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  1. Article ; Online: Failure to Launch: The Endocrine Disruptor Screening Program at the U.S. Environmental Protection Agency.

    Maffini, Maricel V / Vandenberg, Laura N

    Frontiers in toxicology

    2022  Volume 4, Page(s) 908439

    Abstract: It has been 25 years since the U.S. Congress passed the Food Quality Protection Act of 1996, an amendment to the Food Drug and Cosmetic Act, which mandated that the US Environmental Protection Agency (EPA) test all pesticide chemicals used in food for ... ...

    Abstract It has been 25 years since the U.S. Congress passed the Food Quality Protection Act of 1996, an amendment to the Food Drug and Cosmetic Act, which mandated that the US Environmental Protection Agency (EPA) test all pesticide chemicals used in food for endocrine disruption. Soon after the law passed, EPA established the Endocrine Disruptor Screening and Testing Advisory Committee (EDSTAC) to provide recommendations to the agency on how its Endocrine Disruptor Screening Program (EDSP) should work. Among them, the committee recommended that EDSP screening should 1) evaluate both human and ecological effects; 2) test for disruption of the estrogen, androgen, and thyroid systems; 3) evaluate pesticide and non-pesticide chemicals; and 4) implement a tiered approach. EPA adopted the recommendations and the EDSP was created in 1998. To date, the EPA has yet to fully implement the law; in other words, it has failed to test all pesticide chemicals for endocrine disruption. Of the small number that have been tested, not a single pesticide chemical has been determined to be an endocrine disruptor, and no regulatory actions have been taken. Here, we review the missed opportunities EPA had to make the EDSP a functional and effective program aimed at protecting human health and the environment. Two reports by the EPA's Office of Inspector General from 2011 to 2021 provide the framework for our discussion.
    Language English
    Publishing date 2022-05-30
    Publishing country Switzerland
    Document type Journal Article
    ISSN 2673-3080
    ISSN (online) 2673-3080
    DOI 10.3389/ftox.2022.908439
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Out of balance: conflicts of interest persist in food chemicals determined to be generally recognized as safe.

    Matouskova, Klara / Neltner, Thomas G / Maffini, Maricel V

    Environmental health : a global access science source

    2023  Volume 22, Issue 1, Page(s) 59

    Abstract: Manufacturers of chemicals added to food are responsible for determining that the use of their products is safe. There are two major legal definitions of chemicals in food: (1) food additives which includes ingredients and chemicals indirectly entering ... ...

    Abstract Manufacturers of chemicals added to food are responsible for determining that the use of their products is safe. There are two major legal definitions of chemicals in food: (1) food additives which includes ingredients and chemicals indirectly entering food from packaging and processing equipment, and (2) generally recognized as safe (GRAS) substances mostly used as ingredients. The law requires food additives to undergo approval by the U.S. Food and Drug Administration (FDA) before they are sold, but it GRAS substances are exempted from pre-market approval. In 1997, FDA created a voluntary program for manufacturers to submit their chemical's safety determination in the form of a GRAS notice to the agency. Manufacturers make GRAS determinations regardless of whether they voluntarily submit a notice to FDA for review. They rely on their own employees, the employee of a hired consulting firm or a panel of experts, known as GRAS panel, to review the safety information. Because this process determines whether a chemical is safe for use in food, conflicts of interest and biases need to be avoided or minimized to credibly ensure food is safe. Recently, FDA has published guidance for industry on best practices to convene GRAS panels to manage conflicts of interest and reduce biases that have plagued the process. Here, we perform a qualitative assessment of the compliance of GRAS panels with basic elements of FDA's guidance. We assessed 403 GRAS notices filed by FDA between 2015 and 2020 and identified whether a GRAS panel was convened and by whom, its members, affiliations, and relationships between panelists and panel conveners. Then, we compared FDA's recommendations against the information included in the notices voluntarily submitted by manufacturers. We found no evidence that GRAS panels have adhered to FDA's guidance. Panels are populated from a very small pool of professionals; we found that seven panel members alone occupied almost half of all available panel positions and that they often serve together. Against guidance recommendations, ad-hoc panels have been substituted by panels with recurring members in hired consulting firms' payroll. The widespread persistence of conflicts of interest, appearance of conflict and bias in GRAS determinations continue to put the health of Americans at risk and undermine confidence in the safety of food ingredients in the US market. FDA should require notice for all GRAS determinations including how the financial conflicts of interest of those who make these determinations are minimized.
    MeSH term(s) Humans ; Conflict of Interest ; Food Additives ; Industry
    Chemical Substances Food Additives
    Language English
    Publishing date 2023-09-06
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2092232-2
    ISSN 1476-069X ; 1476-069X
    ISSN (online) 1476-069X
    ISSN 1476-069X
    DOI 10.1186/s12940-023-01004-8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: An expanded toxicological profile of tetramethyl bisphenol F (TMBPF), a precursor for a new food-contact metal packaging coating.

