Missing the mark -- new methods needed to detect and address high-risk pesticide residues in the global food supply.

The primary metric used by regulators to track whether pesticide residues in food pose worrisome risks is the percent of samples tested in a given year that contain residues above applicable tolerances in the US and Maximum Residue Limits (MRLs) in most other countries. The Dietary Risk Index (DRI) system is used to determine the degree to which current policies governing allowed pesticide residue levels in food are keeping high-risk residues out of the global food supply. Residue data generated by the US Pesticide Data Program (PDP) and UK-Food Standards Agency (FSA) are utilized. Over the last 10 years 2449 samples of food have contained violative residues over applicable tolerances or MRLs. Of these, about 60% posed low or very-low dietary risks relative to acceptable dietary intake levels set by regulators. Conversely, only about 4% of high- and very-high risk samples tested by the US-PDP contained residues above the applicable tolerance. Accordingly, current US and UK policies are failing to flag most high-risk samples and are triggering more intense scrutiny and/or adverse regulatory actions in the case of many samples posing low or very-low risks. Recommendations are offered to enhance the ability to track and incrementally reduce pesticide dietary risks.

Association between increasing agricultural use of 2,4-D and population biomarkers of exposure: findings from the National Health and Nutrition Examination Survey, 2001-2014.

BACKGROUND: 2,4-Dichlorophenoxyacetic acid (2,4-D) is one of the most extensively used herbicides in the United States. In 2012, 2,4-D was the most widely used herbicide in non-agricultural settings and the fifth most heavily applied pesticide in the US agricultural sector. The objective of this study was to examine trends in 2,4-D urinary biomarker concentrations to determine whether increases in 2,4-D application in agriculture are associated with increases in biomonitoring levels of urine 2,4-D. METHODS: Data from the National Health and Nutrition Examination Survey (NHANES) with available urine 2,4-D biomarker measurements from survey cycles between 2001 and 2014 were utilized. Urine 2,4-D values were dichotomized using the highest limit of detection (LOD) across all cycles (0.40 µg/L or 0.4 ppb). Agricultural use of 2,4-D was estimated by compiling publicly available federal and private pesticide application data. Logistic regression models adjusted for confounders were fitted to evaluate the association between agricultural use of 2,4-D and urine 2,4-D level above the dichotomization threshold. RESULTS: Of the 14,395 participants included in the study, 4681 (32.5%) had urine 2,4-D levels above the dichotomization threshold. The frequency of participants with high 2,4-D levels increased significantly (p < .0001), from a low of 17.1% in 2001-2002 to a high of 39.6% in 2011-2012. The adjusted odds of high urinary 2,4-D concentrations associated with 2,4-D agricultural use (per ten million pounds applied) was 2.268 (95% CI: 1.709, 3.009). Children ages 6-11 years (n = 2288) had 2.1 times higher odds of having high 2,4-D urinary concentrations compared to participants aged 20-59 years. Women of childbearing age (age 20-44 years) (n = 2172) had 1.85 times higher odds than men of the same age. CONCLUSIONS: Agricultural use of 2,4-D has increased substantially from a low point in 2002 and it is predicted to increase further in the coming decade. Because increasing use is likely to increase population level exposures, the associations seen here between 2,4-D crop application and biomonitoring levels require focused biomonitoring and epidemiological evaluation to determine the extent to which rising use and exposures cause adverse health outcomes among vulnerable populations (particularly children and women of childbearing age) and highly exposed individuals (farmers, other herbicide applicators, and their families).

Commentary: Novel strategies and new tools to curtail the health effects of pesticides.

