Table 3.
Human biomonitoring studies of chlorpyrifos/chlorpyrifos-methyl exposure based on urine samples from European populations.
| Country, Region, (Cohort) | Study Population | Sampling Year and Method | Analytical Method and Quality Control (QC), Correction Method for Urine Dilution | LOD/LOQ, DF, and Urinary Concentrations (μg/L Unless Other Stated) | Exposure Determinants Reported | Ref |
|---|---|---|---|---|---|---|
| Northern EU | TCPy | |||||
| Denmark, Funen (OCC) | Pregnant women (n = 948) | 2010–2012; Spot urine (morning after overnight fasting), GW 28 |
Enzymatic hydrolyses; LC-MS/MS; QC: isotope-labelled internal standards, participation in G-EQUAS; Creatinine |
LOD: 0.3 DF: 90.4 P50: 1.61 P95: 8.49 |
TCPy associated with higher education level in binary analyses, no information on diet or home use of pesticides | Dalsager et al., 2019 [39] |
| Denmark, Funen, (DGCC) | Children, 10–16 y (n = 143) | 2010–2012; Spot urine |
Enzymatic hydrolyses; LC-MS/MS; QC: isotope-labelled internal standards, participation in G-EQUAS; Creatinine |
LOD: 0.3 DF: 95.8 P50: 1.43 P95: 6.05 |
No significant associations with age, SES, urban or rural residence or sampling season | Andersen et al., 2021 [38] |
| Norway, MoBa | Pregnant women (n = 110, urine samples were combined into 10 pools, each comprising 1 mL urine sample from 11 women), nationwide | 1999–2008; Spot urine |
Acidic hydrolysis; GC-MS/MS; QC: Internal standards; Creatinine |
LOD: 0.15 Mean: 2.33 GM (estimated): 0.99 |
NR | Ye et al., 2009 [70] |
| Sweden, Scania | Adolescents aged 17–21 y (n = approx. 200 per year in 2000, 2004, 2009, 2013, and 2017), | 2000–2017; Spot urine |
Enzymatic hydrolyses; LC-MS/MS; QC: Internal spiked standards, participation in Erlangen inter-laboratory comparison; Urine density and creatinine |
LOD: 0.063 DF: 99–100 P50: 0.82–1.41 (max in 2009) P95: 3.50–6.54 (max in 2017) |
Increasing temporal trend for TCPy with peak for median concentration in 2009 and indication of a downward trend thereafter | Noren et al., 2020 [23] |
| Sweden, Uppsala County (POPUP) | Women (n = 178), after delivery | 2009–2014; Morning spot urine, 3 weeks after delivery |
Enzymatic hydrolyses; LC-MS/MS; QC: Isotope-labelled internal standards, participate in Erlangen inter-laboratory comparison; Urine density |
LOD: 0.02 DF: 100 P50: 1.32 Max: 14.2 |
NR | Gyllenhammar et al., 2017 [32] |
| Sweden, Värmland county (SELMA) | Pregnant women (n = 718) | 2007–2010; FMV, GW 10 |
Enzymatic hydrolyses; LC-MS/MS; QC: Isotope-labelled internal standards, participate in Erlangen inter-laboratory comparison; Creatinine |
LOD: 0.3035 DF: 100 GM (GSD): 1.25 (2.5) |
NR | Tanner et al., 2020 [53] |
| Western EU | ||||||
| Belgium, Flanders, FLEHS IV | Adolescents, 14–15 y (n = 415) | 2017–2018; Spot urine |
Enzymatic hydrolyses; LC-MS/MS; QC: Isotope-labelled internal standards; Specific gravity |
LOD: 0.3 DF: 98.5 P50: 4.45 P95: 12.3 specific gravity normalised |
NR | Schoeters et al., 2022 [36] |
| Belgium, Wallonia | Children, 9–12 y (n = 229), from five different locations (urban or agricultural) | 2016; FMV |
Enzymatic hydrolyses; GC-MS/MS; QC: Internal standards and materials from previous G-EQUAS programs; Creatinine |
LOQ: 0.08 DF: 100 P50: 3.87 P95: 12.12 |
Negatively associated with intake of grey bread (graubrot) | Pirard et al., 2020 [37] |
| Germany, Mecklenburg-Vorpommern | Adults, 22–57 y (n = 50) | No information on sampling year; Spot urine |
Acidic hydrolysis; GC-MS/MS; QC: Internal standards, Creatinine |
LOD: 0.05 DF: 100 P50: 1.4 P95: 4.8 |
NR | Koch et al., 2001 [75] |
| Netherlands, Generation R | Pregnant women (n = 100) | 2002–2006; Spot urine |
Acidic hydrolysis; GC-MS/MS; QC: Internal standards; Creatinine |
LOD: 0.15 DF: 100 P50: 1.2 P95: 6.4 |
Women with other ethnicity than Dutch had higher concentrations | Ye et al., 2008 [76] |
| Eastern EU | ||||||
| Polen, Lodz, | Adult men, age <45 y (n = 315) recruited from fertility clinic | 2008–2011; Spot urine |
Enzymatic hydrolyses; GC-MS/MS; QC: Isotope-labelled internal standards; Creatinine |
LOD: 0.50 DF: 100 P50: 1.14 P95: 7.99 |
NR | Dziewirska et al., 2019 [77] |
| Slovenia, Ljubljana (PHIME), | Children 7–8 y (n = 168) and their mothers (n = 168) | 2016; Spot urine |
Enzymatic hydrolyses; UPLC-MS-MS; QC: Isotope-labelled internal standards and participation in G-EQUAS; Specific gravity and creatinine |
LOD: 0.02 Children: DF: 88 P50: 0.06 Max: 2.8 Mothers: DF: 84 P50: 0.18 Max: 4.5 |
