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Academic Editor: Pan Yang
Received: 8 January 2025
Revised: 2 March 2025
Accepted: 10 March 2025
Published: 16 March 2025
Citation: Rubilar, P.; Hirmas-Adauy,
M.; Apablaza, M.; Awad, C.; Molina,
X.; Muñoz, M.P.; Delgado, I.;
Zanetta-Colombo, N.C.;
Castillo-Laborde, C.; Matute, M.I.; et al.
Arsenic Exposure During Pregnancy
and Childhood: Factors Explaining
Changes over a Decade. Toxics 2025,13,
215. https://doi.org/10.3390/
toxics13030215
Copyright: © 2025 by the authors.
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licenses/by/4.0/).
Article
Arsenic Exposure During Pregnancy and Childhood: Factors
Explaining Changes over a Decade
Paola Rubilar 1, * , Macarena Hirmas-Adauy 1, Mauricio Apablaza 2, Camila Awad 1, Xaviera Molina 1,
María Pía Muñoz
3,4
, Iris Delgado
1
, Nicolás C. Zanetta-Colombo
5,6
, Carla Castillo-Laborde
1
, María Isabel Matute
1
,
Mauricio A. Retamal 7, Andrea Olea 1, Paulina Pino 3, Claudia González 1, Cristóbal Carvajal 8
and Verónica Iglesias 3,*
1Centro de Epidemiología y Políticas de Salud, Facultad de Medicina Clínica Alemana, Universidad del
Desarrollo, Santiago 7610658, Chile; mhirmas@udd.cl (M.H.-A.); c.awad@udd.cl (C.A.);
xmolinaa@udd.cl (X.M.); idelgado@udd.cl (I.D.); carlacastillo@udd.cl (C.C.-L.); mimatute@udd.cl (M.I.M.);
aolea@udd.cl (A.O.); claudiagonzalez@udd.cl (C.G.)
2Facultad de Gobierno, Universidad del Desarrollo, Santiago 7610658, Chile; mapablaza@udd.cl
3Programa de Epidemiología, Escuela de Salud Pública, Facultad de Medicina, Universidad de Chile,
Santiago 8380453, Chile; maria.munoz.qu@uchile.cl (M.P.M.); ppino@uchile.cl (P.P.)
4Programa de Doctorado en Salud Pública, Escuela de Salud Pública, Facultad de Medicina, Universidad de
Chile, Santiago 8380453, Chile
5Department of Geography, South Asia Institute, Heidelberg University, 69120 Heidelberg, Germany;
nicolas.zanetta@stud.uni-heidelberg.de
6Heidelberg Center for the Environment (HCE), Heidelberg University, 69120 Heidelberg, Germany
7Programa de Comunicación Celular en Cáncer, Instituto de Ciencias e Innovación en Medicina, Facultad de
Medicina Clínica Alemana, Universidad del Desarrollo, Santiago 7610658, Chile; mretamal@udd.cl
8Centro de Informática Biomédica, Instituto de Ciencias e Innovación en Medicina, Facultad de Medicina
Clínica Alemana, Universidad del Desarrollo, Santiago 7610658, Chile; cristobalcar@gmail.com
*Correspondence: paolarubilar@udd.cl (P.R.); viglesia@uchile.cl (V.I.); Tel.: +56-9-99992012 (P.R.);
+56-9-98640035 (V.I.)
Abstract: Arsenic chronic exposure, particularly in its inorganic form, represents a signifi-
cant public health concern. This study was conducted in Arica, the northernmost city in the
country, whose inhabitants have been exposed to inorganic arsenic both naturally through
drinking water and anthropogenically due to a toxic waste disposal site. We explored
changes in inorganic arsenic levels in a cohort of pregnant women and their children over
a decade, identifying exposure trends and their determinants. We used data on arsenic
exposure through maternal urine samples during pregnancy, collected by the Health Au-
thority between 2013 and 2016 (measurement 1), and followed up with assessments of their
children in 2023 (measurement 2). Temporal changes in inorganic arsenic concentration
were analyzed using the Wilcoxon Signed-Rank test, and a mixed linear regression model
was employed to determine which factors contributed to urinary inorganic arsenic levels.
We did not observe significant differences in mean arsenic concentrations between the
two-time points (p= 0.4026). The mixed linear regression model revealed that children
consuming bottled water had 8.3% lower urinary inorganic arsenic concentrations than
those drinking tap water (95% CI:
−
15.36 to
−
0.54%). Additionally, children from ethnic
groups had 8.64% higher inorganic arsenic concentrations (95% CI: 0.49 to 17.5%), while
those with caregivers with higher education showed a 13.67% reduction (95% CI:
−
25.06 to
−
0.56%). Despite mitigation efforts, these findings underscore the ongoing risk of inorganic
arsenic exposure among vulnerable populations. They further emphasize the importance
of addressing natural arsenic contamination in water and implementing targeted interven-
tions to reduce disparities associated with socioeconomic and demographic factors.
