How does formal and informal industry contribute to lead exposure? A narrative review from Vietnam, Uruguay, and Malaysia.

INTRODUCTION: Lead industries are one of the major sources of environmental pollution and can affect human through different activities, including industrial processes, metal plating, mining, battery recycling, etc. Although different studies have documented the various sources of lead exposure, studies highlighting different types of industries as sources of environmental contamination are limited. Therefore, this narrative review aims to focus mainly on lead industries as significant sources of environmental and human contamination. CONTENT: Based on the keywords searched in bibliographic databases we found 44 relevant articles that provided information on lead present in soil, water, and blood or all components among participants living near high-risk areas. We presented three case scenarios to highlight how lead industries have affected the health of citizens in Vietnam, Uruguay, and Malaysia. SUMMARY AND OUTLOOK: Factories conducting mining, e-waste processing, used lead-acid battery recycling, electronic repair, and toxic waste sites were the primary industries for lead exposure. Our study has shown lead exposure due to industrial activities in Vietnam, Uruguay, Malaysia and calls for attention to the gaps in strategic and epidemiologic efforts to understand sources of environmental exposure to lead fully. Developing strategies and guidelines to regulate industrial activities, finding alternatives to reduce lead toxicity and exposure, and empowering the public through various community awareness programs can play a crucial role in controlling exposure to lead.

Lead in traditional and complementary medicine: a systematic review.

Lead in the environment remains a matter of grave concern for public health. Lead has been associated with some traditional medicines and has been linked to cases of lead poisoning. A comprehensive compilation of these reports has not previously been conducted. The objective of this review is to explore how common is lead exposure after traditional medicine use, and which countries, systems and/or products are of most concern when it comes to lead contamination. A systematic search was conducted on PubMed, Ovid and EMBASE for studies published between 2005 and 2020. A grey literature search was conducted. Search terms related to lead and traditional medicine were developed for each database, and there were no limitations on language. Studies were included if they examined elevated lead in humans resulting from the use of traditional medicines reported in case reports, case-series, or observational studies. Of the papers discussing lead exposure, 85 case reports were identified and synthesized for the current review. Several themes were identified in the included studies. Traditional medicine has been used in the many parts of the world, however use is more common in South and Southeast Asian countries. The level of detectable lead in products varied widely by region and product types. Consumers of traditional medicines sought products for a wide variety of symptoms and ailments. The symptoms of lead poisoning from traditional medicine use reflected the typical symptom profile of lead poisoning, highlighting the need for awareness of traditional medicine products as a source of lead exposure. Traditional medicine usage remains an important part of health care in many regions, however there is a risk of lead exposure from several products. Health care practitioners in all regions of the world should be aware of the risk and explore the potential for traditional medicine use for patients presenting with elevated blood lead levels. Countries with a strong traditional medicine culture should explore policies for reducing lead exposure from traditional medicine products. JG, LO and MNBD are staff members of the World Health Organization. The authors alone are responsible for the views expressed in this publication and they do not necessarily represent the decisions, policy, or views of the World Health Organization.

Narrative review of lead poisoning in humans caused by industrial activities and measures compatible with sustainable industrial activities in Republic of Zambia.

Lead (Pb) pollution and human exposure to Pb, is an important issue for the international community to address being associated with 0.90 million deaths from long-term effects. The Republic of Zambia is a typical mineral resource-rich country, with long-standing mining and smelting activities of metals including Pb in several parts of the country. This narrative review provides a comprehensive overview of previous papers that have assessed human exposure to Pb and related health effects in Zambia. Environmental remediation methods that should be applied locally, ways to reduce Pb exposure of the population, and issues that need to be addressed by various sectors are discussed. Environmental remediation methods using locally available and affordable materials are needed to ensure both sustainable industrial activities and pollution prevention. In the Zambian mining towns, including Kabwe, various research activities have been conducted, including environmental monitoring, human biomonitoring and health impact assessments. The town of Kabwe, which was one of Zambia's largest Pb mining area in the 20th century, continues to have formal and informal Pb-related industries and is known as one of the most polluted areas in the world. For example, despite the World Health Organization asserting that "For an individual with a blood Pb concentration ≥ 5 µg/dL, appropriate action should be taken to terminate exposure", there are reports of blood Pb levels in Kabwe children exceeding 100 µg/dL. While Pb pollution is a global issue, not many places have such continuous and comprehensive research has been conducted, and there is much to be learned from the knowledge accumulated in these areas. Because the high levels of Pb accumulation in humans and the adverse health effects were clarified, we consider that it is important to combine mining activities, which are a key industry, with measures to prevent environmental pollution.

Online media coverage of air pollution risks and current policies in India: A content analysis.

