Environment International 152 (2021) 106481

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Environment International
journal homepage: www.elsevier.com/locate/envint

Hair versus urine for the biomonitoring of pesticide exposure: Results from
a pilot cohort study on pregnant women
Emilie M. Hardy a, Clémentine Dereumeaux b, Laurence Guldner b, Olivier Briand c,
Stéphanie Vandentorren b, Amivi Oleko b, Cécile Zaros d, Brice M.R. Appenzeller a, *
a
Human Biomonitoring Research Unit, Luxembourg Institute of Health (LIH), Strassen, Luxembourg
b
Santé Publique France, Saint-Maurice, France
c
French Ministry of Agriculture, Agrifood, and Forestry, Paris, France
d
Institut National d’Etudes Démographiques, Aubervilliers, France

A R T I C L E I N F O A B S T R A C T

Handling editor: Adrian Covaci Background/Aim: The quantitative assessment of human exposure to contaminants such as pesticides is a crucial
step in the characterization of exposure-associated risk. For this purpose, biomonitoring is often privileged as it
Keywords: presents the advantage of integrating all the possible sources and routes of exposure and of being representative
Pesticides of the internal dose resulting from exposure. Although biological fluids such as urine and blood have been used to
Human biomonitoring
date for this purpose, increasing interest has also been observed over the past decade for hair analysis. The
Hair
present work aimed at comparing the information obtained from the analysis of urine versus hair regarding
Urine
Exposure assessment exposure to pesticides in a pilot cohort of pregnant women.
Methods: In ninety-three pregnant women included in the pilot of the French cohort ELFE, one urine and one hair
sample were collected simultaneously from each subject at the maternity. Samples were analyzed using GC–MS/
MS analytical methods allowing for the detection of both parent pesticides and metabolites, and designed to be as
similar as possible between urine and hair for reliable inter-matrix comparison. Fifty-two biomarkers of exposure
were targeted, including parents and metabolites of organochlorines, organophosphates, pyrethroids, carba­
mates, phenylpyrazoles and other pesticides.
Results: The number of different compounds detected ranged from 16 to 27 (median = 22) in hair, and from 3 to
22 (median = 12) in urine. In hair, 24 compounds were found in > 40% of the individuals, whereas only 12
compounds presented the same frequency of detection in urine. Among the chemicals detected in > 80% of both
hair and urine samples, only one (pentachlorophenol) showed a signification correlation between hair and urine
concentrations.
Conclusions: The present results highlight the multiple exposure of the pregnant women included in this cohort
and suggest that hair provides more comprehensive information on pesticide exposure than urine analysis. This
study thus supports the relevance of hair analysis in future epidemiological studies investigating association
between exposure and adverse health effects.

1. Introduction exposure to these chemicals, including in the general population, have

been documented by an increasing amount of datasets. Organophos­
Both the adverse effects of pesticides and the ubiquity of human phate and pyrethroid pesticides, which have been associated in different

Abbreviations: 2-ClBA, 2-(4-chlorophenyl)-3-methylbutyric acid; 3Me4NP, 3-methyl-4-nitrophenol; 3-PBA, 3-phenoxybenzoic acid; 4F3PBA, 4-fluoro-3-phenox­
ybenzoic acid; Br2CA, cis-3-(2,2dibromovinyl)-2,2-dimethylcyclopropane-carboxylic acid; Cl2CA, cis-3-(2,2dichlorovinyl)-2,2-dimethylcyclopropane-carboxylic acid;
ClCF3CA, 3-(2-chloro-3,3,3-trifluoro-1-propenyl)-2,2-dimethylcyclopropanecarboxylic acid; DDD, dichlorodiphenyldichloroethane; DDE, dichlorodiphenyldi­
chloroethylene; DDT, dichlorodiphenyltrichloroethane; DEDTP, di-ethyl-di-thiophosphate; DEP, di-ethylphosphate; DETP, di-ethyl-thiophosphate; DMDTP, di-
methyl-di-thiophosphate; DMP, di-methyl-phosphate; DMTP, di-methyl-thiophosphate; HCB, hexachlorobenzene; HCH, hexachlorocyclohexane; Malathion CA,
malathion monocarboxylic acid; PCP, pentachlorophenol; PNP, p-nitrophenol; TCPy, 3,5,6-trichloro-2-pyridinol.
* Corresponding author.
E-mail address: brice.appenzeller@lih.lu (B.M.R. Appenzeller).