    Maffini, Maricel V / Canatsey, Ryan D

    Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association

    2019  Volume 135, Page(s) 110889

    Abstract: Tetramethyl bisphenol F (TMBPF) has been shown to impart unique physical properties critical for high performance of epoxy can coatings without the estrogenic activity concerns associated with other bisphenols. To further characterize the toxicological ... ...

    Abstract Tetramethyl bisphenol F (TMBPF) has been shown to impart unique physical properties critical for high performance of epoxy can coatings without the estrogenic activity concerns associated with other bisphenols. To further characterize the toxicological profile of TMBPF, additional endocrine-related endpoints including in vitro aromatase inhibition and steroidogenesis assays, and in vivo androgen agonism/antagonism were performed. Systemic toxicity was also assessed by a repeat dose 90-day dietary toxicity study followed by 28-day recovery period. TMBPF did not inhibit aromatase activity, and induced estradiol and testosterone at highest non-cytotoxic concentrations (10 μM) in the steroidogenesis assay. In the Hershberger assay, TMBPF showed no androgenic activity at any dose and equivocal anti-androgenic activity at the highest dose (1000 mg/kg-bw/d). In a 90-day dietary toxicity study with 28-day recovery period, observations including changes in clinical pathology, absolute and relative organ weights, and microscopic findings are discussed. In this current study, the no observed adverse effect level was considered to be 750 mg/kg-bw/d for female rats and 1000 mg/kg-bw/d for male rats with no biologically significant changes to endocrine endpoints at any dose level. Our findings provide further evidence that TMBPF is a low-toxicity substance with a toxicology profile distinct from some other bisphenols.
    MeSH term(s) Animals ; Benzhydryl Compounds/administration & dosage ; Benzhydryl Compounds/chemistry ; Benzhydryl Compounds/toxicity ; Cell Line, Tumor ; Dose-Response Relationship, Drug ; Female ; Food Packaging ; Gonadal Steroid Hormones/antagonists & inhibitors ; Humans ; Male ; Metals/chemistry ; No-Observed-Adverse-Effect Level ; Phenols/administration & dosage ; Phenols/chemistry ; Phenols/toxicity ; Rats ; Rats, Sprague-Dawley
    Chemical Substances Benzhydryl Compounds ; Gonadal Steroid Hormones ; Metals ; Phenols ; bisphenol F
    Language English
    Publishing date 2019-10-17
    Publishing country England
    Document type Journal Article
    ZDB-ID 782617-5
    ISSN 1873-6351 ; 0278-6915
    ISSN (online) 1873-6351
    ISSN 0278-6915
    DOI 10.1016/j.fct.2019.110889
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Overgeneralization by Anderson et al. and Luz et al. regarding safety of fluorotelomer-based chemistry.

    Maffini, Maricel V / Neltner, Thomas G

    Regulatory toxicology and pharmacology : RTP

    2019  Volume 105, Page(s) 99

    MeSH term(s) Caproates ; Cognition ; Fluorocarbons ; Humans ; Risk Assessment
    Chemical Substances Caproates ; Fluorocarbons ; perfluorohexanoic acid (ZP34Q2220R)
    Language English
    Publishing date 2019-04-05
    Publishing country Netherlands
    Document type Letter ; Comment
    ZDB-ID 604672-1
    ISSN 1096-0295 ; 0273-2300
    ISSN (online) 1096-0295
    ISSN 0273-2300
    DOI 10.1016/j.yrtph.2019.04.002
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Diet quality and exposure to endocrine-disrupting chemicals among US adults.

