Best practices for exposure model peer review - A SciPinion advisory panel report.

The extent and rigor of peer review that a model undergoes during and after development influences the confidence of users and managers in model predictions. A process for determining the breadth and depth of peer review of exposure models was developed with input from a panel of exposure-modeling experts. This included consideration of the tiers and types of models (e.g., screening, deterministic, probabilistic, etc.). The experts recommended specific criteria be considered when evaluating the degree to which a model has been peer reviewed, including quality of documentation and the model peer review process (e.g., internal review with a regulatory agency by subject matter experts, expert review reports, formal Scientific Advisory Panels, and journal peer review). In addition, because the determination of the confidence level for an exposure model's predictions is related to the degree of evaluation the model has undergone, irrespective of peer review, the experts recommended the approach include judging the degree of model rigor using a set of specific criteria: (1) nature and quality of input data, (2) model verification, (3) model corroboration, and (4) model evaluation. Other key areas considered by the experts included recommendations for addressing model uncertainty and sensitivity, defining the model domain of applicability, and flags for when a model is used outside its domain of applicability. The findings of this expert engagement will help developers as well as users of exposure models have greater confidence in their application and yield greater transparency in the evaluation and peer review of exposure models.

Assessment of acetochlor use areas in the sahel region of Western Africa using geospatial methods.

The goal of this study was to determine the co-occurrence between acetochlor use on crops and potentially vulnerable soils in the Permanent Interstate Committee for Drought Control in the Sahel region of Western Africa. Acetochlor, a pre-emergence herbicide, is used primarily on row crops and has the potential to reach groundwater or surface water following a rain event shortly after application. Off-field transport is often determined by soil properties; therefore, soils within potential use areas were assessed and mapped to establish areas with soils vulnerable to leaching and/or runoff. Corn and cotton production areas were used as surrogate crops for high potential use areas of acetochlor within areas identified using GlobCover land use data and the Spatial Production Allocation Model agricultural statistics data. The geospatial analysis identified approximately 462 million ha of potentially vulnerable soils in the Sahel region of which 65.7 million ha are within agricultural areas. An adjustment for corn and cotton production areas showed that 2.2 million ha or 3.3% of agricultural fields could have potential restrictions for acetochlor use. Approximately 0.159 million ha of soils or 0.24% of agricultural fields are in the presence of shallow groundwater, defined by depth < 9 m. In addition, 0.0128 million ha or 0.02% were determined to be adjacent to surface water bodies. To understand the uncertainty associated with the use of specific land cover datasets, an overlay assessment was conducted using alternative data sources. Overlap between selected land cover datasets in the Sahel region varies and ranges from 24.7% to 75.5% based on a merged 2009 GlobCover and CCI LC datasets. In comparison with the merged 2005 and 2009 GlobCover dataset, the cropland overlaps range from 38.9% to 85.0%. This demonstrates that the choice of land cover dataset can have a significant impact on a spatial assessment. Results from this assessment demonstrate that only a small fraction of vulnerable agricultural soils across the region may be a risk for contamination by acetochlor of groundwater or surface resources, based on product label recommendations. Given the availability of spatial data in a region, the methods contained herein may additionally be used in other localities to provide similar information that can be helpful for water quality management.

Weight of evidence analysis of the tumorigenic potential of 1,3-dichloropropene supports a threshold-based risk assessment.