Toxics 2025,13, 215 https://doi.org/10.3390/toxics13030215
Toxics 2025,13, 215 2 of 14
Keywords: inorganic arsenic; prenatal exposure; biomarker; exposure in children; environ-
mental justice; water exposure
1. Introduction
Arsenic exposure is a global public health problem. Arsenic, in its inorganic form, is
naturally found in the groundwater of many countries and is highly toxic. The main threat
comes from using water contaminated with arsenic for human consumption, cooking, and
the irrigation of vegetables [
1
]. Exposure can also result from anthropogenic pollution,
mainly from mining and metallurgic activities or industrial waste deposition [
2
]. Arsenic
can cross the placental barrier during pregnancy when the fetus is still developing, which
can be risky for fetal and child health, in addition to generating premature diseases in
adulthood [
1
,
3
–
5
]. This relates to the concept of Developmental Origins of Health and
Disease (DOHaD), which suggests that certain environmental factors during critical stages
of development can influence tissue formation and function, leading to adverse health
effects throughout life [6].
In 2001, the World Health Organization (WHO) set a limit of 10
µ
g/L (0.01 mg/L)
of arsenic in safe drinking water to protect public health. However, evidence indicates
that arsenic can cause harm even at concentrations below 10
µ
g/L [
7
,
8
], especially among
vulnerable populations [
2
,
9
,
10
], who often cannot protect against arsenic contamination. In
urban settings, low-income and marginalized communities usually reside in neighborhoods
with inadequate water and sewage systems, higher pollution levels, proximity to industrial
or mining waste sites, and less access to healthcare and environmental information [
11
,
12
].
The lack of policies and investment in health infrastructure perpetuates toxic exposure,
increasing health disparities and the burden of arsenic-related diseases [
2
,
13
]. There is
concern about whether current safety standards are adequate, especially for vulnerable
populations [2,9,10].
This research was conducted in Arica, the northernmost city of Chile, where 98.2%
of the region’s population lives [
14
]. Arica is in a geological area rich in minerals, where
arsenic is naturally present in rock formations and leaches into groundwater [
15
]. In the
1980s, over 20,000 tons of toxic waste was imported for recycling and abandoned in an
urban area of the city [
16
]. Years later, housing complexes were built near this area. An
analysis of the composition of the toxic waste showed high concentrations of heavy metals,
including arsenic and lead. This situation led to a public health and environmental crisis,
prompting Law No. 20,590 in 2012, which considered interventions and the monitoring
of the exposed population [
17
]. This study explores changes in inorganic arsenic levels
among expectant mothers and their children over a decade, identifying exposure trends
and their determinants. Specifically, we will evaluate socioeconomic and environmental
determinants of inorganic arsenic concentrations.
2. Methods
2.1. Design and Study Population
This article presents a follow-up study of a pregnant women–child cohort. Baseline
data were collected by the Health Authority of the Region of Arica and Parinacota between
2013 and 2016 from 1644 pregnant women receiving care at the Regional Hospital of Arica
before delivery (measurement 1). During that period, surveys were administered, and
inorganic arsenic concentrations in urine samples were measured. The Health Authority
provided this information as part of a collaboration agreement.
Toxics 2025,13, 215 3 of 14
The original sample size was calculated, assuming a blood lead prevalence of 1%
(samples > 10
µ
g/dL) and inorganic arsenic prevalence in urine >35
µ
g/L of 12%, with
margins of error of <0.5% for lead and <2% for arsenic, resulting in a sample size of
1519 mother-newborn pairs, accounting for a 10% loss rate.
Measurement 2 was carried out in 2023 as part of a study titled “Arsenic exposure and
its association with proinflammatory cytokines in children born between 2013 and 2016
in Arica”. For this purpose, 980 women (59.6% of the original cohort) were successfully
re-contacted, and 782 agreed to participate and met the inclusion criterion of still residing
in the city, representing 47.6% of the original sample and 79.8% of those re-contacted. A
random subsample of mothers was selected, resulting in a cohort of 450 children aged 7 to
10 (seven mothers had multiple births).
Comparison between the entire sample of measurement 1 (1644 pregnant women)
and the subsample of mothers enrolled in measurement 2 (443) showed similar maternal
characteristics and no differences in the distribution of inorganic arsenic concentration (see
Supplementary Materials). In 2023, both mothers and children provided informed consent
and assent, respectively. Additionally, a survey was administered to the adult responsible
for the child at enrollment.
2.2. Inorganic Arsenic Exposure
In the first measurement (2013–2016), trained healthcare personnel collected a spot
urine sample from each mother during prenatal care visits or hospitalization before delivery.
