Background: The Global Burden of Disease (GBD) study, coordinated by the Institute for Health
Metrics and Evaluation (IHME), produces influential, data-driven estimates of the
burden of disease and premature death due to major risk factors. Expanded quantification
of disease due to environmental health (EH) risk factors, including climate change,
will enhance accuracy of GBD estimates, which will contribute to developing cost-effective
policies that promote prevention and achieving Sustainable Development Goals.
Objectives: We review key aspects of the GBD for the EH community and introduce the Global Burden
of Disease–Pollution and Health Initiative (GBD-PHI), which aims to work with IHME
and the GBD study to improve estimates of disease burden attributable to EH risk factors
and to develop an innovative approach to estimating climate-related disease burden—both
current and projected.
Methods: We discuss strategies for improving GBD quantification of specific EH risk factors,
including air pollution, lead, and climate change. We highlight key methodological
challenges, including new EH risk factors, notably evidence rating and global exposure
Discussion: A number of issues present challenges to the scope and accuracy of current GBD estimates
for EH risk factors. For air pollution, minimal data exist on the exposure–risk relationships
associated with high levels of pollution; epidemiological studies in high pollution
regions should be a research priority. For lead, the GBD’s current methods do not
fully account for lead’s impact on neurodevelopment; innovative methods to account
for subclinical effects are needed. Decisions on inclusion of additional EH risk–outcome
pairs need to be guided by findings of systematic reviews, the size of exposed populations,
feasibility of global exposure estimates, and predicted trends in exposures and diseases.
Neurotoxicants, endocrine-disrupting chemicals, and climate-related factors should
be high priorities for incorporation into upcoming iterations of the GBD study. Enhancing
the scope and methods will improve the GBD’s estimates and better guide prevention
Background: The substitution of bisphenol A (BPA) by bisphenol B (BPB), a very close structural
analog, stresses the need to assess its potential endocrine properties.
Objective: This analysis aimed to investigate whether BPB has endocrine disruptive properties
in humans and in wildlife as defined by the World Health Organization (WHO) definition
used in the regulatory field, that is, a) adverse effects, b) endocrine activity, and c) plausible mechanistic links between the observed endocrine activity and adverse
Methods: We conducted a systematic review to identify BPB adverse effects and endocrine activities
by focusing on animal models and in vitro mechanistic studies. The results were grouped by modality (estrogenic, androgenic,
thyroid hormone, steroidogenesis-related, or other endocrine activities). After critical
analysis of results, lines of evidence were built using a weight-of-evidence approach
to establish a biologically plausible link. In addition, the ratio of BPA to BPB potency
was reported from studies investigating both bisphenols.
Results: Among the 36 articles included in the analysis, 3 subchronic studies consistently
reported effects of BPB on reproductive function. In rats, the 28-d and 48-week studies
showed alteration of spermatogenesis associated with a lower height of the seminiferous
tubules, the alteration of several sperm parameters, and a weight loss for the testis,
epididymis, and seminal vesicles. In zebrafish, the results of a 21-d reproductive
study demonstrated that exposed fish had a lower egg production and a lower hatching
rate and viability. The in vitro and in vivo mechanistic data consistently demonstrated BPB’s capacity to decrease testosterone
production and to exert an estrogenic-like activity similar to or greater than BPA’s,
both pathways being potentially responsible for spermatogenesis impairment in rats
Conclusion: The available in vivo, ex vivo, and in vitro data, although limited, coherently indicates that BPB meets the WHO definition of
an endocrine disrupting chemical currently used in a regulatory context. https://doi.org/10.1289/EHP5200
Background: Bisphenol A (BPA) is an endocrine disruptor that affects fetal growth in experimental
studies. Bisphenol F (BPF) and bisphenol S (BPS), which have been substituted for
BPA in some consumer products, have also shown endocrine-disrupting effects in experimental
models. However, the effects of BPF and BPS on fetal growth in humans are unknown.
Objectives: Our goal was to investigate trimester-specific associations of urinary concentrations
of BPA, BPF, and BPS with size at birth.
