| 11. |
- van Duursen, MBM, et al.
(författare)
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Safeguarding Female Reproductive Health against Endocrine Disrupting Chemicals-The FREIA Project
- 2020
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Ingår i: International journal of molecular sciences. - : MDPI AG. - 1422-0067. ; 21:9
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Tidskriftsartikel (refereegranskat)abstract
- Currently available test methods are not well-suited for the identification of chemicals that disturb hormonal processes involved in female reproductive development and function. This renders women’s reproductive health at increasing risk globally, which, coupled with increasing incidence rates of reproductive disorders, is of great concern. A woman’s reproductive health is largely established during embryonic and fetal development and subsequently matures during puberty. The endocrine system influences development, maturation, and function of the female reproductive system, thereby making appropriate hormone levels imperative for correct functioning of reproductive processes. It is concerning that the effects of human-made chemicals on the endocrine system and female reproductive health are poorly addressed in regulatory chemical safety assessment, partly because adequate test methods are lacking. Our EU-funded project FREIA aims to address this need by increasing understanding of how endocrine disrupting chemicals (EDCs) can impact female reproductive health. We will use this information to provide better test methods that enable fit-for-purpose chemical regulation and then share our knowledge, promote a sustainable society, and improve the reproductive health of women globally.
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| 16. |
- Stenberg, Mia, 1979-, et al.
(författare)
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Multivariate toxicity profiles and QSAR modeling of non-dioxin-like PCBs : an investigation of in vitro screening data from ultra-pure congeners
- 2011
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Ingår i: Chemosphere. - : Elsevier. - 0045-6535 .- 1879-1298. ; 85:9, s. 1423-1429
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Tidskriftsartikel (refereegranskat)abstract
- The non-dioxin-like PCBs (NDL-PCBs) found in food and human samples have a complex spectrum of adverse effects, but lack a detailed risk assessment. The toxicity profiles of 21 carefully selected PCBs (19 NDL-PCBs) were identified by in vitro screening in 17 different assays on specific endpoints related to neurotoxicity, endocrine disruption and tumor promotion. To ensure that the test results were not affected by polychlorinated dioxins, dibenzofurans or DL-PCB contaminants, the NDL-PCB congeners were thoroughly purified before testing. Principal component analysis (PCA) was used to derive general toxicity profiles from the in vitro screening data. The toxicity profiles indicated different structure-activity relationships (SAR) and distinct mechanisms of action. The analysis also indicated that the NDL-PCBs could be divided into two groups. The first group included generally smaller, ortho-substituted congeners, comprising PCB 28, 47, 51, 52, 53, 95, 100, 101, 104 and 136, with PCB 95, 101 and 136 as generally being most active. The second group comprising PCB 19, 74, 118, 122, 128, 138, 153, 170, 180 and 190 had lower biological activity in many of the assays, except for three endocrine-related assays. The most abundant congeners, PCB 138, 153, 170, 180 and 190, cluster in the second group, and thereby show similar SAR. Two quantitative structure-activity relationship (QSAR) models could be developed that added information to the SAR and could aid in risk assessments of NDL-PCBs. The QSAR models predicted a number of congeners as active and among these e.g., PCB 18, 25, 45 and 49 have been found in food or human samples.
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