Inorganic arsenic and its methylated metabolites were analyzed using atomic absorption
spectrophotometry with hydride generation (AAS-HG) at the Occupational Health Labo-
ratory of the Institute of Public Health laboratory (ISO/IEC 17025:2017) [
18
]. The limit of
detection (LOD) was 5
µ
g/L, and concentrations below the LOD (10.6%) were assigned
a value of 2.5
µ
g/L (LOD/2). Information on the urinary concentration of inorganic ar-
senic and its methylated metabolites in pregnant women as well as the urinary creatinine
concentration was provided by the Arica and Parinacota Region Health Authority.
For the second measurement (2023), a trained nursing assistant visited each child’s
residence to collect a 50 mL spot urine sample. This visit was scheduled one or two
days in advance, during which participants received specific instructions which were
reinforced on the day of the visit. Caregivers were instructed to ensure children avoided
liquids or urination for four hours before the appointment and abstained from seafood
consumption for 72 h. The urine samples were code-labeled, stored at
−
4
◦
C, and delivered
to an accredited private laboratory [
19
]. The analyses were performed within the same
week using inductively coupled plasma mass spectrometry (Perkin Elmer NexION®2000
ICP-MS), allowing arsenic speciation and the individual determination of each species of
interest: arsenite (AsIII), arsenate (AsV), monomethylarsonic acid (MMA), dimethylarsinic
acid (DMA), and arsenobetaine. The detection limit for each analyte was 0.1
µ
g/L. In
this second measurement, we summed the inorganic arsenic species (AsIII and AsV) and
methylated arsenic species (MMA and DMA) as a measurement of “inorganic arsenic
concentration” based on evidence establishing it as a reliable biomarker for assessing recent
inorganic arsenic exposure from multiple sources [
20
–
23
]. All samples had inorganic arsenic
values above the detection limit. Urinary creatinine concentration was also determined in
the same laboratory.
2.3. Covariates
Sociodemographic information like age, ethnic group, and years of education were
collected through a survey, along with health history data such as comorbidities, body
mass index, and maternal tobacco use. Additionally, risk factors related to arsenic exposure
Toxics 2025,13, 215 4 of 14
were assessed, including living on paved streets, using pesticides or derivatives within
the household, and consuming fish three days before urine sampling. During the first
measurement, participants were asked if they lived in an area classified as at risk by
the Health Authority. In the second measurement, they were asked whether they were
beneficiaries of Law 20,590, which primarily applies to those who had lived in high-risk
areas [
24
]. Additionally, the second measurement gathered information on the drinking
water source used by both the child and the mother during pregnancy.
2.4. Statistical Analysis
Unadjusted and creatinine-adjusted inorganic arsenic concentration (for values be-
tween 0.3 and 3.0 gr/L) were described using descriptive statistics, including maximum
and minimum values, 25th, 50th, 75th, 90th, and 95th percentiles, arithmetic mean, standard
deviation, and geometric mean. Creatinine adjustment reduced the sample size by 405
mothers and 408 children.
Differences in creatinine-adjusted inorganic arsenic concentration between measure-
ments 1 and 2 were compared with the Wilcoxon Signed-Rank test. We use the same test to
compare the creatinine-adjusted inorganic arsenic concentration in specific subgroups of the
study, such as pregnant women who lived in the area considered at risk of exposure to toxic
waste in measurement 1, and the inorganic arsenic concentration of their children in mea-
surement 2. Similarly, the inorganic arsenic concentration of children whose parents were
covered by Law 20.590, established in measurement 2, was compared with the inorganic
arsenic concentration of their mothers during pregnancy, established in measurement 1.
Due to the non-normal distribution of inorganic arsenic concentrations, values were
transformed to a logarithmic scale. Spearman’s correlation coefficient was used to eval-
uate the relationship between the concentration of inorganic arsenic in the mother and
their children. A bivariate analysis of creatinine-adjusted inorganic arsenic concentration
was conducted using the Wilcoxon, Mann–Whitney, and Kruskal–Wallis tests to explore
differences across sociodemographic, health, and exposure-related factors.
A log-transformed linear mixed model for inorganic arsenic was implemented to
assess the factors explaining the baseline inorganic arsenic exposure and its trajectory
over time. Covariates with a p-value <0.10 in the bivariate analysis were included in the
model: ethnicity, schooling, the age of the child, a change of address since birth, drinking
water source, the use of pesticide, and living on a street with paving. Since these last three
correspond to risk variables for arsenic exposure, they were assessed using information
from measurements 1 and 2. The random effect of the model was given by the individual
(child). The intraclass correlation (ICC) was calculated to assess the variance decomposition.
