National Center for Environmental Health

The constituents of tobacco smoke that specifically contribute to lung cancer risk have yet to be fully identified. We evaluated associations between biomarkers of potentially harmful constituents-polycyclic aromatic hydrocarbons (PAHs), tobacco-specific nitrosamines (TSNAs), nicotine, and volatile organic compounds (VOCs)-and lung cancer incidence among US women. In a case-cohort study nested within the Sister Study (women aged 35 to 74 years at baseline, enrolled 2003 to 2009), data were obtained for a random subcohort and all remaining incident lung cancers through September 2017 (median follow-up 9.6 years), stratified by race and ethnicity (Hispanic, non-Hispanic Black, non-Hispanic White, others) and smoking status (current, former, never). The analytic sample included 356 cases and 433 non-cases. We quantified 30 biomarkers in baseline urine samples and calculated hazard ratios (HRs) for associations between one-unit increase in biomarker concentrations (log-scale) and lung cancer incidence using weighted Cox regression models adjusted for urinary creatinine and demographic, health, and lifestyle factors. Among women who were currently smoking at enrolment, positive associations were observed for biomarkers of PAHs (naphthalene, phenanthrene, pyrene, fluorene; HRs 1.4 to 5.3), TSNAs (particularly 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK); HRs : 1.3-2.2), and VOCs (xylene, acrylamide, acrylonitrile, 1,2-dibromoethane/vinyl-chloride/ethylene-oxide/acrylonitrile, acrolein, styrene/ethylbenzene, benzene, dimethylformamide/methylisocyanate, 1,3-butadiene, crotonaldehyde, isoprene; HRs : 1.6-4.4). Associations with biomarkers of most PAHs, NNK, xylene, and dimethylformamide/methylisocyanate remained after additional adjustment for smoking frequency, duration, and nicotine metabolites. In women who did not smoke, positive associations were observed for styrene/ethylbenzene and dimethylformamide/methylisocyanate biomarkers. Exposure to PAHs, TSNAs and several VOCs through tobacco smoking were associated with increased lung cancer risk among women.

Gestational polybrominated diphenyl ethers (PBDE) exposure is linked with adverse neurobehavioral outcomes in children, but scientists do not fully understand how these flame retardants damage the developing brain. We estimated the association of gestational PBDE serum concentrations and intrinsic functional connectivity in 143 adolescents from the Health Outcomes and Measures of the Environment (HOME) Study, a prospective pregnancy and birth cohort enrolling from 2003 to 2006. We measured maternal serum concentrations of five PBDE congeners and created a summary variable (∑5BDE) during pregnancy. At age 12 years, we acquired high resolution anatomical and resting state functional magnetic resonance neuroimaging to examine the relationship between gestational concentrations and intrinsic functional connectivity, adjusting for covariates. We assessed behaviors, mental health symptoms, and executive function using self- and caregiver-reports. We examined whether functional connectivity patterns mediated the observed associations between gestational PBDE concentrations and neurobehavioral outcomes. Higher gestational BDE-153 serum concentrations were associated with higher local correlation in the left inferior lateral occipital cortex. Higher gestational PBDE serum concentrations (BDE-28, -47, -99, -100, and the ∑5BDE) were associated with reduced global correlation in the primary visual cortex. Seed-to-voxel connectivity patterns showed significant mediation for associations between ∑5BDE and neurobehavioral outcomes. Higher gestational PBDE serum concentrations were associated with diminished connectivity in the primary visual cortex. Connectivity patterns also mediated the relationship between gestational ∑5BDE concentrations and neurobehavioral outcomes at age 12. These findings suggest that gestational PBDE exposure alters how the brain processes visual information across global networks.

