Two approaches for assessing human safety of disperse blue 1

摘要: Abstract Disperse Blue 1 is an anthraquinone dye used at low levels in semipermanent hair color formulations. Dietary administration of a National Toxicology Program (NTP) carcinogenesis bioassay produced transitional- and squamous-cell tumors, leiomyomas, leiomyosarcomas the urinary bladders male female F344/N rats. The occurrence tumors bladder rats was associated with urothelial hyperplasia presence calculi. Despite calculi other nonneoplastic changes, there no evidence B6C3F1 mice fed diet for up to 2 years. A study conducted same strain by Burnett Squire confirmed transitional-cell neoplasms rat bladder. However, mesenchymal-cell were detected comparable dietary level. Further, found reversibility proliferative changes following cessation treatment 6 months. has been tested variety vivo vitro genotoxicity assays negative but weak mixed pattern genotoxic responses which may be attributable constituent commercial preparations. Evaluation available data comparison observed administered rodent carcinogens considered act through secondary mechanism indicate that threshold approach appropriate assessing risk. With this approach, uncertainty factor 1000 applied no-observed-adverse-effect level NTP yielded safe exposure 45-56 μg/kg/day. In contrast, conventional quantitative risk assessment corresponding upper limit on lifetime 10−6 10−5 0.39 3.9 μg/kg/day, respectively. derived using approximately 20 times greater than maximum average daily dose 2.7 μg/kg/day its use formulations, while linearized multistage model determined 1.5 greater. Because oral absorption substantially more dermal absorption, actual margin safety most likely much either these comparisons suggests. difference estimates two approaches demonstrates importance incorporating information action into process.