Mary E Ingle1, Lidia Mínguez-Alarcón2, Courtney C Carignan3, Craig M Butt4, Heather M Stapleton4, Paige L Williams5, Jennifer B Ford2, Russ Hauser6, John D Meeker7. 1. Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, MI, USA. 2. Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA. 3. Department of Food Science and Nutrition, Michigan State University, East Lansing, MI, USA; Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI, USA. 4. Nicholas School of the Environment, Duke University, Durham, NC, USA. 5. Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA. 6. Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Obstetrics and Gynecology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. 7. Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, MI, USA. Electronic address: meekerj@umich.edu.
Abstract
BACKGROUND: The use of PFRs has steadily increased as brominated compounds have been or are being phased out. Human exposure is widespread and animal studies have shown adverse impacts on male reproduction, but human data are lacking. OBJECTIVE: To study the associations between urinary concentrations of phosphorous-containing flame retardant (PFR) metabolites and semen parameters. METHODS: A subset of 220 men from an existing longitudinal cohort of couples were recruited from Massachusetts General Hospital fertility clinic between 2005 and 2015. Semen parameters included sperm count, concentration, motility, and morphology; some men had samples measured from multiple clinic visits (up to five visits; n = 269 semen samples). Metabolites [bis(1,3-dichloro-2-propyl) phosphate (BDCIPP), diphenyl phosphate (DPHP), isopropylphenyl phenyl phosphate (ip-PPP), tert-butylphenyl phenyl phosphate (tb-PPP) and bis(1-chloro-2-propyl) phosphate (BCIPP)] were measured in urine samples (between one and five urine samples per participant; n = 355 urine samples). Semen parameters were evaluated continuously and dichotomized for models. Metabolites were assessed for associations with semen parameters as continuous and categorized into quartiles using multivariable generalized mixed models, adjusted for specific gravity, age, BMI, smoking, and abstinence period. RESULTS: Metabolites BDCIPP, DPHP, and ip-PPP were detected in a high proportion of urine samples (85%, 86%, and 65% respectively). Concentrations varied by season of collection, particularly for BDCIPP where samples collected in the summer were approximately 2-fold higher than concentrations of other seasons (p < 0.0001). The odds of having a sperm count less than 39 mil/ejaculate decreased by 20% for increasing BDCIPP concentrations (p = 0.04). When regressing semen parameters on PFR metabolite quartiles, some negative associations were observed for individual quartiles among sample volume and morphology, but overall associations were weak and inconsistent. CONCLUSION: Detection rates were high for BDCIPP, DPHP, and ip-PPP. We did not observe consistent associations between PFR metabolites and semen parameters. Due to the high prevalence of exposure, further investigation of other potential health effects should be conducted.
BACKGROUND: The use of PFRs has steadily increased as brominated compounds have been or are being phased out. Human exposure is widespread and animal studies have shown adverse impacts on male reproduction, but human data are lacking. OBJECTIVE: To study the associations between urinary concentrations of phosphorous-containing flame retardant (PFR) metabolites and semen parameters. METHODS: A subset of 220 men from an existing longitudinal cohort of couples were recruited from Massachusetts General Hospital fertility clinic between 2005 and 2015. Semen parameters included sperm count, concentration, motility, and morphology; some men had samples measured from multiple clinic visits (up to five visits; n = 269 semen samples). Metabolites [bis(1,3-dichloro-2-propyl) phosphate (BDCIPP), diphenyl phosphate (DPHP), isopropylphenyl phenyl phosphate (ip-PPP), tert-butylphenyl phenyl phosphate (tb-PPP) and bis(1-chloro-2-propyl) phosphate (BCIPP)] were measured in urine samples (between one and five urine samples per participant; n = 355 urine samples). Semen parameters were evaluated continuously and dichotomized for models. Metabolites were assessed for associations with semen parameters as continuous and categorized into quartiles using multivariable generalized mixed models, adjusted for specific gravity, age, BMI, smoking, and abstinence period. RESULTS: Metabolites BDCIPP, DPHP, and ip-PPP were detected in a high proportion of urine samples (85%, 86%, and 65% respectively). Concentrations varied by season of collection, particularly for BDCIPP where samples collected in the summer were approximately 2-fold higher than concentrations of other seasons (p < 0.0001). The odds of having a sperm count less than 39 mil/ejaculate decreased by 20% for increasing BDCIPP concentrations (p = 0.04). When regressing semen parameters on PFR metabolite quartiles, some negative associations were observed for individual quartiles among sample volume and morphology, but overall associations were weak and inconsistent. CONCLUSION: Detection rates were high for BDCIPP, DPHP, and ip-PPP. We did not observe consistent associations between PFR metabolites and semen parameters. Due to the high prevalence of exposure, further investigation of other potential health effects should be conducted.