https://doi.org/10.1016/j.envint.2021.106481
Received 13 November 2020; Received in revised form 26 January 2021; Accepted 20 February 2021
Available online 9 March 2021
0160-4120/© 2021 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license
(http://creativecommons.org/licenses/by-nc-nd/4.0/).
E.M. Hardy et al.
cohorts with poorer intellectual development after in utero exposure or
with behavioral problems and cognitive developmental disabilities in
exposed children (Bouchard, 2011; Engel, 2011; Oulhote and Bouchard,
2013; Rauh, 2011; Viel, 2015), have yet been detected in a large part of
the population in different countries. Para-nitrophenol (PNP) and 3,5,6-
trichloro-2-pyridinol (TCPy), two organophosphate metabolites, were
detected in the urine of 30 to 58% and 70% of American pregnant
women respectively (Castorina, 2010). Urinary dialkylphosphates
(DAP), metabolites common to several organophosphate pesticides,
were detected in > 93% of Canadian children (Oulhote and Bouchard,
2013), in 88.5 to 100% of pregnant women from an agricultural area in
California (Bradman, 2005), and in > 90% of pregnant women in Israel
(Berman, 2011). Cl2CA and 3-PBA, pyrethroid metabolites, were
detected in the urine of 96.5% and 64% of French 6-years-old children
respectively (Viel, 2015) and in > 99% of Canadian children (Oulhote
and Bouchard, 2013). Organochlorine pesticides have been associated in
children with reduced growth and reduced birth weight and length after
in utero exposure (Burns, 2012), and in adults with increased cardio­
vascular diseases (Ha et al., 2007). Exposure to organochlorines has also
been correlated with prevalence of metabolic syndrome (Lee, 2007) and
diabetes (Lee, 2006), but also with neurodegenerative diseases (Steen­
land, 2014) and early menopause (Grindler, 2015). These chemicals yet
remain detected in a large part of the general population despite their
ban or restricted use. In serum collected from Romanian people
(n = 142) (Dirtu, 2006) and Russian boys aged 8–9 years old (n = 350)
(Burns, 2012), β-HCH, HCB and p,p’-DDE have all been detected in
100% of the individuals. HCB and p,p’-DDE were also both detected in
almost 100% of pregnant (n = 268) and non-pregnant (n = 1489)
American women (Woodruff et al., 2011). The ubiquity of exposure was
also demonstrated in remote populations such as Cree communities of
Northern Quebec (Canada) in which p-p’-DDE was detected in > 94%
and HCB ranged from 34.3 to 92.7% despite their relative isolation
(Liberda, 2014). In cord blood specimens collected between 2004 and
2007 in Guadaloupe (French carribean) from > 1000 women at delivery,
DDE was detected in 81% of the individuals (Cordier, 2020). The
metabolite of lindane (γ-HCH), 2,5-DCP, was also detected in the urine
of 67% to 84% of American pregnant women. More recently, a study
conducted on another group of French pregnant women demonstrated
that the concentration of several pesticides (insecticides, herbicides and
fungicides from different chemical classes) in the mothers’ hair was
associated with changes in weight, length and head circumference in the
newborns (Beranger, 2020).
Biomonitoring, consisting in the analysis of biomarkers of exposure
in biological matrices, is one of the most common approaches for the
assessment of exposure. In the field of pesticide exposure, different types
of specimens can be analyzed depending on the context. Blood is typi­
cally used for the detection of persistent compounds such as organo­
chlorines whereas urine is preferred for the analysis of metabolites of
different pesticides such as organophosphates and pyrethroids (Centers
for Diseases Control and Prevention, 2019; Kokkinaki, 2014). In parallel
to biological fluids, an increasing interest has also been observed for
hair, which allows the detection of pesticides from different classes, both
parent and metabolites, and provides an information representative of
the chronic level of exposure (Appenzeller and Tsatsakis, 2012; Peng,
2020; Lehmann, 2018; Iglesias-González et al., 2020). Hair presents the
advantage of an easy sampling and does not require refrigerated con­
dition like fluids. On top of the technical constraints associated with
specimen collection, transport and storage, other aspects related to
human such as pain, privacy, ethics and safety have to be considered.
Non-invasive samples are therefore generally preferred when possible,
especially for sensitive populations such as children or pregnant women
(Iglesias-González et al., 2020; Palazzi et al., 2019; Esteban and Castaño,
2009). The choice of the matrix is therefore not trivial and may have a
significant impact on the quality of exposure assessment and on data
interpretation. Nevertheless, only very few studies compared the results
obtained with different types of specimens collected from the same
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Environment International 152 (2021) 106481
individuals, and research is still needed to understand which informa­
tion can be provided by each matrix respectively, in order to better
design biomonitoring and epidemiological studies.
In order to fill this gap, the present study was conducted on a group
of 93 French pregnant women included in the ELFE cohort pilot study, in
order to describe their multiple exposure to pesticides and to compare
which information could be obtained from hair and urine respectively.
For this purpose, hair and urine samples were analyzed with a method
allowing for the detection of fifty-two compounds, including parents and
metabolites of organochlorines, organophosphates, pyrethroids, carba­
mates, phenylpyrazoles and other pesticides, and designed to be as
similar as possible between urine and hair for reliable inter-matrix
comparison.
2. Material and methods
2.1. Population description and sample collection
Hair and urine samples analyzed in the present study were collected
from pregnant women participating in the pilot-study ELFE (Etude
Longitudinale Française depuis l’Enfance) and were provided by the
“Institut de Veille Sanitaire” (former “Santé Publique France”, Saint-
Maurice, France) and the “Institut National des Etudes
Démographiques” (INED, Paris, France). The pilot survey was carried
out in thirty hospital maternity units between the 1st and 4th of October
2007, in different French departments selected for their diversity
regarding population density and urbanization (Seine-Saint-Denis,
Ardèche, Isère, Loire and Savoie) (Oleko, 2011). Before the study, the
personnel in charge of sample collection had trainings on urine and hair
collection in order to ensure the homogeneity in the collection proced­
ure between the different centers. Out of 571 selected newborns, 301
mothers accepted to participate in the study and 296 actually provided a
written approval. Urine and hair samples were obtained from 252 and
269 mothers respectively. Hair samples were collected just after de­
livery, from the occipital region (back of head) as close as possible to the
skin and stored at room temperature. Urine was collected on arrival of
the mother at the maternity for delivery and stored at − 80 ◦ C. All the
samples were stored in the biobanks of the CHRU of Tours (France) and
the “Etablissement Français du Sang” located in Annemasse (France)
until analysis. They were then transferred to the Human Biomonitoring
Research Unit of the Luxembourg Institute of Health located in
Luxembourg under refrigerated conditions. Ninety-three couples of
hair/urine presented a sufficient amount of matrix for analysis and were
then analyzed for pesticide determination. According to visual inspec­
tion, no hair sample originated from bleached hair.
2.2. Determination of pesticide concentration levels in hair and urine
The pesticide concentration levels in hair and urine were determined
according to the methods routinely used at the HBRU laboratory and
published in a previous article detailing the protocol for sample prepa­
ration, the GC and MS/MS parameters and the validation data for the
two matrices (Hardy, 2014). Only the decontamination procedure was
the one used from Duca et al., (Duca, 2014) (Duca, 2014). Only the first
3 cm (close to the skin) of each hair strand were used for analysis.
Considering the growth rate of 1 cm per month admitted for human, this
corresponds to the last 3 months before sampling (Harkey, 1993).
Identification of proximal part (close to the skin) of the hair strand was
ensured by experienced laboratory staff through visual examination.
The protocol used for hair analysis enabled to reach limits of quantifi­
cation ranging from 0.02 pg/mg for trifluralin to 8 pg/mg for para-
nitrophenol (PNP). The urinary analysis protocol, designed to be as
similar as possible to the one used for hair, allowed limits of quantifi­
cation ranging from 0.4 pg/mL for α-endosulfan to 4000 pg/mL for
dimethyldithiophosphate (DMDTP).
Briefly, after decontamination with sodium dodecyl sulfate solution
E.M. Hardy et al. Environment International 152 (2021) 106481