The model is as follows:
log inorganic arsenic Yij =β0+β1drinking water +β2belongs to ethnic +β3schooling +β4u se o f p esticides
+β5paved street +β6age o f the child +β7chan ge o f address +u0j+ϵij
To improve the interpretation of the coefficients, the beta values were transformed
using the following formula:
Percentage = (exp(β)−1) ×100
The statistical analyses were conducted using R (version 4.2.3) within R Studio.
Toxics 2025,13, 215 5 of 14
3. Results
3.1. Characteristics of Pregnant Women in Measurement 1 and Their Children in Measurement 2
Table 1describes the current study sample, including the characteristics of the pregnant
women during measurement 1 (2013–2016) and the characteristics of their children in 2023
(measurement 2). The children’s survey was answered by the adult responsible for the
child, which in 86.4% of cases was the mother, in 6.4% of cases the father, and in 7.1% of
cases another caregiver (sibling, grandparent, or uncle/aunt).
Table 1. Sociodemographic and risk characteristics of arsenic exposure in pregnant women measured
in 2013–2016 and their children in 2023, Arica, (Chile).
Sample Size
(Pregnant
Women/Children)
Measurement 1
(Pregnant Women)
Measurement 2
(Children)
n%n%
Age of the mother 443 Under 20 years of age 61 13.8
20 to 39 years old 373 84.2
40 years old or older 9 2
Age of the children 450 7 years old 146 32.4
8 years old 233 51.8
9 years old or older 71 15.8
Sex Female 223 49.6
Male 227 50.4
Body mass index 441/448 Malnourished 0 0 21 4.7
Normal weight 65 14.7 178 39.7
Overweight 167 37.8 101 22.5
Obese 209 47.4 148 33.0
Belongs to ethnic minority 438/450 Yes 171 39.0 204 45.3
Schooling 441/450 Basic education or less 21 4.8 50 11.1
(mother/responsible adult)
Highschool or less 348 78.9 247 54.9
At least one year of
tertiary education 72 16.3 153 34.0
Use of pesticides 437/450 Yes 12 2.7 214 47.6
Smoking 437/450 Yes 3 0.7 113 25.1
(pregnant/mother of the
child) No 239 54.3 337 74.9
Quit smoking (6 months
to 1 year ago) 198 45
Comorbidity 333/450 Yes 54 16.2 55 12.2
Living on a paved street 443/449 No 86 19.4 77 17.2
Drinking water 443/450 Tap water 173 39.0 64 14.2
Rural drinking water or
well water 11 2.5 4 0.9
Bottled water 259 59.5 382 84.9
Fish consumption (last 3
days) 443/450 Yes 136 30.7 72 16
Living in an exposed
area/beneficiary law 443/410 Yes 43 9.7 72 16
Change of address since
birth 450 No 156 34.7
In measurement 1, 84.2% of the pregnant women were between 20 and 39 years old,
with a high prevalence of overweight and obesity (85.2%) before pregnancy. Of these
women, 39% reported belonging to an ethnic group, which increased to 45.3% among their
children in measurement 2. Regarding educational attainment, only 16.3% of the pregnant
Toxics 2025,13, 215 6 of 14
women reported completing more than 12 years of education in measure 1, compared to
34% of the caregivers in 2023. Pesticide use increased significantly, from 2.7% of mothers
during pregnancy to 47.6% in measurement 2. The street pavement remained consistent at
around 80%, while 34.7% of the children had changed residences since birth. Significant
changes were observed in drinking water sources, with a decrease in tap water use, an
increase in bottled water consumption, and a further reduction in the use of well water
in measurement 2. Regarding residence in areas at risk of soil contamination, as asked in
measurement 1, 9.7% of the mothers lived in such areas. In measurement 2, 16% of the
children had at least one parent registered as a beneficiary of the law in question.
3.2. Inorganic Arsenic Concentration During Pregnancy and Childhood
The median concentrations of creatinine-corrected inorganic arsenic were 17.0
µ
g/g
for pregnant women (measurement 1) and 16.3
µ
g/g for children (measurement 2), with
geometric means of 16.9
µ
g/g and 16.6
µ
g/g, respectively. No significant differences
were observed between the two measurements over time (Wilcoxon Signed-Rank test p-
value = 0.4026). Similarly, no significant differences were found in the median concentration
of inorganic arsenic between measurements 1 and 2 among pregnant women who were
living in the exposure area (Wilcoxon Signed-Rank test p-value = 0.3042) or among children
whose parents were beneficiaries of the Law No. 20,590 (Wilcoxon Signed-Rank test p-
value = 0.8015). However, a lower median concentration of inorganic arsenic measured in
2023 was observed in this group (Table 2).
Table 2. Concentration of inorganic arsenic in urine of pregnant women (2013–2016) and children
(2023) in Arica.