IntroductionLead is an environmental toxin that may cause severe damage to vital organs including the brain, kidneys, liver, and bones. Children are particularly susceptible due to higher rates of gastrointestinal absorption and detrimental effects of lead on their developing nervous systems.MethodsThis report highlights the case of a 4-year-old boy with severe lead poisoning resulting from prolonged exposure to ayurvedic herbal supplements.ResultsThe child was initially admitted with anemia, arterial hypertension, abdominal pain, and mild neurological impairment. His blood smear revealed pronounced basophilic stippling of erythrocytes. His venous blood lead level (BLL) was markedly elevated at 123 μg/dl. Detailed review of his history uncovered that he had been ingesting an ayurvedic herbal medicine for asthma. He received chelation therapy with 2,3-dimercapto-1-propanesulfonic acid and calcium disodium EDTA, resulting in rapid resolution of symptoms and gradually decreasing BLLs.ConclusionsThe case is a striking example of the significant health risks due to heavy metal contamination in ayurveda products. Better strategies to control the composition of ayurvedic products and educate families about their possible heavy metal contamination are essential to reduce the risk of lead poisoning.

BackgroundBiomarkers can clarify the mechanistic bases of health effects associated with opiate use and improve evaluating dose-response relationships by quantifying the absorbed dose through different routes and patterns of use, supporting the generalizability of opium research findings to broader opioid use.MethodsWe recruited 449 individuals who used opium and 66 individuals who did not, 10 years after baseline evaluation in a cohort study. At both time points, we collected self-reported characteristics of opium use (route, frequency, type, and dose) and measured urinary concentrations of codeine, hydrocodone, hydromorphone, morphine, morphine-3-glucuronide, and morphine-6-glucuronide in spot urine samples. We used multivariate linear regression models to determine the independent effects of each opium use characteristic on biomarker concentrations. Reliability of biomarker concentrations over the 10-year interval was assessed using intraclass correlation coefficients (ICCs) from linear mixed-effect models.ResultsAt the follow-up, 229 (51.0 %) subjects used opium by ingestion, which showed a significant shift compared with baseline (24.4 % ingestion). In adjusted models, opium ingestion, daily use, and presence of opioid use disorder (OUD) were associated with higher concentrations of all opioid biomarkers compared with opium smoking, non-daily use, and absence of OUD, respectively. All opioid biomarkers showed significant dose-response relationships relative to self-reported doses. Biomarker concentrations peaked when opium was used 3–4 h before sample collection and declined afterwards, remaining detectable for several days. Biomarker measurements were reliable (ICCs between 0.69 and 0.78) over the 10-year interval.ConclusionsOpioid biomarkers are valid markers of lifetime history, route, frequency, dose, and recency of opium use and OUD diagnosis, and demonstrate good long-term reliability.

Harmful cyanobacterial blooms (HCBs) are a public health concern and require ongoing surveillance to monitor the negative water quality effects and cyanotoxins associated with these blooms. (+)-Anatoxin-a (ATX) is a potent neurotoxin produced by select cyanobacteria during HCB formation. Many HCB toxins are commonly associated with discolored water; however, ATX can be present in clear water, which results in a high risk of exposure by accidental ingestion for humans and animals. In this work, we used a qualitative, semitargeted liquid chromatography high resolution mass spectrometry (LC-HRMS) method and a discovery data analysis workflow to detect and identify ATX and its predicted mammalian metabolites in urine samples from ATX-dosed mice. Potential compounds were evaluated for identification with product-ion spectral matching to a local library, accurate mass list matching, further data processing and interpretation, and comparison to undosed mice urine samples. As a result, ATX and dihydroanatoxin-a (dhATX) were successfully identified in the dosed mice samples through retention time (RT) and product-ion spectral matching to their respective commercial standards. The positive identification of dhATX suggests its formation as an abundant metabolic product of ATX within mammalian systems. Additionally, multiple chromatographic peaks were observed that matched the exact mass of 3-OH ATX and were further identified by the presence of diagnostic product ions and comparison to a standard synthesized in-house. In total, seven potential ATX metabolites, including dhATX and 3-OH ATX, were detected and characterized in the dosed mice samples. All identified metabolites were either oxidized or reduced forms of ATX, which suggests that oxidation and reduction are the main pathways for endogenous ATX metabolism in mice. These results are among the first reports of metabolic products of ATX in biological samples and provide a metabolic profile of ATX for higher confidence screening for ATX after a suspected exposure event.