Methods: The present study included 845 pregnant women from Wuhan, China (2013–2015), who provided
one urine sample in each of the first, second, and third trimesters. Linear regressions
with generalized estimating equations were applied to estimate trimester-specific
associations of urinary bisphenol concentrations with birth weight, birth length,
and ponderal index. Linear mixed-effects models were used to identify potential critical
windows of susceptibility to bisphenols by comparing the exposure patterns of newborns
in the 10th percentile of each birth anthropometric measurement to that of those in
the 90th percentile.
Results: Medians (25th–75th percentiles) of urinary concentrations of BPA, BPF, and BPS were
1.40 (0.19–3.85), 0.65 (0.34–1.39), and 0.38 (0.13–1.11) ng/mL, respectively. Urinary
BPA concentrations in different trimesters were inversely, but not significantly,
associated with birth weight and ponderal index. Urinary concentrations of BPF and
BPS during some trimesters were associated with significantly lower birth weight,
birth length, or ponderal index, with significant trend p-values () across quartiles of BPF and BPS concentrations. The observed associations were unchanged
after additionally adjusting for other bisphenols. In addition, newborns in the 10th
percentile of each birth anthropometry measure had higher BPF and BPS exposures during
pregnancy than newborns in the 90th percentile of each outcome.
Conclusions: Prenatal exposure to BPF and BPS was inversely associated with size at birth in this
cohort. Replication in other populations is needed. https://doi.org/10.1289/EHP4664
Background: Particulate matter (PM) is a complex mixture. Geographic variations in PM may explain
the lack of consistent associations with breast cancer.
Objective: We aimed to evaluate the relationship between air pollution, PM components, and breast
cancer risk in a United States-wide prospective cohort.
Methods: We estimated annual average ambient residential levels of particulate matter and in aerodynamic diameter ( and , respectively) and nitrogen dioxide () using land-use regression for 47,433 Sister Study participants (breast cancer–free
women with a sister with breast cancer) living in the contiguous United States. Cox
proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence
intervals (CIs) for risk associated with an interquartile range (IQR) increase in
pollutants. Predictive k-means were used to assign participants to clusters derived from component profiles to evaluate the impact of heterogeneity in the mixture. For , we investigated effect measure modification by component cluster membership and
by geographic region without regard to air pollution mixture.
Results: During follow-up (), 2,225 invasive and 623 ductal carcinoma in situ (DCIS) cases were identified. and were associated with breast cancer overall [ (95% CI:0.99, 1.11) and 1.06 (95% CI:1.02, 1.11), respectively] and with DCIS but
not with invasive cancer. Invasive breast cancer was associated with only in the Western United States [ (95% CI:1.02, 1.27)] and only in the Southern United States [ (95% CI:1.01, 1.33)]. was associated with a higher risk of invasive breast cancer among two of seven identified
composition-based clusters. A higher risk was observed [ (95% CI: 0.97, 1.60)] in a California-based cluster characterized by low S and high
Na and nitrate () fractions and for another Western United States cluster [ (95% CI: 0.90, 2.85)], characterized by high fractions of Si, Ca, K, and Al.
Conclusion: Air pollution measures were related to both invasive breast cancer and DCIS within
certain geographic regions and PM component clusters. https://doi.org/10.1289/EHP5131
Background: Per- and polyfluoroalkyl substances (PFASs) are common industrial and consumer product
chemicals with widespread human exposures that have been linked to adverse health
effects. PFASs are commonly detected in foods and food-contact materials (FCMs), including
fast food packaging and microwave popcorn bags.
Objectives: Our goal was to investigate associations between serum PFASs and consumption of restaurant
food and popcorn in a representative sample of Americans.
Methods: We analyzed 2003–2014 serum PFAS and dietary recall data from the National Health
and Nutrition Examination Survey (NHANES). We used multivariable linear regressions
to investigate relationships between consumption of fast food, restaurant food, food
eaten at home, and microwave popcorn and serum levels of perfluorooctanoic acid (PFOA),
perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluorohexanesulfonic
acid (PFHxS), and perfluorooctanesulfonic acid (PFOS).
Results: Calories of food eaten at home in the past 24 h had significant inverse associations
with serum levels of all five PFASs; these associations were stronger in women. Consumption
of meals from fast food/pizza restaurants and other restaurants was generally associated
with higher serum PFAS concentrations, based on 24-h and 7-d recall, with limited
statistical significance. Consumption of popcorn was associated with significantly
higher serum levels of PFOA, PFNA, PFDA, and PFOS, based on 24-h and 12-month recall,
up to a 63% (95% CI: 34, 99) increase in PFDA among those who ate popcorn daily over
the last 12 months.