and methanol, hair strands were pulverized with a ball mill. For each
sample, 50 mg of hair powder was extracted with 1 mL of acetonitrile/
water (80:20, v/v) at 40 ◦ C and under overnight agitation. The day after,
the sample was centrifuged and the supernatant was divided into two
aliquots of 300 µL, one dedicated to the analysis of parent pesticides by
SPME-GC-NCI-MS/MS and the other used for pesticide metabolites
determination by GC-NCI-MS/MS after derivatization with PFBBr.
For urine analysis, parent pesticides were directly analyzed by SPME-
GC-NCI-MS/MS after dilution of 500 µL of urine in phosphate buffer.
Concerning pesticide metabolites, the protocol consisted of a first step of
acidic hydrolysis followed by a double liquid–liquid extraction with a
mixture of acetonitrile-cyclohexane-ethyl acetate (1:1:1, v/v/v). After
evaporation of the combined organic phases, the residue was submitted
to a derivatization step with PFBBr before injection into the GC-NCI-MS/
MS for analysis.
The analytical equipment used was composed of an Agilent 7890 gas
chromatograph system equipped with a HP-5MS capillary column
(30 m, 0.25 mm I.D., 0.25 mm film thickness), an Agilent CTC Pal
autosampler and an Agilent 7000A triple quadrupole mass spectrometer
operating in negative chemical ionization mode (methane as reagent
gas).
For each compound, the limit of quantification (LOQ) is the one
defined thanks to the method validation already published (Hardy,
2014) and represents the level for which accuracy and precision of the
measurement were within 25%. For the biomarkers detected in all the
samples at concentration above the LOQ, the limit of detection (LOD)

Table 1
Pesticide concentration levels (pg/mg) measured in hair samples from the ELFE pilot cohort, 2007 (n = 93).
Pesticides LOD (pg/mg) % Detection Min P5 P25 P50 P75 P95 Max

