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Bornehag, Carl-GustafORCID iD iconorcid.org/0000-0003-0417-1686
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Publications (10 of 117) Show all publications
Bornehag, C.-G., Kitraki, E., Stamatakis, A., Panagiotidou, E., Rudén, C., Shu, H., . . . Gennings, C. (2019). A Novel Approach to Chemical Mixture Risk Assessment—Linking Data from Population-Based Epidemiology and Experimental Animal Tests. Risk Analysis, 39(10), 2259-2271
Open this publication in new window or tab >>A Novel Approach to Chemical Mixture Risk Assessment—Linking Data from Population-Based Epidemiology and Experimental Animal Tests
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2019 (English)In: Risk Analysis, ISSN 0272-4332, E-ISSN 1539-6924, Vol. 39, no 10, p. 2259-2271Article in journal (Refereed) Published
Abstract [en]

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%).

Place, publisher, year, edition, pages
Blackwell Publishing Inc., 2019
Keywords
Chemical exposure, mixtures, risk assessment, sexual development, Animals, Chemicals, Endocrine disrupters, Health risks, Population statistics, Risk management, Risk perception, Adverse health effects, Assessment strategies, Endocrine disrupting chemicals, Experimental evidence, Statistical measures, Systematic integration
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Research subject
Public Health Science
Identifiers
urn:nbn:se:kau:diva-73364 (URN)10.1111/risa.13323 (DOI)000489373200010 ()31173660 (PubMedID)2-s2.0-85067401773 (Scopus ID)
Available from: 2019-07-02 Created: 2019-07-02 Last updated: 2019-11-12Bibliographically approved
Derakhshan, A., Shu, H., Peeters, R. P., Kortenkamp, A., Lindh, C. H., Demeneix, B., . . . Korevaar, T. I. (2019). Association of urinary bisphenols and triclosan with thyroid function during early pregnancy. Environment International, 133, Article ID 105123.
Open this publication in new window or tab >>Association of urinary bisphenols and triclosan with thyroid function during early pregnancy
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2019 (English)In: Environment International, ISSN 0160-4120, E-ISSN 1873-6750, Vol. 133, article id 105123Article in journal (Refereed) Published
Abstract [en]

Background: Bisphenols and triclosan are considered as potential thyroid disruptors. While mild alterations in maternal thyroid function can result in adverse pregnancy and child developmental outcomes, there is still uncertainty whether bisphenols or triclosan can interfere with thyroid function during pregnancy. Objectives: We aimed to investigate the association of urinary bisphenol A (BPA), bisphenol S (BPS), bisphenol F (BPF) and triclosan with early pregnancy thyroid function. Methods: This study was embedded in the Swedish Environmental Longitudinal, Mother and child, Asthma and allergy study (SELMA), a population-based prospective pregnancy cohort. In total, 1996 participants were included in the current study. Maternal urinary concentrations of three bisphenols and triclosan, collected at median (95% range) 10 (6–14) weeks of pregnancy as well as serum concentrations of thyroid stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3), total thyroxine (TT4), and total triiodothyronine (TT3) were measured. Results: Higher BPA levels were associated with lower TT4 concentrations (non-monotonic, P = 0.03), a lower FT4/FT3 ratio (β [SE] -0.02 [0.01], P = 0.03) and a lower TT4/TT3 ratio (β [SE] -0.73 [0.27], P = 0.008). Higher BPF levels were associated with a higher FT3 (β [SE] 0.01 [0.007], P = 0.04). There were no associations between other bisphenols or triclosan and absolute TSH, (F)T4 or (F)T3 concentrations. The association of BPA with thyroid function differed with gestational age. The negative association of BPA with FT4/FT3 and TT4/TT3 ratios was only apparent in early but not late gestation (P for interaction: 0.003, 0.008, respectively). Conclusion: These human data during pregnancy substantiate experimental findings suggesting that BPA could potentially affect thyroid function and deiodinase activities in early gestation.