1,3-Dichloropropene (1,3-D; CAS #542-75-6) is a fumigant used for preplant treatment of soil to control parasitic nematodes and manage soil borne diseases for numerous fruit, vegetable, field and tree and vine crops across diverse global agricultural areas. In the USA, 1,3-D has historically been classified by the U.S. EPA as likely to be carcinogenic to humans via both oral and inhalation routes. This classification for the oral route was primarily based upon increases in multiple tumor types observed in National Toxicology Program (NTP) cancer bioassays in rats and mice, while the classification for the inhalation route was based upon increased benign bronchioloalveolar adenomas in a mouse study conducted by The Dow Chemical Company. Based on U.S. EPA standard risk assessment methodologies, a low-dose linear extrapolation approach has been used to estimate risks to humans. Furthermore, genotoxicity associated with 1,3-D was historically considered a potential mode of action (MOA) for its tumorigenicity. New information is available and additional studies have been conducted that reveal a different picture of the tumorigenic potential of 1,3-D. These data and information include: (1) initial cancer studies by the NTP were conducted on an antiquated form of 1,3-D which contained a known mutagen/carcinogen, epichlorohydrin, as a stabilizer while current 1,3-D fumigants use epoxidized soybean oil (ESO) as the stabilizer; (2) results from two additional oral rodent cancer bioassays conducted on the modern form of 1,3-D became available and these two studies reveal a lack of carcinogenicity; (3) a newly conducted Big Blue study in F344 rats via the oral route further confirms that 1,3-D is not an in vivo genotoxicant; and (4) a newly conducted repeat dose inhalation toxicokinetic (TK) study shows that linear dose proportionality is observed below 30 ppm, which demonstrates the non-relevance of 60 ppm 1,3-D-induced benign lung tumors in mice for human health assessment. This weight of evidence review is organized as follows: (a) the TK of 1,3-D are presented because of relevant considerations when evaluating test doses/concentrations and reported findings of tumorigenicity; (b) the genotoxicity profile of 1,3-D is presented, including a contemporary study in order to put a possible genotoxicity MOA into perspective; (c) the six available bioassays are reviewed followed by (d) scientifically supported points of departure (PODs) and evaluation of human exposure for use in risk assessment. Through this assessment, all available data support the conclusion that 1,3-D is not a tumorigen at doses below 12.5 mg/kg bw/day via the oral route or at doses below 30 ppm via the inhalation route. These findings and clearly identified PODs show that a linear low dose extrapolation approach is not appropriate and a threshold-based risk assessment for 1,3-D is human health protective. Finally, in 2019, the Cancer Assessment Review Committee (CARC) reevaluated the carcinogenic potential of 1,3-D. In accordance with the EPA's Final Guidelines for Carcinogen Risk Assessment, the CARC classified 1,3-D (Telone) as "Suggestive Evidence of Carcinogenic Potential based on the presence of liver tumors by the oral route in male rats only." Given this finding, EPA stated that "quantification of human cancer risk is not required. The CARC recommends using a non-linear approach (i.e. reference dose (RfD)) that will adequately account for all chronic toxicity including carcinogenicity, that could result from exposure to 1,3-dichloropropene."

Groundwater monitoring for 1,3-dichloropropene in high fumigant use areas of North America and Europe.

BACKGROUND: 1,3-Dichloropropene (1,3-D) is a soil fumigant used for the control of nematodes in high-value fruit, nut and vegetable crops globally. Extensive water monitoring efforts have been undertaken over the past four decades by public and private institutions, given the widespread agricultural use of 1,3-D, and environmental fate and metabolism data suggesting the potential for 1,3-D to leach into groundwater. The aim of this study is to review the results of groundwater monitoring studies for 1,3-D conducted in North America and the European Union (EU) since 1980. RESULTS: Analysis of > 50 000 water samples by state and federal agencies in the USA resulted in 151 detections of 1,3-D. An additional 4000 samples analyzed in groundwater studies specifically targeting high 1,3-D use areas in Europe and the USA resulted in 74 detections of 1,3-D or its primary metabolites. The combined detection rate of 1,3-D and its primary metabolites in high-use areas of the EU and North America was 0.7%. CONCLUSIONS: The availability of extensive groundwater monitoring information developed through decades of study supports the conclusion that soil fumigation with 1,3-D poses an inconsequential risk for drinking water exposure. The lack of significant detections of 1,3-D from targeted monitoring studies is due to the high volatility of 1,3-D, the rapid degradation of 1,3-D in most agricultural soils, the rapid degradation of 1,3-D and its metabolites in aerobic aquatic systems, and the rapid hydrolysis of 1,3-D in water. © 2019 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Application rate affects the degradation rate and hence emissions of chloropicrin in soil.

