E. RISK CHARACTERIZATION

In this section, the results of the exposure assessment are integrated with the toxicity values identified and derived in the toxicity assessment in order to characterize the hypothetical risks. Investigators identified a total of 64 pesticides and related products (37 active ingredients) as having possibly been used during the Gulf War. Most of these products posed little or no health threat given the combinations of their prevalence, toxicity, and the ways in which they would have almost certainly been handled in the field. Therefore, investigators identified a subset of 15 pesticide formulations known as the pesticides of potential concern (POPCs) for detailed evaluation in the HRA. The 15 POPCs contain 12 different active ingredients.

The noncancer health threat is evaluated by the calculation of a hazard quotient (HQ), where possible, for each POPC, via each route of exposure within each exposure scenario. These HQs are then added together to produce what is known as a hazard index (HI). HIs are presented by scenario/route combination for each active ingredient, and are added together for some combinations of active ingredients to assess potential cumulative effects. Likewise, the cancer risks are determined for each pesticide formulation retained, as appropriate, via each route of exposure within each exposure scenario. The risks are summed to a limited extent to assess cumulative risks.

The chemical-specific HQs and HIs, for the evaluation of noncarcinogenic effects, are presented first, followed by the chemical-specific cancer risks. Next, the potential cumulative hazards and risks are presented. The results for the medium exposure group are the most reliable; the results for the low and high exposure groups are less reliable. Finally, the findings are put into some perspective in the uncertainty and variability analysis at the end of this section.

2. Noncarcinogenic Effects Based on Standard Toxicity Values

The HQs are then added together in various ways to assess potential combined effects of pesticide active ingredient exposure by calculating hazard indices (HIs). Each chemical-specific and scenario-specific HI is calculated as follows:

An HI for the cumulative effects of multiple concurrent chemical exposures is calculated by adding up appropriate combinations of chemical-specific and scenario-specific HIs, as follows:

If the HI > 1, this indicates that the risk-based level of concern is exceeded due to individual and/or cumulative effects.^[586] An HQ or HI is a relative measure of the potential to cause adverse noncancer effects; neither HQ nor HI are normally associated with a numerical probability of adverse effects occurring. Additionally, an HQ or HI > 1 does not mean that adverse health effects are guaranteed. Ideally, HQs for multiple chemicals should only be summed for combinations of pesticide active ingredients acting by a similar mechanism, such as cholinesterase inhibition.

Table 106 presents the HQs and scenario-specific HIs for application exposure. In all but one case, the low exposure level HI was well below 1, indicating that adverse health effects would be unlikely for servicemembers in this group. The exception was bendiocarb, with a low exposure HI of 3. About 18% of the medium exposure level HIs exceeded 1, and 75% of the high-exposure HIs exceeded 1. The highest HQs of 1138-1183 are for diazinon EC. In most cases, the high-exposure level is the only level of concern, and relatively few servicemembers would have been exposed at the high level. An important factor that accounts for the dramatic difference between high exposure and medium exposure HIs for ECs and ULV fogs was the use of PPE, assumed by investigators to be appropriate gloves and respirator. Applicators who used appropriate PPE reduced their exposures tremendously.

Diazinon EC and Malathion ULV are associated with the largest contribution to the noncancer hazards for application at the high-exposure level (Table 106); hence, additional discussion of the potential health threat is warranted. About 15% of the PM exposure interviews cited use of diazinon EC. If we assume that a maximum of 4,500 servicemembers were designated as applicators in the KTO, and that the high-exposure level applies to possibly 10% of the applicators who applied diazinon, we conclude that fewer than 70 applicators (4,500 x 0.15 x 0.10) may have been exposed to diazinon EC at the high level. Likewise, fewer than 70 applicators may have been exposed to malathion ULV at the high level.

Table 107 presents the HQs and scenario-specific HIs for post-application exposure. In all but one case, the low exposure level HI was well below 1, indicating that adverse health effects would be unlikely for servicemembers in this group. The exception was dichlorvos, with a low exposure level HI = 12. Only two (14%) medium exposure level HIs exceeded 1, while five (36%) high exposure level HIs exceeded 1.

Dichlorvos may be considered of elevated concern, as the largest number of servicemembers may have received doses exceeding the RfD. According to the RAND survey (Table 11), 7% of ground troops (about 30,530 servicemembers) may have been exposed to dichlorvos, and most of these servicemembers may have had doses above the RfD. The 7% value should be relatively reliable, since the survey was conducted in a scientific manner, and the average veteran would probably remember resin strips fairly well. The HRA determined that even when used at the recommended rate of one resin strip per 1,000 ft³, the RfD would be exceeded at all three exposure levels. The latter finding is in line with a recent EPA human health risk assessment for dichlorvos.^[587] The EPA found that all their residential receptor groups exposed to resin strips were exposed above levels of concern (equivalent in this case to inhalation doses well above appropriate RfDs). Additionally, in one respect the HRA may have underestimated the high-exposure HQ for dichlorvos, given that we conducted air modeling based on the label application rate of 1 strip per 1,000 ft³, and some personnel reported in the RAND survey that higher application rates were used.