Organochlorines
α-HCH 0.01 52 – – <0.01 0.02 0.07 0.17 0.96
β-HCH 0.14 57 – – <0.14 0.28 0.94 3.34 26.71
γ-HCH 0.35 100 0.50 0.78 1.38 2.00 3.07 9.33 90.5
δ-HCH 0.1 3 – – – – – <0.1 0.81
ε-HCH 0.1 2 – – – – – <0.1 0.32
o,p’-DDE 0.5 0 – – – – – – <0.5
p,p’-DDE 1.1 5 – – – – – <1.1 32.4
o,p’-DDD 5 0 – – – – – – <5
p,p’-DDD 2 0 – – – – – – <2
o,p’-DDT 2 0 – – – – – – <2
p,p’-DDT 0.83 10 – – – – <0.83 2.52 15.2
Aldrin 0.5 0 – – – – – – <0.5
Isodrin 0.5 0 – – – – – – <0.5
Dieldrin 0.03 97 <0.03 0.04 0.12 0.28 0.40 1.17 3.69
Endrin 1 0 – – – – – – <1
α-Endosulfan 0.04 100 0.04 0.10 0.18 0.32 0.55 1.48 6.17
β-Endosulfan 0.03 91 – <0.03 0.18 0.29 0.62 2.13 7.81
Heptachlor 0.5 0 – – – – – – <0.5
Heptachlor-exo-epoxide 0.18 1 – – – – – <0.18 0.18
Heptachlor-endo-epoxide 1 0 – – – – – – <1
trans-Chlordane 0.01 10 – – – – <0.01 0.02 0.03
cis-Chlordane 0.14 14 – – – – <0.14 0.26 0.79
oxy-Chlordane 1 0 – – – – – – <1
Pentachlorophenol 1.4 100 1.37 3.01 9.24 19.6 42.6 417 1041
Hexachlorobenzene 0.12 100 0.22 0.31 0.39 0.48 0.59 0.79 1.22
Organophosphates
DMP 0.07 87 – <0.07 0.34 1.16 2.54 18.9 700
DMTP 0.02 4 – – – – – <0.02 12.5
DMDTP 1.3 0 – – – – – – <1.3
DEP 1.7 100 1.75 3.10 23.5 51.1 93.8 175 454
DETP 0.14 100 0.14 0.29 0.51 0.85 1.16 6.35 41.1
TCPy 0.8 100 0.85 1.38 3.26 5.78 10.7 50.9 197
PNP 5.4 100 5.44 8.97 12.9 16.3 23.3 34.0 61.9
3Me4NP 0.17 83 – <0.17 0.24 0.59 1.85 4.82 9.05
Malathion CA 5 0 – – – – – – <5
Pyrethroids
Cyhalothrin 0.3 4 – – – – – <0.3 2.04
Permethrin 3.5 94 – <3.5 10.1 27.9 67.6 297 1241
Cypermethrin 0.07 74 – – <0.07 0.35 0.78 2.86 15.3
Fenvalerate 0.3 0 – – – – – – <0.3
Deltamethrin 0.4 4 – – – – – <0.4 44.1
2-ClBA 0.1 0 – – – – – – <0.1
Br2CA 0.1 1 – – – – – <0.1 1.71
Cl2CA 0.4 96 <0.4 0.42 1.43 3.16 8.59 21.4 49.5
ClCF3CA 0.11 15 – – – – <0.11 0.57 3.69
4F3PBA 0.05 4 – – – – – <0.05 0.21
3-PBA 0.2 100 0.20 0.33 0.62 1.10 2.44 7.02 35.3
Carbamates
2-Isopropoxyphenol 0.5 56 – – <0.5 5.75 92.7 403 805
Carbofuranphenol 0.1 8 – – – – <0.1 0.48 12.3
Phenylpyrazoles
Fipronil 0.05 99 <0.05 0.09 0.19 0.44 1.73 69.3 234
Fipronil sulfone 0.04 99 <0.04 0.07 0.20 0.41 1.20 17.1 48.7
Miscellaneous
Trifluralin 0.02 100 0.07 0.10 0.14 0.19 0.27 0.70 1.34
Oxadiazon 0.01 83 – <0.01 0.06 0.13 0.23 0.47 1.96
Diflufenican 0.1 100 0.13 0.17 0.34 0.57 0.72 1.29 45.3

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E.M. Hardy et al. Environment International 152 (2021) 106481

was set at LOQ, since no value could be measured below. For the bio­
markers that presented non-detects, LOD corresponded to the lowest
concentration detected among all the samples of the present study.
Tables provide for each chemical and each matrix the percentage of
samples detected (>LOD) (Table 1, Table 2).
correlation between hair and urine concentrations, only the compounds
detected in at least 80% in the two matrices were considered. Only the
samples positive for both matrices were considered for correlation tests
(Helsel, 2006). Pearson and Spearman correlation coefficients and their
corresponding p-value were obtained with SigmaPlot software.

2.3. Statistical analysis 3. Results

Percentiles and median concentrations were calculated with Micro­
soft Excel software. Results below the limit of quantification and above
the limit of detection were taken into account for all the calculations
since we considered more relevant to use the measured values than
replacing them by arbitrary values (Helsel, 2006). To investigate
3.1. Detection frequency and concentration range in hair
Among the 25 organochlorines investigated, 15 were detected in the
hair strands with detection frequencies (>LOD) ranging from 1% (for
heptachlor-exo-epoxide) to 100% (for γ-HCH, α-endosulfan,

Table 2
Pesticide concentration levels (pg/mL) measured in urine samples from the ELFE pilot cohort, 2007 (n = 93).
Pesticides LOD (pg/mL) % Detection Min P5 P25 P50 P75 P95 Max

