B.5  RISK CHARACTERIZATION

A.  Introduction

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.

B.  Noncarcinogenic Effects Based on Standard Toxicity Values

Each hazard quotient is calculated as follows:
HQ = Dose/RfD
where,
Dose = appropriate calculated route specific dose
RfD = appropriate route-specific reference dose from the toxicity assessment

For a single chemical, if the HQ > 1, this indicates that the dose exceeds the RfD. The RfD is a conservative value, usually based on animal studies, deliberately set low to be maximally protective of human health in the regulatory setting. Human exposure at or above the RfD, while noteworthy, does not necessarily mean that there will be any real negative impact on human health. Although the higher the actual exposure above the RfD, the greater the likelihood of adverse effects occurring. "Actual" exposure is distinguished from the hypothetical exposures estimated here.

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:

HI = HQO + HQD +HQI

where,

HQO = HQ for oral exposure

HQD = HQ for dermal exposure

HQI = HQ for inhalation exposure

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:

HI = HQ1 + HQ2 + … + HQi

where,

HQ1 = HQ for active ingredient Number 1

HQ2 = HQ for active ingredient Number 2

HQi = HQs for all other active ingredients up to the "ith" or last chemical

If the HI > 1, this indicates that the risk-based level of concern is exceeded due to individual and/or cumulative effects.[546] 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 about 500 servicemembers were officially 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 10 applicators (500 x 0.15 x 0.10) may have been exposed to diazinon EC at the high level. Likewise, fewer than 10 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.[547] 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 effectsa

Formulation

Exp. Level

Typeb

Route-Specific Dosec (mg/kg/d)