Children had lower concentrations than mothers, women with normal BMI had higher concentrations than overweight women | Bravo et al., 2020 [41] |
| Southern EU | ||||||
| Cyprus (ORGANIKO) | Children, 10–11 y (n = 177) | 2017; FMV |
No information on deconjugation; LC-MS/MS; QC: analysed in HBM4EU-accredited lab; Creatinine |
LOQ: 0.8 DF: 100 P50: 6.72 P95: 13.7 |
Negatively associated with maternal education | Makris et al., 2022 [33] |
| Italy, NACII (PHIME) | Children, 7 y (n = 199) | 2014–2015; Spot urine |
Enzymatic hydrolyses; UPLC-MS-MS; QC: Isotope-labelled internal standards and participation in G-EQUAS; Specific gravity |
LOD: 0.02 DF: 80 P50: 0.36 Max: 6.0 |
No associations with population characteristics, girls had higher concentrations than boys | Bravo et al., 2019 [67] |
| Italy, EPIC (substudy) | Adults (n = 69, 51 from Florence and 18 from Ragusa) | 1993–1998; 24 h urine |
Acidic hydrolysis; GLC-MS; QC: Internal spiked standards |
LOD: 5.0 nmol/L DF: 78.3 P50: 29.5 nmol/day Max: 87.9 nmol/day |
Highest concentration in Florence, no associations with other population characteristics | Saieva et al., 2004 [68] |
| Israel, IBS (nationwide) and Amirim community in Northern Israel | Adults from Amirim community with rural residence (n = 42) and Jewish participants from the Israel Biomonitoring Study (IBS) (n = 182) | 2013–2014 (IBS in 2011); Spot urine |
Enzymatic hydrolyses; GC-MS-MS; QC: Isotope-labelled internal standards and participation in G-EQUAS; Creatinine |
LOD: 0.2 DF: 100 Amirim: P50: 4.32 P95: 21.8 IBS: P50: 2.34 P95: 8.52 |
Highest in the Amirim population and associated positively with vegetable intake and negatively with organic food intake. | Berman et al., 2016 [73] |
| Spain, Granada, INMA | Adolescent males, 15–17 y (n = 117) | 2017–2019; FMV |
No information on deconjugation; HPLC-MS/MS, QC: Internal standards; Creatinine |
LOD: 0.039 DF: 34.2 Max: 1.21 |
NR | Suarez et al., 2021 [72] |
| Spain, Tarragona (EXHES-Spain) | Pregnant women (n = 54) from area of intense agricultural activity | 2016–2017; Spot urine samples during each trimester (repeated samples) |
Enzymatic hydrolyses, LC-MS/MS, QC: Isotope-labelled internal standards and participation in G-EQUAS;, Creatinine |
LOD: 0.02 DF: 4 Max: 0.15 |
Not investigated due to low detection frequency | Bravo et al., 2020 [71] |
| Spain, Valencia Region, BIOVAL | Children, 5–12 y (n = 568), 78% from urban area |
2016; FMV |
Enzymatic hydrolyses; LC-MS/MS; QC: Isotope-labelled internal standards and participation in G-EQUAS; Creatinine |
LOQ: 0.50 DF: 74 P50: 1.13 P95: 11.08 |
Lower if foreign birth country, differed between province of residence | Fernández et al., 2020 [34] |
| Spain, Valencia | Lactating mothers (n = 116), 2–8 weeks after birth, 80 % from urban areas | 2015; FMV |
Enzymatic hydrolyses; LC-MS/MS; QC: Isotope-labelled internal standards and participation in G-EQUAS; Creatinine |
LOQ: 0.25 DF: 85 P50: 2.0 P95: 7.9 |
Associated with living near farming activities (<200 m). Negatively associated with pre-pregnancy BMI. | Fernandez et al., 2020 [35] |
| Spain, Valencia | Children 6–11 y (n = 125) | 2010; FMV |
Enzymatic hydrolyses; LC-MS/MS; QC: Isotope-labelled internal standards; Creatinine |
LOQ: 0.8 DF: 86 P50: 3.40 μg/g crea P95: 12.97 μg/g crea |
Positively associated with vegetable consumption. | Roca et al., 2014 [69] |
| Spain, Valencia, INMA | Pregnant women (n = 573) | 2003–2006; Spot urine, GW 32 |
Hydrolysed urine (deconjugation method not described); UPLC-HRMS; QC: Internal spiked standards; Creatinine |
LOQ: 0.8 DF: 39.1 GM: 0.49 Max: 117.3 |
Positively associated with vegetable consumption and sample season (highest in summer) | Llop et al., 2017 [74] |
| Spain, Catalonia and Galicia | Adults (n = 125) 36% farmworkers, occupational exposure |
No information on sampling year; Spot urine |
Enzymatic hydrolyses; UPLC-MS-MS; QC: Isotope-labelled internal standards and participation in G-EQUAS Specific gravity and creatinine |
LOD: 0.02 DF: 95 P50: 3.2 Max: 20.0 |
Higher concentrations in farmworkers | Gari et al., 2018 [49] |
DF: detection frequency (%>LOD/LOQ); FMV: first morning void; German External Quality Assessment Scheme (G-EQUAS); NR: not reported; P50: 50th percentile (median); P25, P75, P90, P95: the respective percentile; GM: geometric mean; GSD: geometric standard derivation; SD: standard derivation; GW: gestational week; TCPy: 3,5,6-trichloro-2-pyridinol; crea: creatinine.