title: Human Health Effects of Biphenyl: Key Findings and Scientific Issues.
abstract: In support of the Integrated Risk Information System (IRIS), the U.S. Environmental Protection Agency (EPA) has evaluated the human health hazards of biphenyl exposure.
  
  
  
  We review key findings and scientific issues regarding expected human health effects of biphenyl.
  
  
  
  Scientific literature from 1926 through September 2012 was critically evaluated to identify potential human health hazards associated with biphenyl exposure. Key issues related to the carcinogenicity and noncancer health hazards of biphenyl were examined based on evidence from experimental animal bioassays and mechanistic studies.
  
  
  
  Systematic consideration of experimental animal studies of oral biphenyl exposure took into account the variety of study designs (e.g., study sizes, exposure levels, and exposure durations) to reconcile differing reported results. The available mechanistic and toxicokinetic evidence supports the hypothesis that male rat urinary bladder tumors arise through urinary bladder calculi formation but is insufficient to hypothesize a mode of action for liver tumors in female mice. Biphenyl and its metabolites may induce genetic damage, but a role for genotoxicity in biphenyl-induced carcinogenicity has not been established.
  
  
  
  The available health effects data for biphenyl provides suggestive evidence for carcinogenicity in humans, based on increased incidences of male rat urinary bladder tumors at high exposure levels and on female mouse liver tumors. Kidney toxicity is also a potential human health hazard of biphenyl exposure.
  
  
  
  Li Z, Hogan KA, Cai C, Rieth S. 2016. Human health effects of biphenyl: key findings and scientific issues. Environ Health Perspect 124:703-712; http://dx.doi.org/10.1289/ehp.1509730.
authors.affiliation: National Center for Environmental Assessment, U.S. Environmental Protection Agency, Washington, DC, USA.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Li
authors.forename: Karen A
authors.initials: KA
authors.lastname: Hogan
authors.forename: Christine
authors.initials: C
authors.lastname: Cai
authors.forename: Susan
authors.initials: S
authors.lastname: Rieth
mesh_terms: D000818:Animals; D001713:Biphenyl Compounds / Q000633:toxicity*; D015197:Carcinogenicity Tests; D015386:Hazardous Substances / Q000633:toxicity*; D006801:Humans; D008113:Liver Neoplasms; D051379:Mice; D009152:Mutagenicity Tests; D051381:Rats; D014481:United States; D014484:United States Environmental Protection Agency; D001749:Urinary Bladder Neoplasms
chemical_list: D001713:Biphenyl Compounds; D015386:Hazardous Substances; C010574:biphenyl