggregate and cumulative risk assessments. 

Probabilistic risk assessment methods are described herein for determining a popnlation s distribution of the dose from exposure and the combination of that exposnre characterization with appropriate toxicological information to form aggregate and cumulative risk assessments. An individual s dose from exposure is characterized as a set of chemical- and route-specific dose profiles over time. Toxic equivalence factors (TEFs) that reflect the toxic endpoint and exposure duration of concern are used to scale chemical- and route-specific doses to toxic equivalent doses (TEDs). The latter are combined in a temporally consistent manner to form a profile over time of the Total TED. For each individual, a Total MOE is calculated by dividing a toxicologically relevant benchmark dose (e.g. an EDio) by the individual s Total TED. The distribution of the Total MOE in a popnlation provides important information for risk management decisions. 

OCCUPATIONAL AND RESIDENTIAL RISK ASSESSMENT 371 AOELs Versus MOEs 371 Route Considerations 372 Uncertainty and Safety Factor Selection 372 Aggregation and Cumulative Risk Assessment 372 CO-OPERATIVE REGULATORY ACTIVITIES 373 SUMMARY AND CONCLUSIONS 374 Terminology 374 Framework 374 Data Requirements 374 Methodological Guidance 375 Development and Utility of Databases 375 Modeling Initiatives 375 Data Analysis 375 Metric Selection 376 Research Needs 376 Exposure Mitigation 376 Risk Assessment 376 REFERENCES 376... 

Co-ordinated method development for aggregate and cumulative risk assessment. 

The cumulative assessment for endpoint (1) combines only those chemicals and routes that are associated with endpoint (1) via a common mechanism and incorporates only those No Observed Adverse Effect Levels (NOAELs), benchmark doses, uncertainty factors, etc. associated with endpoint (1). A similar cumulative assessment would be carried out for endpoint (2). Guidance on aggregate exposure and cumulative risk assessment has been recently published (USEPA, 2003). 

Cumulative risk assessments evaluate the health risk for aggregate exposures accumulated over time and for multiple contaminants or stressors. In some contexts (e.g. USEPA pesticide risk assessments), cumulative refers specifically to combined exposures to chemicals that share a common mechanism of toxicity (see http // www.epa.gov/oppsrrdl/cumulative/). Populations may be defined by their location relative to sources, their activities and customs, and their susceptibility to exposures. In this context, populations can include different ethnic groups, different communities, or different age groups. Cumulative risk is a very important concept in understanding environmental health risks to children in different settings, particularly in underdeveloped countries where children may be facing multiple stressors. 

LifeLine Group (2005) Aggregate and Cumulative Exposure and Risk Assessment Software, Version 4.3. Annandale, VA, The LifeLine Group, Inc. (http // www.thelifelinegroup.org/index.htm software accessed 5 May 2005). 

For classes of pesticides that cause their toxic effects through a common mechanism of toxicity, the non-occupational exposures to all members of the class have to be aggregated and used in a cumulative risk assessment. In 2003, the United States Environmental Protection Agency (USEPA) published a framework outlining how cumulative risk assessments should be conducted. There is no question that this approach has provided significant challenges to toxicologists, exposure assessors and risk assessors. Much of the developmental work on how to conduct... 

The need for aggregate and cumulative non-occupational exposure assessments, and lower reference doses for all assessments, means that some pesticides will fail lower-tier risk assessments and without more refined exposure data they might even fail higher-tiered assessments. For example, in North America many of the residential uses of the OPs have been discontinued as a result of the aggregate risk assessments. As a result, there has been increased emphasis on gathering better toxicology and exposure data to reduce the conservatisms that are contained in the current system. 

This chapter describes and illustrates probabilistic approaches to aggregate and cumulative assessments of exposure, dose and risk. Aggregate assessments account for multiple sources (e.g. food, water, residence and occupation) and multiple routes (ingestion, dermal and inhalation) of exposure for a single pesticide. Cumulative assessments combine exposures for chemicals that share a... 

This chapter illustrates probabilistic approaches to residential and occupational exposnre assessment and their incorporation into aggregate and cumulative assessments of exposure, dose and risk. 

The next step in the fields of exposure and risk assessment is simulation modeling. Simulation models of exposure and risk have been developed in recent years by the US EPA, industry trade associations, private firms, nonprofit organizations, and academia to answer a need, the obligation to understand aggregate and cumulative exposure. 

The Food Quality Protection Act (FQPA) of 1996 mandated that the US EPA carry out risk assessments that consider the cumulative effects of exposure to pesticides having a common mechanism of toxicity, as well as consider exposure to each pesticide by various routes of exposure (e.g., dermal, dietary, inhalation) and sources (e.g., residues in food and water) in an aggregate manner [19]. To accomplish this, there needs to be sufficient evidence supporting a common adverse effect that is associated with a common mechanism of action in specific target tissues. To date, the required criteria necessary to establish a common mechanism of toxicity with a specific toxic effect for the pyrethroids are not available [1,8,98]. 

Until recently, most risk assessments focused on a single pesticide, considered each route separately, and evaluated each separately. Aggregate assessments consider a single pesticide but combine multiple routes and multiple sources of exposure. Cumulative assessments combine exposure assessments for chemicals that share a common mechanism of toxicity. 

The Food Quality Protection Act of 1996 mandated USA EPA to "upgrade its risk assessment process as part of the tolerance setting procedures" (3), The changes to risk assessment were based in part on recommendations from the National Academy of Sciences report (22), The act required an explicit determination that tolerances were safe to children. US EPA was required to use an extra 10-fold safety factor to take into account both pre-/post natal developmental toxicity and the completeness of the database, unless US EPA determined, based on reliable data, that a different margin would be safe. In addition, US EPA must consider available information on 1/ aggregate exposure from all non-occupational sources 2/ effects of cumulative exposure to the pesticide plus others with a common mechanism of toxicity 3/ effects of in utero exposure 4/ the potential for endocrine disrupting effects. 

The methodology in the case study for chronic exposure, as well as several advances in probabilistic assessment methodology for acute exposure (e.g., a person s exposure on a single day), are being incorporated into the Cumulative and Aggregate Risk Evaluation System (CARES) begun in 2000 and being further developed with the International Life Sciences Institute (ILSI) in 2004. 

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