Increasingly stringent regulations to control soil-air emissions of soil fumigants has led to much research effort aimed at reducing emission potential. Using laboratory soil columns, we aimed to investigate the relationship between chloropicrin (CP) application rate and its emissions from soil across a wide range of CP applications (equivalent to 56-392kgha-1). In contrast to the known behavior of other fumigants, total emission percentages were strongly and positively related to application rate (i.e., initial mass), ranging from 4 to 34% across the application rate range. When combined, data from a previous study and the present study showed good overall comparability in terms of CP application rate vs. emission percentage, yielding a second-order polynomial relationship with an R2 value of 0.93 (n=12). The study revealed that mass losses of CP were strongly disproportional to application rate, also showing a polynomial relationship. Based on degradation studies, we consider that a shorter half-life (faster degradation) at lower application rates limited the amount of CP available for emission. The non-linear relationship between CP application rate and CP emissions (both as % of that applied and as total mass) suggests that low application rates likely lead to disproportionally low emission losses compared with higher application rates; such a relationship could be taken into account when assessing/mitigating risk, e.g., in the setting of buffer zone distances.

Evaluation of potential human health effects associated with the agricultural uses of 1,3-D: Spatial and temporal stochastic risk analysis.

Dow AgroSciences (DAS) markets and sells 1,3-Dichloropropene (1,3-D), the active ingredient in Telone®, which is used as a pre-plant soil fumigant nematicide in economically important crops in California. 1,3-D has been regulated as a "probable human carcinogen" and the California Department of Pesticide Regulation limits use of 1,3-D based on human health risk assessments for bystanders. This paper presents a risk characterization for bystanders based on advances in the assessment of both exposure and hazard. The revised bystander risk assessment incorporates significant advances: 1) new data on residency duration and mobility in communities where 1,3-D is in high demand; 2) new information on spatial and temporal concentrations of 1,3-D in air based on multi-year modeling using a validated model; and 3) a new stochastic spatial and temporal model of long-term exposures. Predicted distributions of long-term, chronic exposures indicate that current, and anticipated uses of 1,3-D would result in lifetime average daily doses lower than 0.002mg/kg/d, a dose associated with theoretical lifetime excess cancer risk of <10(-5) to >95% of the local population based on a non-threshold risk assessment approach. Additionally, examination of 1,3-D toxicity studies including new chronic toxicity data and mechanism of action supports the use of a non-linear, threshold based risk assessment approach. The estimated maximum annual average daily dose of <0.0016mg/kg/d derived from the updated exposure assessment was then compared with a threshold point of departure. The calculated margin of exposure is >1000-fold, a clear indication of acceptable risk for human health. In summary, the best available science supports 1,3-D's threshold nature of hazard and the revised exposure assessment supports that current agricultural uses of 1,3-D are associated with reasonable certainty of no harm, i.e., estimated long-term exposures pose insignificant health risks to bystanders even when the non-threshold approach is assumed.

An Improved Indirect Procedure for Estimating Pesticide Volatility from Field Trials.

Conventional indirect approaches for estimating pesticide volatility from agricultural fields require an air dispersion model and near-field, temporal air concentration measurements. The model pesticide flux profile is chosen such that field observations are recovered. Ross et al. (1996) first proposed a back-calculation method (BCM) using a single iteration of the Industrial Source Complex Short Term (ISCST) parameterized by a unit source flux. The unit flux is updated by scaling with the slope of a linear regression line between model predictions and actual field observations at each measured time point and location, yielding an estimate for the field flux that occurred over the sampling period. The BCM is expanded using a downhill simplex optimization procedure requiring many ISCST iterations to consecutively adjust the volatility flux rate such that the sum of the squared residuals between predicted and measured air concentrations is minimized (denoted as BCMO). The BCMO is ideally suited for comparing the volatility of different pesticide formulations of the same active from field studies performed simultaneously. Comparison of the BCM and BCMO from field trials containing single (Texas) and multiple simultaneously treated fields (Indiana) are provided for pesticides ranging from low to high volatility. The advanced BCMO is a better alternative than the original BCM, as shown by closer model predictions to measured air concentrations. A major advantage of the BCMO is the ability to extract unique flux source strengths for each field when multiple fields are present and treated consecutively and contiguously with each field emitting pesticide mass at different rates.

Effect of co-formulation of 1,3-dichloropropene and chloropicrin on evaporative emissions from soil.