Background Air pollution is of particular concern in India, which contains 11 of the 20 most polluted cities in the world. Media coverage of air pollution issues plays an important role in influencing public opinion and increasing citizen demand for action on clean air policy. Hence, this study was designed to assess news coverage of air pollution in India and its implications for policy advancement. Methods Articles published online between 1 January 2014 and 31 October 2015 that discussed air pollution in India were systematically content analysed. From 6435 articles in the national media and 271 articles in the international media, a random selection of 500 articles (400 from national and 100 from international media) were analysed and coded by two independent coders, after high inter-rater reliability (kappa statistic above 0.8) was established. Results There was an increase in the number of news stories on air pollution in India in the national media over the study period; 317 (63%) stories described the risk to health from air pollution as moderately to extremely severe, and 393 (79%) stories described the situation as needing urgent action. Limited information was provided on the kinds of illnesses that can result from exposure. Less than 30% of stories in either media specifically mentioned the common illnesses resulting from air pollution. Very few articles in either media mentioned the population groups most at risk from air pollution, such as children or older people. Vehicles were presented most often as the cause of air pollution in India (in over 50% of articles in both national and international media). Some of the most important sources of air pollution were mentioned less often: 6% of national and 18% of international media articles mentioned unclean sources of household energy; 3% of national and 9% of international media articles mentioned agricultural field burning. Finally, the majority of articles (405; 81%) did not mention any specific institution or organization - such as the government or industry groups - as the primary responsible stakeholder, thus leaving ambiguous the organizations whose leadership was necessary to mitigate air pollution. Conclusion Gaps exist in the current media discourse on air pollution, suggesting the need for strengthening engagement with the media as a means of creating citizen engagement and enabling policy action. Through greater elaboration of the health burdens and evidence-based policy actions, the media can play a critical role in galvanizing India's action on air quality. These data may suggest opportunities for media advocacy and greater public and policy engagement to address issues around air quality in India.

The OECD program to validate the rat Hershberger bioassay to screen compounds for in vivo androgen and antiandrogen responses. Phase 1: use of a potent agonist and a potent antagonist to test the standardized protocol.

The Organisation for Economic Cooperation and Development (OECD) has completed phase 1 of the Hershberger validation intended to identify in vivo activity of suspected androgens and antiandrogens. Seventeen laboratories from 7 countries participated in phase 1, and results were collated and evaluated by the OECD with the support of an international committee of experts. Five androgen-responsive tissues (ventral prostate, paired seminal vesicles and coagulating glands, levator ani and bulbocavernosus muscles, glans penis, and paired Cowper's or bulbourethral glands) were evaluated. The standardized protocols used selected doses of a reference androgen, testosterone propionate (TP), and an antiandrogen, flutamide (FLU). All laboratories successfully detected TP-stimulated increases in androgen-responsive tissue weight and decreases in TP-stimulated tissue weights when FLU was co-administered. The standardized protocols performed well under a variety of conditions (e.g., strain, diet, housing protocol, bedding). There was good agreement among laboratories with regard to the TP doses inducing significant increases in tissue weights and the FLU doses decreasing TP-stimulated tissue weights. Several additional procedures (e.g., weighing of the dorsolateral prostate and fixation of tissues before weighing) and serum component measurements (e.g., luteinizing hormone) were also included by some laboratories to assess their potential utility. The results indicated that the OECD Hershberger protocol was robust, reproducible, and transferable across laboratories. Based on this phase 1 validation study, the protocols have been refined, and the next phase of the OECD validation program will test the protocol with selected doses of weak androgen agonists, androgen antagonists, a 5alpha-reductase inhibitor, and chemicals having no androgenic activity.

How can toxicogenomics inform risk assessment?

Technologies that generate information about the genome are being used to explore changes in gene expression and related proteins following exposure to chemicals. Conceptually, this information allows a greater understanding of genomic level mRNA expression (transcriptomics), cell and tissue protein expression (proteomics) and information about metabolite profiles (metabonomics). Having a greater understanding of this information alongside, empirical toxicological reference data provide for the continued evolution in our ability to understand toxicological modes of action, thereby providing a more scientific basis for extrapolation of toxicological information from animals to humans. Toxicogenomics also provides specific opportunities for improvements at different stages of the risk assessment process such as the development of new predictive models for identifying human health hazards and the identification of more precise molecular biomarkers of exposure. One possibility is that molecular fingerprinting in vivo or in vitro can be used to categorize chemicals and mixtures of chemicals into different mode of action groups. As there is indication that molecular signals differ at dose levels, it is hoped that toxicogenomic information can also contribute to the understanding and interpretation of effects seen with low dose exposure. Several gene polymorphisms have already been identified which play a role in the differing intra-species response to chemicals thus providing explanation for the observed differences in effects. It is therefore likely that a better understanding of genomic expression will enable a greater insight into the factors behind the observed variability in susceptibility to chemical exposure that can be seen in human populations.

The OECD program to validate the rat uterotrophic bioassay. Phase 2: dose-response studies.