Place, publisher, year, edition, pages
Elsevier, 2019
Keywords
Bisphenol, Pregnancy, Thyroid function, Triclosan, Endocrine disruption, Association reactions, Obstetrics, Bisphenols, Early pregnancy, Endocrine disruption, Gestational age, Serum concentration, Thyroid stimulating hormones, Phenols, 4, 4' isopropylidenediphenol, bisphenol F, bisphenol S, liothyronine, phenol derivative, thyrotropin, thyroxine, triclosan, unclassified drug, concentration (composition), endocrine disruptor, hormone, urine, adult, Article, cohort analysis, controlled study, electrochemiluminescence, female, first trimester pregnancy, histogram, human, limit of detection, liothyronine blood level, liquid chromatography-mass spectrometry, nonhuman, population research, priority journal, prospective study, thyrotropin blood level, thyroxine blood level, urinalysis
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Research subject
Public Health Science
Identifiers
urn:nbn:se:kau:diva-75711 (URN)10.1016/j.envint.2019.105123 (DOI)2-s2.0-85072052188 (Scopus ID)
Available from: 2019-11-12 Created: 2019-11-12 Last updated: 2019-12-02Bibliographically approved
Wikström, S., Lindh, C. H., Shu, H. & Bornehag, C.-G. (2019). Early pregnancy serum levels of perfluoroalkyl substances and risk of preeclampsia in Swedish women.. Scientific Reports, 9(1), 1-7, Article ID 9179.
Open this publication in new window or tab >>Early pregnancy serum levels of perfluoroalkyl substances and risk of preeclampsia in Swedish women.
2019 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, no 1, p. 1-7, article id 9179Article in journal (Refereed) Published
Abstract [en]

Preeclampsia is a major cause of maternal and fetal morbidity. Emerging research shows an association with environmental exposures. The present aim was to investigate associations between early pregnancy serum levels of perfluoroalkyl substances (PFAS) and preeclampsia. Within the Swedish SELMA study, eight PFAS were measured at median 10 gestational weeks and cases of preeclampsia were postnatally identified from registers. Associations between individual PFAS and preeclampsia were assessed, adjusting for parity, age, weight and smoking. Out of 1,773 women in the study group, 64 (3.6%), developed preeclampsia. A doubling of PFOS and PFNA exposure, corresponding to an inter-quartile increase, was associated with an increased risk for preeclampsia of about 38-53% respectively. Serum PFOS within the highest quartile was associated with an odds ratio of 2.68 (CI 95%: 1.17-6.12), equal to the increased risk associated with nulliparity, when compared to exposure in the first quartile. The same associations were identified, although with higher risk estimates, in analyses restricted to nulliparous women. For other PFAS, there were no associations. In conclusion and consistent with limited previous research only on PFOS, increasing serum levels of PFOS and PFNA during early pregnancy were associated with a clinically relevant risk of preeclampsia, adjusting for established confounders.

Place, publisher, year, edition, pages
Springer, 2019
National Category
Health Sciences
Research subject
Public Health Science
Identifiers
urn:nbn:se:kau:diva-73525 (URN)10.1038/s41598-019-45483-7 (DOI)31235847 (PubMedID)2-s2.0-85067898845 (Scopus ID)
Funder
Swedish Research Council FormasLandstinget i Värmland
Available from: 2019-07-08 Created: 2019-07-08 Last updated: 2019-07-15Bibliographically approved
Tanner, E., Unenge Hallerbäck, M., Wikström, S., Lindh, C., Kiviranta, H., Gennings, C. & Bornehag, C.-G. (2019). Early prenatal exposure to suspected endocrine disruptor mixtures is associated with lower IQ at age seven. Environment International
Open this publication in new window or tab >>Early prenatal exposure to suspected endocrine disruptor mixtures is associated with lower IQ at age seven
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2019 (English)In: Environment International, ISSN 0160-4120, E-ISSN 1873-6750Article in journal (Refereed) Epub ahead of print
Abstract [en]

Background: Endocrine disrupting chemicals (EDCs) are xenobiotics with the ability to interfere with hormone action, even at low levels. Prior environmental epidemiology studies link numerous suspected EDCs, including phthalates and bisphenol A (BPA), to adverse neurodevelopmental outcomes. However, results for some chemicals were inconsistent and most assessed one chemical at a time.

Objectives: To evaluate the overall impact of prenatal exposure to an EDC mixture on neurodevelopment in school-aged children, and identify chemicals of concern while accounting for co-exposures.

Methods: Among 718 mother-child pairs from the Swedish Environmental Longitudinal, Mother and child, Asthma and allergy study (SELMA) study, we used Weighted Quantile Sum (WQS) regression to assess the association between 26 EDCs measured in 1st trimester urine or blood, with Wechsler Intelligence Scale for Children (IV) Intelligence Quotient (IQ) scores at age 7 years. Models were adjusted for child sex, gestational age, mother's education, mother's IQ (RAVEN), weight, and smoking status. To evaluate generalizability, we conducted repeated holdout validation, a machine learning technique.ResultsUsing repeated holdout validation, IQ scores were 1.9-points (CI = −3.6, −0.2) lower among boys for an inter-quartile-range (IQR) change in the WQS index. BPF made the largest contribution to the index with a weight of 14%. Other chemicals of concern and their weights included PBA (9%), TCP (9%), MEP (6%), MBzP (4%), PFOA (6%), PFOS (5%), PFHxS (4%), Triclosan (5%), and BPA (4%). While we did observe an inverse association between EDCs and IQ among all children when training and testing the WQS index estimate on the full dataset, these results were not robust to repeated holdout validation.