    Melough, Melissa M / Maffini, Maricel V / Otten, Jennifer J / Sathyanarayana, Sheela

    Environmental research

    2022  Volume 211, Page(s) 113049

    Abstract: Human exposure to endocrine-disrupting chemicals (EDCs) may increase risk for chronic disease. Diet is a significant source of EDC exposure, yet healthy diets recommended for chronic disease prevention have not been thoroughly examined for associations ... ...

    Abstract Human exposure to endocrine-disrupting chemicals (EDCs) may increase risk for chronic disease. Diet is a significant source of EDC exposure, yet healthy diets recommended for chronic disease prevention have not been thoroughly examined for associations with EDC exposure. Using data from the National Health and Nutrition Examination Survey 2013-2016, we examined associations of dietary patterns with exposure to non-persistent EDCs potentially consumed through diet. EDCs were measured in spot urine samples. Diet was assessed using 24-h recalls. Multivariable linear regression was used to examine associations of three healthy diet scores [Healthy Eating Index (HEI), relative Mediterranean Diet (rMED), and Dietary Approaches to Stop Hypertension] and fast-food consumption with EDCs. In fully adjusted models, no diet was associated with exposure to the bisphenols, phthalates, or polycyclic aromatic hydrocarbons examined. A 1-point increase in rMED (of 18 possible points) was associated with 2.7% (95% CI: 1.7%, 3.8%) greater urinary nitrate. A 10-point increase in HEI (of 100 possible points) was associated with 5.3% (95% CI: 2.8%, 7.9%) greater nitrate and 6.8% (95% CI: 4.5%, 9.2%) greater perchlorate. Because perchlorate and nitrate can disrupt thyroid hormone production, we conducted an exploratory analysis to examine whether these chemicals mediate an association between diet and thyroid hormones. A 10-point increase in HEI was associated with 0.6% reduced serum total thyroxine (95% CI: 1.7%, 0.5%) among all adults, with 57.5% of the effect explained by perchlorate. Nitrate mediated an association of rMED with modestly reduced total triiodothyronine among females. Most EDCs examined had no association with the diets evaluated, indicating that recommended healthy diets were not protective against EDC exposures. As observed with two thyroid antagonists, some recommended diets may increase EDC exposures and related adverse health outcomes. Additional work should identify effective food production and processing practices to reduce dietary exposures to potentially harmful EDCs.
    MeSH term(s) Adult ; Diet ; Endocrine Disruptors ; Female ; Humans ; Nitrates ; Nutrition Surveys ; Perchlorates ; Thyroid Hormones
    Chemical Substances Endocrine Disruptors ; Nitrates ; Perchlorates ; Thyroid Hormones
    Language English
    Publishing date 2022-02-28
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 205699-9
    ISSN 1096-0953 ; 0013-9351
    ISSN (online) 1096-0953
    ISSN 0013-9351
    DOI 10.1016/j.envres.2022.113049
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: The regulation of endocrine-disrupting chemicals to minimize their impact on health.

    Duh-Leong, Carol / Maffini, Maricel V / Kassotis, Christopher D / Vandenberg, Laura N / Trasande, Leonardo

    Nature reviews. Endocrinology

    2023  Volume 19, Issue 10, Page(s) 600–614

    Abstract: Endocrine-disrupting chemicals (EDCs) are substances generated by human industrial activities that are detrimental to human health through their effects on the endocrine system. The global societal and economic burden posed by EDCs is substantial. Poorly ...