BACKGROUND: Flaws in the science supporting pesticide risk assessment and regulation stand in the way of progress in mitigating the human health impacts of pesticides. Critical problems include the scope of regulatory testing protocols, the near-total focus on pure active ingredients rather than formulated products, lack of publicly accessible information on co-formulants, excessive reliance on industry-supported studies coupled with reticence to incorporate published results in the risk assessment process, and failure to take advantage of new scientific opportunities and advances, e.g. biomonitoring and "omics" technologies. RECOMMENDED ACTIONS: Problems in pesticide risk assessment are identified and linked to study design, data, and methodological shortcomings. Steps and strategies are presented that have potential to deepen scientific knowledge of pesticide toxicity, exposures, and risks. We propose four solutions: (1) End near-sole reliance in regulatory decision-making on industry-supported studies by supporting and relying more heavily on independent science, especially for core toxicology studies. The cost of conducting core toxicology studies at labs not affiliated with or funded directly by pesticide registrants should be covered via fees paid by manufacturers to public agencies. (2) Regulators should place more weight on mechanistic data and low-dose studies within the range of contemporary exposures. (3) Regulators, public health agencies, and funders should increase the share of exposure-assessment resources that produce direct measures of concentrations in bodily fluids and tissues. Human biomonitoring is vital in order to quickly identify rising exposures among vulnerable populations including applicators, pregnant women, and children. (4) Scientific tools across disciplines can accelerate progress in risk assessments if integrated more effectively. New genetic and metabolomic markers of adverse health impacts and heritable epigenetic impacts are emerging and should be included more routinely in risk assessment to effectively prevent disease. CONCLUSIONS: Preventing adverse public health outcomes triggered or made worse by exposure to pesticides will require changes in policy and risk assessment procedures, more science free of industry influence, and innovative strategies that blend traditional methods with new tools and mechanistic insights.

The dietary risk index system: a tool to track pesticide dietary risks.

BACKGROUND: For years the United States Department of Agriculture's Pesticide Data Program and the United Kingdom's Food Standards Agency have published annual or quarterly data on pesticide residues in foods. Both programs report residues in conventionally grown, organic, and imported foods. The US program has tested about 288,000 food samples since 1992, primarily fruits and vegetables consumed by children. Since 1999 the UK has tested about 72,000 samples of a wider range of foods. These data are vital inputs in tracking trends in pesticide dietary risks. METHODS: The Dietary Risk Index (DRI) system facilitates detailed analyses of US and UK pesticide residue data, trends, and chronic risk distributions. The DRI value for a pesticide is the dietary intake of that pesticide from a single serving of food divided by the pesticide's acceptable daily intake as set by the US Environmental Protection Agency. It can be calculated based on average annual residue concentrations, and on residue levels in individual samples of food. DRI values can be aggregated over multiple pesticides in single foods, and over individual pesticides in multiple foods. RESULTS: The DRI system provides insights into the levels, trends, and distribution of pesticide dietary risk across most widely consumed foods. By drawing on both US Pesticide Data Program and UK-Food Standards Agency residue data, the DRI is capable of assessing pesticide risks in a significant portion of the global food supply. Substantial reductions in pesticide dietary risks occurred in the early 2000s, primarily from replacement of organophosphate insecticides with seemingly lower-risk neonicotinoids. However, there remain several areas of concern and opportunities to reduce risks. Both herbicide and fungicide dietary risks are rising. Organically grown produce poses risks far lower than corresponding, conventionally grown produce. Risk differences are inconsistent between domestic and imported foods. CONCLUSIONS: The surest ways to markedly reduce pesticide dietary risks are to shift relatively high-risk fruits and vegetables to organic production. For other foods, reducing reliance on pesticides overall, and especially high-risk pesticides, will incrementally lower risks. The DRI system can help focus such efforts and track progress in reducing pesticide dietary risk.

Insight into the confusion over surfactant co-formulants in glyphosate-based herbicides.

Glyphosate is the active ingredient in glyphosate-based herbicides (GBHs). Other chemicals in GBHs are presumed as inert by regulatory authorities and are largely ignored in pesticide safety evaluations. We identified the surfactants in a cross-section of GBH formulations and compared their acute toxic effects. The first generation of polyethoxylated amine (POEA) surfactants (POE-tallowamine) in Roundup are markedly more toxic than glyphosate and heightened concerns of risks to human health, especially among heavily-exposed applicators. Beginning in the mid-1990s, first-generation POEAs were progressively replaced by other POEA surfactants, ethoxylated etheramines, which exhibited lower non-target toxic effects. Lingering concern over surfactant toxicity was mitigated at least in part within the European Union by the introduction of propoxylated quaternary ammonium surfactants. This class of POEA surfactants are ∼100 times less toxic to aquatic ecosystems and human cells than previous GBH-POEA surfactants. As GBH composition is legally classified as confidential commercial information, confusion concerning the identity and concentrations of co-formulants is common and descriptions of test substances in published studies are often erroneous or incomplete. In order to resolve this confusion, laws requiring disclosure of the chemical composition of pesticide products could be enacted. Research to understand health implications from ingesting these substances is required.