Authors: Kate Hoffman; Amelia Lorenzo; Craig M Butt; Linda Adair; Amy H Herring; Heather M Stapleton; Julie L Daniels Journal: Environ Int Date: 2016-10-13 Impact factor: 9.621
Authors: Ryan C Lewis; Lidia Mínguez-Alarcón; John D Meeker; Paige L Williams; Gabor Mezei; Jennifer B Ford; Russ Hauser Journal: Reprod Toxicol Date: 2016-11-09 Impact factor: 3.143
Authors: Enrique Cequier; Amrit Kaur Sakhi; Rosa Maria Marcé; Georg Becher; Cathrine Thomsen Journal: Environ Int Date: 2014-11-26 Impact factor: 9.621
Authors: Maurizio Macaluso; Tracie J Wright-Schnapp; Anjani Chandra; Robert Johnson; Catherine L Satterwhite; Amy Pulver; Stuart M Berman; Richard Y Wang; Sherry L Farr; Lori A Pollack Journal: Fertil Steril Date: 2008-11-06 Impact factor: 7.329
Authors: Kate Hoffman; Craig M Butt; Thomas F Webster; Emma V Preston; Stephanie C Hammel; Colleen Makey; Amelia M Lorenzo; Ellen M Cooper; Courtney Carignan; John D Meeker; Russ Hauser; Adelheid Soubry; Susan K Murphy; Thomas M Price; Cathrine Hoyo; Emma Mendelsohn; Johanna Congleton; Julie L Daniels; Heather M Stapleton Journal: Environ Sci Technol Lett Date: 2017-02-08
Authors: Mary E Ingle; Deborah Watkins; Zaira Rosario; Carmen M VélezVega; Antonia M Calafat; Maria Ospina; Kelly K Ferguson; José F Cordero; Akram Alshawabkeh; John D Meeker Journal: Sci Total Environ Date: 2019-11-04 Impact factor: 7.963
Authors: Kathryn M Rodgers; Deborah Bennett; Rebecca Moran; Kristin Knox; Tasha Stoiber; Ranjit Gill; Thomas M Young; Arlene Blum; Robin E Dodson Journal: Environ Int Date: 2021-03-23 Impact factor: 13.352
Authors: Mary E Ingle; Lidia Mínguez-Alarcón; Courtney C Carignan; Craig M Butt; Heather M Stapleton; Paige L Williams; Jennifer B Ford; Russ Hauser; John D Meeker Journal: J Expo Sci Environ Epidemiol Date: 2019-02-06 Impact factor: 5.563
Authors: Mary E Ingle; Lidia Mínguez-Alarcón; Courtney C Carignan; Heather M Stapleton; Paige L Williams; Jennifer B Ford; Molly B Moravek; Marie S O'Neill; Lu Wang; Russ Hauser; John D Meeker Journal: Environ Res Date: 2020-09-22 Impact factor: 6.498
Authors: Diana Poli; Roberta Andreoli; Lucia Moscato; Giovanna Pelà; Giuseppe de Palma; Delia Cavallo; Marta Petyx; Giorgio Pelosi; Massimo Corradi; Matteo Goldoni Journal: Int J Environ Res Public Health Date: 2020-03-13 Impact factor: 3.390