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

Abstract

Estudos de biomonitoração do sistema urinário, circulatório e tecidos indicam grande exposição ao Bisfenol A Resumo Bisfenol A (BPA) é um dos produtos quí-micos 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 toxicocinéti-ca 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. Palavras-chave Disruptor endócrino, Exposição humana, Modelo PBPK/PBTK, Gravidez, Avaliação de risco, Toxicocinética Abstract 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.

Exposure to Low-Dose Bisphenol A Impairs Meiosis in the Rat Seminiferous Tubule Culture Model: A Physiotoxicogenomic Approach

“…According to physiologically based pharmacokinetic studies, BPA is found in human serum, urine, milk and fat, with plasma levels ranging from 0.2 to 20 ng/mL (or 1 to 100 nM) [1], [2], [3], [4], [5], [6]. This substance is mainly absorbed by the digestive tract.…”

Bisphenol A at concentrations relevant to human exposure enhances histamine and cysteinyl leukotriene release from bone marrow-derived mast cells

“…BPA has also been demonstrated to bind to the membrane-bound G-protein coupled ER 1 (GPER, also GRP30) (Bouskine et al, 2009; Sheng and Zhu, 2011), as well as the nuclear receptor estrogen-related receptor (ERR)-γ (Matsushima et al, 2007). BPA levels in human samples including urine, serum, blood, and saliva can vary depending on sample type, study population, and detection method, though reports repeatedly indicated that levels of BPA in humans are in the nanomolar range (Vandenberg et al, 2007, 2012). For example, typical total BPA levels in adult serum and urine range from ~1–90 nM and ~5–10 nM, respectively (Vandenberg et al, 2007).…”

Science of problems, science of solutions or both? A case example of bisphenol A

“…Unconjugated BPA in blood and conjugated BPA in urine samples have been found in biomonitoring throughout the world 4. Despite the number of studies demonstrating human and environmental exposures and identifying hazards in animal and cellular models, there is still uncertainty as to the major sources and significance of exposure, pharmacokinetics of exposure, and to what extent the effects in animal models are transferable to humans 5.…”