Why Regulators Lost Track and Control of Pesticide Risks: Lessons From the Case of Glyphosate-Based Herbicides and Genetically Engineered-Crop Technology.

PURPOSE OF REVIEW: The approval of genetically engineered (GE) crops in the late 1990s triggered dramatic changes in corn, soybean, and cotton pest management systems, as well as complex, novel regulatory challenges. Lessons learned are reviewed and solutions described. RECENT FINDINGS: Government-imposed resistance management provisions can work and adapt to changing circumstances, but within the private sector, pressures to gain and hold market share have thus far trumped the widely recognized need for resistance management. Risks arising from the use of formulated pesticides often exceed by a wide margin those in regulatory risk assessments based on data derived from studies on nearly 100% pure active ingredients. Innovative policy changes are needed in four problem areas: excessive faith in the accuracy of pre-market risk assessments and regulatory thresholds; post-approval monitoring of actual impacts; risk arising from formulated pesticides, rather than just pure active ingredient; challenges inherent in assessing and mitigating the combined impacts of all GE traits and associated pesticides on agroecosystems, as opposed to each trait or pesticide alone; and, tools to deal with failing pest management systems.

Enhancing the fatty acid profile of milk through forage-based rations, with nutrition modeling of diet outcomes.

Consumer demand for milk and meat from grass-fed cattle is growing, driven mostly by perceived health benefits and concerns about animal welfare. In a U. S.-wide study of 1,163 milk samples collected over 3 years, we quantified the fatty acid profile in milk from cows fed a nearly 100% forage-based diet (grassmilk) and compared it to profiles from a similar nationwide study of milk from cows under conventional and organic management. We also explored how much the observed differences might help reverse the large changes in fatty acid intakes that have occurred in the United States over the last century. Key features of the fatty acid profile of milk fat include its omega-6/omega-3 ratio (lower is desirable), and amounts of total omega-3, conjugated linoleic acid, and long-chain omega-3 polyunsaturated fatty acids. For each, we find that grassmilk is markedly different than both organic and conventional milk. The omega-6/omega-3 ratios were, respectively, 0.95, 2.28, and 5.77 in grassmilk, organic, and conventional milk; total omega-3 levels were 0.049, 0.032, and 0.020 g/100 g milk; total conjugated linoleic acid levels were 0.043, 0.023, and 0.019 g/100 g milk; and eicosapentaenoic acid levels were 0.0036, 0.0033, and 0.0025 g/100 g milk. Because of often high per-capita dairy consumption relative to most other sources of omega-3 fatty acids and conjugated linoleic acid, these differences in grassmilk can help restore a historical balance of fatty acids and potentially reduce the risk of cardiovascular and other metabolic diseases. Although oily fish have superior concentrations of long-chain omega-3 fatty acids, most fish have low levels of α-linolenic acid (the major omega-3), and an omega-6/omega-3 ratio near 7. Moreover, fish is not consumed regularly, or at all, by ~70% of the U. S.

Is it time to reassess current safety standards for glyphosate-based herbicides?

Use of glyphosate-based herbicides (GBHs) increased ∼100-fold from 1974 to 2014. Additional increases are expected due to widespread emergence of glyphosate-resistant weeds, increased application of GBHs, and preharvest uses of GBHs as desiccants. Current safety assessments rely heavily on studies conducted over 30 years ago. We have considered information on GBH use, exposures, mechanisms of action, toxicity and epidemiology. Human exposures to glyphosate are rising, and a number of in vitro and in vivo studies challenge the basis for the current safety assessment of glyphosate and GBHs. We conclude that current safety standards for GBHs are outdated and may fail to protect public health or the environment. To improve safety standards, the following are urgently needed: (1) human biomonitoring for glyphosate and its metabolites; (2) prioritisation of glyphosate and GBHs for hazard assessments, including toxicological studies that use state-of-the-art approaches; (3) epidemiological studies, especially of occupationally exposed agricultural workers, pregnant women and their children and (4) evaluations of GBHs in commercially used formulations, recognising that herbicide mixtures likely have effects that are not predicted by studying glyphosate alone.

