title: Safety assessment of boron by application of new uncertainty factors and their subdivision.
abstract: The available toxicity information for boron was reevaluated and four appropriate toxicity studies were selected in order to derive a tolerable daily intake (TDI) using newly proposed uncertainty factors (UFs) presented in Hasegawa et al. (2010). No observed adverse effect levels (NOAELs) of 17.5 and 8.8 mgB/kg/day for the critical effect of testicular toxicity were found in 2-year rat and dog feeding studies. Also, the 95% lower confidence limit of the benchmark doses for 5% reduction of fetal body weight (BMDL(05)) was calculated as 44.9 and 10.3 mgB/kg/day in mouse and rat developmental toxicity studies, respectively. Measured values available for differences in boron clearance between rats and humans and variability in the glomerular filtration rate (GFR) in pregnant women were used to derive chemical specific UFs. For the remaining uncertainty, newly proposed default UFs, which were derived from the latest applicable information with a probabilistic approach, and their subdivided factors for toxicokinetic and toxicodynamic variability were applied. Finally, overall UFs were calculated as 68 for rat testicular toxicity, 40 for dog testicular toxicity, 247 for mouse developmental toxicity and 78 for rat developmental toxicity. It is concluded that 0.13 mgB/kg/day is the most appropriate TDI for boron, based on rat developmental toxicity.
authors.affiliation: National Institute of Health Sciences, 1-18-1 Kamiyoga, Tokyo 158-8501, Japan.
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Hasegawa
authors.forename: Mutsuko
authors.initials: M
authors.lastname: Hirata-Koizumi
authors.forename: Michael L
authors.initials: ML
authors.lastname: Dourson
authors.forename: Ann
authors.initials: A
authors.lastname: Parker
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ono
authors.forename: Akihiko
authors.initials: A
authors.lastname: Hirose
mesh_terms: D000818:Animals; D019985:Benchmarking; D001895:Boron / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D008297:Male; D051379:Mice; D019055:No-Observed-Adverse-Effect Level; D011247:Pregnancy; D051381:Rats; D018570:Risk Assessment / Q000379:methods*; D013045:Species Specificity; D035501:Uncertainty
chemical_list: D001895:Boron