    Abstract Endocrine-disrupting chemicals (EDCs) are substances generated by human industrial activities that are detrimental to human health through their effects on the endocrine system. The global societal and economic burden posed by EDCs is substantial. Poorly defined or unenforced policies can increase human exposure to EDCs, thereby contributing to human disease, disability and economic damage. Researchers have shown that policies and interventions implemented at both individual and government levels have the potential to reduce exposure to EDCs. This Review describes a set of evidence-based policy actions to manage, minimize or even eliminate the widespread use of these chemicals and better protect human health and society. A number of specific challenges exist: defining, identifying and prioritizing EDCs; considering the non-linear or non-monotonic properties of EDCs; accounting for EDC exposure effects that are latent and do not appear until later in life; and updating testing paradigms to reflect 'real-world' mixtures of chemicals and cumulative exposure. A sound strategy also requires partnering with health-care providers to integrate strategies to prevent EDC exposure in clinical care. Critical next steps include addressing EDCs within global policy frameworks by integrating EDC exposure prevention into emerging climate policy.
    MeSH term(s) Humans ; Endocrine Disruptors/adverse effects ; Endocrine System
    Chemical Substances Endocrine Disruptors
    Language English
    Publishing date 2023-08-08
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2489381-X
    ISSN 1759-5037 ; 1759-5029
    ISSN (online) 1759-5037
    ISSN 1759-5029
    DOI 10.1038/s41574-023-00872-x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: Diet quality and exposure to endocrine-disrupting chemicals among US adults

    Melough, Melissa M. / Maffini, Maricel V. / Otten, Jennifer J. / Sathyanarayana, Sheela

    Environmental research. 2022 Aug., v. 211

    2022  

    Abstract: Human exposure to endocrine-disrupting chemicals (EDCs) may increase risk for chronic disease. Diet is a significant source of EDC exposure, yet healthy diets recommended for chronic disease prevention have not been thoroughly examined for associations ... ...

    Abstract Human exposure to endocrine-disrupting chemicals (EDCs) may increase risk for chronic disease. Diet is a significant source of EDC exposure, yet healthy diets recommended for chronic disease prevention have not been thoroughly examined for associations with EDC exposure. Using data from the National Health and Nutrition Examination Survey 2013–2016, we examined associations of dietary patterns with exposure to non-persistent EDCs potentially consumed through diet. EDCs were measured in spot urine samples. Diet was assessed using 24-h recalls. Multivariable linear regression was used to examine associations of three healthy diet scores [Healthy Eating Index (HEI), relative Mediterranean Diet (rMED), and Dietary Approaches to Stop Hypertension] and fast-food consumption with EDCs. In fully adjusted models, no diet was associated with exposure to the bisphenols, phthalates, or polycyclic aromatic hydrocarbons examined. A 1-point increase in rMED (of 18 possible points) was associated with 2.7% (95% CI: 1.7%, 3.8%) greater urinary nitrate. A 10-point increase in HEI (of 100 possible points) was associated with 5.3% (95% CI: 2.8%, 7.9%) greater nitrate and 6.8% (95% CI: 4.5%, 9.2%) greater perchlorate. Because perchlorate and nitrate can disrupt thyroid hormone production, we conducted an exploratory analysis to examine whether these chemicals mediate an association between diet and thyroid hormones. A 10-point increase in HEI was associated with 0.6% reduced serum total thyroxine (95% CI: 1.7%, 0.5%) among all adults, with 57.5% of the effect explained by perchlorate. Nitrate mediated an association of rMED with modestly reduced total triiodothyronine among females. Most EDCs examined had no association with the diets evaluated, indicating that recommended healthy diets were not protective against EDC exposures. As observed with two thyroid antagonists, some recommended diets may increase EDC exposures and related adverse health outcomes. Additional work should identify effective food production and processing practices to reduce dietary exposures to potentially harmful EDCs.
    Keywords Mediterranean diet ; National Health and Nutrition Examination Survey ; blood serum ; chronic diseases ; disease prevention ; food production ; food quality ; healthy diet ; humans ; hypertension ; nitrates ; perchlorates ; phthalates ; regression analysis ; research ; risk ; triiodothyronine ; urine
    Language English
    Dates of publication 2022-08
    Publishing place Elsevier Inc.
    Document type Article
    ZDB-ID 205699-9
    ISSN 1096-0953 ; 0013-9351
    ISSN (online) 1096-0953
    ISSN 0013-9351
    DOI 10.1016/j.envres.2022.113049
    Database NAL-Catalogue (AGRICOLA)

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  8. Article: An expanded toxicological profile of tetramethyl bisphenol F (TMBPF), a precursor for a new food-contact metal packaging coating

    Maffini, Maricel V / Canatsey, Ryan D

    Food and chemical toxicology. 2020 Jan., v. 135

    2020  

    Abstract: Tetramethyl bisphenol F (TMBPF) has been shown to impart unique physical properties critical for high performance of epoxy can coatings without the estrogenic activity concerns associated with other bisphenols. To further characterize the toxicological ... ...

