Bibliography Tag: 2 4 d

Freisthler et al., 2022

Freisthler, Marlaina S., Robbins, C. Rebecca, Benbrook, Charles M., Young, Heather A., Haas, David M., Winchester, Paul D., & Perry, Melissa J.; “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;” Environmental Health, 2022, 21(1); DOI: 10.1186/s12940-021-00815-x.


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 mug/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).


Bakke et al., 2009

Bakke, B., De Roos, A. J., Barr, D. B., Stewart, P. A., Blair, A., Freeman, L. B., Lynch, C. F., Allen, R. H., Alavanja, M. C., & Vermeulen, R.; “Exposure to atrazine and selected non-persistent pesticides among corn farmers during a growing season;” Journal of Exposure Science & Environmental Epidemiology, 2009, 19(6), 544-554; DOI: 10.1038/jes.2008.53.


The aim was to develop quantitative estimates of farmers’ pesticide exposure to atrazine and to provide an overview of background levels of selected non-persistent pesticides among corn farmers in a longitudinal molecular epidemiologic study. The study population consisted of 30 Agricultural Health Study farmers from Iowa and 10 non-farming controls. Farmers completed daily and weekly diaries from March to November in 2002 and 2003 on pesticide use and other exposure determinants. Urine samples were collected at 10 time points relative to atrazine application and other farming activities. Pesticide exposure was assessed using urinary metabolites and diaries. The analytical limit of detection (LOD) ranged between 0.1 and 0.2 microg/l for all pesticide analytes except for isazaphos (1.5 microg/l) and diazinon (0.7 microg/l). Farmers had higher geometric mean urinary atrazine mercapturate (AZM) values than controls during planting (1.1 vs <LOD microg/g creatinine; P<0.05). AZM levels among farmers were significantly related to the amount of atrazine applied (P=0.015). Interestingly, farmers had a larger proportion of samples above the LOD than controls even after exclusion of observations with an atrazine application within 7 days before urine collection (38% vs 6%, P<0.0001). A similar pattern was observed for 2,4-D and acetochlor (92% vs 47%, P<0.0001 and 45% vs 4%, P<0.0001, respectively). Urinary AZM levels in farmers were largely driven by recent application of atrazine. Therefore, the amount of atrazine applied is likely to provide valid surrogates of atrazine exposure in epidemiologic studies. Elevated background levels of non-persistent pesticides, especially 2,4-D, indicate importance in epidemiologic studies of capturing pesticide exposures that might not be directly related to the actual application.


Baharuddin et al., 2011

Baharuddin, M. R., Sahid, I. B., Noor, M. A., Sulaiman, N., & Othman, F.; “Pesticide risk assessment: A study on inhalation and dermal exposure to 2,4-D and paraquat among Malaysian paddy farmers;” Journal of Environmental Science and Health, Part B, 2011, 46(7), 600-607; DOI: 10.1080/03601234.2011.589309.


A cross-section analytical study was conducted to evaluate the risk of pesticide exposure to those applying the Class II pesticides 2,4-D and paraquat in the paddy-growing areas of Kerian, Perak, Malaysia. It investigated the influence of weather on exposure as well as documented health problems commonly related to pesticide exposure. Potential inhalation and dermal exposure for 140 paddy farmers (handlers of pesticides) were assessed. Results showed that while temperature and humidity affected exposure, windspeed had the strongest impact on pesticide exposure via inhalation. However, the degree of exposure to both herbicides via inhalation was below the permissible exposure limits set by United States National Institute of Occupational Safety and Health (NIOSH). Dermal Exposure Assessment Method (DREAM) readings showed that dermal exposure with manual spraying ranged from moderate to high. With motorized sprayers, however, the level of dermal exposure ranged from low to moderate. Dermal exposure was significantly negatively correlated with the usage of protective clothing. Various types of deleterious health effects were detected among users of manual knapsack sprayers. Long-term spraying activities were positively correlated with increasing levels of the gamma-glutamyl transpeptidase (GGT) liver enzyme. The type of spraying equipment, usage of proper protective clothing and adherence to correct spraying practices were found to be the most important factors influencing the degree of pesticide exposure among those applying pesticides.

Andreotti et al., 2015

Andreotti, G., Hoppin, J. A., Hou, L., Koutros, S., Gadalla, S. M., Savage, S. A., Lubin, J., Blair, A., Hoxha, M., Baccarelli, A., Sandler, D., Alavanja, M., & Beane Freeman, L. E.; “Pesticide Use and Relative Leukocyte Telomere Length in the Agricultural Health Study;” Plos One, 2015, 10(7), e0133382; DOI: 10.1371/journal.pone.0133382.