In contrast to dichlorvos, on the order of 7,000 servicemembers may have had post-application exposure to diazinon at levels exceeding RfDs. The latter estimate is based on 469,047 ground troops, 15% potentially exposed to diazinon EC (from PM interviews) 10% of whom were exposed at the high exposure level. This estimate is rather crude, however, since the 15% overall exposure rate is drawn from the PM interviews, which resulted from highly biased and unscientific sampling, and the 10% value is only a rough estimate. By "biased and unscientific" here, we do not mean that the PM interview data are of poor quality, only that usage rates cannot be extrapolated to the general deployed population with much certainty.

Table 106. Application hazards for evaluation of noncarcinogenic effects^a

Table 107. Post-application hazards for evaluation of noncarcinogenic effects^a

3. Noncarcinogenic Effects Based on Other Human Benchmarks

Detailed information regarding the other human benchmarks (the epidemiological approach) is presented in Tab J; a brief summary of each risk characterization portion is summarized below. If a dose calculated in the exposure assessment (EA) is above a benchmark, this indicates that it may exceed a level of concern. If the EA dose is at or below a benchmark, then it does not exceed the level of concern for the associated endpoint described in Tab J. However, the user should review the details, especially the uncertainty descriptions, in Tab J before drawing conclusions. In most cases, there is significant uncertainty associated with the risk characterizations.

a. DEET

The high-exposure EA dermal doses for DEET slightly exceed the chronic benchmark from the literature, while the low- and medium-exposure values are below the benchmark.

b. Permethrin

The EA dermal and inhalation dose estimates for permethrin are well below the acute/subacute benchmarks for application exposure. Investigators did not identify subchronic or chronic benchmarks, nor benchmarks for post-application exposure.

c. d-Phenothrin

The EA dermal and inhalation dose estimates for permethrin are well below the acute/subacute benchmarks for application exposure. The EA inhalation dose estimates are also well below the acute/subacute benchmarks for post-application exposure. Investigators did not identify subchronic or chronic benchmarks for either application or post-application exposure.

d. Azamethiphos

Investigators were unable to identify useful human benchmarks for azamethiphos in the literature.

e. Methomyl

The EA oral, dermal, and inhalation dose estimates for methomyl are below the benchmarks for application exposure. The EA oral dose estimates are below the benchmark for post-application exposure. The EA high-exposure inhalation dose is slightly above the benchmark for post-application exposure.

f. Dichlorvos

In the dichlorvos post-application inhalation exposure scenarios, the EA-estimated doses were close to the levels at which health effects occurred in the research literature. The low-exposure EA dose is lower than the benchmark, the medium exposure dose is roughly equivalent, and the high-exposure dose is above the benchmark.

g. Chlorpyrifos

Based on the EA/literature comparison for chlorpyrifos EC and ULV application exposure, the EA-calculated route-specific doses are well below the doses at which human health effects occur. This same pattern holds true for the post-application exposure scenarios.

h. Diazinon

The EA low- and medium-exposure dermal dose estimates for diazinon are well below the benchmarks for application exposure. The EA high-exposure dermal doses are higher than the benchmarks. All EA inhalation doses are below benchmarks. The high-exposure EA dermal dose exceeds the benchmark, while the high-exposure EA inhalation dose is well below the benchmark.

i. Malathion

The EA low- and medium-exposure dermal dose estimates for malathion EC and ULV are well below the benchmark for application exposure; while the high-exposure doses exceed this benchmark. All EA inhalation doses are well below the benchmark for application exposure. The EA high-exposure dermal dose estimate exceeds the benchmark for post-application exposure, while the EA high-exposure inhalation dose is well below the benchmark.

j. Propoxur

All EA-estimated doses for relevant scenarios and exposure routes are well below the available benchmarks for both application and post-application exposure.

k. Bendiocarb

The EA-estimated low-exposure dermal dose for application exposure is below the benchmark, while the medium- and high-exposure doses are above the benchmark. All EA-estimated inhalation doses for application exposure are well below the benchmark. The EA-estimated medium- and high-exposure dermal doses for post-application exposure exceed the benchmark.

l. Lindane

The EA-estimated oral and inhalation doses for application exposure are below the benchmarks. Investigators did not identify appropriate benchmarks for dermal exposure.