    Abstract Tetramethyl bisphenol F (TMBPF) has been shown to impart unique physical properties critical for high performance of epoxy can coatings without the estrogenic activity concerns associated with other bisphenols. To further characterize the toxicological profile of TMBPF, additional endocrine-related endpoints including in vitro aromatase inhibition and steroidogenesis assays, and in vivo androgen agonism/antagonism were performed. Systemic toxicity was also assessed by a repeat dose 90-day dietary toxicity study followed by 28-day recovery period. TMBPF did not inhibit aromatase activity, and induced estradiol and testosterone at highest non-cytotoxic concentrations (10 μM) in the steroidogenesis assay. In the Hershberger assay, TMBPF showed no androgenic activity at any dose and equivocal anti-androgenic activity at the highest dose (1000 mg/kg-bw/d). In a 90-day dietary toxicity study with 28-day recovery period, observations including changes in clinical pathology, absolute and relative organ weights, and microscopic findings are discussed. In this current study, the no observed adverse effect level was considered to be 750 mg/kg-bw/d for female rats and 1000 mg/kg-bw/d for male rats with no biologically significant changes to endocrine endpoints at any dose level. Our findings provide further evidence that TMBPF is a low-toxicity substance with a toxicology profile distinct from some other bisphenols.
    Keywords antagonism ; aromatase ; bisphenol F ; coatings ; dietary exposure ; enzyme activity ; enzyme inhibition ; epoxides ; estradiol ; estrogenic properties ; females ; hormone antagonists ; males ; no observed adverse effect level ; packaging ; physical properties ; rats ; steroidogenesis ; testosterone
    Language English
    Dates of publication 2020-01
    Publishing place Elsevier Ltd
    Document type Article
    ZDB-ID 782617-5
    ISSN 1873-6351 ; 0278-6915
    ISSN (online) 1873-6351
    ISSN 0278-6915
    DOI 10.1016/j.fct.2019.110889
    Database NAL-Catalogue (AGRICOLA)

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  9. Article ; Online: Characterization of a new polymeric food contact coating with emphasis on the chemical analysis and safety assessment of non-intentionally added substances (NIAS)

    Mallen, Thomas R. / Abston, Kadijah D. / Parizek, Nathanial J. / Negley, Judith / Shores, Kevin S. / Canatsey, Ryan D. / Dubail, Sarah / Maier, Mark S. / Maffini, Maricel V.

    Food and Chemical Toxicology. 2023 Mar., v. 173 p.113635-

    2023  

    Abstract: Regulators have established safety requirements for food packaging raw materials and finished products, including by-products of polymer synthesis known as non-intentionally added substances (NIAS). However, there are no official guidance or regulations ... ...

