We reviewed eight studies that reported personal exposure to glyphosate in occupational settings; overall, 423 subjects were tested. Three of these studies reported data on para-occupational exposure and included 73 spouses and 148 children of farmworkers (Table 1). Two studies were conducted in the US [11,12,13], four in Europe [13,14,15,16], one in Mexico [17], and one in Sri Lanka [18]. The studies mostly involved farmers [11, 12, 15, 17]; one study recruited forest workers [13], and two focused on horticulturalists [14, 16]. The reported measures of central tendency ranged from 0.26 to 73.5 μg/L [17, 18]. All the studies involved urinary measures, although the laboratory methods and LOD varied greatly from 0.05 to 100 μg/L [13, 17]. Central tendency estimates and ranges are plotted in Fig. 2. Except for one study published in 1991 [13] including data collected in 1988, data reported in these studies was collected within the last 20 years, with the most recent sample collected in 2017.

Fig. 2 Urinary GM glyphosate concentrations in occupational and para-occupational exposure settings& & Mesange 2012 excluded because values were only available from one participant. *indicates that when the lower end of the range was below the LOD, we replaced this value with 0. ** the reported range excluded values below the LOD. +values below the LOD imputed using single imputation Full size image

A study conducted in South Carolina and Minnesota examined urinary glyphosate concentrations in farmers and their families (n = 175) the day before, day of, and 3 days after glyphosate application to crops [11]. Farm families who applied for pesticide applicators licenses were sent solicitation letters for inclusion in the study. From those willing to be contacted, farmers with families (defined as one spouse and at least one child between the ages of 4 and 18 years of age) were asked to collect the urine voids from five consecutive days and fill out pre- and post-study questionnaires detailing family activities from the week before and week of the study. Glyphosate was measured with HPLC, with an LOD of 1 μg/L. The percentage of farmers with detectable values of glyphosate was 60% on application days and declined to 27% on day three after exposure. For farmers, the GM value of glyphosate was 3.2 μg/L on the application day. The percentage of spouses with levels of glyphosate above the LOD was 2% on pre-application days, 4% on application days, and 2% on the third day post-application. The percentage of children with urinary glyphosate levels above the LOD was 7% on pre-application days, 12% on application days, and 5% by the third day post-application. The GMs were not reported for spouses or children, as they were not calculated if less than 25% of the individuals in the group had detectable values.

In a study of glyphosate concentrations among farming households in Iowa after glyphosate application conducted in 2001 (n = 114), the adjusted GM of glyphosate was 1.9 μg/L (95% CI: 1.3–2.5) in the urine of children in farming families (adjusted for age, sex and urinary creatinine) [12]. The fathers had a urinary creatinine adjusted GM of 1.6 μg/L (95% CI: 1.1–2.4), the mothers of 1.1 μg/L (95% CI: 0.71–1.8).

In another study, morning urine samples were collected from 76 farmers across several geographic areas in Mexico [17]. Assessment of glyphosate concentration was carried out using ELISA with a LOD of 0.05 μg/L. The mean value observed in the farming communities was 0.26 μg/L.

A small Finnish study conducted in 1988 examined five forest workers who sprayed a solution containing 8% Roundup with a brush saw for 6 hours per day [13]. Workers used limited personal protective equipment, wearing only cotton overalls, cotton or rubber gloves, hats or safety helmets and rubber boots. Rain clothes were also worn on days with precipitation. The hypothesized route of exposure was reported by the authors as skin contamination, likely due to the limited personal protective equipment and Roundup dispersed through the air. Air samples collected at midweek during spraying contained < 1.25 μg glyphosate/ m3 air. After a 3-week work period, the glyphosate concentration in the urine remained below detection level (< 100 μg/L). Only one urine sample was further quantified and found to contain a glyphosate concentration of 85 μg/L.

A case study in France tested the presence of glyphosate in the urine of a farmer and his family (n = 5) because of the occurrence of birth defects in the family [15]. Glyphosate concentration in the farmer’s urine reached a peak of 9.5 μg/L 7 h after spraying, without personal protective equipment, and plateaued at 2 μg/L 2 days after spraying. The concentration of 2 μg/L was also measured in one child 2 days after spraying. The mother and 2 other children had no detectable levels of glyphosate.

A study conducted in 2015 of amenity horticulturalists (n = 18) was conducted in Ireland with the aim of measuring urinary biomarkers of occupational exposures, including to glyphosate [14]. Public workers at parks and other green spaces in Ireland were asked to collect urine immediately before and after spraying glyphosate, and biosamples were analyzed with mass spectrometry (LOD: 0.5 μg/L). Pre-spraying samples had significantly lower concentrations of urinary pesticide concentrations, including glyphosate (mean: 0.71 (SD: 0.92) μg/L) compared to post-spraying samples (mean: 1.35 (SD: 2.18) μg/L).