4. Carcinogenic Effects

Investigators assessed potential carcinogenic effects by calculating a risk (probability) of excess cancer development associated with each relevant pesticide formulation retained, via each route of exposure, based on the medium exposure level, where available, or high exposure level if not. These route-specific risks have also been summed for each POPC for all three routes of exposure within each scenario.

The risk characterization for cancer is determined somewhat differently than that for noncancer effects as there are no specific thresholds for adverse effects. Thus, the following risk range benchmarks have been used here to establish the significance of risk:

• less than 1E-06 (one in one million) = insignificant
  
  
• 1E-06 to 1E-04 (one in one million to one in ten thousand) = marginally significant
  
  
• greater than 1E-04 (one in ten thousand) = significant

5. Cumulative Hazards and Risks

Tables 110 and 111 present the representative hazard indices (HIs) by branch of service, and the cumulative HIs for organophosphates and carbamates combined. Table 110 presents values for post-application exposure, while Table 111 presents values for applicators (application and post-application exposure). The phrase, "representative hazard index," as used here, means an HI that is potentially relevant to the most servicemembers within each major exposure subdivision (post-application or application). Probably well below 7% of servicemembers who served on the ground in the KTO might have been associated with cumulative HIs for OPs and carbamate approaching those presented in Table 110, and less than 0.2% might have been associated with total HIs for OPs and carbamate approaching those presented in Table 111. Cumulative HIs were compiled as follows:

• We reviewed information on use by branch of service to identify which pesticide formulations were used by each (Section IV.C, "Pesticides - Identification, Use, Exposures, and Potential Health Effects," and Tab F, "Pest Management and Operations").
  
  
• For pesticide formulations selected for each branch, each value listed is the highest medium scenario-specific HI value for the associated formulation. The medium HIs are relevant for the most servicemembers, and are associated with the highest levels of certainty (versus low and high HI values).
  
  
• The cumulative HIs for carbamates and OPs also sum the listed chemical-specific HIs. The rationale is that OPs and carbamates exert their toxic effects by a common mechanism, and therefore are presumed by investigators to exert an additive effect.
  
  
• For pesticide applicators (Table 111), post-application exposure is added to application exposure.
  
  
• The highest appropriate medium HI from among all ECs and the WP was selected as representative. Part of the rationale is that ECs and the WP were used for similar purposes, and that concurrent exposure to multiple ECs and the WP did not occur. Likewise, only one of the two ULV fogs was selected.

The criteria for grouping pesticides are fairly straightforward. For post-application exposure, the only difference among the branches has to do with ECs and bendiocarb. The Army did not use much bendiocarb, while the Navy (including Marines) and Air Force did. Since the medium HI for bendiocarb is higher than that for ECs, it was used to represent exposure for the Navy and Air Force in lieu of an EC HI. Conversely, the HI for propoxur was used for the Army in lieu of a bendiocarb HI. Propoxur had the highest medium HI of the ECs. All branches were assumed to be exposed to DEET, permethrin, d-phenothrin, azamethiphos, and dichlorvos. The medium HI for azamethiphos is higher than that for methomyl.

For applicators, the differences have to do with ECs, bendiocarb, and post-application exposure. Again, the bendiocarb medium HI was used for the Navy and Air Force, while an EC medium HI was used for the Army. The EC in the latter case was diazinon, as the HI was higher than for the other ECs. Since applicators would have also experienced post-application exposure similar to non-applicators, post-application exposure is added in.

The rationale for grouping OP and carbamate pesticide formulations together is fully supported by a large body of literature, spanning decades, documenting a common mechanism of action: inhibition of cholinesterase. Details regarding the common mechanism of action are available in many sources, including the RAND pesticides literature review,^[589] Ecobichon, ^[590] Karczmar^[591] Furthermore, draft policy at EPA's Office of Pesticide Programs (OPP) groups the OPs and carbamates together, and describes the rationale in detail.^[592]

The cumulative HIs presented in Table 111 are higher than the comparable values in Table 110, but are potentially relevant mainly to a small subset of servicemembers who applied specific pesticide formulations, such as ECs and bendiocarb WP.

The cumulative HIs listed for OPs and carbamates all exceed one, and are therefore presumed by investigators to indicate that veterans may have been exposed to levels of pesticide active ingredients capable of causing an identifiable physiological response such as the suppression of plasma cholinesterase. The fact that the HIs not only exceed 1, but significantly exceed one, indicates a relatively greater potential for such a response than if the HIs were closer to or below one. The HIs for lindane are small in comparison to the cumulative HIs shown for OPs and carbamate, and the HIs for permethrin and d-phenothrin, well below one, are relatively insignificant.

Cumulative cancer risks were not calculated because it was unnecessary.

Table 110. Cumulative hazard indicies for post-application exposure