Organochlorines
α-HCH 10 0 – – – – – – <10
β-HCH 100 0 – – – – – – <100
γ-HCH 0.7 8 – – – – <0.7 0.81 1.35
δ-HCH 100 0 – – – – – – <100
ε-HCH 20 0 – – – – – – <20
o,p’-DDE 10 1 – – – – – <10 15.2
p,p’-DDE 8.4 5 – – – – – <8.4 47.9
o,p’-DDD 20 0 – – – – – – <20
p,p’-DDD 40 0 – – – – – – <40
o,p’-DDT 20 0 – – – – – – <20
p,p’-DDT 100 0 – – – – – – <100
Aldrin 10 0 – – – – – – <10
Isodrin 20 0 – – – – – – <20
Dieldrin 5 0 – – – – – – <5
Endrin 20 0 – – – – – – <20
α-Endosulfan 0.4 0 – – – – – – <0.4
β-Endosulfan 0.7 5 – – – – – <0.7 5.50
Heptachlor 20 0 – – – – – – <20
Heptachlor-exo-epoxide 20 0 – – – – – – <20
Heptachlor-endo-epoxide 10 0 – – – – – – <10
trans-Chlordane 2 0 – – – – – – <2
cis-Chlordane 2 0 – – – – – – <2
oxy-Chlordane 10 0 – – – – – – <10
Pentachlorophenol 60 100 75.0 99.9 199 360 878 1 929 11 300
Hexachlorobenzene 0.1 17 – – – – <0.1 0.65 50.3
Organophosphates
DMP 90 95 – <90 891 2 775 8 275 38 444 126 201
DMTP 206 100 206 638 2 905 7 795 25 438 115 712 761 940
DMDTP 32 89 – <32 137 657 1894 16 805 143 875
DEP 355 100 355 709 1939 5 132 10 554 30 252 75 153
DETP 15 100 15.3 140 369 1 221 3 338 12 375 51 527
TCPy 63 100 63.2 473 1 827 6 709 16 553 98 835 302 628
PNP 134 100 134 232 395 602 1 055 2 214 4 205
3Me4NP 10 41 – – – <10 54.7 291 1 778
Malathion CA 1000 0 – – – – – – <1000
Pyrethroids
Cyhalothrin 10 0 – – – – – – <10
Permethrin 50 0 – – – – – – <50
Cypermethrin 0.75 1 – – – – – <0.75 0.75
Fenvalerate 6 2 – – – – – <6 40.6
Deltamethrin 160 0 – – – – – – <160
2-ClBA 10 1 – – – – – <10 365
Br2CA 20 86 – <20 61.6 125 306 536 6 276
Cl2CA 40 100 61.2 74.9 157 343 1 149 4 125 11 171
ClCF3CA 4.1 18 – – – – <4.1 149 388
4F3PBA 100 2 – – – – – <100 17 659
3-PBA 46 100 45.7 97.8 207 369 658 3 059 5 189
Carbamates
2-Isopropoxyphenol 45 22 – – – – <45 534 746 525
Carbofuranphenol 105 10 – – – – <105 600 8 225
Phenylpyrazoles
Fipronil 0.9 2 – – – – – <0.9 2.41
Fipronil sulfone 3.7 2 – – – – – <3.7 5.06
Miscellaneous
Trifluralin 0.2 34 – – – <0.2 0.82 4.78 7.47
Oxadiazon 10 0 – – – – – – <10
Diflufenican 1 25 – – – – <1 48.2 54.1