Co-formulations of 1,3-dichloropropene (1,3-D) and chloropicrin (CP) are commonly used for preplant fumigation in the production of high-value crops. Various ratios of 1,3-D to CP are available in these co-formulations. Collation of previous field data suggested that when the two fumigants were co-applied, the emissions of CP were significantly lower than when CP was applied singly. However, none of these previous studies had a control treatment with CP applied alone, alongside a treatment where CP was co-applied with 1,3-D under the same climatic and edaphic conditions. This work aimed to address this issue by measuring emission fluxes from soil columns maintained under controlled conditions in which 1,3-D and CP were applied alone and as four commercial co-formulations with various 1,3-D:CP ratios. A strong positive relationship between CP emissions and CP percentage in the formulation was observed. Furthermore, strong positive relationships between CP degradation half-life and CP percentage in the formulation and between CP degradation half-life and total column emissions suggested that the lower emissions were due to faster CP degradation when the CP percentage (and hence initial application mass) in the formulation was low. The presence of 1,3-D did not significantly affect the degradation rate of CP, and, therefore, it is hypothesized that co-application was, in itself, not a significant factor in emission losses from the columns. The findings have implications for the accurate modeling of CP because the effect of initial mass applied on CP degradation rate is not usually considered.

Correlation of chemical evaporation rate with vapor pressure.

A new one-parameter correlation is developed for the evaporation rate (ER) of chemicals as a function of molar mass (M) and vapor pressure (P) that is simpler than existing correlations. It applies only to liquid surfaces that are unaffected by the underlying solid substrate as occurs in the standard ASTM evaporation rate test and to quiescent liquid pools. The relationship has a sounder theoretical basis than previous correlations because ER is correctly correlated with PM rather than P alone. The inclusion of M increases the slope of previous log ER versus log P regressions to a value close to 1.0 and yields a simpler one-parameter correlation, namely, ER (µg m(-1) h(-1)) = 1464P (Pa) × M (g mol(-1)). Applications are discussed for the screening level assessment and ranking of chemicals for evaporation rate, such as pesticides, fumigants, and hydrocarbon carrier fluids used in pesticide formulations, liquid consumer products used indoors, and accidental spills of liquids. The mechanistic significance of the single parameter as a mass-transfer coefficient or velocity is discussed.

Relationship between the evaporation rate and vapor pressure of moderately and highly volatile chemicals.

Volatilization of chemicals can be an important form of dissipation in the environment. Rates of evaporative losses from plant and soil surfaces are useful for estimating the potential for food-related dietary residues and operator and bystander exposure, and can be used as source functions for screening models that predict off-site movement of volatile materials. A regression of evaporation on vapor pressure from three datasets containing 82 pesticidal active ingredients and co-formulants, ranging in vapor pressure from 0.0001 to >30,000 Pa was developed for this purpose with a regression correlation coefficient of 0.98.

The acetochlor registration partnership: prospective ground water monitoring program.

The Acetochlor Registration Partnership conducted a prospective ground water (PGW) monitoring program to investigate acetochlor [2-chloro-N-(ethoxymethyl)-N-(2-ethyl-6-methylphenyl)-acetamide] transport to ground water at eight sites. The distribution of soil textures among these sites was weighted toward coarser soil types, while also including finer-textured soils that dominate most corn (Zea mays L.)-growing areas of the United States. Each site consisted of a 1.2-ha test plot adjacent to a 0.2-ha control plot. Suction lysimeters and monitoring wells were installed at multiple depths within each test and control plot to sample soil-pore water and near-surface ground water. Irrigation was applied to each site during the growing season to ensure water input of 110 to 200% of average historical rainfall. Acetochlor dissipated rapidly from surface soils at all sites with a DT(50) (time for 50% of the initial residues to dissipate) of only 3 to 9 d, but leaching was not an important loss mechanism, with only 0.25% of the 15,312 soil-pore water and ground water samples analyzed containing parent acetochlor at or above 0.05 microg L(-1). However, quantifiable residues of a soil degradation product, acetochlor ethanesulfonic acid, were more common, with approximately 16% of water samples containing concentrations at or above 1.0 microg L(-1). A second soil degradation product, acetochlor oxanilic acid, was present at concentrations at or above 1.0 microg L(-1) in only 0.15% of water samples analyzed. The acetochlor PGW program demonstrated that acetochlor lacks the potential to leach to ground water at detectable concentrations, and when applied in accordance with label restrictions, is unlikely to move to ground water at concentrations hazardous to human health.