Conclusions: Associations between serum PFAS and popcorn consumption may be a consequence of PFAS
migration from microwave popcorn bags. Inverse associations between serum PFAS and
food eaten at home—primarily from grocery stores—is consistent with less contact between
home-prepared food and FCMs, some of which contain PFASs. The potential for FCMs to
contribute to PFAS exposure, coupled with concerns about toxicity and persistence,
support the use of alternatives to PFASs in FCMs. https://doi.org/10.1289/EHP4092
Background: Pregnancy is a sensitive condition during which adverse environmental exposures should
be monitored thoroughly and minimized whenever possible. In particular, the hormone
balance during gestation is delicate, and disturbance may cause acute or chronic long-term
health effects. A potential endocrine disruption may be provoked by in utero exposure to xenoestrogens mimicking endogenous estrogens. The mycoestrogen zearalenone
(ZEN), a toxic fungal secondary metabolite and mycotoxin found frequently in food
and feed, constitutes a prominent example.
Objectives: We performed a comprehensive assessment of the transfer as well as phase I and phase
II metabolism of ZEN at the human placental barrier.
Methods: Human placentas were perfused with () ZEN for 6 h. Samples from the maternal and fetal compartment, placental tissue,
and fetal plasma were analyzed by a highly sensitive UHPLC-MS/MS assay to detect ZEN
as well as nine key metabolites (, , zearalanone, , , ZEN-14-glucuronide, , , ZEN-14-sulfate).
Results: The model revealed a fast maternofetal transfer of ZEN across the human placental
barrier. We also unraveled phase I and phase II metabolism of the parent toxin ZEN
into the approximately 70-times more estrogenic and the less active ZEN-14-sulfate conjugate, which are effectively released into
the maternal and fetal circulation in considerable amounts.
Conclusions: Our findings suggest that exposure to ZEN (such as through consumption of ZEN-contaminated
cereal-based products) during pregnancy may result in in utero exposure of the fetus, not only to ZEN but also some of its highly estrogenically
active metabolites. In the light of the known affinity of ZEN and potentially co-occurring
xenoestrogens to the estrogen receptor, and our results demonstrating placental transfer
of ZEN and its metabolites in an ex vivo model, we recommend further research and more comprehensive assessment of gestational
exposures in women. https://doi.org/10.1289/EHP4860
Background: Pregnant women and children are especially vulnerable to exposures to food contaminants,
and a balanced diet during these periods is critical for optimal nutritional status.
Objectives: Our objective was to study the association between diet and measured blood and urinary
levels of environmental contaminants in mother–child pairs from six European birth
cohorts ( mothers and 1,288 children).
Methods: We assessed the consumption of seven food groups and the blood levels of organochlorine
pesticides, polybrominated diphenyl ethers, polychlorinated biphenyls (PCBs), per-
and polyfluoroalkyl substances (PFAS), and heavy metals and urinary levels of phthalate
metabolites, phenolic compounds, and organophosphate pesticide (OP) metabolites. Organic
food consumption during childhood was also studied. We applied multivariable linear
regressions and targeted maximum likelihood based estimation (TMLE).
Results: Maternal high () versus low () fish consumption was associated with 15% higher PCBs [geometric mean (GM) ; 95% confidence interval (CI): 1.02, 1.29], 42% higher perfluoroundecanoate (PFUnDA)
(; 95% CI: 1.20, 1.68), 89% higher mercury (Hg) (; 95% CI: 1.47, 2.41) and a 487% increase in arsenic (As) (; 95% CI: 2.57, 9.23) levels. In children, high () versus low () fish consumption was associated with 23% higher perfluorononanoate (PFNA) (; 95% CI: 1.08, 1.40), 36% higher PFUnDA (; 95% CI: 1.12, 1.64), 37% higher perfluorooctane sulfonate (PFOS) (; 95% CI: 1.22, 1.54), and higher Hg and As [ (95% CI: 1.91, 4.31) and (95% CI: 2.23, 3.21)] concentrations. Using TMLE analysis, we estimated that fish
consumption within the recommended 2–3 times/week resulted in lower PFAS, Hg, and
As compared with higher consumption. Fruit consumption was positively associated with
OP metabolites. Organic food consumption was negatively associated with OP metabolites.