Trends in glyphosate herbicide use in the United States and globally.

BACKGROUND: Accurate pesticide use data are essential when studying the environmental and public health impacts of pesticide use. Since the mid-1990s, significant changes have occurred in when and how glyphosate herbicides are applied, and there has been a dramatic increase in the total volume applied. METHODS: Data on glyphosate applications were collected from multiple sources and integrated into a dataset spanning agricultural, non-agricultural, and total glyphosate use from 1974-2014 in the United States, and from 1994-2014 globally. RESULTS: Since 1974 in the U.S., over 1.6 billion kilograms of glyphosate active ingredient have been applied, or 19 % of estimated global use of glyphosate (8.6 billion kilograms). Globally, glyphosate use has risen almost 15-fold since so-called "Roundup Ready," genetically engineered glyphosate-tolerant crops were introduced in 1996. Two-thirds of the total volume of glyphosate applied in the U.S. from 1974 to 2014 has been sprayed in just the last 10 years. The corresponding share globally is 72 %. In 2014, farmers sprayed enough glyphosate to apply ~1.0 kg/ha (0.8 pound/acre) on every hectare of U.S.-cultivated cropland and nearly 0.53 kg/ha (0.47 pounds/acre) on all cropland worldwide. CONCLUSIONS: Genetically engineered herbicide-tolerant crops now account for about 56 % of global glyphosate use. In the U.S., no pesticide has come remotely close to such intensive and widespread use. This is likely the case globally, but published global pesticide use data are sparse. Glyphosate will likely remain the most widely applied pesticide worldwide for years to come, and interest will grow in quantifying ecological and human health impacts. Accurate, accessible time-series data on glyphosate use will accelerate research progress.

Enhancements Needed in GE Crop and Food Regulation in the U.S.

Genetically engineered (GE) crops, multi-ingredient foods derived from one or more GE ingredients, and GE agricultural inputs are regulated in the United States under a "Coordinated Framework" that was literally cobbled together in the early 1990s. Via this Framework, responsibility is spread across three federal agencies for the assessment and management of potential risks arising from the planting of GE crops, the raising of GE animals, or uses of GE inputs. The Framework was incomplete and conceptually flawed from the beginning. Despite multiple, piecemeal efforts to update aspects of GE risk assessment and regulatory policy, the Coordinated Framework survives to this day largely unchanged. Its shortcomings are recognized in both the scientific and legal communities, but meaningful reforms thus far remain out of reach, blocked by the intense controversy now surrounding all things biotech. Five generic reforms and another five specific initiatives are described to create a more robust, science-driven GE regulatory infrastructure in the U.S.

Higher PUFA and n-3 PUFA, conjugated linoleic acid, α-tocopherol and iron, but lower iodine and selenium concentrations in organic milk: a systematic literature review and meta- and redundancy analyses.

Demand for organic milk is partially driven by consumer perceptions that it is more nutritious. However, there is still considerable uncertainty over whether the use of organic production standards affects milk quality. Here we report results of meta-analyses based on 170 published studies comparing the nutrient content of organic and conventional bovine milk. There were no significant differences in total SFA and MUFA concentrations between organic and conventional milk. However, concentrations of total PUFA and n-3 PUFA were significantly higher in organic milk, by an estimated 7 (95 % CI -1, 15) % and 56 (95 % CI 38, 74) %, respectively. Concentrations of α-linolenic acid (ALA), very long-chain n-3 fatty acids (EPA+DPA+DHA) and conjugated linoleic acid were also significantly higher in organic milk, by an 69 (95 % CI 53, 84) %, 57 (95 % CI 27, 87) % and 41 (95 % CI 14, 68) %, respectively. As there were no significant differences in total n-6 PUFA and linoleic acid (LA) concentrations, the n-6:n-3 and LA:ALA ratios were lower in organic milk, by an estimated 71 (95 % CI -122, -20) % and 93 (95 % CI -116, -70) %. It is concluded that organic bovine milk has a more desirable fatty acid composition than conventional milk. Meta-analyses also showed that organic milk has significantly higher α-tocopherol and Fe, but lower I and Se concentrations. Redundancy analysis of data from a large cross-European milk quality survey indicates that the higher grazing/conserved forage intakes in organic systems were the main reason for milk composition differences.