The acetochlor registration partnership state ground water monitoring program.

The Acetochlor Registration Partnership (ARP) conducted a 7-yr ground water monitoring program at a total of 175 sites in seven states: Illinois, Indiana, Iowa, Kansas, Minnesota, Nebraska, and Wisconsin. While acetochlor [2-chloro-N-(ethoxymethyl)-N-(2-ethyl-6-methylphenyl)-acetamide] was the primary focus, the analytical methods also quantified alachlor [2-chloro-N-(2,6-diethylphenyl)-N-(methoxymethyl)-acetamide], atrazine [6-chloro-N-ethyl-N'-(1-methylethyl)-1,3,5-triazine-2,4-diamine], metolachlor [2-chloro-N-(2-ethyl-6-methylphenyl)-N-(2-methoxy-1-methylethyl)-acetamide], and two classes of soil degradates for acetochlor, alachlor, and metolachlor. Ground water samples were collected monthly for five years and quarterly for two additional years. All samples were analyzed for the presence of parent herbicides, and degradates were monitored during the last three years. Parent acetochlor was detected above 0.1 microg L(-1) in three or more samples at just seven sites. Alachlor and metolachlor were also rarely detected, but atrazine was detected in 36% of all samples analyzed. Even more widespread were the tertiary amide sulfonic acid (ethanesulfonic acid, ESA) degradates of acetochlor, alachlor, and metolachlor, which were detected at 81, 76, and 106 sites, respectively. The other class of monitored soil degradates (oxanilic acid, OXA) was detected less frequently, at 26, 16, and 63 sites for acetochlor OXA, alachlor OXA, and metolachlor OXA, respectively. The geographic distribution of detections did not follow the pattern originally expected when the study began. Rather than being a function primarily of soil texture, the detection of these herbicides in shallow ground water was related to site-specific factors associated with local topography, the occurrence of surface water drainage features, irrigation practices, and the vertical positioning of the well screen.

The acetochlor registration partnership surface water monitoring program for four corn herbicides.

A surface drinking water monitoring program for four corn (Zea mays L.) herbicides was conducted during 1995-2001. Stratified random sampling was used to select 175 community water systems (CWSs) within a 12-state area, with an emphasis on the most vulnerable sites, based on corn intensity and watershed size. Finished drinking water was monitored at all sites, and raw water was monitored at many sites using activated carbon, which was shown capable of removing herbicides and their degradates from drinking water. Samples were collected biweekly from mid-March through the end of August, and twice during the off-season. The analytical method had a detection limit of 0.05 microg L(-1) for alachlor [2-chloro-N-(2,6-diethylphenyl)-N-(methoxymethyl)-acetamide] and 0.03 microg L(-1) for acetochlor [2-chloro-N-(ethoxymethyl)-N-(2-ethyl-6-methylphenyl)-acetamide], atrazine [6-chloro-N-ethyl-N'-(1-methylethyl)-1,3,5-triazine-2,4-diamine], and metolachlor [2-chloro-N-(2-ethyl-6-methylphenyl)-N-(2-methoxy-1-methylethyl)-acetamide]. Of the 16528 drinking water samples analyzed, acetochlor, alachlor, atrazine, and metolachlor were detected in 19, 7, 87, and 53% of the samples, respectively. During 1999-2001, samples were also analyzed for the presence of six major degradates of the chloroacetanilide herbicides, which were detected more frequently than their parent compounds, despite having higher detection limits of 0.1 to 0.2 microg L(-1). Overall detection frequencies were correlated with product use and environmental fate characteristics. Reservoirs were particularly vulnerable to atrazine, which exceeded its 3 microg L(-1) maximum contaminant level at 25 such sites during 1995-1999. Acetochlor annualized mean concentrations (AMCs) did not exceed its mitigation trigger (2 microg L(-1)) at any site, and comparisons of observed levels with standard measures of human and ecological hazards indicate that it poses no significant risk to human health or the environment.