Discussion: Fish consumption is related to higher PFAS, Hg, and As exposures. In addition, fruit
consumption is a source of exposure to OPs. https://doi.org/10.1289/EHP5324
Background: Piperonyl butoxide (PBO) is a pesticide synergist used in residential, commercial,
and agricultural settings. PBO was recently found to inhibit Sonic hedgehog (Shh)
signaling, a key developmental regulatory pathway. Disruption of Shh signaling is
linked to birth defects, including holoprosencephaly (HPE), a malformation of the
forebrain and face thought to result from complex gene–environment interactions.
Objectives: The impact of PBO on Shh signaling in vitro and forebrain and face development in vivo was examined.
Methods: The influence of PBO on Shh pathway transduction was assayed in mouse and human cell
lines. To examine its teratogenic potential, a single dose of PBO () was administered by oral gavage to mice at gestational day 7.75, targeting the critical period for HPE. Gene–environment
interactions were investigated using mice, which model human HPE-associated genetic mutations.
Results: PBO attenuated Shh signaling in vitro through a mechanism similar to that of the known teratogen cyclopamine. In utero PBO exposure caused characteristic HPE facial dysmorphology including dose-dependent
midface hypoplasia and hypotelorism, with a lowest observable effect level of . Median forebrain deficiency characteristic of HPE was observed in severely affected
animals, whereas all effective doses disrupted development of Shh-dependent transient
forebrain structures that generate cortical interneurons. Normally silent heterozygous
Shh null mutations exacerbated PBO teratogenicity at all doses tested, including .
Discussion: These findings demonstrate that prenatal PBO exposure can cause overt forebrain and
face malformations or neurodevelopmental disruptions with subtle or no craniofacial
dysmorphology in mice. By targeting Shh signaling as a sensitive mechanism of action
and examining gene–environment interactions, this study defined a lowest observable
effect level for PBO developmental toxicity in mice more than 30-fold lower than previously
recognized. Human exposure to PBO and its potential contribution to etiologically
complex birth defects should be rigorously examined. https://doi.org/10.1289/EHP5260
Background: The autonomic nervous system plays a key role in maintaining homeostasis and responding
to external stimuli. In adults, exposure to fine particulate matter () has been associated with reduced heart rate variability (HRV), an indicator of cardiac
Objectives: Our goal was to investigate the associations of exposure to fine particulate matter
() with HRV as an indicator of cardiac autonomic control during early development.
Methods: We studied 237 maternal–infant pairs in a Boston-based birth cohort. We estimated
daily residential using satellite data in combination with land-use regression predictors. In infants
at 6 months of age, we measured parasympathetic nervous system (PNS) activity using
continuous electrocardiogram monitoring during the Repeated Still-Face Paradigm, an
experimental protocol designed to elicit autonomic reactivity in response to maternal
interaction and disengagement. We used multivariable linear regression to examine
average exposure across pregnancy in relation to PNS withdrawal and activation, indexed by
changes in respiration-corrected respiratory sinus arrhythmia ()—an established metric of HRV that reflects cardiac vagal tone. We examined interactions
with infant sex using cross-product terms.
Results: In adjusted models we found that a 1-unit increase in (in micrograms per cubic meter) was associated with a 3.53% decrease in baseline
(95% CI: , 0.02). In models examining change between episodes, higher was generally associated with reduced PNS withdrawal during stress and reduced PNS
activation during recovery; however, these associations were not statistically significant.
We did not observe a significant interaction between and sex.
Discussion: Prenatal exposure to may disrupt cardiac vagal tone during infancy. Future research is needed to replicate
these preliminary findings. https://doi.org/10.1289/EHP4434
Background: Ambient fine particulate air pollution with aerodynamic diameter () is an important contributor to the global burden of disease. Information on the
shape of the concentration–response relationship at low concentrations is critical
for estimating this burden, setting air quality standards, and in benefits assessments.
