Urinary, Circulating, and Tissue Biomonitoring Studies Indicate Widespread Exposure to Bisphenol A

Bisphenol A (BPA) is one of the highest-volume chemicals produced worldwide, and human exposure to BPA is thought to be ubiquitous. Thus, there are concerns that the amount of BPA to which humans are exposed may cause adverse health effects. We examined many possibilities for why biomonitoring and toxicokinetic studies could come to seemingly conflicting conclusions. More than 80 published human biomonitoring studies that measured BPA concentrations in human tissues, urine, blood, and other fluids, along with two toxicokinetic studies of human BPA metabolism were examined. Unconjugated BPA was routinely detected in blood (in the nanograms per milliliter range), and conjugated BPA was routinely detected in the vast majority of urine samples (also in the nanograms per milliliter range). In stark contrast, toxicokinetic studies proposed that humans are not internally exposed to BPA. Available data from biomonitoring studies clearly indicate that the general population is exposed to BPA and is at risk from internal exposure to unconjugated BPA. The two toxicokinetic studies that suggested human BPA exposure is negligible have significant deficiencies, are directly contradicted by hypothesis-driven studies, and are therefore not reliable for risk assessment purposes.Bisfenol A (BPA) é um dos produtos químicos mais produzido em todo o mundo, e a exposição humana a ele é considerada onipresente. Assim, há preocupações de que a quantidade de BPA para o qual os seres humanos estão expostos podem causar efeitos adversos à saúde. Nós examinamos muitas possibilidades sobre o porquê estudos de biomonitorização e toxicocinética podem chegar a conclusões aparentemente conflitantes. Mais de 80 estudos publicados de biomonitorização humana que mediram a concentração de BPA em tecidos humanos, urina, sangue e outros fluidos, juntamente com dois estudos de toxicocinética do metabolismo humano BPA foram examinados. BPA não conjugado foi detectado no sangue (nonanogramas por mililitro gama), e BPA conjugado foi detectado na grande maioria das amostras de urina. Em contraste, estudos de toxico-cinética propuseram que os seres humanos não são internamente expostos ao BPA. Dados disponíveis de estudos de biomonitorização indicam que a população em geral está exposta ao BPA e em risco de exposição interna ao BPA não conjugado. Os dois estudos de toxicocinética, que sugeriram a exposição humana ao BPA é insignificante, têm deficiências significativas e estão diretamente refutados por outros estudos e, portanto não são confiáveis para fins de avaliação de risco

Biomonitoring Studies Should Be Used by Regulatory Agencies to Assess Human Exposure Levels and Safety of Bisphenol A

BACKGROUND: Within the past 3 years, four major evaluations of bisphenol A (BPA) safety have been undertaken. However, these assessments have arrived at quite different conclusions regarding the safety of BPA at current human exposure levels. OBJECTIVES: We compared the reasons provided by the European Food Safety Authority (EFSA) BPA risk assessment panel for their conclusion that human exposures are negligible with the conclusions reached by the other panels, with all panels having the same body of literature at their disposal. DISCUSSION: The EFSA panel dismissed \u3e or = 80 biomonitoring studies that documented significant levels of BPA exposure in humans, including internal exposures to unconjugated BPA, on the basis that they did not match a model of BPA metabolism. Instead, the EFSA panel relied on two toxicokinetic studies-conducted in 15 adults administered BPA-to draw conclusions about exposure levels in the population, including exposures of neonates. CONCLUSIONS: As with all exposure assessments, models should be developed to explain actual data that are collected. In the case of BPA, samples from a large number of human subjects clearly indicate that humans are internally exposed to unconjugated BPA. The dismissal of these biomonitoring studies simply because their results do not conform to a model violates scientific principles. Expert panels should evaluate all data-including human biomonitoring studies-to make informed risk assessments

A critical appraisal of the harm reduction argument for heat-not-burn tobacco products

Heat-not-burn products (HNBs) are efficient nicotine delivery devices that heat tobacco instead of burning it, as conventional cigarettes do. Since heating yields less carbon monoxide and other tobacco pyrolysis–derived toxicants, tobacco companies claim that HNBs are less harmful than conventional cigarettes are. Although this hypothesis is plausible, no long-term clinical trials and/or observational studies are available to corroborate it. To overcome barriers to the entry of tobacco products to the market, manufacturers of HNBs argue that they are a new wave of harm reduction alternatives. Nonetheless, even if HNBs were in fact less harmful than conventional cigarettes, they would still have the potential to cause nicotine addiction (a major health hazard) and other harms to smokers’ health. HNBs deliver nicotine, provide users a tobacco aroma and flavor and some rituals of smoking, and are supposedly safer than conventional cigarettes. Owing to these features, HNBs are likely to enhance smoking appeal and initiation among young persons and discourage smokers’ attempts to quit. In other words, if HNBs were freely available on the market, they would increase the prevalence of smoking. However, HNBs may constitute a harm reduction alternative for nicotine-dependent smokers who are unable or unwilling to quit smoking. Given these facts, approval of HNBs for use under medical supervision (prescription only), along with strict restrictions on advertising, is a balanced regulatory option that would reconcile the therapeutic needs of nicotine-addicted patients with the public heath goal of achieving a smoke-free generation in the near future

Traditional use and safety of herbal medicines

In the European Union, traditional herbal medicines that are regarded as "acceptably safe, albeit not having a recognized level of efficacy" fit into a special category of drugs ("traditional herbal medicine products") for which requirements of non-clinical and clinical studies are less rigorous. A regulation proposal published by the Brazilian National Health Surveillance (Anvisa) defines a similar drug category ("traditional phytotherapeutic products") for registration purposes. Regarding herbal medicines, both agencies seem to be lenient regarding proof of efficacy, and consider long-standing folk use as evidence of safety and a waiver of a thorough toxicological evaluation. Nonetheless, several herbal products and constituents with a long history of folk usage are suspected carcinogenic and/or hepatotoxic. Herbal products have also been shown to inhibit and/or induce drug-metabolizing enzymes. Since herbal medicines are often used in conjunction with conventional drugs, kinetic and clinical interactions are a cause for concern. A demonstration of the safety of herbal medicines for registration purposes should include at least in vitroand in vivogenotoxicity assays, long-term rodent carcinogenicity tests (for drugs intended to be continuously used for > 3 months or intermittently for > 6 months), reproductive and developmental toxicity studies (for drugs used by women of childbearing age), and investigation of the effects on drug-metabolizing enzymes