Conclusion: Among boys, early prenatal exposure to EDCs was associated with lower intellectual functioning at age 7. We identified bisphenol F as the primary chemical of concern, suggesting that the BPA replacement compound may not be any safer for children. Future studies are needed to confirm the potential neurotoxicity of replacement analogues.

Keywords
Neurodevelopment Replacement analogues Chemical mixtures Multipollutant Repeated holdout validation Uncertainty plot
National Category
Public Health, Global Health, Social Medicine and Epidemiology Occupational Health and Environmental Health
Research subject
Public Health Science
Identifiers
urn:nbn:se:kau:diva-75443 (URN)10.1016/j.envint.2019.105185 (DOI)
Available from: 2019-10-25 Created: 2019-10-25 Last updated: 2019-10-25
Soomro, M. H., Baiz, N., Huel, G., Yazbeck, C., Botton, J., Heude, B. & Bornehag, C.-G. (2019). Exposure to heavy metals during pregnancy related to gestational diabetes mellitus in diabetes-free mothers. Science of the Total Environment, 656, 870-876
Open this publication in new window or tab >>Exposure to heavy metals during pregnancy related to gestational diabetes mellitus in diabetes-free mothers
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2019 (English)In: Science of the Total Environment, ISSN 0048-9697, E-ISSN 1879-1026, Vol. 656, p. 870-876Article in journal (Refereed) Published
Abstract [en]

Evidence is cumulating on the adverse health effects of environmental exposures on health of the fetus and the childbearing mothers. Among mother's conditions, gestational diabetes mellitus has been considered rarely in spite of its importance for both mother and child. We determined the role of maternal exposure to lead (Pb), cadmium (Cd) and manganese (Mn) to gestational diabetes mellitus (GDM) on diagnosed GDM and impaired glucose tolerance (IGT) in diabetes-free mothers from the French EDEN mother-child cohort. 623 pregnant women without pre-existing diabetes were included in the study. GDM and IGT were diagnosed by a gynecologist during consultations after blood analysis. Pb, Cd and Mn were measured in second-trimester blood samples. Associations between In-transformed concentrations of metals and GDM and IGT respectively were examined using multiple logistic regression analysis adjusted for potential confounders. The prevalences of GDM and IGT were 7.1% and 10.1% respectively. After adjustment for confounders, Cd was statistically related to having had a diagnosis of GDM or IGT (Adjusted Odds-Ratio (AOR): 1.61, 1.05-2.48), and Pb to GDM at borderline significance (AOR: 1.65, 0.82-3.34). Our findings add to the growing evidence supporting the role of maternal exposure to heavy toxic metals that persist longtime in the environment as a risk factor for GDM. (C) 2018 Elsevier B.V. All rights reserved.

National Category
Public Health, Global Health, Social Medicine and Epidemiology
Research subject
Public Health Science
Identifiers
urn:nbn:se:kau:diva-71058 (URN)10.1016/j.scitotenv.2018.11.422 (DOI)000455039600084 ()30625673 (PubMedID)
Available from: 2019-02-14 Created: 2019-02-14 Last updated: 2019-02-21Bibliographically approved
Repouskou, A., Panagiotidou, E., Panagopoulou, L., Bisting, P. L., Tuck, A. R., Sjödin, M. O. D., . . . Kitraki, E. (2019). Gestational exposure to an epidemiologically defined mixture of phthalates leads to gonadal dysfunction in mouse offspring of both sexes.. Scientific Reports, 9(1), 1-17, Article ID 6424.
Open this publication in new window or tab >>Gestational exposure to an epidemiologically defined mixture of phthalates leads to gonadal dysfunction in mouse offspring of both sexes.
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2019 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, no 1, p. 1-17, article id 6424Article in journal (Refereed) Published
Abstract [en]