Objectives: We examined the concentration–response relationship between and nonaccidental mortality in three Canadian Census Health and Environment Cohorts
(CanCHECs) based on the 1991, 1996, and 2001 census cycles linked to mobility and
Methods: Census respondents were linked with death records through 2016, resulting in 8.5 million
adults, 150 million years of follow-up, and 1.5 million deaths. Using annual mailing
address, we assigned time-varying contextual variables and 3-y moving-average ambient
at a spatial resolution from 1988 to 2015. We ran Cox proportional hazards models for
adjusted for eight subject-level indicators of socioeconomic status, seven contextual
covariates, ozone, nitrogen dioxide, and combined oxidative potential. We used three
statistical methods to examine the shape of the concentration–response relationship
between and nonaccidental mortality.
Results: The mean 3-y annual average estimate of exposure ranged from 6.7 to over the three cohorts. We estimated a hazard ratio (HR) of 1.053 [95% confidence
interval (CI): 1.041, 1.065] per change in after pooling the three cohort-specific hazard ratios, with some variation between
cohorts (1.041 for the 1991 and 1996 cohorts and 1.084 for the 2001 cohort). We observed
a supralinear association in all three cohorts. The lower bound of the 95% CIs exceeded
unity for all concentrations in the 1991 cohort, for concentrations above in the 1996 cohort, and above in the 2001 cohort.
Discussion: In a very large population-based cohort with up to 25 y of follow-up, was associated with nonaccidental mortality at concentrations as low as . https://doi.org/10.1289/EHP5204
Background: The rapidly increasing dissemination of carbapenem-resistant Enterobacteriaceae (CRE)
in both humans and animals poses a global threat to public health. However, the transmission
of CRE between humans and animals has not yet been well studied.
Objectives: We investigated the prevalence, risk factors, and drivers of CRE transmission between
humans and their backyard animals in rural China.
Methods: We conducted a comprehensive sampling strategy in 12 villages in Shandong, China.
Using the household [residents and their backyard animals (farm and companion animals)]
as a single surveillance unit, we assessed the prevalence of CRE at the household
level and examined the factors associated with CRE carriage through a detailed questionnaire.
Genetic relationships among human- and animal-derived CRE were assessed using whole-genome
sequencing–based molecular methods.
Results: A total of 88 New Delhi –type carbapenem-resistant Escherichia coli (NDM-EC), including 17 from humans, 44 from pigs, 12 from chickens, 1 from cattle,
and 2 from dogs, were isolated from 65 of the 746 households examined. The remaining
12 NDM-EC were from flies in the immediate backyard environment. The NDM-EC colonization
in households was significantly associated with a) the number of species of backyard animals raised/kept in the same household, and
b) the use of human and/or animal feces as fertilizer. Discriminant analysis of principal
components (DAPC) revealed that a large proportion of the core genomes of the NDM-EC
belonged to strains from hosts other than their own, and several human isolates shared
closely related core single-nucleotide polymorphisms and genetic contexts with isolates from backyard animals.
Conclusions: To our knowledge, we are the first to report evidence of direct transmission of NDM-EC
between humans and animals. Given the rise of NDM-EC in community and hospital infections,
combating NDM-EC transmission in backyard farm systems is needed. https://doi.org/10.1289/EHP5251
Background: Previous studies suggest that prenatal exposure to phthalates, ubiquitous synthetic
chemicals, may adversely affect neurodevelopment. However, data are limited on how
phthalates affect cognition, executive function, and behavioral function into adolescence.
Objective: We aimed to investigate associations of prenatal phthalate exposure with neurodevelopment
in childhood and adolescence in the Center for the Health Assessment of Mothers and
Children of Salinas (CHAMACOS) study.
Methods: We examined associations between maternal urinary phthalate metabolite concentrations
measured twice during pregnancy and a range of neurodevelopmental outcomes from ages
7 through 16 y in the CHAMACOS birth cohort (). We used age-specific linear regression models and generalized estimating equation
models to assess longitudinal effects and examined differences by sex.
Results: Phthalate metabolites were detected in 88%–100% of samples, depending on the metabolite.
Associations of phthalates with neurodevelopmental outcomes were largely null with
some noteworthy patterns. Higher prenatal concentrations of metabolites of low-molecular
weight phthalates () were associated with more self-reported hyperactivity [, 95% confidence interval (CI): 0.1, 1.4 per 2-fold increase in phthalates], attention problems (, 95% CI: 0.7, 2.2), and anxiety (, 95% CI: 0.0, 1.8) at age 16. We observed sex-specific differences for the sums of
high-molecular-weight and di(2-ethylhexyl) metabolites and cognitive outcomes (e.g.,
for Full-Scale IQ for , 95% CI: , 0.3 and , 95% CI: , 0.3, respectively; for , 95% CI: 0.1, 3.4 and 1.6, 95% CI: 0.0, 3.2, respectively; for both).
