(including carcinogenicity, neurotoxicity, and reproductive and developmental toxicity) are assessed by the CPSC staff using guidelines issued by the Commission (CPSC, 1992). If it is concluded that a substance is “toxic” due to chronic toxicity, then a quantitative assessment of exposure and risk is performed to evaluate whether the chemical may be considered a “hazardous substance”. This memo represents the first step in the risk assessment process; that is, the hazard identification step. * These comments are those of the CPSC staff, have not been reviewed or approved by, and may not necessarily represent the views of, the Commission. Page 2 of 2 KRC Table of Contents Tables ...................................................................................................................................v Figures............................................................................................................................... vii Appendices ........................................................................................................................ vii Abbreviations ................................................................................................................... viii Executive Summary .............................................................................................................x 1. Introduction ....................................................................................................................1 2. Physico-chemical Characteristics ..................................................................................1 3. Manufacture, Supply, and Use .......................................................................................4 4. Toxicokinetics ..............................................................................................................12 Absorption Oral exposure ...........................................................................................................15 Humans ............................................................................................................15 Monkeys ...........................................................................................................16 Rats ..................................................................................................................16 General Comparison ........................................................................................16 Dermal exposure ......................................................................................................17 Inhalation exposure ..................................................................................................18 Humans ............................................................................................................18 Rats ..................................................................................................................19 Other exposure .........................................................................................................19 Distribution Oral exposure ...........................................................................................................20 Humans ............................................................................................................20 Monkeys ...........................................................................................................20 Rats ..................................................................................................................20 Mice .................................................................................................................22 Hamsters ..........................................................................................................22 Dogs and Miniature Pigs ..................................................................................22 Hens .................................................................................................................23 Page i KRC Distribution into the Milk and Across the Placenta .........................................23 Enterohepatic Recirculation .............................................................................23 Dermal exposure ......................................................................................................24 Humans ............................................................................................................24 Rats ..................................................................................................................24 Guinea Pigs ......................................................................................................24 Pigs ...................................................................................................................25 Inhalation exposure ..................................................................................................25 Humans ............................................................................................................25 Rodents ............................................................................................................25 Other exposure .........................................................................................................25 Metabolism Oral exposure ...........................................................................................................27 Humans ............................................................................................................27 Monkeys ...........................................................................................................28 Rats ..................................................................................................................28 Mice .................................................................................................................29 Guinea Pigs ......................................................................................................29 Hamsters ..........................................................................................................29 Dogs and Miniature Pigs ..................................................................................29 Conjugation (Glucuronidation and Glucosidation) ..........................................30 Dermal exposure ......................................................................................................30 Inhalation exposure ..................................................................................................31 Other exposure .........................................................................................................31 Excretion Oral exposure ...........................................................................................................32 Humans ............................................................................................................32 Monkeys ...........................................................................................................32 Rats ..................................................................................................................33 Mice .................................................................................................................34 Hamsters ..........................................................................................................34 Dogs and Pigs ..................................................................................................34 Dermal exposure ......................................................................................................34 Inhalation exposure ..................................................................................................35 Humans ............................................................................................................35 Rats ..................................................................................................................35 Other exposure .........................................................................................................35 Page ii KRC Overall Toxicokinetic Conclusion Oral exposure ...........................................................................................................37 Dermal exposure ......................................................................................................37 Inhalation exposure ..................................................................................................37 Intraperitoneal or Intravenous Exposure (injection exposures) ...............................37 5. Hazard Information ......................................................................................................38 Acute Single Dose Toxicity Acute oral toxicity....................................................................................................39 Acute dermal toxicity ...............................................................................................40 Acute inhalation toxicity ..........................................................................................41 Primary skin irritation ..............................................................................................41 Primary eye irritation ...............................................................................................42 Respiratory irritation ................................................................................................43 Sensitization