The increasing concern for the reproductive toxicity of abundantly used phthalates requires reliable tools for exposure risk assessment to mixtures of chemicals, based on real life human exposure and disorder-associated epidemiological evidence. We herein used a mixture of four phthalate monoesters (33% mono-butyl phthalate, 16% mono-benzyl phthalate, 21% mono-ethyl hexyl phthalate, and 30% mono-isononyl phthalate), detected in 1st trimester urine of 194 pregnant women and identified as bad actors for a shorter anogenita I distance (AGD) in their baby boys. Mice were treated with 0, 0.26, 2.6 and 13 mg/kg/d of the mixture, corresponding to 0x, 10x, 100x, 500x levels detected in the pregnant women. Adverse outcomes detected in the reproductive system of the offspring in pre-puberty and adulthood included reduced AGD index and gonadal weight, changes in gonadal histology and altered expression of key regulators of gonadal growth and steroidogenesis. Most aberrations were apparent in both sexes, though more pronounced in males, and exhibited a non-monotonic pattern. The phthalate mixture directly affected expression of steroidogenesis as demonstrated in a relevant in vitro model. The detected adversities at exposures close to the levels detected in pregnant women, raise concern on the existing safety limits for early-life human exposures and emphasizes the need for re-evaluation of the exposure risk.

Place, publisher, year, edition, pages
Nature Publishing Group, 2019
Keywords
Testis endocrine disruption, germ-cell number, anogenital distance, in-utero, dose-response, fetal testis, diethylhexyl phthalate, sexual-differentiation, perinatal exposure, prenatal exposure
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Research subject
Public Health Science
Identifiers
urn:nbn:se:kau:diva-71996 (URN)10.1038/s41598-019-42377-6 (DOI)000465216700012 ()31015488 (PubMedID)
Available from: 2019-05-09 Created: 2019-05-09 Last updated: 2019-05-10Bibliographically approved
Bornehag, C.-G., Reichenber, A. & Swan, S. H. (2019). Language Development of Young Children Is Not Linked to Phthalate Exposure: Reply [Letter to the editor]. JAMA pediatrics, 173(5), 499-499
Open this publication in new window or tab >>Language Development of Young Children Is Not Linked to Phthalate Exposure: Reply
2019 (English)In: JAMA pediatrics, ISSN 2168-6203, E-ISSN 2168-6211, Vol. 173, no 5, p. 499-499Article in journal, Letter (Other academic) Published
Place, publisher, year, edition, pages
American Medical Association, 2019
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Research subject
Public Health Science
Identifiers
urn:nbn:se:kau:diva-71762 (URN)10.1001/jamapediatrics.2019.0282 (DOI)000467505200037 ()2-s2.0-85063328649 (Scopus ID)
Available from: 2019-04-05 Created: 2019-04-05 Last updated: 2019-05-31Bibliographically approved
Shu, H., Jönsson, B., Gennings, C., Lindh, C., Nånberg, E. & Bornehag, C.-G. (2019). PVC flooring at home and uptake of phthalates in pregnant women. Indoor Air (1), 43-54
Open this publication in new window or tab >>PVC flooring at home and uptake of phthalates in pregnant women
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2019 (English)In: Indoor Air, ISSN 0905-6947, E-ISSN 1600-0668, no 1, p. 43-54Article in journal (Other academic) Published
Abstract [en]

Phthalates are used as plasticizers in polyvinyl chloride (PVC) materials and it is known that phthalates may migrate into the surrounding environment and then become a source for human uptake. The aim of the study was to investigate whether residential PVC flooring was related to the urinary levels of phthalate metabolites determined in pregnant women. The data were from the Swedish SELMA study where sampling was conducted during the time period 2007-2010. Spot urine samples from 1674 women at the end of the first trimester were analyzed for 14 metabolites from seven phthalates and one phthalate alternative. Data on flooring material in the kitchen and the parents' bedrooms as well as potential confounders were collected by postal questionnaires at the same time as the urine samples were taken. Multiple regression modeling by least square geometric mean and weighted quantile sum regression was applied to log-transformed and creatinine-adjusted phthalate metabolite concentrations adjusted for potential confounders from questionnaire data. This study has found significantly higher urinary levels of the BBzP metabolite (MBzP) in pregnant women living in homes with PVC flooring as compared to homes with other flooring materials

Place, publisher, year, edition, pages
Wiley-Blackwell, 2019
Keywords
Human Breast-Milk; Anogenital Distance; Urinary Concentrations; Prenatal Exposure; Care Products; Male Infants; Metabolites; Association; Dust; Bisphenols
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:kau:diva-62630 (URN)10.1111/ina.12508 (DOI)
Available from: 2017-08-11 Created: 2017-08-11 Last updated: 2019-03-14Bibliographically approved
Levie, D., Derakhshan, A., Shu, H., Broeren, M. A. C., de Poortere, R. A., Peeters, R. P., . . . Korevaar, T. I. M. (2019). The Association of Maternal Iodine Status in Early Pregnancy with Thyroid Function in the Swedish Environmental Longitudinal, Mother and Child, Asthma and Allergy Study. Thyroid, 29(11), 1660-1668
Open this publication in new window or tab >>The Association of Maternal Iodine Status in Early Pregnancy with Thyroid Function in the Swedish Environmental Longitudinal, Mother and Child, Asthma and Allergy Study
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2019 (English)In: Thyroid, ISSN 1050-7256, E-ISSN 1557-9077, Vol. 29, no 11, p. 1660-1668Article in journal (Refereed) Published
Abstract [en]