Hazard Quotiente

Scenario Hazard Indexf

Oral

Dermald

Inhalation

Oral

Dermald

Inhalation

PDRD

ADD

PDRD

ADD

DEET
33% stick/cream
Low

--

--

--

--

--

--

--

--

--

--

Med

--

--

--

--

--

--

--

--

--

--

High

--

--

--

--

--

--

--

--

--

--

DEET
75% liquid
Low

--

--

--

--

--

--

--

--

--

--

Med

--

--

--

--

--

--

--

--

--

--

High

--

--

--

--

--

--

--

--

--

--

Permethrin 0.5% aerosol Low

A

--

2.20E-03

--

3.53E-06

--

5.11E-05

--

1.41E-05

0.00007

Med

S

--

--

1.03E-04

3.53E-05

--

--

9.49E-04

7.06E-04

0.002

High

S

--

--

1.03E-04

3.53E-05

--

--

9.49E-04

7.06E-04

0.002

d-Phenothrin 2% aerosol Low

A

--

--

1.04E-04

3.55E-05

--

--

2.09E-03

5.00E-04

0.003

Med

S

--

--

1.04E-04

3.55E-05

--

--

2.09E-03

5.00E-04

0.003

High

S

--

--

4.15E-04

1.42E-04

--

--

8.36E-03

2.00E-03

0.01

Azamethiphos 1% crystals Low

A

--

1.16E-02

--

6.71E-05

--

5.78E-01

--

2.24E-02

0.6

Med

S

--

2.17E-02

--

1.34E-04

--

1.08E+00

--

4.48E-02

1.1

High

C

7.14E-03

--

1.48E-02

2.69E-04

2.86E+00

--

5.90E+00

1.07E-01

9

Methomyl
1% crystals
Low

A

--

1.16E-02

--

6.71E-05

--

1.28E-02

--

5.16E-04

0.01

Med

S

--

2.17E-02

--

1.34E-04

--

2.41E-02

--

1.03E-03

0.03

High

C

7.14E-03

--

1.48E-02

2.69E-04

8.57E-01

--

1.88E+00

2.07E-03

3

Dichlorvos 20% resin strip Low

--

--

--

--

--

--

--

--

--

--

Med

--

--

--

--

--

--

--

--

--

--

High

--

--

--

--

--

--

--

--

--

--

Chlorpyrifos 45% liquid (EC) (Handwand) Low

A

--

2.56E-04

--

1.79E-06

--

5.12E-03

--

1.79E-03

0.007

Med

S

--

--

3.84E-05

8.94E-06

--

--

1.42E-01

8.94E-03

0.2

High

C

--

--

7.15E-02

7.15E-04

--

--

2.65E+02

2.38E+00

267

Chlorpyrifos 45% liquid (EC) (Backpack) Low

A

--

1.49E-03

--

1.79E-06

--

2.98E-02

--

1.79E-03

0.03

Med

S

--

--

2.23E-04

8.94E-06

--

--

8.27E-01

8.94E-03

0.8

High

C

--

--

7.43E-02

7.15E-04

--

--

2.75E+02

2.38E+00

278

Diazinon
48% liquid (EC) (Handwand)
Low

A

--

--

4.10E-06

7.15E-07

--

--

1.93E-03

8.31E-03

0.01

Med

S

--

--

5.12E-05

8.94E-06

--

--

3.01E-01

1.04E-01

0.4

High

C

--

--

1.91E-01

1.43E-03

--

--

1.12E+03

1.66E+01

1138

Diazinon
48% liquid (EC) (Backpack)
Low

A

--

--

2.38E-05

7.15E-07

--

--

1.12E-02

8.31E-03

0.02

Med

S

--

--

2.98E-04

8.94E-06

--

--

1.75E+00

1.04E-01

2

High

C

--

--

1.98E-01

1.43E-03

--

--

1.17E+03

1.66E+01

1183

Malathion
57% liquid (EC) (Handwand)
Low

A

--

5.12E-04

--

3.57E-06

--

1.02E-03

--

1.28E-05

0.001

Med

S

--

2.56E-03

--

1.79E-05

--

5.12E-03

--

1.88E-04

0.005

High

C

--

7.15E+00

--

2.14E-03

--

1.79E+02

--

2.26E-02

179

Malathion 57% liquid (EC) (Backpack) Low

A

--

2.98E-03

--

3.57E-06

--

5.96E-03

--

1.28E-05

0.006

Med

S

--

1.49E-02

--

1.79E-05

--

2.98E-02

--

1.88E-04

0.03

High

C

--

7.43E+00

--

2.14E-03

--

1.86E+02

--

2.26E-02

186

Propoxur 14.7% liquid (EC) (Handwand) Low

A

--

5.12E-04

--

3.57E-06

--

5.12E-05

--

5.69E-07

0.00005

Med

S

--

2.56E-03

--

1.79E-05

--

2.56E-04

--

2.85E-06

0.0003

High

S

--

8.04E+00

--

2.41E-03

--

8.04E-01

--

3.84E-04

0.8

Propoxur 14.7% liquid (EC) (Backpack) Low

A

--

2.98E-03

--

3.57E-06

--

2.98E-04

--

5.69E-07

0.0003

Med

S

--

1.49E-02

--

1.79E-05

--

1.49E-03

--

2.85E-06

0.001

High

S

--

8.36E+00

--

2.41E-03

--

8.36E-01

--

3.84E-04

0.8

Bendiocarb 76% solid (WP) Low

A

--

3.92E-02

--

4.31E-04

--

2.36E-01

--

2.54E+00

3

Med

S

--

1.96E-01

--

2.16E-03

--

3.92E+00

--

1.27E+01

17

High

S

--

5.88E-01

--

6.47E-03

--

1.18E+01

--

3.80E+01

50

Chlorpyrifos 19% liquid (ULV) Low

A

--

1.71E-03

--

8.91E-06

--

3.42E-02

--

8.91E-03

0.04

Med

S

--

--

1.02E-04

1.77E-05

--

--

3.76E-01

1.77E-02

0.4

High

S

--

--

2.61E-02

3.60E-04

--

--

9.67E+01

3.60E-01

97

Malathion 91% liquid (ULV) Low

A

--

5.22E-02

--

2.73E-04

--

1.04E-01

--

9.73E-04

0.1

Med

S

--

1.59E-01

--

8.31E-04

--

3.19E-01

--

8.75E-03

0.3

High

C

--

4.64E+01

--

1.92E-02

--

1.16E+03

--

2.02E-01

1160

Lindane
1% dust
Low

A

--

--

6.53E-05

6.87E-04

--

--

6.60E-04

6.87E-03

0.008

Med

S

--

--

1.58E-03

1.15E-02

--

--

1.59E-02

1.15E-01

0.13

High

S

6.86E-02

--

3.81E-02

2.44E-01

6.86E-01

--

3.85E-01

2.44E+00

4

a)  In most cases, a dash ("--") indicates that the scenario/route combination was inconsequential, and was not evaluated. In cases where at least one dermal dose is provided, the dash indicates that the other dose available is not listed because such dose is unnecessary to calculate the hazard quotient.
b)  Exposure type: A = acute/subacute; S = subchronic; C = chronic. Based on the maximum days exposed.
c)  Dose used to calculate hazard quotient (HQ).
d)  PDRD = potential dose rate for dermal contact; ADD = absorbed dermal dose.
e)  HQ = dose/RfD. HQs are presented for the oral (HQO), dermal (HQD), and inhalation (HQI) routes.
f)  Scenario HQ = HQO + HQD + HQI.

Table 107. Post-application hazards for evaluation of noncarcinogenic effectsa

Formulation

Exp. Level

Typeb

Route-Specific Dosec (mg/kg/d)