Conclusion: We found predominantly null associations of prenatal phthalates with neurodevelopment
in CHAMACOS, and weak associations of phthalates with internalizing and externalizing behaviors in adolescence. No previous
studies have examined associations of prenatal phthalate exposure with neurodevelopment
into adolescence, an important time for manifestations of effects. https://doi.org/10.1289/EHP5165
Background: The timing of puberty is highly sensitive to environmental factors, including endocrine
disruptors. Among them, bisphenol A (BPA) has been previously analyzed as potential
modifier of puberty. Yet, disparate results have been reported, with BPA advancing,
delaying, or being neutral in its effects on puberty onset. Likewise, mechanistic
analyses addressing the central and peripheral actions/targets of BPA at puberty remain
incomplete and conflictive.
Objective: We aimed to provide a comprehensive characterization of the impact of early BPA exposures,
especially at low, real-life doses, on the postnatal development of hypothalamic Kiss1/NKB
neurons, and its functional consequences on female pubertal maturation.
Methods: Pregnant CD1 female mice were orally administered BPA at 5, 10, or body weight (BW)/d from gestational day 11 to postnatal day 8 (PND8). Vaginal opening,
as an external marker of puberty onset, was monitored daily from PND19 to PND30 in
the female offspring. Blood and brain samples were collected at PND12, 15, 18, 21,
and 30 for measuring circulating levels of gonadotropins and analyzing the hypothalamic
expression of Kiss1/kisspeptin and NKB.
Results: Perinatal exposure to BPA, in a range of doses largely below the no observed adverse
effect level (NOAEL; BW/d, according to the FDA), was associated with pubertal differences in the female
progeny compared with those exposed to vehicle alone, with an earlier age of vaginal
opening but consistently lower levels of circulating luteinizing hormone. Mice treated
with BPA exhibited a persistent, but divergent, impairment of Kiss1 neuronal maturation,
with more kisspeptin cells in the rostral (RP3V) hypothalamus but consistently fewer
kisspeptin neurons in the arcuate nucleus (ARC). Detailed quantitative analysis of
the ARC population, essential for pubertal development, revealed that mice treated
with BPA had persistently lower Kiss1 expression during (pre)pubertal maturation,
which was associated with lower Tac2 (encoding NKB) levels, even at low doses ( BW/d), in the range of the tolerable daily intake (TDI), recently updated by the
European Food Safety Authority.
Conclusions: Our data attest to the consistent, but divergent, effects of gestational exposures
to low concentrations of BPA, via the oral route, on phenotypic and neuroendocrine
markers of puberty in female mice, with an unambiguous impact on the developmental
maturation not only of Kiss1, but also of the NKB system, both essential regulators
of puberty onset. https://doi.org/10.1289/EHP5570
Background: Long-term exposure to particulate matter (PM) in ambient air has been associated with
cardiovascular mortality, but few studies have considered incident disease in relation
to PM from different sources.
Objectives: We aimed to study associations between long-term exposure to different types of PM
and sources, and incident ischemic heart disease (IHD) and stroke in three Swedish
Methods: Based on detailed emission databases, monitoring data, and high-resolution dispersion
models, we calculated source contributions to PM with aerodynamic diameter (), PM with aerodynamic diameter (), and black carbon (BC) from road wear, traffic exhaust, residential heating, and
other sources in Gothenburg, Stockholm, and Umeå. Registry data for participants from
four cohorts were used to obtain incidence of IHD and stroke for first hospitalization
or death. We constructed time windows of exposure for same-year, 1- to 5-y, and 6-
to 10-y averages preceding incidence from annual averages at residential addresses.
Risk estimates were based on random effects meta-analyses of cohort-specific Cox proportional
Results: We observed 5,166 and 3,119 incident IHD and stroke cases, respectively, in 114,758
participants. Overall, few consistent associations were observed between the different
air pollution measures and IHD or stroke incidence. However, same-year levels of ambient
locally emitted BC (range: ) were associated with a 4.0% higher risk of incident stroke per interquartile range
(IQR), [95% confidence interval (CI): 0.04, 7.8]. This association was primarily related
to BC from traffic exhaust. (range: ) and (range: ) were not associated with stroke. Associations with incident IHD were observed only
for exposure from residential heating.