The Organisation for Economic Co-operation and Development has completed phase 2 of an international validation program for the rodent uterotrophic bioassay. The purpose of the validation program was to demonstrate the performance of two versions of the uterotrophic bioassay, the immature female rat and the adult ovariectomized rat, in four standardized protocols. This article reports the dose-response studies of the validation program; the coded single-dose studies are reported in an accompanying paper. The dose-response study design used five selected weak estrogen agonists, bisphenol A, genistein, methoxychlor, nonylphenol, and o,p -DDT. These weak agonists were administered in a prescribed series of doses to measure the performance and reproducibility of the protocols among the participating laboratories. All protocols successfully detected increases in uterine weights when the weak agonists were administered. Within each protocol, there was good agreement and reproducibility of the dose response among laboratories with each substance. Substance-specific variations were observed in the influence of the route of administration on the uterine response, the potency as related to the dose producing the first statistically significant increase in uterine weights, and the maximum increase in uterine weight. Substantive performance differences were not observed between the uterotrophic bioassay versions or among the standardized protocols, and these were judged to be qualitatively equivalent. It is noteworthy that these results were reproducible under a variety of different experimental conditions (e.g., animal strain, diet, housing, bedding, vehicle, animal age), indicating that the bioassay's performance as a screen is robust. In conclusion, both the intact, immature, and adult OVX versions, and all protocols appear to be reproducible and transferable across laboratories and are able to detect weak estrogen agonists.

The OECD program to validate the rat uterotrophic bioassay. Phase 2: coded single-dose studies.

The Organisation for Economic Co-operation and Development has completed phase 2 of an international validation program for the rodent uterotrophic bioassay. This portion of phase 2 assessed the reproducibility of the assay with a battery of positive and negative test substances. Positive agonists of the estrogen receptor included the potent reference estrogen 17-ethinyl estradiol (EE), and the weak estrogen agonists bisphenol A, genistein, methoxychlor, nonylphenol, and o,p -DDT. The negative test substance or nonagonist was n-dibutylphthalate. The test substances were coded, and prescribed doses of each test substance were administered in 16 laboratories. Two versions of the uterotrophic assay, the intact immature and the adult ovariectomized female rat, were tested and compared using four standardized protocols covering both sc and po administration. Assay reproducibility was compared using a) EE doses identical to those used in phase 1 and in parallel dose-response studies, b) single doses of the weak agonists identical to one of five doses from the dose-response studies, and c) a single dose of the negative test substance. The results were reproducible and in agreement both within individual laboratories and across the participating laboratories for the same test substance and protocol. The few exceptions are examined in detail. The reproducibility was achieved despite a variety of different experimental conditions (e.g., variations in animal strain, diet, housing protocol, bedding, vehicle, animal age). In conclusion, both versions of the uterotrophic bioassay and all protocols appear robust, reproducible, and transferable across laboratories and able to detect weak estrogen agonists. These results will be submitted along with other data for independent peer review to provide support for the validation of the uterotrophic bioassay.

The OECD program to validate the rat uterotrophic bioassay. Phase 2: dietary phytoestrogen analyses.

Many commercial laboratory diets have detectable levels of isoflavones (e.g., phytoestrogens such as genistein [GN]) that have weak estrogenic activity both in vitro and in vivo. During validation studies of the uterotrophic bioassay, diet samples from 20 participating laboratories were collected and analyzed for three major phytoestrogens: GN, daidzein (DN), and coumestrol (CM). Soy phytoestrogens GN and DN were found at total phytoestrogen levels from 100 to 540 microg/g laboratory diet; a forage phytoestrogen, CM, ranged from nondetectable to 4 microg/g laboratory diet. The phytoestrogen levels were compared with both baseline uterine weights of the control groups and with the relative uterine weight increase of groups administered two weak estrogen agonists: bisphenol A (BPA) and nonylphenol (NP). The comparison uses a working assumption of additivity among the phytoestrogens, despite several significant qualifications to this assumption, to estimate total genistein equivalents (TGE). Some evidence was found that phytoestrogen levels in the diet > 325-350 microg/g TGE could diminish the responsiveness of the uterotrophic bioassay to weak agonists. This was especially true for the case of the intact, immature female version of the uterotrophic bioassay, where higher food consumption relative to body weight leads to higher intakes of dietary phytoestrogens versus ovariectomized adults. This dietary level is sufficient in the immature female to approach a biological lowest observable effect level for GN of 40-50 mg/kg/day. These same data, however, show that low to moderate levels of dietary phytoestrogens do not substantially affect the responsiveness of the assay with weak estrogen receptor agonists such as NP and BPA. Therefore, laboratories conducting the uterotrophic bioassay for either research or regulatory purposes may routinely use diets containing levels of phytoestrogens < 325-350 microg/g TGE without impairing the responsiveness of the bioassay.