Measure 1 (Pregnant Women) Measure 2 (Children)
Inorganic Arsenic (*)
Inorganic Arsenic (*)
Corrected by
Creatinine
Inorganic
Arsenic (***)
Inorganic
Arsenic (***)
Corrected by
Creatinine
(n= 443) (n= 405) (n= 450) (n= 408)
µg/L µg/g ** µg/L µg/g **
P25 10 13.1 9.0 11.7
P50 15 17.0 14.6 16.3
P75 23 23.0 20.8 23.0
P90 33 29.8 29.3 31.8
P95 41 38.9 35.9 36.5
Media 18.6 18.9 17.1 19.0
Standard deviation 14.8 9.4 14.8 11.9
Minimum 2.5 3.4 2.5 4.0
Maximum 126 72.8 202.0 146.4
Geometric mean 14.2 16.9 13.5 16.6
Pregnant woman living in an
exposure area (n= 33) 17.0 18.5
Children with a parent who
is a beneficiary of the
Polymetallic Law (n= 55)
17.0 15.4
* inorganic arsenic and its methylated metabolites; ** inorganic arsenic adjusted for creatinine when creatinine is
>0.3 and <3.0 gr/L; *** sum of inorganic arsenic (AsIII + AsV) + MMA + DMA.
A positive correlation was observed between the log-transformed inorganic arsenic
concentration in pregnant women and children (r = 0.2138; p< 0.0001).
Toxics 2025,13, 215 7 of 14
3.3. Bivariate Analysis Between Study Variables and Inorganic Arsenic Concentration in Pregnant
Women and Children
Table 3shows that pregnant women who self-identified as belonging to an ethnic
group had a higher median concentration of inorganic arsenic than those who did not (18.4
vs. 16.3
µ
g/g). Similarly, children reported as belonging to an ethnic group also exhibited
higher concentrations (p-value = 0.009). Both in pregnant women during measurement 1
and the adults responsible for the children during measurement 2, lower years of education
were associated with a higher median concentration of inorganic arsenic.
Table 3. Bivariate analysis of creatinine-adjusted inorganic arsenic concentration (
µ
g/g) in relation to
sociodemographic, health, and arsenic exposure factors in pregnant women (2013–2016) and their
children (2023).
Pregnant Women Children
n(%)
Median
IQR p
Value n(%)
Median
IQR pValue
Age of the
mother
Under 20 years of
age 55 (13.6) 17.2 12.3–23.2 0.884
20 to 39 years old 341 (84.2) 17.0 13.2–22.7
40 years old or
older 9 (2.2) 16.7 15.7–23.9
Age of the
children 7 years old 127 (31.1) 17.3 13.3–23.8 0.026 *
8 years old 216 (52.9) 16.8 11.1–24.1
9 years old or older
65 (15.9) 14.7 11.5–19.3
Sex Female 210 (51.5) 16.7 11.7–22.8 0.985
Male 198 (48.5) 16.0 11.7–23.8
Body mass
index Malnourished 0.926 19 (4.7) 13.5 10.8–21.4 0.679
Normal weight 59 (14.6) 17.1 13.1–23.1 155 (38.2) 16.3 11.4–23.8
Overweight 153 (38.0) 17.2 13.2–22.6 96 (23.7) 17.4 11.6–24.0
Obese 191 (47.4) 16.5 12.8–23.1 136 (33.5) 16.1 12.4–22.7
Belongs to
ethnic Yes 154 (38.5) 18.4 13.6–25.4 0.017 * 185 (45.3) 17.8 13.0–24.2 0.009 *
Schooling
(mother/
Basic education or
less 19 (4.7) 19.4 13.5–24.1 0.220 43 (10.5) 21.1 10.8–28.2 0.029 *
responsible
adult) Highschool or less 315 (78.2) 17.1 13.0–23.5 222 (54.4) 16.8 12.3–23.8
At least one year of
tertiary education 69 (17.1) 15.5 13.1–20.4 143 (35.1) 15.0 10.8–21.4
Use of
pesticides Yes 9 (2.3) 21.2 13.1–22.6 0.295 194 (47.6) 18.8 12.0–24.9 0.006 *
Smoking
(preg-
nant/mother
of the
children)
Yes 3 (0.8) 25.8 16.7–28.6 0.112 100 (24.5) 15.1 11.2–22.7
No 212 (52.7) 17.9 13.3–23.1 308 (75.5) 16.7 11.8–23.2
Quit smoking (6
months to 1 year
ago)
187 (46.5) 15.8 12.4–22.6
Comorbidity Yes 49 (16.3) 16.4 13.9–22.6 0.925 51 (12.5) 14.3 11.8–22.1 0.608
Living on a
paved street No 78 (19.3) 17.9 13.7–23.5 0.442 69 (17.0) 19.1 13.3–28.2 0.025 *
Drinking
water Tap water 158 (39.0) 17.6 13.6–23.5 0.014 * 57 (14) 17.4 13.3–24.7 0.005 *
Rural drinking
water or well water
9 (2.2) 21.2 20.2–35.3 4 (1.0) 33.7 30.0–64.2
Bottled water 238 (58.8) 16.4 12.5–22.6 347 (85.1) 16.0 11.5–22.2
Toxics 2025,13, 215 8 of 14
Table 3. Cont.