In a similar study conducted in 2016 and 2017 on a separate population of amenity horticulturalists (n = 20), urinary biomarkers of glyphosate exposure were measured before, immediately after (within 1 hour), and the first urine void the morning after spraying with Roundup® at work [16]. Each worker was also given the option to collect additional urine voids. For each worker, a peak urinary glyphosate level was identified. In the study, 27% of the samples were below the LOQ, 76% of which were either pre-task samples or morning-after samples. Of the post-work samples, only 7% were below the LOQ. There was a statistically significant difference between the pre-task samples levels (mean (SD): 1.08 (1.20) μg/L) and the post-task sample levels (mean (SD):1.72(1.53) μg/L) or peak sample levels (mean (SD):2.53 (1.89) μg/L). There was not a statistically significant difference between the pre-sample levels and first morning void levels (mean (SD): 1.32 (1.32)).

In a study of 20 paddy farmers in Sri Lanka, researchers examined the urinary metabolites of pesticides, including glyphosate, and sampled well water from active and abandoned wells near the farmers to examine whether pesticides were related to kidney disease [18]. The study included 10 healthy farmers without kidney disease living in a region with endemic CKDu; their median urinary glyphosate levels was 73.5 (range: 40.2-80.0) μg/L.

We identified 14 studies reporting on glyphosate levels in biofluids from the general population, with 3298 subjects tested (Table 1). Exposure assessment in these studies was primarily based on urine samples (n = 11), though some studies utilized maternal milk and urine (n = 1) or the serum of umbilical cord and maternal blood (n = 2). Four studies were conducted on pregnant women. While most studies reported arithmetic means, others reported GM [12], or medians [18,19,20]. The arithmetic mean levels of glyphosate detected in urine samples ranged from 0.16 to 7.6 μg/L. The central tendencies and ranges of these urinary levels are presented in Fig. 3. Where possible, the GM and range are reported, or estimated from the median or arithmetic mean and reported. There was a large degree of variability in the LOD, which ranged from 0.02 to 15 μg/L [21, 22].

Fig. 3 Urinary GM glyphosate concentrations in the general population. * indicates that > 50% of the values were below the LOD, and therefore the LOD was selected as the central tendency. **indicates that when the lower end of the range was below the LOD, we replaced this value with 0. +Highest value reported was 130 μg/L Full size image

In a study completed in 2001 comparing farming and non-farming households in Iowa (n = 98) [12], glyphosate concentrations in urine of children from non-farming families ranged from 0.10–9.4 μg/L and the adjusted GM of glyphosate was 2.5 μg/L (95% CI: 2.1–3.1) (adjusted for age, sex and urinary creatinine). The fathers in these families had a urinary creatinine adjusted GM of 1.5 μg/L (95% CI: 1.2–2.0), the mothers of 1.2 μg/L (95% CI: 0.91–1.6); 65% of non-farming mothers and 88% of non-farming children had detectable levels of glyphosate in their urine.

A study conducted in 2014 and 2015 used HPLC and mass spectrometry to examine milk and urine samples from 41 lactating women in Idaho and Washington State to determine whether glyphosate and AMPA could be detected in either fluid [21]. Researchers sampled human milk and urine from women of 18 years and older who were 1–3 months postpartum and were breastfeeding and/or pumping milk at least five times per day. The LOD and LOQ for glyphosate in milk were 1.0 μg/L and 10.0 μg/L respectively, in urine were 0.02 μg/L and 0.10 μg/L respectively. The LOD and LOQ for AMPA in milk were 1.0 μg/L and 10.0 μg/L, respectively, in urine were 0.03 μg/L and 0.10 μg/L respectively. All milk samples had glyphosate and AMPA levels below the LOD. The mean ± SD urinary glyphosate level was 0.28 ± 0.38 μg/L, while the mean urinary AMPA level was 0.30 ± 0.33 μg/L. Glyphosate was detected in 37 of the 40 urine samples tested; the highest value was 1.93 μg/L. There was no statistically significant difference between glyphosate or AMPA levels in those living near an urban versus suburban area, or between self-reported diet containing mostly organic versus conventional foods.

