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- Bornehag, Carl-Gustaf, 1957-, et al.
(författare)
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A Novel Approach to Chemical Mixture Risk Assessment—Linking Data from Population-Based Epidemiology and Experimental Animal Tests
- 2019
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Ingår i: Risk Analysis. - : John Wiley & Sons. - 0272-4332 .- 1539-6924. ; 39:10, s. 2259-2271
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Tidskriftsartikel (refereegranskat)abstract
- Humans are continuously exposed to chemicals with suspected or proven endocrine disrupting chemicals (EDCs). Risk management of EDCs presents a major unmet challenge because the available data for adverse health effects are generated by examining one compound at a time, whereas real-life exposures are to mixtures of chemicals. In this work, we integrate epidemiological and experimental evidence toward a whole mixture strategy for risk assessment. To illustrate, we conduct the following four steps in a case study: (1) identification of single EDCs (“bad actors”)—measured in prenatal blood/urine in the SELMA study—that are associated with a shorter anogenital distance (AGD) in baby boys; (2) definition and construction of a “typical” mixture consisting of the “bad actors” identified in Step 1; (3) experimentally testing this mixture in an in vivo animal model to estimate a dose–response relationship and determine a point of departure (i.e., reference dose [RfD]) associated with an adverse health outcome; and (4) use a statistical measure of “sufficient similarity” to compare the experimental RfD (from Step 3) to the exposure measured in the human population and generate a “similar mixture risk indicator” (SMRI). The objective of this exercise is to generate a proof of concept for the systematic integration of epidemiological and experimental evidence with mixture risk assessment strategies. Using a whole mixture approach, we could find a higher rate of pregnant women under risk (13%) when comparing with the data from more traditional models of additivity (3%), or a compound-by-compound strategy (1.6%).
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| 2. |
- Caporale, N., et al.
(författare)
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From cohorts to molecules: Adverse impacts of endocrine disrupting mixtures
- 2022
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 375:6582
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Tidskriftsartikel (refereegranskat)abstract
- Convergent evidence associates exposure to endocrine disrupting chemicals (EDCs) with major human diseases, even at regulation-compliant concentrations. This might be because humans are exposed to EDC mixtures, whereas chemical regulation is based on a risk assessment of individual compounds. Here, we developed a mixture-centered risk assessment strategy that integrates epidemiological and experimental evidence. We identified that exposure to an EDC mixture in early pregnancy is associated with language delay in offspring. At human-relevant concentrations, this mixture disrupted hormone-regulated and disease-relevant regulatory networks in human brain organoids and in the model organisms Xenopus leavis and Danio rerio, as well as behavioral responses. Reinterrogating epidemiological data, we found that up to 54% of the children had prenatal exposures above experimentally derived levels of concern, reaching, for the upper decile compared with the lowest decile of exposure, a 3.3 times higher risk of language delay. © 2022 American Association for the Advancement of Science. All rights reserved.
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| 3. |
- Gao, Shang, et al.
(författare)
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Dipolar Spin Ice States with a Fast Monopole Hopping Rate in CdEr2X4 (X = Se, S)
- 2018
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Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 120:13
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Tidskriftsartikel (refereegranskat)abstract
- Excitations in a spin ice behave as magnetic monopoles, and their population and mobility control the dynamics of a spin ice at low temperature. CdEr2Se4 is reported to have the Pauling entropy characteristic of a spin ice, but its dynamics are three orders of magnitude faster than the canonical spin ice Dy2Ti2O7. In this Letter we use diffuse neutron scattering to show that both CdEr2Se4 and CdEr2S4 support a dipolar spin ice state-the host phase for a Coulomb gas of emergent magnetic monopoles. These Coulomb gases have similar parameters to those in Dy2Ti2O7, i.e., dilute and uncorrelated, and so cannot provide three orders faster dynamics through a larger monopole population alone. We investigate the monopole dynamics using ac susceptometry and neutron spin echo spectroscopy, and verify the crystal electric field Hamiltonian of the Er3+ ions using inelastic neutron scattering. A quantitative calculation of the monopole hopping rate using our Coulomb gas and crystal electric field parameters shows that the fast dynamics in CdEr2X4 (X = Se, S) are primarily due to much faster monopole hopping. Our work suggests that CdEr2X4 offer the possibility to study alternative spin ice ground states and dynamics, with equilibration possible at much lower temperatures than the rare earth pyrochlore examples.
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