Some studies suggest that telomere length (TL) may be influenced by environmental exposures, including pesticides. We examined associations between occupational pesticide use reported at three time points and relative telomere length (RTL) in the Agricultural Health Study (AHS), a prospective cohort study of pesticide applicators in Iowa and North Carolina. RTL was measured by qPCR using leukocyte DNA from 568 cancer-free male AHS participants aged 31-94 years with blood samples collected between 2006 and 2008. Self-reported information, including pesticide use, was collected at three time points: enrollment (1993-1997) and two follow-up questionnaires (1998-2003, 2005-2008). For each pesticide, we evaluated cumulative use (using data from all three questionnaires), and more recent use (using data from the last follow-up questionnaire). Multivariable linear regression was used to examine the associations between pesticide use (ever, lifetime days, intensity-weighted lifetime days (lifetime days*intensity score)) and RTL, adjusting for age at blood draw and use of other pesticides. Of the 57 pesticides evaluated with cumulative use, increasing lifetime days of 2,4-D (p-trend=0.001), diazinon (p-trend=0.002), and butylate (p-trend=0.01) were significantly associated with shorter RTL, while increasing lifetime days of alachlor was significantly associated with longer RTL (p-trend=0.03). Only the association with 2,4-D was significant after adjustment for multiple comparisons. Of the 40 pesticides evaluated for recent use, malathion was associated with shorter RTL (p=0.03), and alachlor with longer RTL (p=0.03). Our findings suggest that leukocyte TL may be impacted by cumulative use and recent use of certain pesticides.


Alexander et al., 2007

Alexander, B. H., Mandel, J. S., Baker, B. A., Burns, C. J., Bartels, M. J., Acquavella, J. F., & Gustin, C.; “Biomonitoring of 2,4-dichlorophenoxyacetic acid exposure and dose in farm families;” Environmental Health Perspectives, 2007, 115(3), 370-376; DOI: 10.1289/ehp.8869.


OBJECTIVE: We estimated 2,4-dichlorophenoxyacetic acid (2,4-D) exposure and systemic dose in farm family members following an application of 2,4-D on their farm.

METHODS: Farm families were recruited from licensed applicators in Minnesota and South Carolina. Eligible family members collected all urine during five 24-hr intervals, 1 day before through 3 days after an application of 2,4-D. Exposure profiles were characterized with 24-hr urine 2,4-D concentrations, which then were related to potential predictors of exposure. Systemic dose was estimated using the urine collections from the application day through the third day after application.

RESULTS: Median urine 2,4-D concentrations at baseline and day after application were 2.1 and 73.1 microg/L for applicators, below the limit of detection, and 1.2 microg/L for spouses, and 1.5 and 2.9 microg/L for children. The younger children (4-11 years of age) had higher median post-application concentrations than the older children (> or = 12 years of age) (6.5 vs. 1.9 microg/L). The geometric mean systemic doses (micrograms per kilogram body weight) were 2.46 (applicators), 0.8 (spouses), 0.22 (all children), 0.32 (children 4-11 years of age), and 0.12 (children > or = 12 years of age). Exposure to the spouses and children was primarily determined by direct contact with the application process and the number of acres treated. Multivariate models identified glove use, repairing equipment, and number of acres treated as predictors of exposure in the applicators.

CONCLUSIONS: We observed considerable heterogeneity of 2,4-D exposure among farm family members, primarily attributable to level of contact with the application process. Awareness of this variability and the actual magnitude of exposures are important for developing exposure and risk characterizations in 2,4-D-exposed agricultural populations.


Nishioka et al., 2001

Nishioka, M. G., Lewis, R. G., Brinkman, M. C., Burkholder, H. M., Hines, C. E., & Menkedick, J. R.; “Distribution of 2,4-D in air and on surfaces inside residences after lawn applications: comparing exposure estimates from various media for young children;” Environmental Health Perspectives, 2001, 109(11), 1185-1191; DOI: 10.1289/ehp.011091185.


We collected indoor air, surface wipes (floors, table tops, and window sills), and floor dust samples at multiple locations within 11 occupied and two unoccupied homes both before and after lawn application of the herbicide 2,4-D. We measured residues 1 week before and after application. We used collected samples to determine transport routes of 2,4-D from the lawn into the homes, its subsequent distribution between the indoor surfaces, and air concentration as a function of airborne particle size. We used residue measurements to estimate potential exposures within these homes. After lawn application, 2,4-D was detected in indoor air and on all surfaces throughout all homes. Track-in by an active dog and by the homeowner applicator were the most significant factors for intrusion. Resuspension of floor dust was the major source of 2,4-D in indoor air, with highest levels of 2,4-D found in the particle size range of 2.5-10 microm. Resuspended floor dust was also a major source of 2,4-D on tables and window sills. Estimated post application indoor exposure levels for young children from nondietary ingestion may be 1-10 microg/day from contact with floors, and 0.2-30 microg/day from contact with table tops. These are estimated to be about 10 times higher than the preapplication exposures. By comparison, dietary ingestion of 2,4-D is approximately 1.3 microg/day. FULL TEXT

Malagoli et al., 2016

Malagoli, C., Costanzini, S., Heck, J. E., Malavolti, M., De Girolamo, G., Oleari, P., Palazzi, G., Teggi, S., & Vinceti, M.; “Passive exposure to agricultural pesticides and risk of childhood leukemia in an Italian community;” International Journal of Hygiene and Environmental Health, 2016, 219(8), 742-748; DOI: 10.1016/j.ijheh.2016.09.015.