4
E.M. Hardy et al.
pentachlorophenol and hexachlorobenzene) (Table 1). Concerning the 9
organophosphate metabolites tested, 2 were never detected and the
detection frequencies of the others ranged from 4% for DMTP to 100%
for DEP, DETP, TCPy and PNP. All the parent pyrethroids except fen­
valerate were detected in at least 4% of the hair samples. Among the 6
pyrethroid metabolites, 5 were detected in 1% (Br2CA) to 100% (3-PBA)
of the samples. Carbamates, phenylpyrazoles and other miscellaneous
pesticides were also found in the samples with a frequency ranging from
8% for carbofuranphenol to 100% for trifluralin and diflufenican.
For the 19 pesticides detected in at least 50% of the samples, the
median concentration was below 1 pg/mg for 9 compounds (min.
0.13 pg/mg for oxadiazon) and higher than 10 pg/mg for 4 of them
(max. 51.1 pg/mg for diethylphosphate (DEP)). The highest concentra­
tion was observed for pentachlorophenol (organochlorine) and
permethrin (pyrethroid), with values of 1041 and 1241 pg/mg
respectively.
3.2. Detection frequency and concentration range in urine
Only 6 out of the 25 organochlorines analysed in this study were
detected in urine. Five of them were detected in<20% of the samples
while pentachlorophenol was the only one detected in all the samples
analyzed. Among the 9 organophosphate metabolites investigated, only
malathion carboxylic acid (malathion CA) was never detected and all the
other ones were detected with frequencies ranging from 41% for 3-
methyl-4-nitrophenol (3Me4NP) to 100% (for five of them). Parent py­
rethroids were almost never found in urine whereas 3 of their metabo­
lites were detected in > 80% of the samples. Among the other classes of
chemicals tested here, phenylpyrazoles were poorly detected in urine
(2%) and the detection frequencies of trifluralin, diflufenican and the 2
carbamates in urine did not exceed 35%.
In the 11 compounds found in at least 50% of the samples, median
concentrations varied from 125 pg/mL (for Br2CA) to 7795 pg/mL (for
DMTP) and maximum concentrations were observed for DMTP (0.76 µg/
mL) and 2-IPP (2-Isopropoxyphenol)(0.75 µg/mL).
4. Discussion
The detection rates and levels of concentration observed in hair in
the present work were in line with data available in the literature.
Concerning organochlorines, the detection rates of γ-HCH, α-endo­
sulfan, pentachlorophenol and hexachlorobenzene were above 92% in
other studies conducted on the French population (metropolitan)
(Iglesias-González et al., 2020; Beranger, 2018), which is in agreement
with the 100% detection observed here. The median concentrations
reported in these studies were in the range of 1.58–2.43 pg/mg (vs.
2.00 pg/mg here) for γ-HCH, 0.09–0.15 pg/mg (vs. 0.32 pg/mg here) for
α-endosulfan, 10.0–10.2 pg/mg (vs. 19.6 pg/mg here) for pentachloro­
phenol and 0.10–0.12 pg/mg (vs. 0.48 pg/mg here) for hexa­
chlorobenzene. The low detection rates of DDEs, DDDs and DDTs (from
0% to 10%) observed in the present work were also in line with the
previous studies conducted on other population groups of metropolitan
France (Iglesias-González et al., 2020; Beranger, 2018) but were lower
than values reported in studies conducted in other countries, reaching
detection rates of 100% (Salquebre, 2012; Schummer, 2012; Wielgomas
et al., 2012; Tsatsakis et al., 2008; Tsatsakis, 2008; Covaci, 2008).
Because the sensitivity of the methods used in these studies were in the
same range as in the present work, the low frequency of detection of
DDT congeners observed in the French women suggests lower exposure
to these chemicals than in the other countries.
For the organophosphate metabolites detected in > 80% (DMP, DEP,
DETP), similar trend was also observed in the studies conducted on other
European populations (Kokkinaki, 2014; Iglesias-González et al., 2020;
Beranger, 2018; Hernandez, 2019). For instance, in Europe, DEP
detection rates were between 86% and 100% and median concentrations
ranged from 3.43 pg/mg to 85.4 pg/mg compared to a detection rate of
5
Environment International 152 (2021) 106481
100% and a median value at 51.1 pg/mg in the present work. The results
obtained for pyrethroid biomarkers were also in keeping with the ones
reported in French and Luxembourgish populations (Iglesias-González
et al., 2020; Beranger, 2018; Salquebre, 2012; Schummer, 2012) since
permethrin was found here in 94% of the samples at a median concen­
tration of 27.9 pg/mg while it was found in 87–100% of the samples,
with a median concentration ranging from 33 pg/mg to 100 pg/mg in
these other studies.
The detection rates and levels of concentration of urinary pesticide
metabolites found in the present work were also in accordance with the
literature. For pentachlorophenol, the detection rate of 100% and the
median concentration of 360 pg/mL were in line with the results on
French pregnant women published by Fréry et al. (Frery, 2017)
reporting a detection rate of 66.2% and a median concentration of
850 pg/mL. Other authors reported much lower detection rates for
pentachlorophenol (2.3–10.3%) but the study was conducted on the US
population and the method also had a higher limit of detection (Cas­
torina, 2010). Among organophosphate metabolites, dialkylphosphates
were detected in 89% to 100% of the samples, which is comparable to
the literature reporting rates between 77.6% and 100% (Frery, 2017; Ye,
2008). The ranges of concentrations reported in these studies were also
similar to what was observed in the present work (for instance, DMTP
median concentration at 7795 pg/mL vs. 10600 pg/mL for a Dutch
pregnant women population). Furthermore, TCPy, which is specific to
chlorpyrifos, was found in 71.2–100% of urine samples from Dutch and
US pregnant women with median concentrations ranging from 1200 to
3200 pg/mL (Castorina, 2010; Ye, 2008) while it was here detected in all
the samples at a median concentration of 6709 pg/mL. The results ob­
tained in the present study for pyrethroid metabolites were also in line
with previous data on French pregnant women cohorts (Viel, 2015;
Frery, 2017; Dereumeaux, 2018). The metabolite 4F3PBA was poorly
detected here (2% with a LOD at 100 pg/mL), as it is observed in these
studies (8.8–29.8% with LODs from 3 to 30 pg/mL). Other pyrethroid
metabolites such as Br2CA, Cl2CA and 3-PBA presented here high rates of
detection (86–100%) which is comparable to the values reported in the
latter studies (detection rates from 30.2% to 100%). Likewise, we
observed here median concentrations for Br2CA and 3-PBA at 125 pg/
mL and 369 pg/mL respectively, whereas Dereumeaux et al. (Der­
eumeaux, 2018) and Fréry et al. (Frery, 2017) indicated medians at
150–230 pg/mL and 51–360 pg/mL respectively. In parallel, the lack of
published results on parent pesticides and their extremely low rates of
detection in the present work confirmed the poor relevance of the
determination of these lipophilic chemicals in urine.
The information provided by urine and hair respectively can be
30
25
Number of biomarkers detected
22
20
15
12
10
5
0
Hair Urine
Fig. 1. Number of biomarkers (pesticides and metabolites) of exposure detec­
ted in each hair and urine sample.
E.M. Hardy et al.
appreciated by the number of compounds detected in each of these
