title: Multiple exposures to indoor contaminants: Derivation of benchmark doses and relative potency factors based on male reprotoxic effects.
abstract: Semi-Volatile Organic Compounds (SVOCs) are commonly present in dwellings and several are suspected of having effects on male reproductive function mediated by an endocrine disruption mode of action. To improve knowledge of the health impact of these compounds, cumulative toxicity indicators are needed. This work derives Benchmark Doses (BMD) and Relative Potency Factors (RPF) for SVOCs acting on the male reproductive system through the same mode of action. We included SVOCs fulfilling the following conditions: detection frequency (>10%) in French dwellings, availability of data on the mechanism/mode of action for male reproductive toxicity, and availability of comparable dose-response relationships. Of 58 SVOCs selected, 18 induce a decrease in serum testosterone levels. Six have sufficient and comparable data to derive BMDs based on 10 or 50% of the response. The SVOCs inducing the largest decrease in serum testosterone concentration are: for 10%, bisphenol A (BMD10 = 7.72E-07 mg/kg bw/d; RPF10 = 7,033,679); for 50%, benzo[a]pyrene (BMD50 = 0.030 mg/kg bw/d; RPF50 = 1630), and the one inducing the smallest one is benzyl butyl phthalate (RPF10 and RPF50 = 0.095). This approach encompasses contaminants from diverse chemical families acting through similar modes of action, and makes possible a cumulative risk assessment in indoor environments. The main limitation remains the lack of comparable toxicological data.
authors.affiliation: EHESP School of Public Health, Sorbonne Paris Cité, Avenue du Professeur Léon Bernard, 35043 Rennes Cedex, France; INSERM UMR1085 IRSET (Research Institute in Environmental and Occupational Health), Rennes, France. Electronic address: kevin.fournier@ehesp.fr.
authors.forename: K
authors.initials: K
authors.lastname: Fournier
authors.affiliation: INERIS, Unité Modèles pour l'Ecotoxicologie et la Toxicologie (METO), Verneuil-en-Halatte, France. Electronic address: cleo.tebby@ineris.fr.
authors.forename: C
authors.initials: C
authors.lastname: Tebby
authors.affiliation: INERIS, Unité Modèles pour l'Ecotoxicologie et la Toxicologie (METO), Verneuil-en-Halatte, France. Electronic address: florence.zeman@ineris.fr.
authors.forename: F
authors.initials: F
authors.lastname: Zeman
authors.affiliation: EHESP School of Public Health, Sorbonne Paris Cité, Avenue du Professeur Léon Bernard, 35043 Rennes Cedex, France; INSERM UMR1085 IRSET (Research Institute in Environmental and Occupational Health), Rennes, France. Electronic address: Philippe.glorennec@ehesp.fr.
authors.forename: P
authors.initials: P
authors.lastname: Glorennec
authors.affiliation: EHESP School of Public Health, Sorbonne Paris Cité, Avenue du Professeur Léon Bernard, 35043 Rennes Cedex, France; INSERM UMR1085 IRSET (Research Institute in Environmental and Occupational Health), Rennes, France; Lorraine University Medical School, Nancy, France. Electronic address: denis.zmirou@ehesp.fr.
authors.forename: D
authors.initials: D
authors.lastname: Zmirou-Navier
authors.affiliation: EHESP School of Public Health, Sorbonne Paris Cité, Avenue du Professeur Léon Bernard, 35043 Rennes Cedex, France; INSERM UMR1085 IRSET (Research Institute in Environmental and Occupational Health), Rennes, France. Electronic address: nathalie.bonvallot@ehesp.fr.
authors.forename: N
authors.initials: N
authors.lastname: Bonvallot
mesh_terms: D000393:Air Pollutants / Q000009:adverse effects* / Q000032:analysis; D016902:Air Pollution, Indoor / Q000009:adverse effects* / Q000032:analysis; D000818:Animals; D019985:Benchmarking; D015415:Biomarkers / Q000097:blood; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D052244:Endocrine Disruptors / Q000009:adverse effects*; D004781:Environmental Exposure / Q000009:adverse effects*; D004784:Environmental Monitoring; D005602:France; D006801:Humans; D008297:Male; D015233:Models, Statistical; D019055:No-Observed-Adverse-Effect Level; D012098:Reproduction / Q000187:drug effects*; D018570:Risk Assessment; D013739:Testosterone / Q000097:blood; D055549:Volatile Organic Compounds / Q000009:adverse effects* / Q000032:analysis
chemical_list: D000393:Air Pollutants; D015415:Biomarkers; D052244:Endocrine Disruptors; D055549:Volatile Organic Compounds; D013739:Testosterone
keywords: Benchmark doses; Cumulative risk assessment; Mixture; Reproduction; Semi-volatile organic compounds; Toxicity