Long-Term Effect of Early-Life Arsenic Exposure on Morning Plasma Cortisol in Adults

Overview

This source page is a mechanical bulk-ingest record for a PDF in the research-pulls corpus. It preserves source-level identity, routeable product/analyte scope, and exact extracted numeric lines for later human or fresh-context audit. It does not derive HMTc thresholds, percentiles, or brand-by-brand comparisons.

Key numbers

The worker extracted the full PDF text with layout preservation twice and compared extraction hashes before commit. The following lines are copied from numeric/table-bearing regions of the PDF and retain the source units and wording where legible:

highest lifetime 5-year average of arsenic exposure had approximately 11% lower mean log
lowest quartile (β = -0.248; 95% CI: -0.444, -0.053) and the test for interaction by sex was
of 10 µg/L (Podgorski and Berg, 2020). This widespread exposure to arsenic poses a major
with rivers containing arsenic concentrations of 860 µg/L and ended in 1970 with the installation
drinking water containing 11-50 μg/L of arsenic had two-fold higher plasma cortisol levels than
women exposed to <10 μg/L arsenic (Sinha et al., 2014). While results from this study were
included in this analysis (n=233). Consistent with the 1958-1970 exposure window, participant
(median age 48 vs 54 years), included more females (35.7% vs. 50.0%), ever smokers (66.7% vs
2013 (Supplemental Table 1). Arsenic exposure levels were also greater among participants in
et al., 2000). While arsenic levels outside of Antofagasta were generally below 10 µg/L (Smith et
water standard of 50 µg/L (this standard was later reduced to 10 µg/L in 2005). Therefore, we
draw was 9:00 AM and ranged from 6:10AM to 12:35PM. All samples were processed within 8
Gibco) containing 10% fetal bovine serum (FBS; Atlanta Biologicals). One week prior to
experiments, cells were cultured using phenol red-free DMEM (Hyclone) with 10% charcoal-
replaced with 100µL of media containing either a range of cortisol standards (0, 1.56, 3.13, 6.25,
cortisol standards (0-25nM in 0.1% DMSO) and a common reference plasma sample (diluted
model. The standard curves for cortisol on each plate fit well with a median R2 value of 0.994
account for the plasma dilution factor. Assay CVs for all participant samples ranged from 0.6%
conducted to rule out potential confounding by stratifying analyses by median age (52 years) and
Of the total 232 study participants, 114 (49.1%) were born in Antofagasta during the high
arsenic exposure period and 118 (50.9%) were born elsewhere. Table 1 summarizes the
52 vs 51 years) and sex (54.4% vs 55.9% male) to those born elsewhere. The two groups were
(52.6% vs 66.1%) and completing secondary school (75.4% vs 84.7%) among participants born
lifetime average after age 20, were higher among participants born in Antofagasta. The median
concentration of arsenic in drinking water at birth was 860 μg/L for participants born in
Antofagasta and 6.2 μg/L for those born elsewhere. In contrast, lifetime average concentration
Table 2 lists associations between sociodemographic factors and log-transformed
participants was 5.1nM (range: 4.3-6.0nM). Blood collection time was inversely associated with
cortisol concentrations were ~15% lower among females compared to males (ß=-0.162; 95% CI:
ages 0–10 years, individuals in the highest exposure quartile had approximately 11% lower mean
the lowest quartile (≤ 63 μg/L). For cumulative lifetime arsenic exposure, lower cortisol
-0.119; 95% CI: -0.229, -0.009) quartiles relative to the first exposure quartile. Adjusting models
males and female participants (Figure 1, Supplemental Table 2). Higher arsenic exposure was
among female participants. Specifically, females with a peak arsenic exposure of 860 μg/L
participants whose highest level of exposure was ≤ 10 μg/L before age 10 (ß = -0.184; 95% CI: -
0.356, -0.012). Among males, this association was not statistically significant (ß = -0.043; 95%
CI: -0.171, 0.086). We also observed that females in the second (ß = -0.196; 95% CI: -0.367, -
arsenic exposure had approximately 18% lower mean cortisol concentrations than female
associated with 23.3% and 22.0% lower cortisol concentrations, respectively, than females in the
interaction was observed with lifetime cumulative exposure (p-interaction=0.036), but not for
for participants ≤ 52 years and >52 years (Supplemental Table 3). One exception was that
2017 (Supplemental Table 4). Statistically significant associations were only observed among

Methods (brief)

inversely correlated with plasma cortisol levels among a convenience sample of male runners
Participants were a convenience sample of employees from the Antofagasta
(described in section 2.3), resulting in a final sample of 232 participants. When comparing
and sample collection for this study were approved by institutional review boards at the
We collected a detailed lifetime residential history from each participant using a
summing yearly concentrations from birth until the time of sample collection.
A single fasted blood sample was collected in EDTA tubes from each willing participant
and time of sample collection was recorded by research personnel. The average time of blood
draw was 9:00 AM and ranged from 6:10AM to 12:35PM. All samples were processed within 8
analysis. Cortisol assays were performed in two separate batches. Samples collected during the
linked immunosorbent assay measurements in plasma collected from 12 healthy individuals.
12.5, 25 nM) or human plasma samples diluted 1:20 in hormone-depleted media. Cells were
cortisol standards (0-25nM in 0.1% DMSO) and a common reference plasma sample (diluted
containing diluted plasma samples. Wells with RLUs below the lowest cortisol standard on the
concentration. This resulted in one participant being dropped from the analysis. Sample RLUs
concentration values were normalized using a common reference plasma sample included on
concentration of the reference sample on its respective plate and then multiplied by the overall
median concentration of the reference sample across all plates. Plate (random) and batch (fixed)

Implications

This page makes the source discoverable for category-level evidence routing. Values remain source-native and should be used only with the stated matrix, species, basis, geography, and censoring context from the paper. The page does not convert total mercury to methylmercury or use total arsenic as inorganic arsenic.

Wiki pages this source may touch

Verification notes

Identity check: DOI, raw handle, candidate cite-key, and SHA-256 were compared against existing wiki/sources/ pages before creation.
Full-PDF read: pdftotext -layout was run on the full PDF twice; extracted text hashes matched before the page was written.
Numeric verification: numeric/table-bearing lines were selected mechanically from the verified extraction and preserved without unit conversion or rounding.
Brand firewall: the worker skips PDFs when extracted numeric lines appear brand/manufacturer-sensitive; this page contains category-level or species-level evidence only.
HMTc firewall: no threshold, percentile, pass/fail, clean/dirty, or certification math is stated.

Update history

The five most recent substantive edits to this page, classified major (evidence or structure moved), correction (a published value or statement was wrong and has been fixed), or minor (narrative rewritten without changing the underlying evidence). Each description is derived from what the edit did to this page; the linked commit is the authoritative record, routine regeneration passes are excluded, and the full version history lives in git. When DOI minting comes online (see schema docs), each entry below will also link to a version-pinned DataCite DOI.

Commit	Date	Change	Description
b01ec52c	2026-08-04	major	2 sections added
d49e450f	2026-08-03	major	5 sections added; narrative text revised