matrices. As observed on Fig. 1, 22 different biomarkers of exposure
were detected on average in each hair sample, whereas only 12 were
detected per urine sample. These observations are in accordance with
previous results obtained from rats under controlled exposure to a
mixture of pesticides from different chemical classes, where the number
of compounds detected in hair was always higher than in urine
(Appenzeller, 2017). Similarly, previous studies conducted on human
populations also reported higher detection frequency in hair compared
to urine samples collected from the same individuals (Kokkinaki, 2014;
Hernandez, 2019; Kim et al., 2019; Wang, 2018). This difference can be
explained by the different time window covered by each matrix. On the
one hand, most chemicals are transferred in urine within a few hours
after exposure, and their concentration may become undetectable
rapidly after exposure stops. The moment of urine sampling has there­
fore a direct and significant impact on the chemicals present in the
sample. On the other hand, hair may contain the chemicals that have
been present in the body (even for a short time) over a period of weeks to
months, depending of the length of the hair strand. This wide window of
detection highly increases the chances to cover the time of exposure and
to detect the corresponding biomarkers. Moreover, the moment of hair
sampling has almost no impact on the result.
Physicochemical properties may also influence the transfer of
chemicals into urine and hair. As observed on Fig. 2, parent pesticides
(mostly hydrophobic) were almost never detected in urine, contrary to
hydrophilic metabolites that were highly detected in this matrix. This
observation is in line with general metabolism principles, aiming at
increasing the solubility of xenobiotics to facilitate their elimination in
urine. Contrary to metabolites, unmodified (hydrophobic) chemicals are
not soluble in aqueous media and are therefore not or barely transferred
to urine, explaining their absence in the urine samples analyzed in this
study. In parallel, both parent and metabolites were detected in hair. As
previously demonstrated, chemicals are mainly incorporated into hair
from blood (Chata, 2016). Although hydrophilic metabolites are trans­
ferred from blood to urine through renal excretion, their concentration
and residence time in blood can be comparable or even higher than the
ones of the parents (Chata, 2019). As a consequence, both parent pes­
ticides and their metabolites can be incorporated into hair, explaining
the results observed in the present study. Only a few metabolites of
organophosphates (DMTP and DMDTP) and pyrethroid (Br2CA) were
not or seldom detected in hair despite their frequent presence in urine.
This discrepancy might be explained by a very fast transfer to urine,
short after their formation in blood, leading to insufficient residence
time and concentration in blood to allow their incorporation in hair at
detectable levels.
Allowing for the detection of both parent pesticides from different
chemical classes and their metabolites, hair provides a more compre­
hensive and more specific information on exposome than urine, which
only allows the detection of metabolites (often non-specific). Moreover,
the presence of parent pesticides in hair ensures that individuals have
Hair Urine
100
90
Detection frequency (%)
80
70
60
50
40
30
20
10
0
Organochlorines Organophosphate metabolites
Fig. 2. Detection frequency of the pesticides and metabolites in hair and urine. Only biomarkers detected in at least one matrix are presented.
6
Environment International 152 (2021) 106481
been exposed to the parent itself, contrary to urine, which does not allow
differentiating exposure to the parent from exposure to the metabolite.
For the metabolites detected in urine only, this matrix remains relevant
but the short time window it is representative of has to be taken into
account. Repeated samplings might thus be necessary to compensate for
the high variability of urinary biomarkers concentration (Faÿs, 2020).
Only a limited amount of data is available in the literature con­
cerning the effect of cosmetic treatment on the biomarkers analyzed in
hair. These data mainly concerned illicit drugs and nothing was pub­
lished on pesticides. According to these studies, bleaching and thermal
treatment may decrease the concentration of some chemicals in hair,
whereas coloring has a limited or no effect (Ettlinger et al., 2014; Van
Elsué and Yegles, 2019; Gambier, 2019). In the present study, although
visual inspection did not suggest bleaching for any of the sample, ther­
mal treatment cannot be excluded. Should this have occurred, it could
only have induced a decrease in the concentration and frequency of
detection of the biomarkers. This would therefore no contradict the
statement that hair analysis provides more comprehensive information
on pesticides exposure than urine.
In order to appreciate multiple exposure of the pregnant women, the
concentration of all the compounds detected were summed for each
participant (Fig. 3). Although this approach does not allow a direct
assessment of the risk associated with exposure due to the different
toxicity and mode of action of each pesticide, it provides a simplified
overview highlighting disparities between individuals. The use of moles
(pmol/mg for hair and pmol/mL for urine respectively) was preferred to
limit the bias due to different molecular weight compounds. The sum­
med concentration of pesticides measured in the hair samples from the
pregnant women ranged from 0.22 pmol/mg to 8.19 pmol/mg, i.e.
covering almost 2 orders of magnitude. Similar wide distribution in
pesticide concentration in hair were already reported on children pop­
ulations. This result confirm the disparities in exposure that can exist
between different subjects, even within small groups of individuals from
the same area. A wider concentration range was observed for urinary
analysis since the summed concentration covered almost 3 orders of
magnitude (between 10.91 pmol/mL and 7420 pmol/mL). This differ­
ence of range width in urine could suggest a wider distribution in the
level of exposure of the individuals, which would be correct on the short
term but might not reflect the long term. Actually, the wide distribution
of chemicals concentration in urine rather reflects the high variability in
urinary biomarker concentration (Faÿs, 2020). Consequently, the wider
distribution of pesticides/metabolites concentration in urine compared
to hair does not necessarily mean that urine allows a more reliable
classification of the individuals according to their level of exposure than
hair. Indeed, intra-class correlation coefficients (ICCs) values reported in
different studies for urinary pesticides/metabolites ranged from 0.08 to
0.35 (Faÿs, 2020; Meeker, 2005; Attflied, 2014), indicating a poor
reproducibility of the concentration in different samples collected from
the same individual. On the other hand, a study from Beranger et al.
(Beranger, 2018) analyzing pesticides/metabolites in hair reported ICC
Parents Metabolites
Pyrethroids Carbamates
es Phenyl pyrazoles
les Miscellaneous
E.M. Hardy et al. Environment International 152 (2021) 106481