Discussion: Few consistent associations were observed between different particulate components
and IHD or stroke. However, long-term residential exposure to locally emitted BC from
traffic exhaust was associated with stroke incidence. The comparatively low exposure
levels may have contributed to the paucity of associations. https://doi.org/10.1289/EHP4757
Background: The question of whether exposure to bisphenol A (BPA) contributes to the development
of type 2 diabetes is still unresolved. Most epidemiological evidence on the association
between BPA and diabetes is from cross-sectional studies or longitudinal studies with
single urinary measurements. No prospective study has examined exposure to BPA analogs
such as bisphenol S (BPS) in relation to incident type 2 diabetes.
Objectives: We aimed to investigate whether exposure to BPA and BPS, assessed at up to two time
points, was associated with the incidence of type 2 diabetes.
Methods: We performed a case–cohort study on 755 participants without diabetes at baseline
and followed-up over 9 y as part of the French prospective cohort Data from an Epidemiological
Study on the Insulin Resistance Syndrome (D.E.S.I.R.). BPA-glucuronide (BPA-G) and
BPS-glucuronide (BPS-G) were assessed in fasting spot urine samples collected during
the health examinations at baseline and 3 y later. Associations with incident diabetes
were examined using Prentice-weighted Cox regression models adjusted for potential
Results: A total of 201 incident cases of type 2 diabetes were diagnosed over the follow-up,
including 30 in the subcohort. Compared with participants with the lowest average
BPA exposure (below the first quartile), participants in the second, third, and fourth
quartile groups of exposure had a near doubling of the risk of type 2 diabetes, with
a hazard ratio 2.56 (95% CI: 1.16, 5.65), 2.35 (95% CI: 1.07, 5.15), and 1.56 (95% CI: 0.68, 3.55),
respectively. The detection of BPS-G in urine at one or both time points was associated
with incident diabetes, with an 2.81 (95% CI: 1.74, 4.53).
Discussion: This study shows positive associations between exposure to BPA and BPS and the incidence
of type 2 diabetes, independent of traditional diabetes risk factors. Our results
should be confirmed by recent, population-based observational studies in different
populations and settings. Overall, these findings raise concerns about using BPS as
a BPA substitute. Further research on BPA analogs is warranted. https://doi.org/10.1289/EHP5159
Background: The geographic range of the tick Amblyomma americanum, a vector of diseases of public health significance such as ehrlichiosis, has expanded
from the southeast of the United States northward during the 20th century. Recently,
populations of this tick have been reported to be present close to the Canadian border
in Michigan and New York states, but established populations are not known in Canada.
Previous research suggests that changing temperature patterns with climate change
may influence tick life cycles and permit northward range expansion of ticks in the
Objectives: We aimed to estimate minimal temperature conditions for survival of A. americanum populations at the northern edge of the tick’s range and to investigate the possibility
of range expansion of A. americanum into northern U.S. states and southern Canada in the coming decades.
Methods: A simulation model of the tick A. americanum was used, via simulations using climate data from meteorological stations in the
United States and Canada, to estimate minimal temperature conditions for survival
of A. americanum populations at the northern edge of the tick’s range.
Results: The predicted geographic scope of temperature suitability [ annual cumulative degree days (DD) ] included most of the central and eastern U.S. states east of longitude 110°W, which
is consistent with current surveillance data for the presence of the tick in this
region, as well as parts of southern Quebec and Ontario in Canada. Regional climate
model output raises the possibility of northward range expansion into all provinces
of Canada from Alberta to Newfoundland and Labrador during the coming decades, with
the greatest northward range expansion (up to by the year 2100) occurring under the greenhouse gas (GHG) emissions of Representative
Concentration Pathway (RCP) 8.5. Predicted northward range expansion was reduced by
approximately half under the reduced GHG emissions of RCP4.5.
Discussion: Our results raise the possibility of range expansion of A. americanum into northern U.S. states and southern Canada in the coming decades, and conclude
that surveillance for this tick, and the diseases it transmits, would be prudent.