An analogous study was conducted in Quebec, Canada on serum from 30 pregnant and 39 non-pregnant women with similar age and BMI [22]. Glyphosate assessment was conducted with mass spectrometry, with an LOD of 15 μg/L. For pregnant women, the umbilical cord was also available for analysis. Glyphosate was not detected in serum of pregnant women or in the umbilical cord. Non-pregnant women had a glyphosate mean level of 73.6 ± 28.2 μg/L. AMPA was not detected in any of the samples tested.

A study conducted in central Indiana enrolled 71 pregnant women aged 18 to 39 years during their prenatal visits in 2015 and 2016 [23]. Each participant answered an online questionnaire about their diet and demographic information and provided two urine samples during their clinical visits between 11 and 38 weeks of gestation. Participants also provided a water sample from their residential source, either public supply or private well, at the time of the second prenatal urine sample. Glyphosate levels were measured by LC-MS/MS, with a LOD of 0.2 μg/L and 0.1 μg/L in drinking water and urine, respectively. Glyphosate was detected in 93% of the urine samples, with a mean (SD) of 3.40 (1.24) μg/L. Women in rural areas had higher levels of glyphosate (mean: 4.19 μg/L, SD: 1.58 μg/L) compared to women in suburban areas (mean: 3.17 μg/L, SD: 1.13 μg/L) and urban areas (mean: 3.47, SD: 0.50 μg/L). Drinking water samples had no detectable glyphosate, which suggests that it was not a relevant source of exposure for the cohort under study.

Researchers in Mexico conducted a cohort study comparing urine glyphosate levels in farm workers with eight fishermen who lived in urban areas [17]. ELISA with a 0.05 μg/L LOD in water was used; the mean urinary glyphosate level in the urban fisherman, which could be considered a control sample of subjects not exposed through occupation, was 0.16 μg/L.

In a pilot study conducted in 2017 in Ireland, 50 adults without a specific diet who did not use pesticides as part of their profession provided first morning void urine samples for glyphosate analysis [19]. Only urine samples with creatinine levels between 3.0 and 30 nmol/L were assumed to be valid (n = 47). Of these samples, 10 had glyphosate concentrations above the LOD. The median concentration of glyphosate for those 10 samples was 0.87 μg/L, with a minimum value of 0.80 μg/L and a maximum value of 1.35 μg/L. Six of the 10 samples with detectable glyphosate were from women, and three were from individuals who indicated past use of glyphosate in their homes, but not within the last month. None of the three samples that were excluded due to creatinine levels had detectable glyphosate.

In a study of mothers (n = 13) and children (n = 14) conducted in 2011 and 2012 in Denmark [24], urine spot samples revealed concentrations of glyphosate above the LOD (2.5 μg/L) in both urban and rural dwelling populations. Children had higher concentrations of glyphosate in their urine than their mothers, with a mean of 1.96 (range: 0.85–3.31) μg/L compared to 1.28 (range: 0.49–3.22) μg/L in the mothers. The authors did not detect a statistically significant difference in concentrations between rural and urban populations.

Similar results showing children having higher concentrations of glyphosate than their mothers were found in a German study conducted in 2009 including 2009 volunteers [25]. The mean value for all samples was 1.08 μg/L and the maximum value 4.2 μg/L. Participants between 0 to 19 years of age had the highest mean concentrations of urinary glyphosate (1.55 μg/L); the mean concentration decreased with age and was the lowest for participants older than 70 years (0.77 μg/L).

A previous study from the same German group tested 140 urine samples from subjects with mass spectrometry and reported an average value in all subjects of approximately 1.8 μg/L [26]. A subset of 41 subjects who self-reported eating organic food had mean urinary values of approximately 0.5 μg/L, which was significantly lower than those on a conventional, non-organic diet.

Conrad et al. [27] used 24-h urine samples from 399 subjects stored in the German Environmental Specimen Bank. Samples from 20 males and 20 females aged between 20 and 29 years were collected between March and April in selected years between 2001 and 2011 and every year from 2012 to 2015; 127 samples (31.8%) contained glyphosate concentrations at or above the LOD (0.1 μg/L). The maximum glyphosate levels peaked in the years 2013 (2.80 μg/L) and 2014 (1.78 μg/L). Males had the highest median level (0.18 μg/L) in 2013. A sub-analysis of subjects who self-reported being vegetarians showed no differences compared to the values obtained from the main sample population. A more in depth discussion of the exposure trends seen in this study follows below.

A non-peer reviewed report on glyphosate residues in 182 urine samples from 18 different European countries, commissioned by the European Community in 2013, documented exposure to glyphosate and AMPA with mass spectrometry (LOQ: 0.15 μg/L) [28]. Glyphosate and AMPA were detected in 44 and 36% of the urine samples analyzed, respectively.