Fig. 3. Distribution of summed concentrations of biomarkers of exposure in hair and urine for the entire population.

values between 0.7 and 0.94 for most of the biomarkers tested, indi­
cating low intra-individual variability and hence robust classification of
the individuals according to their level of exposure.
In order to assess the correlation between pesticide levels measured
in hair and urine from the same individuals, Pearson and Spearman
coefficients were calculated for the 8 biomarkers detected in at least
80% of the urine and hair samples, namely 1 organochlorine (PCP), 5
metabolites of organophosphates (DMP, DEP, DETP, TCPy, PNP) and 2
metabolites of pyrethroids (Cl2CA, 3-PBA). No significant association
was observed for almost all the chemicals tested, with the exception of
pentachlorophenol (PCP) (Fig. 4). The poor correlation between hair
and urine biomarker concentration was already observed on other
human groups for organophosphate metabolites (Kokkinaki, 2014;
Hernandez, 2019). The lack of correlation between the two matrices is
most likely due to the high variability observed in the concentration of
biomarkers of exposure in urine. As mentioned above, hair provides
information representative of the average level of exposure over periods
covering up to several months, and repeated samples collected from the
same subject usually contain similar biomarker concentration
(Beranger, 2018). On the contrary, urinary biomarkers usually corre­
spond to the exposure within the few hours before sampling only, and a
single urine sample fails to represent the chronic level of exposure due to
the high variability of urinary biomarkers over time (Faÿs, 2020). This
difference in the time window covered by each matrix most likely ex­
plains the poor correlation between them regarding biomarker
concentration.

Fig. 4. Correlations between pesticide metabolite concentration in hair and urine for the same individuals.

7
E.M. Hardy et al.
5. Conclusion
To the best of our knowledge, the present study is the first one
analyzing parent and metabolites of pesticides from different chemical
classes in urine and hair samples collected from the same population.
This study highlights the multiple exposure of the pregnant women
included in this cohort and gives an overview of the information that can
be obtained from urine and hair respectively regarding pesticide expo­
sure. The comparison of the two matrices suggests that hair would
provide a more comprehensive information on exposome than urine. In
particular, hair allows the detection of both parent pesticides (mainly
hydrophobic) and hydrophilic metabolites, whereas urine only allows
for the detection of metabolites. The presence of some metabolites in
urine only, however suggests that urine and hair would be comple­
mentary for the exposure assessment, but the difference in the time
window covered by each matrix has to be considered in data interpre­
tation. The results also demonstrated the absence of correlation between
the two matrices, probably due to the different time windows covered by
each of them. This study thus supports the relevance of hair analysis in
future epidemiological studies investigating association between expo­
sure and adverse health effects.
CRediT authorship contribution statement
Emilie M. Hardy: Methodology, Formal analysis, Investigation,
Data curation, Writing - original draft. Clémentine Dereumeaux:
Writing - review & editing. Laurence Guldner: Writing - review &
editing. Olivier Briand: Writing - review & editing. Stéphanie Van­
dentorren: Project administration, Resources, Writing - review & edit­
ing. Amivi Oleko: Project administration, Resources, Writing - review &
editing. Cécile Zaros: Project administration, Resources, Writing - re­
view & editing. Brice M.R. Appenzeller: Conceptualization, Method­
ology, Formal analysis, Resources, Writing - original draft, Visualization,
Supervision, Project administration, Funding acquisition.
Declaration of Competing Interest
The authors declare that they have no known competing financial
interests or personal relationships that could have appeared to influence
the work reported in this paper.
Acknowledgements
This study was carried out in the framework of the call for Research
Project 2010 of the National Research Programme for Environmental
and Occupational Health’ (PNR-EST) of the French Agency for Food,
Environmental and Occupational Health Safety (ANSES, Agence natio­
nale de sécurité sanitaire, de l’alimentation, de l’environnement et du
travail), with the financial support of the National Office for Water and
Aquatic Environments (ONEMA, Office National de l’Eau et des Milieux
Aquatiques) supporting the implementation of the Plan Ecophyto 2018,
France.
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