Implied Maximum Dose Analysis of Standard Values of 25 Pesticides Based on Major Human Exposure Pathways

Worldwide jurisdictions are making efforts to regulate pesticide standard values in residential soil, drinking water, air, and agricultural commodity to lower the risk of pesticide impacts on human health. Because human may exposure to pesticides from many ways, such as ingestion, inhalation, and dermal contact, it is important to examine pesticide standards by considering all major exposure pathways. Analysis of implied maximum dose limits for commonly historical and current used pesticides was adopted in this study to examine whether worldwide pesticide standard values are enough to prevent human health impact or not. Studies show that only U.S. has regulated pesticides standard in the air. Only 4% of the total number of implied maximum dose limits is based on three major exposures. For Chlorpyrifos, at least 77.5% of the total implied maximum dose limits are above the acceptable daily intake. It also shows that most jurisdictions haven't provided pesticide standards in all major exposures yet, and some of the standards are not good enough to protect human health.


Introduction
The European Commission [1] defines a pesticide as something that prevents, destroys, or controls a harmful organism ("pest") or disease, or protects plants or plant products during production, storage, and transport. The U.S. Environmental Protection Agency (USEPA) [2] defines a pesticide as a matter or mixture of matters applied for preventing, destroying, repelling, or mitigating any pest. Pests can be bacteria, microorganisms, plants, and any other species that are harmful to crops, human beings, and living animals. Pesticides are largely applied worldwide to control pests and they can be classified by function (Table 1). Pesticides are largely used in agricultural, commercial, industrial, home, and garden applications. After applied to the environment, pesticides can be transported to four major environmental sinks which include soil, water, air, and biomass. Pesticides could be absorbed by soil partials and rushed away into river, groundwater, and lake by rain water. Some volatile and semi-volatile pesticides can evaporate into IMDL was introduced in this research to examine the pesticide maximum exposure mass loading based on national jurisdictions PSVs from all major exposure pathways. Pesticide implied dose limits (IDLs) were calculated for each exposure pathway as the following, and because only U.S. regulated pesticide air MCLs, the IDL air calculation was omitted. For drinking water: For residential soil: For agricultural commodities: All IDLs are based on the following set of exposure scenario coefficient values. EF -Exposure Factor (1) [18]; HW -Human Weight (70 kg) [18]; V -Volume of water intake rate (2 L/day) [18]; CF -Convert Factor (10 6 mg/kg); IR -Intake Rate for soil [19]; ABS d -Absorption Factor [19]; GIABS -GastroIntestinal Absorption Factor [19]; IR i -Intake Rate for food i (kg/day) [20].
And IMDL was derived by adding up IDLs from these possible exposures. If a nation regulated more than one PSVs in one of the major exposures, different IMDLs were calculated by combining different IDL with others.

Cumulative Distribution Function (CDF) Analysis
The arithmetic mean (μ), median (m), standard deviation (σ L ), and geometric mean (μ G ) were computed for those selected pesticides IMDLs. CDF analysis was applied to illustrate the distribution of IMDLs. IMDL empirical cumulative distribution for each pesticide was shown as follows. P ≤ ≈ ; ∀ = 1, … , ( IMDL ra random IMDL; IMDL ia known IMDL; n iinteger rank of IMDL in N known values.

Pearson (r) Correlation Coefficient
Pearson (r) correlation coefficient was calculated in Equation 5 for each selected pesticide IMDL to measure the degree that an IMDL empirical cumulative distribution fits a theoretical lognormal cumulative distribution calibrated with the computed mean and standard deviation statistics.
E (IMDL i )probability calculated from IMDL empirical cumulative distribution; F (IMDL i )probability calculated from IMDL theoretical lognormal cumulative distribution.

IMDL Cluster
CDF analysis was also applied to find IMDL clusters. IMDL cluster is defined as IMDL interval (IMDL i − IMDL i+M ) with M non-random values. Binomial probability function expressed in Equation 7 was used to compute the randomly occurring cluster probability (Pc).  There are 100 (77.5% of the total) Chlorpyrifos IMDLs above the ADI which is 0.001 mg/kg-day [22], which suggests that Chlorpyrifos PSVs from most worldwide jurisdiction can hardly protect human health. For the rest of Chlorpyrifos IMDLs which are below the ADI, none of them account for all major pesticide exposures. Among the 129 Chlorpyrifos IMDLs, only seven of them were computed from three exposures. Table 4 provides the statistics summary of Chlorpyrifos IMDLs. Only 22 Diazinon IMDLs are above the arithmetic mean which is 4.26 E-04 mg/kg-day because it is skewed by some extreme values such as 8.90 E-03 mg/kg-day at the high end of the distribution. The median and geometric mean (2.59 E-04 and 1.11 E-04 mg/kg-day, respectively) are probably better measures of vales central tendency. Among the 108 Diazinon IMDLs, only two of them were computed from three exposures. Table 5 provides statistics summary of Diazinon IMDLs. There are 20 (18.5% of the total) Diazinon IMDLs above the ADI which is 0.002 mg/kg-day [23] indicating that these Diazinon PSVs from worldwide jurisdiction can hardly protect human health. For the rest of Diazinon IMDLs which are below the ADI, only jurisdictions from Slovakia and the Czech Republic regulated Diazinon PSVs in major exposures. Table 6 provides statistics information for these selected pesticides (Bromomethane and Toxaphene were omitted due to few jurisdictions regulated PSVs for them). Vietnam contributes ten maximum IMDLs not only because Vietnam provided PSVs in three major exposures but also Vietnam regulated relatively large pesticide drinking water MCLs. Russia and Croatia contribute three maximum IMDLs. For most nations with minimum IMDLs, they only regulated PSVs in one exposure pathway. For example, Moldova contributes four minimum IMDLs which computed from soil RGVs, and Iraq contributes three minimum IMDLs computed from drinking water MCLs only.

Summary and Conclusions
The weighted average Pearson correlation coefficient of selected pesticides IMDLs is 0.926. For some pesticides such as Dieldrin, the correlation coefficient is 0.981. The weighted average order of variance of IMDLs is 6.09. Endosulfan IMDL values have the largest span of 8.29 order of magnitude. It suggests that in general, the IMDLs of selected pesticides are well dispersed over data spans, and worldwide jurisdictions lack the agreement on PSVs regulations in major exposures.
Only 105 IMDLs (4% of the total number of the selected pesticides) were computed from three major exposures. Most worldwide jurisdictions regulated selected pesticides in either two exposures or one exposure. As those are largely used pesticides and they can move and be transported to the soil, water, air, and biomass. It is necessary for worldwide jurisdictions to regulate PSVs in all major exposures. Glyphosate is top used pesticides over the world, however, only four Glyphosate IMDLs were computed from PSVs in soil, water, and agricultural commodity. Although the use of DDT has been banned, it can still be detected in soil, water, and food because of the wide application in the past.
There are 100 Chlorpyrifos IMDLs (77.5% of the total) above the ADI, however, only seven IMDLs were computed from major exposures, indicating that jurisdictions haven't provide safe Chlorpyrifos standard values even in one of the major exposure pathways. Although all IMDLs of Endosulfan are below the ADI value, none of them account for all major human exposures. Above all, it suggests that PSVs in all major exposure pathways should be regulated and comprehensive regulations of PSVs are necessary from human health point of view.   , 5769-5843 (Nov. 29, 1996. http://www.uradni-list.si/_pdf/1996/Ur/u1996068.pdf (accessed 03.09.13).