A study conducted in 2006 of 112 residents of several Colombian regions where glyphosate is aerially administered to eradicate illicit crops reported a mean urinary concentration of glyphosate (LOD: 0.5 μg/L) of 7.6 μg/L (SD: 18.6; range: 0 to 130 μg/L) and a mean AMPA (LOD: 1 μg/L) concentration of 1.6 μg/L (SD: 8.4; range: 0 to 56 μg/L) [29]. Of the 42 subjects with quantifiable levels of glyphosate, four had quantifiable levels of AMPA as well. In these four individuals, the mean glyphosate level was 58.8 μg/L (range: 28–130 μg/L).

A Sri Lankan study examined urinary glyphosate levels in 10 healthy non-farmers living in areas where CKDu was not endemic [18]; the mean level of glyphosate was 3.3 μg/L.

A study conducted in Thailand in 2011 recruited 82 women between the ages of 19–35 years during their seventh month of pregnancy [20]. The women were interviewed about their diet, general health, and work exposures, including potential agricultural exposures, through several questionnaires at the time of recruitment. Maternal blood serum and umbilical cord were collected and tested for glyphosate (LOD: 0.4 μg/L) after giving birth. Of the maternal serum samples, 53.7% were at or above the LOD, while 49.3% of the umbilical cord samples were at or above LOD; 30.5% of the maternal samples had levels of glyphosate between 1 and 50 μg/L, 12.2% between 51 and 100 μg/L, 7.3% between 101 and 50 μg/L and 3.7% between 151 and 200 μg/L. The median glyphosate in maternal serum was 17.5 (range 0.2–189.1) μg/L. For the umbilical cords (n = 75), 28.3% of the samples had levels of glyphosate between 1 and 25 μg/L, 12.0% between 26 and 50 μg/L, 5.3% between 51 and 75 μg/L and 2.7% between 76 and 100 μg/L. The median glyphosate level was 0.2 (range 0.2–94.9) μg/L. Paired comparison between maternal blood serum and cord blood (n = 36) indicated that maternal serum samples exhibited higher levels of glyphosate. Occupational and lifestyle factors were found to be predictive of glyphosate at or above the LOD. The odds of having detectable levels of glyphosate in blood were 11.9 (CI: 3.6–39.5) times higher for women who worked in the fields compared to those who did not. After adjusting for maternal occupation, women who lived near agricultural areas (< 0.5 km) also had higher odds of glyphosate at or above the LOD (OR: 4.2, CI: 1.4–12.3) than those who lived further away.

There is limited information regarding secular trends in glyphosate exposure. In 2017, Mills et al. reported the excretion of glyphosate and AMPA in participants from the Rancho Bernardo Study of Healthy Aging, a study that began in 1972 by monitoring 6629 adults greater than 50 years of age who were residing in Southern California [30]. A small subset of this population (n = 112) had routine morning spot urinary biospecimens taken at all five clinic visits from 1993 to 2016; 100 of these 112 individuals were randomly chosen for urinary measurements of glyphosate and AMPA using chromatography and mass spectrometry. The LODs were 0.03 μg/L for glyphosate and 0.04 μg/L for AMPA. Urinary concentrations were normalized to each sample’s specific gravity to account for dilution. The mean glyphosate concentrations were 0.02 (95% CI: 0.01–0.04) μg/L in samples taken between 1993 and 1996, and 0.31 (95% CI: 0.24–0.39) μg/L in samples taken between 2014 and 2016. The percentage of participants with glyphosate above the LOD increased from 12% for the period 1993–1996 to 70% for the period 2014–2016. The mean levels of AMPA were 0.01 (95% CI: 0.00–0. 02) μg/L between 1993 and 1996, and 0.29 (0.217–0.35) μg/L between 2014 and 2016. During the same period, the percentage of participants with AMPA levels above the LOD increased from 5 to 71%.

The previously mentioned study by Conrad et al. conducted in Germany used 24-h urine samples from 399 subjects stored in the German Environmental Specimen Bank and examined time trends in exposure [27]. The LOQ for glyphosate was 0.1 μg/L. across all 14 years; 31.8% of the samples tested had glyphosate concentrations and 40.1% had AMPA concentrations at or above the LOQ. The percentage of individuals with glyphosate levels higher than the LOQ was 10% in 2001 and showed the highest percentages in 2012 (57.5%) and 2013 (56.4%). The maximum concentrations of glyphosate measured in urine peaked in 2013, with 2.80 μg/L for men and 1.78 μg/L for women. Values plateaued in the following 2 years.