BACKGROUND: Exposure to pesticides has been suggested as a risk factor for childhood leukemia, but definitive evidence on this relation and the specific pesticides involved is still not clear.

OBJECTIVE: We carried out a population-based case-control study in a Northern Italy community to assess the possible relation between passive exposure to agricultural pesticides and risk of acute childhood leukemia.

METHODS: We assessed passive pesticide exposure of 111 childhood leukemia cases and 444 matched controls by determining density and type of agricultural land use within a 100-m radius buffer around children’s homes. We focused on four common crop types, arable, orchard, vineyard and vegetable, characterized by the use of specific pesticides that are potentially involved in childhood induced leukemia. The use of these pesticides was validated within the present study. We computed the odds ratios (OR) of the disease and their 95% confidence intervals (CI) according to type and density of crops around the children’s homes, also taking into account traffic pollution and high-voltage power line magnetic field exposure.

RESULTS: Childhood leukemia risk did not increase in relation with any of the crop types with the exception of arable crops, characterized by the use of 2.4-D, MCPA, glyphosate, dicamba, triazine and cypermethrin. The very few children (n=11) residing close to arable crops had an OR for childhood leukemia of 2.04 (95% CI 0.50-8.35), and such excess risk was further enhanced among children aged <5 years.

CONCLUSIONS: Despite the null association with most crop types and the statistical imprecision of the estimates, the increased leukemia risk among children residing close to arable crops indicates the need to further investigate the involvement in disease etiology of passive exposure to herbicides and pyrethroids, though such exposure is unlikely to play a role in the vast majority of cases. FULL TEXT


Smith et al., 2017

Smith, A. M., Smith, M. T., La Merrill, M. A., Liaw, J., & Steinmaus, C.; “2,4-dichlorophenoxyacetic acid (2,4-D) and risk of non-Hodgkin lymphoma: a meta-analysis accounting for exposure levels;” Annals of Epidemiology, 2017, 27(4), 281-289 e284; DOI: 10.1016/j.annepidem.2017.03.003.


2,4-Dichlorophenoxyacetic acid (2,4-D) is one of the most commonly used selective herbicides in the world. A number of epidemiology studies have found an association between 2,4-D exposure and non-Hodgkin lymphoma (NHL) but these results are inconsistent and controversial. A previous meta-analysis found no clear association overall but did not specifically examine high-exposure groups. We conducted a systematic review and meta-analysis of the peer-reviewed epidemiologic studies of the associations between 2,4-D and NHL, with a particular focus on high-exposure groups, and evaluations of heterogeneity, dose-response, and bias. A total of 12 observational studies, 11 case-control studies, and one cohort study, were included. The summary relative risk for NHL using study results comparing subjects who were ever versus never exposed to 2,4-D was 1.38 (95% confidence interval (CI), 1.07-1.77). However, in analyses focusing on results from highly exposed groups, the summary relative risk for NHL was 1.73 (95% CI, 1.10-2.72). No clear bias based on study design, exposure assessment methodology, or outcome misclassification was seen. Overall, these findings provide new evidence for an association between NHL and exposure to the herbicide 2,4-D. FULL TEXT


Burns and Swaen, 2012

Burns, C. J., & Swaen, G. M.; “Review of 2,4-dichlorophenoxyacetic acid (2,4-D) biomonitoring and epidemiology;” Critical Reviews in Toxicology, 2012, 42(9), 768-786; DOI: 10.3109/10408444.2012.710576.


A qualitative review of the epidemiological literature on the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) and health after 2001 is presented. In order to compare the exposure of the general population, bystanders and occupational groups, their urinary levels were also reviewed. In the general population, 2,4-D exposure is at or near the level of detection (LOD). Among individuals with indirect exposure, i.e. bystanders, the urinary 2,4-D levels were also very low except in individuals with opportunity for direct contact with the herbicide. Occupational exposure, where exposure was highest, was positively correlated with behaviors related to the mixing, loading and applying process and use of personal protection. Information from biomonitoring studies increases our understanding of the validity of the exposure estimates used in epidemiology studies. The 2,4-D epidemiology literature after 2001 is broad and includes studies of cancer, reproductive toxicity, genotoxicity, and neurotoxicity. In general, a few publications have reported statistically significant associations. However, most lack precision and the results are not replicated in other independent studies. In the context of biomonitoring, the epidemiology data give no convincing or consistent evidence for any chronic adverse effect of 2,4-D in humans. FULL TEXT