Concerns over use of glyphosate-based herbicides and risks associated with exposures: a consensus statement.

The broad-spectrum herbicide glyphosate (common trade name "Roundup") was first sold to farmers in 1974. Since the late 1970s, the volume of glyphosate-based herbicides (GBHs) applied has increased approximately 100-fold. Further increases in the volume applied are likely due to more and higher rates of application in response to the widespread emergence of glyphosate-resistant weeds and new, pre-harvest, dessicant use patterns. GBHs were developed to replace or reduce reliance on herbicides causing well-documented problems associated with drift and crop damage, slipping efficacy, and human health risks. Initial industry toxicity testing suggested that GBHs posed relatively low risks to non-target species, including mammals, leading regulatory authorities worldwide to set high acceptable exposure limits. To accommodate changes in GBH use patterns associated with genetically engineered, herbicide-tolerant crops, regulators have dramatically increased tolerance levels in maize, oilseed (soybeans and canola), and alfalfa crops and related livestock feeds. Animal and epidemiology studies published in the last decade, however, point to the need for a fresh look at glyphosate toxicity. Furthermore, the World Health Organization's International Agency for Research on Cancer recently concluded that glyphosate is "probably carcinogenic to humans." In response to changing GBH use patterns and advances in scientific understanding of their potential hazards, we have produced a Statement of Concern drawing on emerging science relevant to the safety of GBHs. Our Statement of Concern considers current published literature describing GBH uses, mechanisms of action, toxicity in laboratory animals, and epidemiological studies. It also examines the derivation of current human safety standards. We conclude that: (1) GBHs are the most heavily applied herbicide in the world and usage continues to rise; (2) Worldwide, GBHs often contaminate drinking water sources, precipitation, and air, especially in agricultural regions; (3) The half-life of glyphosate in water and soil is longer than previously recognized; (4) Glyphosate and its metabolites are widely present in the global soybean supply; (5) Human exposures to GBHs are rising; (6) Glyphosate is now authoritatively classified as a probable human carcinogen; (7) Regulatory estimates of tolerable daily intakes for glyphosate in the United States and European Union are based on outdated science. We offer a series of recommendations related to the need for new investments in epidemiological studies, biomonitoring, and toxicology studies that draw on the principles of endocrinology to determine whether the effects of GBHs are due to endocrine disrupting activities. We suggest that common commercial formulations of GBHs should be prioritized for inclusion in government-led toxicology testing programs such as the U.S. National Toxicology Program, as well as for biomonitoring as conducted by the U.S. Centers for Disease Control and Prevention.

Composition differences between organic and conventional meat: a systematic literature review and meta-analysis.

Demand for organic meat is partially driven by consumer perceptions that organic foods are more nutritious than non-organic foods. However, there have been no systematic reviews comparing specifically the nutrient content of organic and conventionally produced meat. In this study, we report results of a meta-analysis based on sixty-seven published studies comparing the composition of organic and non-organic meat products. For many nutritionally relevant compounds (e.g. minerals, antioxidants and most individual fatty acids (FA)), the evidence base was too weak for meaningful meta-analyses. However, significant differences in FA profiles were detected when data from all livestock species were pooled. Concentrations of SFA and MUFA were similar or slightly lower, respectively, in organic compared with conventional meat. Larger differences were detected for total PUFA and n-3 PUFA, which were an estimated 23 (95 % CI 11, 35) % and 47 (95 % CI 10, 84) % higher in organic meat, respectively. However, for these and many other composition parameters, for which meta-analyses found significant differences, heterogeneity was high, and this could be explained by differences between animal species/meat types. Evidence from controlled experimental studies indicates that the high grazing/forage-based diets prescribed under organic farming standards may be the main reason for differences in FA profiles. Further studies are required to enable meta-analyses for a wider range of parameters (e.g. antioxidant, vitamin and mineral concentrations) and to improve both precision and consistency of results for FA profiles for all species. Potential impacts of composition differences on human health are discussed.