    Abstract Regulators have established safety requirements for food packaging raw materials and finished products, including by-products of polymer synthesis known as non-intentionally added substances (NIAS). However, there are no official guidance or regulations for best practices to evaluate the safety of NIAS. Here we described the process we followed to identify, characterize, and prioritize for safety assessment low molecular weight NIAS from an epoxy coating (V70) made with tetramethyl bisphenol F-based diglycidyl ether resin (TMBPF-DGE). We assembled a database of 15000 potential oligomers with masses up to 1000 Da and conducted extraction and migration testing of V70 coating. Acetonitrile extract contained higher number and concentration of substances compared to ethanolic-based food simulants. The extract contained 16 substances with matches in the database with estimated concentration of 18.27 μg/6 dm²; seven of these substances have potentially genotoxic oxirane functionality. TMBPF-DGE + hydroquinone (TMBPF-DGE + HQ) was most abundant (55% of total concentration) and was synthesized and prioritized for safety assessment. TMBPF-DGE + HQ exposure from can beverage was estimated at 5.2 μg/person/day, and it was not mutagenic or genotoxic in in vitro assays. The overall mixture of substances that migrated into ethanolic simulant was also negative in the mutagenicity bioassay. Our findings suggest that exposure to TMBPF-DGE + HQ from the V70 coating is exceedingly small and that the coating migrates are not genotoxic.
    Keywords acetonitrile ; beverages ; bioassays ; chemical analysis ; databases ; epoxides ; ethylene oxide ; hydroquinone ; molecular weight ; mutagenicity ; mutagens ; polymers ; safety assessment ; toxicology ; Food ; can coating ; NIAS ; Polymer synthesis ; Bioassay
    Language English
    Dates of publication 2023-03
    Publishing place Elsevier Ltd
    Document type Article ; Online
    Note Use and reproduction
    ZDB-ID 782617-5
    ISSN 1873-6351 ; 0278-6915
    ISSN (online) 1873-6351
    ISSN 0278-6915
    DOI 10.1016/j.fct.2023.113635
    Database NAL-Catalogue (AGRICOLA)

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  10. Article ; Online: Role of epidemiology in risk assessment: a case study of five ortho-phthalates.

    Maffini, Maricel V / Geueke, Birgit / Groh, Ksenia / Carney Almroth, Bethanie / Muncke, Jane

    Environmental health : a global access science source

    2021  Volume 20, Issue 1, Page(s) 114

    Abstract: Background: The association between environmental chemical exposures and chronic diseases is of increasing concern. Chemical risk assessment relies heavily on pre-market toxicity testing to identify safe levels of exposure, often known as reference ... ...

    Abstract Background: The association between environmental chemical exposures and chronic diseases is of increasing concern. Chemical risk assessment relies heavily on pre-market toxicity testing to identify safe levels of exposure, often known as reference doses (RfD), expected to be protective of human health. Although some RfDs have been reassessed in light of new hazard information, it is not a common practice. Continuous surveillance of animal and human data, both in terms of exposures and associated health outcomes, could provide valuable information to risk assessors and regulators. Using ortho-phthalates as case study, we asked whether RfDs deduced from male reproductive toxicity studies and set by traditional regulatory toxicology approaches sufficiently protect the population for other health outcomes.
    Methods: We searched for epidemiological studies on benzyl butyl phthalate (BBP), diisobutyl phthalate (DIBP), dibutyl phthalate (DBP), dicyclohexyl phthalate (DCHP), and bis(2-ethylhexyl) phthalate (DEHP). Data were extracted from studies where any of the five chemicals or their metabolites were measured and showed a statistically significant association with a health outcome; 38 studies met the criteria. We estimated intake for each phthalate from urinary metabolite concentration and compared estimated intake ranges associated with health endpoints to each phthalate's RfD.
    Result: For DBP, DIBP, and BBP, the estimated intake ranges significantly associated with health endpoints were all below their individual RfDs. For DEHP, the intake range included associations at levels both below and above its RfD. For DCHP, no relevant studies could be identified. The significantly affected endpoints revealed by our analysis include metabolic, neurodevelopmental and behavioral disorders, obesity, and changes in hormone levels. Most of these conditions are not routinely evaluated in animal testing employed in regulatory toxicology.
    Conclusion: We conclude that for DBP, DIBP, BBP, and DEHP current RfDs estimated based on male reproductive toxicity may not be sufficiently protective of other health effects. Thus, a new approach is needed where post-market exposures, epidemiological and clinical data are systematically reviewed to ensure adequate health protection.
    MeSH term(s) Animals ; Environmental Exposure ; Environmental Pollutants ; Humans ; Male ; Obesity ; Phthalic Acids ; Reproduction ; Risk Assessment
    Chemical Substances Environmental Pollutants ; Phthalic Acids ; phthalic acid (6O7F7IX66E)
    Language English
    Publishing date 2021-11-15
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2092232-2
    ISSN 1476-069X ; 1476-069X
    ISSN (online) 1476-069X
    ISSN 1476-069X
    DOI 10.1186/s12940-021-00799-8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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