Toy dolls manufactured in China and seized by U.S. Customs and Border Protection in 2013 due to high<unk>  levelsA study in the peer-reviewed journal Environmental Pollution published October 12, 2021 found that high<unk>  levels are weakly correlated with a greater risk of dying from any cause and with a stronger correlation to dying from heart problems, but the calculated hazard ratios were below 2 in both cases. The study estimated that<unk> s may contribute to 91,000–107,000 premature deaths each year among people aged 55–64 in the United States. Endocrine disruption<unk> s enter the bloodstream and disrupt sex hormone production, interfering with sexual development in infants and sexual behaviour in adults. Levels of<unk> s have been dose-dependently linked to reduced anogenital distance decreased sexual desire and satisfaction in women, and malformed genital development in rats.<unk> s act by mimicking the female hormone estrogen, which in turn inhibits production of the male hormone testosterone. As such,<unk> s are considered to be endocrine disruptors—a substance that interferes with the normal hormonal mechanisms that allow a biological organism to interact with its environment, and has sparked demands to ban or restrict its use in baby toys. Endocrine disruptors exhibit numerous behaviors that can make studying them a challenge. There can be a lag between when someone is exposed to an endocrine disruptor and any symptoms manifesting themselves–in particular fetal and early childhood exposure may have consequences later in adulthood. Many studies refer to this period of fetal and postnatal development as particularly important to development, but studying this is difficult; it is obviously a huge challenge to measure endocrine disruptor exposure during fetal development and then decades later diagnosing any health problems. Additionally, endocrine disruptor exposure can transmit epigenetically to one's offspring without them being directly exposed to the endocrine disruptors. Finally, particularly low levels of exposure may still have significant effects, and exposure to multiple endocrine disruptors across a variety of compounds (not just<unk> s) may synergistically combine to cause a greater effect. Evaluating the actual effects of a specific compound such as a particular<unk>  requires examining cumulative exposure across multiple compounds, rather than evaluating one compound in isolation. A widespread concern about<unk>  exposure is the possibility (though not conclusive) that it is the cause of a worldwide drop in male fertility. Studies have shown that<unk> s cause abnormalities in the reproductive systems of animals, with the greatest effects when the animal is exposed during gestation and immediately thereafter. Numerous studies on adult male humans show the similar result that<unk>  exposure correlates with worsening metrics of male fertility, such as semen quality, the quantity of damaged DNA in sperm, decreased sperm motility, decreased semen volume, and other metrics.<unk> s causing harm to the male reproductive system is plausible, and continues to be researched. The effect of<unk> s on the female reproductive system is also not fully understood yet. Current studies indicate<unk> s have negative effects on folliculogenesis and steroidogenesis. Early research also shows<unk>  exposure may be associated with diabetes and insulin resistance, breast cancer, obesity, metabolic disorders, and immune function. There are possible (though not conclusive) associations between<unk>  exposure and adverse child neurodevelopment, including the development of ADHD and autistic behaviors and lower cognitive and motor development. Most common associations found in medical reports link the<unk> s exposure to hyperactivity, aggression, and other adverse behaviors. Some studies have found the childhood exposure to be as early as in utero. In many cases, there are studies that show connections between<unk> s and these negative outcomes, as well as studies that show no connection; this is likely due to the research challenges outlined above, and when resolved, could show that<unk>  exposure does not cause health effects, or even that they have a much greater effect than currently predicted. In all cases, larger studies are needed to demonstrate incontrovertibly what effect<unk>  exposure has on human health. A Nature Reviews Endocrinology review paper from 2017 gives some advice for avoiding exposure to<unk> s for concerned people; while they make pains to state that there is no evidence that shows this advice will positively affect one's health, they suggest (1) eating a balanced diet to avoid ingesting too many endocrine disruptors from a single source, (2) eliminating canned or packaged food in order to limit ingestion of DEHP<unk> s leached from plastics, and (3) eliminating use of any personal product such as moisturizer, perfume, or cosmetics that contain<unk> s. Eliminating personal products containing<unk> s can be particularly difficult or impossible due to some countries such as the United States not requiring them to be disclosed in a list of ingredients. Endocannabinoid system disruption<unk> s block CB1 as allosteric antagonists. Other effects There may be a link between the obesity epidemic and endocrine disruption and metabolic interference. Studies conducted on mice exposed to<unk> s in utero did not result in metabolic disorder in adults. However, "in a national cross-section of U.S. men, concentrations of several prevalent<unk>  metabolites showed statistically significant correlations with abnormal obesity and insulin resistance." Mono-ethylhexyl-phthalate (MEHP), a metabolite of DEHP, has been found to interact with all three peroxisome proliferator-activated receptors (PPARs). PPARs are members of the nuclear receptor superfamily. The author of the study stated "The roles of PPARs in lipid and carbohydrate metabolism raise the question of their activation by a sub-class of pollutants, tentatively named metabolic disrupters."<unk> s belong to this class of metabolic disruptors. It is a possibility that, over many years of exposure to these metabolic disruptors, they are able to deregulate complex metabolic pathways in a subtle manner. Large amounts of specific<unk> s fed to rodents have been shown to damage their liver and testes, and initial rodent studies also indicated hepatocarcinogenicity. Following this result, di(2-ethylhexyl)<unk>  was listed as a possible carcinogen by IARC, EC, and WHO. Later studies on primates showed that the mechanism is specific to rodents; humans are resistant to the effect. The carcinogen classification was subsequently withdrawn.
Phthalate
Photoanethole
Tetraethyllead
Dichloroacetic acid
Diiodohydroxyquinoline
Dicoumarol
Selenous acid
Tetrachlorodecaoxide