Pregnant Women Children
n(%)
Median
IQR p
Value n(%)
Median
IQR pValue
Fish
consumption
(last 3 days)
Yes 136 (30.8) 17.3 13.6–23.6 0.231 61 (15.0) 17.4 12.9–23.7 0.468
Living in an
exposed
area/beneficiary
law
Yes 39 (9.7) 17.7 13.6–24.2 0.536 61 (14.9) 16.3 11.7–24.8 0.868
Change of
address since
birth
No 266 (65.2) 17.4 11.7–23.9 0.075
IQR = interquartile range, * p< 0.05.
Significant differences were observed in the water sources used for consumption by
pregnant women (measurement 1) and children (measurement 2). Well water or rural
potable water consumption had the highest median arsenic concentrations, while bottled
water consumption was associated with lower levels than tap water in both measurement
periods. An inverse relationship was observed among children between age and median
inorganic arsenic concentration, where older age corresponded to lower arsenic levels (p-
value = 0.0256). Furthermore, the use of pesticides and the absence of paved streets around
the children’s homes were associated with higher median inorganic arsenic concentrations.
3.4. Multivariate Model
Table 4presents the factors explaining variations in inorganic arsenic concentration
during pregnancy (measurement 1) and approximately 10 years later (measurement 2).
Children who consumed bottled water during measurement 2 exhibited an 8.25% decrease
in inorganic arsenic concentration compared to those who drank tap water, a statistically
significant result. In contrast, children who consumed well water, rural potable water (APR),
or other informal water sources showed a 35.18% higher inorganic arsenic concentration
than those who drank tap water; however, this finding was not statistically significant.
Individuals who identified as belonging to an ethnic group had an 8.64% higher inorganic
arsenic concentration compared to those who did not identify with any group. In addition,
children whose responsible adults had more years of education showed a reduction in the
inorganic arsenic concentration of 13.67%.
Table 4. Linear mixed model for inorganic arsenic in urine measurements 1 and 2 (log-transformed
adjusted for creatinine).
Estimates (%)
Variables (exp(β)−1) ×
100 pValue Confidence Interval
(95%)
Drinking water Tap water Ref
Rural drinking water
or well water 35.18 0.084 −4.00 to 90.34
Bottled water −8.25 0.037 * −15.36 to −0.54
Living on a paved street No −4.98 0.303 −13.78 to 4.72
Belongs to ethnic Yes 8.64 0.037 * 0.49 to 17.45
Toxics 2025,13, 215 9 of 14
Table 4. Cont.
Estimates (%)
Variables (exp(β)−1) ×
100 pValue Confidence Interval
(95%)
Schooling (mother/
responsible adult)
Basic education or
less Ref
Highschool or less −4.02 0.553 −8.61 to 1.02
At least one year of
tertiary education −13.67 0.042 * −25.06 to −0.56
Use of pesticides Yes 6.04 0.150 −2.09 to 14.84
Change of address since birth
No 2.07 0.614 −5.76 to 10.55
Age of the children −2.30 0.416 −7.64 to 3.34
*p< 0.05.
Factors such as the use of pesticides or derivatives in the household, the street pave-
ment where the household resides, a change of address, and the child’s age did not explain
the variations in inorganic arsenic concentration in the two measurements.
The intraclass correlation coefficient (ICC) value was 0.19, meaning that 19% of the
total variability in inorganic arsenic concentrations could be attributed to inter-individual
variability. The remaining 81% was attributable to intra-individual variability.
4. Discussion
The findings reveal that inorganic arsenic concentration in pregnant women and their
children, measured approximately 10 years apart, does not change significantly. This
persistence is consistent with previous longitudinal studies [
23
] and highlights ongoing
arsenic exposure due to natural geological processes [
25
]. The latest National Health Survey
reported a mean urinary arsenic concentration of 16.3
µ
g/L in the northern macrozone,
where Arica is located. This value is similar to the findings of this study and significantly
higher than those reported in the metropolitan, central, and southern macrozones (6.7; 8.8;
and 9.2
µ
g/L, respectively) [
26
]. This reflects natural conditions in some areas. Within the
framework of Law 20,590, interventions have been implemented, such as the provision of
subsidies for housing improvements, the relocation of families living in high-risk areas, the
paving of streets, and implementation of a sanitary control program for affected populations,
among others [
24
]. Additionally, there have been improvements in the quality of potable
water and the increased oversight of water treatment plants [
27
]. Despite the above, no
significant changes were observed in the mean inorganic arsenic concentration in the study
sample between the two periods. Similarly, no differences were found in inorganic arsenic
concentrations between individuals who reported living in areas at risk of exposure at
measurement 1 and those who reported being beneficiaries of the law at measurement 2.
