Statewide Evaluation of the California Medical Supervision Program Using Cholinesterase Electronic Laboratory Reporting Data: An Update.

The California Medical Supervision Program is designed to protect agricultural workers from overexposure to Toxicity Category I and II organophosphate (OP) and carbamate (CB) pesticides by routinely monitoring their blood cholinesterase (ChE) activity levels. ChE testing is conducted at State-approved laboratories and electronically reported to the Department of Pesticide Regulation (DPR) and the Office of Environmental Health Hazard Assessment (OEHHA) for review. In 2015, OEHHA and DPR evaluated the effectiveness of the Program by analyzing ChE data from pesticide handlers performed between 2011 and 2013, which revealed issues with the data quality that hindered the evaluation process. Several interventions have been implemented since then to improve data quality and the overall function of the Program. A new evaluation was conducted in 2020 to 2021 using data from 2014 to 2019 to determine the effectiveness of the Program, Program compliance, and efficacy of the interventions. The analysis revealed similar data quality issues identified in the last evaluation, however, an improvement in data quality was observed. The number of individuals with ChE depression below the action level threshold have decreased in recent years, corresponding to the implementation of certain interventions, indicating that the effectiveness of the Program has improved. Spatial and temporal analysis showed the proportion of pre-exposure baseline tests inversely correlated with pesticide use data while routine follow-up ChE test results showed a positive correlation, indicating a high degree of Program compliance across the state. Major improvements in the data cleaning and analysis since the last evaluation have also improved the evaluation: pesticide handlers under the Program were able to be identified with more certainty and ChE depressions were able to be calculated with increased accuracy. However, further improvements to the data collection process could enhance future evaluations of the Program.

Environmental Justice in the American Public Health Context: Trends in the Scientific Literature at the Intersection Between Health, Environment, and Social Status.

Although various governmental entities in the USA are required to consider environmental justice (EJ) impacts of their actions during decision-making, socially vulnerable groups continue to be disproportionately exposed to environmental hazards. Tools and programs to quantify and mitigate environmental injustices are limited by existing data, which may not capture the full range of health disparities exacerbated by the complex interactions between environmental exposures and social stressors. In this study, we analyzed how the scientific literature approaches EJ issues in the USA. We searched PubMed for journal articles discussing at least one sociodemographic or environmental variable in the context of cumulative impacts and analyzed the relative frequency with which various EJ topics were studied. Our findings indicate that demographic variables are commonly used in epidemiologic studies, though some areas (e.g., age) are better studied than others. Similarly, occupational exposure and ambient air pollution were more studied than other types of exposures. Word frequency analyses revealed which toxicants and health outcomes are the most frequently studied. In addition, temporality analyses showed that the rate of occupational publications rose rapidly in the 1970-1980s and has since plateaued, while other publication rates increased two decades later and are still on the rise. Cumulative impacts are considered in a relatively small portion of journal articles across all topics; nevertheless, they have seen an exponential climb in the last decade. A more equitable distribution of scientific efforts might be needed for a better distribution of funding, policy-making efforts, and other resources to socially and environmentally vulnerable communities.

Impact of Maternal Demographic and Socioeconomic Factors on the Association Between Particulate Matter and Adverse Birth Outcomes: a Systematic Review and Meta-analysis.

BACKGROUND: Numerous studies conducted in the United States found associations between prenatal exposure to particulate matter (PM) and adverse birth outcomes, and some studies identified vulnerable populations, including certain racial/ethnic groups and people with low-socioeconomic status. However, their findings are not always consistent. In this review, we compared the risk of adverse birth outcomes due to PM exposures among subpopulations and investigated whether any particular population is more vulnerable. METHODS: We selected U.S. studies examining associations between PM exposure during pregnancy and birth outcomes that included results for effect modification by race/ethnicity and/or maternal education. We summarized the findings for various sizes of PM and birth outcomes. Meta-analysis was conducted to quantify vulnerable race/ethnicity for the association between fine PM (PM2.5) and birthweight. RESULTS: In total, 19 studies were assessed, and PM-related risks of adverse birth outcomes, particularly those related to fetal growth, likely differ across subpopulations. A meta-analysis from five studies showed that a 10 µg/m3 increase of PM2.5 during the full-gestation reduced birthweight by 21.9 g (95% confidence interval 11.7, 32.0), 15.7 g (10.1, 21.4), 9.3 g (2.7, 15.8), and 5.8 g (- 9.0, 20.7) for Black, White, Hispanic, and Asian mothers, respectively. CONCLUSION: Our review indicated that Black mothers and mothers with low educational attainment are more vulnerable subpopulations. More investigation is needed for effect modification by other maternal factors, such as household income. Characterizing and quantifying vulnerable subpopulations are essential for addressing environmental justice since it can help regulatory agencies allocate resources and design policy interventions.

Review of take-home pesticide exposure pathway in children living in agricultural areas.