Background: Severe maternal iodine deficiency can impact fetal brain development through effects on maternal and/or fetal thyroid hormone availability. The effects of mild-to-moderate iodine deficiency on thyroid function are less clear. The aim was to investigate the association of maternal urinary iodine concentration corrected for creatinine (UI/Creat) with thyroid function and autoantibodies in a mild-to-moderate iodine-deficient pregnant population. Methods: This study was embedded within the Swedish Environmental Longitudinal, Mother and child, Asthma and allergy (SELMA) study. Clinical reference ranges were determined by the 2.5th and 97.5th population-based percentile cutoffs. The associations of UI/Creat with thyrotropin (TSH), free thyroxine (fT4), free triiodothyronine (fT3), total T4 (TT4), and total T3 (TT3) were studied using multivariable linear regression in thyroid peroxidase antibody (TPOAb)-negative women. The association of UI/Creat with TPOAb and thyroglobulin antibody (TgAb) positivity was analyzed using multivariable logistic regression. Results: Urinary iodine and thyroid function were measured at a median (95% range) gestational age of 10 (6-14) weeks in 2009 women. The median (95% range) UI/Creat was 85 mu g/g (36-386) and the UI/Creat was below 150 mu g/g in 80.1% of women. Reference ranges did not differ substantially by UI/Creat. A lower UI/Creat was associated with a lower TSH (p = 0.027), a higher TT4 (p = 0.032), and with a corresponding trend toward slightly higher fT4 (p = 0.081), fT3 (p = 0.079), and TT3 (p = 0.10). UI/Creat was not associated with the fT4/fT3 (p = 0.94) or TT4/TT3 ratios (p = 0.63). Women with a UI/Creat of 150-249 mu g/g had the lowest prevalence of TPOAb positivity (6.1%), while women with a UI/Creat of <150 mu g/g had a higher prevalence (11.0%, odds ratio [OR] confidence interval [95% CI] 1.84 [1.07-3.20], p = 0.029). Women with a UI/Creat >= 500 mu g/g showed the highest prevalence and a higher risk of TPOAb positivity, however, only a small proportion of women had such a UI/Creat (12.5%, OR, [95% CI] 2.36 [0.54-10.43], p = 0.26). Conclusions: We could not identify any meaningful differences in thyroid function reference ranges. Lower iodine availability was associated with a slightly lower TSH and a higher TT4. Women with adequate iodine intake had the lowest risk of TPOAb positivity.

Place, publisher, year, edition, pages
Mary Ann Liebert, 2019
Keywords
thyroid function tests, reference range, thyroid autoimmunity, iodine, pregnancy
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:kau:diva-75614 (URN)10.1089/thy.2019.0164 (DOI)000489707200001 ()31524090 (PubMedID)
Available from: 2019-11-12 Created: 2019-11-12 Last updated: 2019-12-05Bibliographically approved
Bornehag, C.-G. & Gennings, C. (2018). A novel approach to chemical mixture risk assessment: Linking data from population based epidemiology and experimental animal tests. Paper presented at 54th Congress of the European-Societies-of-Toxicology (EUROTOX) - Toxicology Out of the Box, SEP 02-05, 2018, Brussels, BELGIUM. Toxicology Letters, 295, S52-S52
Open this publication in new window or tab >>A novel approach to chemical mixture risk assessment: Linking data from population based epidemiology and experimental animal tests
2018 (English)In: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 295, p. S52-S52Article in journal (Refereed) Published
Place, publisher, year, edition, pages
Elsevier, 2018
National Category
Public Health, Global Health, Social Medicine and Epidemiology Pharmacology and Toxicology
Research subject
Public Health Science
Identifiers
urn:nbn:se:kau:diva-70974 (URN)10.1016/j.toxlet.2018.06.1203 (DOI)000454045100160 ()
Conference
54th Congress of the European-Societies-of-Toxicology (EUROTOX) - Toxicology Out of the Box, SEP 02-05, 2018, Brussels, BELGIUM
Available from: 2019-02-07 Created: 2019-02-07 Last updated: 2019-02-21Bibliographically approved
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Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0003-0417-1686

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