Studies have reported favorable outcomes following the adoption of regulations to reduce
the arsenic maximum contaminant level in drinking water from 50 to 10
µ
g/L [
28
], and
Chile has been no exception [
29
]. However, the continued exposure to low doses of arsenic,
coupled with populations more susceptible to arsenic-related health effects, highlights the
need for more effective and sustainable approaches to mitigate this public health threat [
30
].
The main determinants of change in inorganic arsenic concentration over the study
period include sources of drinking water, ethnicity, and education level. Bottled water
usage increased, serving as the primary drinking water source for approximately 80% of
the sample due to public health recommendations and increased awareness of exposure
risks. Individuals consuming bottled water had an 8.25% reduction in inorganic arsenic
concentration compared to those using tap water, indicating a protective effect. This finding
Toxics 2025,13, 215 10 of 14
can be explained by Chilean regulations, which ensure that bottled water meets the same
standards as public water supplies [
31
]. However, a study suggested that 30% of bottled
water samples in Chile exceed the recommended arsenic concentration [
32
]. Conversely, ru-
ral potable water, wells, and other informal supplies were associated with higher inorganic
arsenic concentrations than tap water. These sources were grouped together statistically
due to the low number of users, revealing a pattern of higher arsenic concentrations. It
is important to note that these water sources adhere to different quality standards. In
Chile, rural potable water is regulated and monitored under a specific legal framework [
33
]
and must comply with water quality standards [
34
]. However, rural water quality is not
always adequate, with challenges in regulating specific components [
35
]. On the other
hand, well water forms part of the informal water supply in semi-concentrated or dispersed
rural populations, and is often associated with poverty [
36
]. Rural potable water systems
in Arica often maintain arsenic concentrations near or above the recommended limits in
some treatment plants. This situation is particularly relevant as studies have indicated
that even arsenic concentrations close to the recommended limit pose a health risk [
37
,
38
].
The World Health Organization (WHO) recommends keeping arsenic concentrations in
water as low as possible and below the provisional guideline wherever resources allow [
39
].
Based on this recommendation, some countries, like the United States, Denmark, and The
Netherlands, have demonstrated that stricter arsenic limits are achievable with a robust
regulatory framework, investment in water treatment technologies, and a commitment to
public health protection [40].
This study shows how arsenic exposure is deeply linked with broader patterns of envi-
ronmental injustice [
41
]. Pregnant women or caregivers, especially those from ethnic groups
or with lower education attainment, exhibited higher inorganic arsenic concentrations.
These findings align with global trends, where marginalized populations disproportionately
face environmental hazards due to inadequate regulatory oversight [
42
]. The persistence of
arsenic exposure despite interventions underscores the need to view these issues within the
framework of structural inequalities rather than as isolated environmental problems. In-
digenous communities and rural populations, often excluded from political representation
and resources, remain particularly vulnerable to environmental risks [
43
]. Addressing these
challenges requires the recognition of how intersecting factors—such as gender, ethnicity,
and socioeconomic status—determine exposure risks and health outcomes. Achieving envi-
ronmental justice demands more than technical solutions like water quality regulations. It
requires tackling systemic inequalities through environmental monitoring, comprehensive
education, and community-led strategies. Only by addressing these primary causes can we
create safe environments for marginalized groups and work toward a more equitable and
sustainable future [44].
The main strength of this study is its efforts to measure inorganic arsenic concentra-
tions in a subsample of children, where original data were obtained from their mothers
during pregnancy. This enables the tracking of inorganic arsenic exposure trajectories over
approximately 10 years, providing critical information regarding changes in exposure levels
in a population affected by natural and anthropogenic sources. It also helps to identify
key determinants and assess the effects of interventions and changes in contamination
sources. Approximately 58.5% of the mothers were successfully identified after 10 years,
of whom 46.7% agreed to participate, a proportion consistent with another cohort study
in the middle of this timeframe [
45
]. Additionally, the mean concentration of inorganic
arsenic among women who participated in the second measurement was similar to that of
the original sample, reducing the risk of selection bias.
One limitation of this study is the use of different analytical techniques to measure
inorganic arsenic at two different time points, reflecting the technology available during
Toxics 2025,13, 215 11 of 14
each period. The inductively coupled plasma mass spectrometry (ICP-MS) technique
offers greater sensitivity and can detect low concentrations of arsenic. In this study, no
samples fell below the detection limit when analyzed with ICP-MS, whereas, with the
atomic absorption spectrophotometry (AAS-HG) technique, 10.6% of samples were below
the detection limit. Nevertheless, both methods are accurate and robust [
46
]. A second
limitation could be associated with recall bias in the question regarding water consumption
during pregnancy, which was included in the most recent survey. However, given that
the mothers are highly aware of the city’s contamination issues, this bias will likely be
less significant. It is important to highlight that the homes of the pregnant women who
participated in the first measurement (n= 1644) were evenly distributed throughout the city.