Higher antioxidant and lower cadmium concentrations and lower incidence of pesticide residues in organically grown crops: a systematic literature review and meta-analyses.

Demand for organic foods is partially driven by consumers' perceptions that they are more nutritious. However, scientific opinion is divided on whether there are significant nutritional differences between organic and non-organic foods, and two recent reviews have concluded that there are no differences. In the present study, we carried out meta-analyses based on 343 peer-reviewed publications that indicate statistically significant and meaningful differences in composition between organic and non-organic crops/crop-based foods. Most importantly, the concentrations of a range of antioxidants such as polyphenolics were found to be substantially higher in organic crops/crop-based foods, with those of phenolic acids, flavanones, stilbenes, flavones, flavonols and anthocyanins being an estimated 19 (95 % CI 5, 33) %, 69 (95 % CI 13, 125) %, 28 (95 % CI 12, 44) %, 26 (95 % CI 3, 48) %, 50 (95 % CI 28, 72) % and 51 (95 % CI 17, 86) % higher, respectively. Many of these compounds have previously been linked to a reduced risk of chronic diseases, including CVD and neurodegenerative diseases and certain cancers, in dietary intervention and epidemiological studies. Additionally, the frequency of occurrence of pesticide residues was found to be four times higher in conventional crops, which also contained significantly higher concentrations of the toxic metal Cd. Significant differences were also detected for some other (e.g. minerals and vitamins) compounds. There is evidence that higher antioxidant concentrations and lower Cd concentrations are linked to specific agronomic practices (e.g. non-use of mineral N and P fertilisers, respectively) prescribed in organic farming systems. In conclusion, organic crops, on average, have higher concentrations of antioxidants, lower concentrations of Cd and a lower incidence of pesticide residues than the non-organic comparators across regions and production seasons.

Organic production enhances milk nutritional quality by shifting fatty acid composition: a United States-wide, 18-month study.

Over the last century, intakes of omega-6 (ω-6) fatty acids in Western diets have dramatically increased, while omega-3 (ω-3) intakes have fallen. Resulting ω-6/ω-3 intake ratios have risen to nutritionally undesirable levels, generally 10 to 15, compared to a possible optimal ratio near 2.3. We report results of the first large-scale, nationwide study of fatty acids in U.S. organic and conventional milk. Averaged over 12 months, organic milk contained 25% less ω-6 fatty acids and 62% more ω-3 fatty acids than conventional milk, yielding a 2.5-fold higher ω-6/ω-3 ratio in conventional compared to organic milk (5.77 vs. 2.28). All individual ω-3 fatty acid concentrations were higher in organic milk--α-linolenic acid (by 60%), eicosapentaenoic acid (32%), and docosapentaenoic acid (19%)--as was the concentration of conjugated linoleic acid (18%). We report mostly moderate regional and seasonal variability in milk fatty acid profiles. Hypothetical diets of adult women were modeled to assess milk fatty-acid-driven differences in overall dietary ω-6/ω-3 ratios. Diets varied according to three choices: high instead of moderate dairy consumption; organic vs. conventional dairy products; and reduced vs. typical consumption of ω-6 fatty acids. The three choices together would decrease the ω-6/ω-3 ratio among adult women by ∼80% of the total decrease needed to reach a target ratio of 2.3, with relative impact "switch to low ω-6 foods" > "switch to organic dairy products" ≈ "increase consumption of conventional dairy products." Based on recommended servings of dairy products and seafoods, dairy products supply far more α-linolenic acid than seafoods, about one-third as much eicosapentaenoic acid, and slightly more docosapentaenoic acid, but negligible docosahexaenoic acid. We conclude that consumers have viable options to reduce average ω-6/ω-3 intake ratios, thereby reducing or eliminating probable risk factors for a wide range of developmental and chronic health problems.