Hazard Quotiente

Scenario Hazard Indexf

Oral

Dermald

Inhalation

Oral

Dermald

Inhalation

PDRD

ADD

PDRD

ADD

DEET
33% stick/cream
Low

A

--

2.36E+01

--

--

--

--

--

--

--

Med

S

--

4.71E+01

--

--

--

--

--

--

--

High

C

--

1.65E+02

--

--

--

--

--

--

--

DEET
75% liquid
Low

A

--

5.36E+01

--

--

--

--

--

--

--

Med

S

--

1.07E+02

--

--

--

--

--

--

--

High

C

--

3.75E+02

--

--

--

--

--

--

--

Permethrin 0.5% aerosol Low

S

--

--

1.07E-03

1.94E-03

--

--

9.86E-03

3.88E-02

0.05

Med

S

--

--

1.07E-03

2.67E-03

--

--

9.86E-03

5.34E-02

0.06

High

C

--

--

1.19E-03

4.74E-03

--

--

3.40E-02

1.58E-01

0.2

d-Phenothrin 2% aerosol Low

A

--

--

--

6.50E-06

--

--

--

9.15E-05

0.00009

Med

S

--

--

--

9.61E-06

--

--

--

1.35E-04

0.00014

High

S

--

--

--

1.89E-05

--

--

--

2.66E-04

0.0003

Azamethiphos 1% crystals Low

--

--

--

--

--

--

--

--

--

--

Med

S

4.29E-06

--

--

--

1.43E-03

--

--

--

0.001

High

C

1.55E-03

--

--

--

6.20E-01

--

--

--

0.6

Methomyl
1% crystals
Low

--

--

--

--

--

--

--

--

--

--

Med

S

4.29E-06

--

--

--

5.14E-04

--

--

--

0.0005

High

C

1.55E-03

--

--

3.47E-02

1.86E-01

--

--

2.67E-01

0.5

Dichlorvos 20% resin strip Low

S

--

--

--

6.01E-03

--

--

--

1.20E+01

12

Med

S

--

--

--

3.32E-02

--

--

--

6.64E+01

66

High

S

--

--

--

9.62E-02

--

--

--

1.92E+02

192

Chlorpyrifos 45% liquid (EC) Low

--

--

--

--

--

--

--

--

--

--

Med

--

--

--

--

--

--

--

--

--

--

High

C

--

--

2.28E-02

6.97E-05

--

--

8.43E+01

2.32E-01

85

Diazinon
48% liquid (EC)
Low

--

--

--

--

--

--

--

--

--

--

Med

--

--

--

--

--

--

--

--

--

--

High

C

--

--

6.07E-02

8.31E-04

--

--

3.57E+02

9.66E+00

367

Malathion 57% liquid (EC) Low

--

--

--

--

--

--

--

--

--

--

Med

--

--

--

--

--

--

--

--

--

--

High

C

--

3.03E+00

--

5.44E-04

--

7.59E+01

--

5.73E-03

76

Propoxur 14.7% liquid (EC) Low

--

--

--

--

--

--

--

--

--

--

Med

A

--

1.52E+00

--

1.06E-05

--

1.52E-01

--

1.69E-06

0.2

High

S

--

7.05E+00

--

2.11E-04

--

7.05E-01

--

3.36E-05

0.7

Bendiocarb 76% solid (WP) Low

--

--

--

--

--

--

--

--

--

--

Med

S

--

3.79E-01

--

--

--

7.59E+00

--

--

8

High

S

--

3.79E-01

--

--

--

7.59E+00

--

--

8

Chlorpyrifos 19% liquid (ULV) Low

A

--

--

--

1.03E-04

--

--

--

1.03E-01

0.1

Med

S

--

--

--

1.03E-04

--

--

--

1.03E-01

0.1

High

S

--

--

--

2.09E-04

--

--

--

2.09E-01

0.2

Malathion 91% liquid (ULV) Low

A

--

--

--

3.28E-03

--

--

--

1.17E-02

0.01

Med

S

--

--

--

3.28E-03

--

--

--

3.45E-02

0.03

High

S

--

--

--

6.65E-03

--

--

--

7.00E-02

0.07

Lindane
1% dust
Low

--

--

--

--

--

--

--

--

--

--

Med

--

--

--

--

--

--

--

--

--

--

High

--

--

--

--

--

--

--

--

--

--

a)  In most cases, a dash ("--") indicates that the scenario/route combination was inconsequential, and was not evaluated. In cases where at least one dermal dose is provided, the dash indicates that the other dose available is not listed because such dose is unnecessary to calculate the hazard quotient.
b)  Exposure type: A = acute/subacute; S = subchronic; C = chronic. Based on the maximum days exposed.
c)  Dose used to calculate hazard quotient (HQ).
d)  PDRD = potential dose rate for dermal contact; ADD = absorbed dermal dose.
e)  HQ = dose/RfD. HQs are presented for the oral (HQO), dermal (HQD), and inhalation (HQI) routes.
f)  Scenario HI = HQO + HQD + HQI.

C.  Noncarcinogenic Effects Based on Other Human Benchmarks

Detailed information regarding the other human benchmarks (the epidemiological approach) is presented in Tab C-8; 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 C-8. However, the user should review the details, especially the uncertainty descriptions, in Tab C-8 before drawing conclusions. In most cases, there is significant uncertainty associated with the risk characterizations.

1.  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.

2.  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.

3.  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.

4.  Azamethiphos

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

5.  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.

6.  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.

7.  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.

8.  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.

9.  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.

10.  Propoxur

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

11.  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.

12.  Lindane

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


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