However, as part of the implemented interventions, most families living in exposed areas,
due to the proximity of their homes to former toxic waste deposits, were relocated. Other
families later informally occupied these homes, most of them immigrants. Consequently,
the study conducted in 2023 may not accurately reflect the exposure of children currently
residing in areas considered to be more exposed.
The assessment of arsenic exposure requires us to consider not only socioeconomic and
environmental determinants but also genetic factors, particularly AS3MT gene expression,
which plays a protective role in arsenic metabolism and excretion [
47
]. Incorporating genetic
factors into future research could be helpful in determining groups more susceptible to the
toxic effects of arsenic, especially in regions with high historic arsenic exposure, such as
northern Chile.
5. Conclusions
In conclusion, this study shows that exposure to inorganic arsenic in Arica has re-
mained sustained over the last decade, highlighting the socioeconomic and environmental
inequalities that influence this exposure. The evidence of the effects of low-dose exposure
on health emphasize the importance of addressing natural arsenic contamination in water
through stricter regulations and targeted interventions to reduce disparities associated with
socioeconomic and demographic factors.
Supplementary Materials: The following supporting information can be downloaded at: https:
//www.mdpi.com/article/10.3390/toxics13030215/s1, Figure S1: Comparison of the distribution of
inorganic arsenic concentration from measurement 1 in pregnant women in the 2013–2016 baseline
sample (n= 1644) and the subsample of mothers who participated with their child in the 2023
subsample (n= 443); Table S1: Comparison of sociodemographic characteristics and inorganic arsenic
concentration (
µ
g/L) from measurement 1 in the baseline sample of pregnant women 2013–2016
(1644) and the subsample of mothers who participated with their child in subsample 2023 (n= 443).
Author Contributions: Conceptualization: P.R. and V.I.; Methodology: P.R., V.I., M.A. and M.H.-A.;
Software: C.C., M.H.-A. and C.A.; Validation: P.R. and M.A.; Formal analysis: P.R., M.A. and I.D.;
Investigation: P.R., V.I., M.H.-A., M.A., C.A., X.M., M.P.M., I.D., N.C.Z.-C., C.C.-L., M.I.M., M.A.R.,
A.O., P.P., C.G. and C.C.; Data curation: P.R. and M.A.; Writing—original draft: P.R., V.I., M.H.-A.,
M.A., C.A., X.M., M.P.M., I.D., N.C.Z.-C., C.C.-L., M.I.M., M.A.R., A.O., P.P., C.G. and C.C.; Writing—
review & editing: P.R., V.I., M.H.-A., M.A., C.A., X.M., M.P.M., I.D., N.C.Z.-C., C.C.-L., M.I.M., M.A.R.,
A.O., P.P., C.G. and C.C.; Visualization: P.R., M.A. and M.H.-A.; Visualization: P.R., M.A. and M.H.-A.;
Supervision: P.R., V.I. and X.M.; Project administration: P.R. and V.I.; Funding acquisition: P.R. and
V.I. All authors have read and agreed to the published version of the manuscript.
Funding: This research was funded by the Agencia Nacional de Investigación y Desarrollo (ANID),
Fondo de Investigación y Desarrollo en Salud (FONIS), grant number #22I0119.
Toxics 2025,13, 215 12 of 14
Institutional Review Board Statement: The study was conducted in accordance with the Declaration
of Helsinki and approved by the Comité Ético Científico de la Facultad de Medicina, Clínica Alemana,
Universidad del Desarrollo (protocol code Nº 2022-81, 18 November 2022).
Informed Consent Statement: Informed consent was obtained from all subjects involved in the study.
Data Availability Statement: Data are not publicly available due to ethical restrictions.
Acknowledgments: The authors gratefully acknowledge Marta Saavedra and Gina Saavedra of the
Department of Public Health, Regional Ministerial Secretariat of Arica y Parinacota, for their interest
and work in the investigation of arsenic exposure in the Region of Arica and Parinacota, and for their
efforts in making this study possible. Additionally, we extend our sincere gratitude to the mothers,
tutors, and children who participated in this study. Their contribution was invaluable to this research.
During the preparation of this work, the authors used ChatGPT 3.5 as an editing tool to improve the
clarity of specific paragraphs and translate the manuscript into English. After using this tool, the
authors reviewed and edited the content as needed and took full responsibility for the content of the
published article.
Conflicts of Interest: The authors declare no conflicts of interest. The funders had no role in the design
of the study, in the collection, analyses, or interpretation of data, in the writing of the manuscript, or
in the decision to publish the results.
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