(VCCEP) Tier 1 Pilot Submission for BENZENE - Tera

6.1.2 Types of Adverse Health Effects Associated with Benzene Exposure.......... 35
6.1.3 Animal Models for Benzene Toxicity ............................................................. 38
6.1.4 Role of Metabolism and Site of Injury............................................................ 38
6.1.5 Dose Metrics for Toxicity ............................................................................... 39
6.1.6 Non-Cancer ................................................................................................... 40
6.1.7 Cancer ........................................................................................................... 44
6.1.8 Ongoing Studies ............................................................................................ 46
6.1.9 Linear versus Non-Linear Extrapolation ........................................................ 47
6.1.10 Petrochemical Industry and Refinery Epidemiology ...................................... 48
6.1.11 Service Station Attendants and Vehicle Mechanic Epidemiology ................. 49
6.1.12 Other Human Data ........................................................................................ 50
6.2 Benzene Toxicology—Animal Hazard Assessment .................................................. 58
6.2.1 Acute Toxicity ................................................................................................ 58
6.2.2 Genetic Toxicity ............................................................................................. 58
6.2.3 Reproductive and Developmental Toxicity .................................................... 70
6.2.4 Transplacental Effects ................................................................................... 80
6.2.5 Repeated-Exposure Toxicity in Experimental Animals.................................. 82
6.2.6 Adult Neurotoxicity......................................................................................... 88
6.2.7 Immunotoxicity............................................................................................... 90
6.2.8 Metabolism .................................................................................................... 92
7.0 Exposure Assessments...................................................................................................... 96
7.1 Methodology/Scope of the Assessment .................................................................... 96
7.2 Sources of Benzene Exposure................................................................................ 100
7.2.1 Ambient Environmental Exposures ............................................................. 100
7.2.2 Source-Specific Exposures ......................................................................... 127
7.2.3 Occupational Exposure ............................................................................... 143
7.2.4 Consumer Products..................................................................................... 147
7.3 Summary of Children’s Exposures .......................................................................... 149
8.0 Risk Assessment.............................................................................................................. 155
8.1 Risk Assessment Approach .................................................................................... 155
8.1.1 Dose Metrics................................................................................................ 156
8.1.2 Mixtures ....................................................................................................... 157
8.1.3 EPA Default Risk Assessment .................................................................... 158
8.2 Toxicology Reference Values.................................................................................. 159
8.2.1 Potential for Increased Sensitivity of Benzene-Induced Hematopoietic Toxicity
and AML in Children................................................................................................ 160
8.2.2 Reference Values for EPA Default Risk Assessment.................................. 163
8.2.3 Points of Departure for Margin of Safety Assessment................................. 167
8.3 Results .................................................................................................................... 169
8.3.1 EPA Default Risk Assessment Approach .................................................... 169
8.3.2 Margin of Safety Analysis ............................................................................ 170
8.4 Risk Characterization Summary.............................................................................. 192
9.0 VCCEP Tier 2 Data Needs Assessment .......................................................................... 195
9.1 Hazard..................................................................................................................... 195
9.2 Exposure ................................................................................................................. 196
10.0 References....................................................................................................................... 197
Benzene VCCEP Submission Page ii
March 2006