BACKGROUND: Children of farmworkers may be chronically exposed to pesticides via the take-home exposure pathway. OBJECTIVE: The goal of this review was to analyze scientific literature evaluating the role of the take-home pesticide exposure pathway in children of agricultural workers. METHODS: A systematic review was undertaken and inclusion criteria were applied to identify original articles of interest. Of the 30 articles included in this review, some belonged to the same studies, resulting in a total of 23 studies. Eight studies assessed environmental samples, nine collected biological samples, and the remaining six analyzed both. Eleven studies compared pesticide levels between farm and non-farm families. RESULTS: There is convincing evidence that children of farmworkers are exposed to pesticides at higher levels than "non-agricultural" children, even when residing in the same agricultural communities. These levels were shown to depend on the season, occupation, number of farmworkers per home, and type of crops. Other factors such as age, gender and, sex seem to also influence this pathway. Some studies have shown that pesticides used solely in agriculture are found only in households of farmworkers spraying these pesticides. Moreover, intervention studies have shown that behaviors among farmworkers can significantly lower exposure of people living in the same households as farmworkers. DISCUSSION AND CONCLUSION: The evidence presented here raises concerns regarding health effects associated with exposure to pesticides in children living in agricultural communities, and indicates that strategies should be developed to reduce exposures in these populations.

Monitoring proliferative activities of hormone-like odorants in human breast cancer cells by gene transcription profiling and electrical impedance spectroscopy.

The human estrogen receptor alpha (ERα) mediates the proliferative action of hormones in breast cancer cells by regulating the expression of target genes to control cellular functions. Current methodologies do not permit a real-time assessment of these processes in living cells. We overcome this limitation using electrical cell-substrate impedance sensing for measuring ERα-regulated signaling processes indicative of the onset of cell proliferation to target them for compound screenings. We report that hormone like odorants regulate, similarly as natural estrogen, ERα-mediated gene expression involved in mitogenic and developmental processes in MCF7 breast cancer cells. An odorant concentration-dependent switch in cell responses was detectable already 10-15 h post-stimulation, providing rapid quantification of hormonal activity before cell division occurred. Though ERα exhibits complex regulatory roles our non-invasive approach captures its activity for accelerated screenings of compounds promoting breast cancer cell proliferation expanding the analysis of ERα signaling networks.

Perinatal exposure to bisphenol a increases adult mammary gland progesterone response and cell number.

Bisphenol A [BPA, 2,2,-bis (hydroxyphenyl) propane] is one of the highest-volume chemicals produced worldwide. It is detected in body fluids of more than 90% of the human population. Originally synthesized as an estrogenic compound, it is currently utilized to manufacture food and beverage containers resulting in uptake with food and drinks. There is concern that exposure to low doses of BPA, defined as less than or equal to 5 mg/kg body weight /d, may have developmental effects on various hormone-responsive organs including the mammary gland. Here, we asked whether perinatal exposure to a range of low doses of BPA is sufficient to alter mammary gland hormone response later on in life, with a possible impact on breast cancer risk. To mimic human exposure, we added BPA to the drinking water of C57/Bl6 breeding pairs. Analysis of the mammary glands of their daughters at puberty showed that estrogen-dependent transcriptional events were perturbed and the number of terminal end buds, estrogen-induced proliferative structures, was altered in a dose-dependent fashion. Importantly, adult females showed an increase in mammary epithelial cell numbers comparable to that seen in females exposed to diethylbestrol, a compound exposure to which was previously linked to increased breast cancer risk. Molecularly, the mRNAs encoding Wnt-4 and receptor activator of nuclear factor κB ligand, two key mediators of hormone function implicated in control of mammary stem cell proliferation and carcinogenesis, showed increased induction by progesterone in the mammary tissue of exposed mice. Thus, perinatal exposure to environmentally relevant doses of BPA alters long-term hormone response that may increase the propensity to develop breast cancer.

Low doses of bisphenol A and diethylstilbestrol impair Ca2+ signals in pancreatic alpha-cells through a nonclassical membrane estrogen receptor within intact islets of Langerhans.

Glucagon, secreted from pancreatic alpha-cells integrated within the islets of Langerhans, is involved in the regulation of glucose metabolism by enhancing the synthesis and mobilization of glucose in the liver. In addition, it has other extrahepatic effects ranging from lipolysis in adipose tissue to the control of satiety in the central nervous system. In this article, we show that the endocrine disruptors bisphenol A (BPA) and diethylstilbestrol (DES), at a concentration of 10(-9) M, suppressed low-glucose-induced intracellular calcium ion ([Ca2+]i) oscillations in alpha-cells, the signal that triggers glucagon secretion. This action has a rapid onset, and it is reproduced by the impermeable molecule estradiol (E2) conjugated to horseradish peroxidase (E-HRP). Competition studies using E-HRP binding in immunocytochemically identified alpha-cells indicate that 17beta-E2, BPA, and DES share a common membrane-binding site whose pharmacologic profile differs from the classical ER. The effects triggered by BPA, DES, and E2 are blocked by the G alpha i- and G alpha o-protein inhibitor pertussis toxin, by the guanylate cyclase-specific inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, and by the nitric oxide synthase inhibitor N-nitro-L-arginine methyl ester. The effects are reproduced by 8-bromo-guanosine 3',5'-cyclic monophosphate and suppressed in the presence of the cGMP-dependent protein kinase inhibitor KT-5823. The action of E2, BPA, and DES in pancreatic alpha-cells may explain some of the effects elicited by endocrine disruptors in the metabolism of glucose and lipid.