June 17, 2004 n-Alkane Category: decane, undecane, dodecane (CAS Nos. 124-18-5, 1120-21-4, 112-40-3) Voluntary Children’s Chemical Evaluation Program (VCCEP) Tier 1 Pilot Submission Docket Number OPPTS – 00274D American Chemistry Council n-Alkane VCCEP Consortium Sponsors: Chevron Phillips Chemical Company LP Sasol North America Inc. Shell Chemical LP June 17, 2004 TABLE OF CONTENTS Glossary of Terms 4 1. Executive Summary 5 2. Basis for Inclusion in the VCCEP Program 2.1 Total Exposure Assessment Methodology Data 10 2.2 Air Monitoring Data 11 2.3 How Sponsors Were Identified for the n-Alkane VCCEP Effort 12 3. Previous and On-Going Health Assessments 3.1 OECD SIDS/ICCA HPV Imitative 14 3.2 Total Petroleum Hydrocarbon Criteria Working Group 15 3.3 Hydrocarbon Solvent Guidance Group Values (GGVs) for Setting Occupational Exposure Limits (OELs) for Hydrocarbon Solvents 15 4. Regulatory Overview 4.1 CPSC Child-Resistant Packaging for Hydrocarbons 16 4.2 Occupational Exposure Limits 16 4.3 VOC Regulations 17 5. Product Overview 5.1 Physical, Chemical, and Environmental Fate Properties 18 5.2 Production of n-Alkanes 20 5.3 Uses for n-Alkane Products 20 5.4 Petroleum Products Which Contain n-Alkanes 21 6. Exposure Assessment 6.1 Summary 25 6.2 Non-Occupational Exposure 28 6.2.1 Indoor Sources of Exposure 6.2.2 Outdoor Source of Exposure 6.2.3 Unique Children’s Exposure 6.3 Integrated 24 hour Exposure 36 6.4 Occupational Exposure 36 6.5 Potential for Dermal and Oral Exposure 40 6.6 Selection of Exposure Scenarios and Exposure Concentrations 43 7. Hazard Assessment 7.1 Category Justification/Overview 47 7.2 Acute Toxicity 48 7.3 Repeat Dose Toxicity 50 7.4 Reproductive and Developmental Toxicity 55 7.5 Genetic Toxicity 58 2 7.6 Neurotoxicity 60 7.7 Carcinogenicity 61 7.8 Disposition and Metabolism 62 7.9 Human Experience 66 7.10 Hazard Assessment Summary and Proposed Health Benchmarks 67 8. Risk Assessment 8.1 Summary 72 8.2 Health Benchmarks 73 8.3 Exposure Assessment 76 8.4 Risk Assessment 77 8.5 Uncertainties 82 9. Data Needs Assessment 9.1 Hazard Characterization 85 9.2 Exposure Characterization 86 10. References 88 n-Alkane VCCEP Submission 2 LIST OF APPENDICES Appendix A Exposure Literature Summary Table Appendix B Toxicity Robust Study Summaries Appendix C Excerpt from Documentation for Proposed Group Guidance Values for OEL Setting for Hydrocarbon Solvents Appendix D Calculation of Inhalation Concentration Equivalent of an Oral Dose Appendix E Ambient Air n-decane Concentrations: Trends Over Time Decrease in National Emissions Appendix F Evaluation Of Human Milk As An Exposure Route Appendix G Analysis of EPA Research House Data Appendix H Margins of Exposure (MOE) and Margins of Safety (MOS) n-Alkane VCCEP Submission 3 GLOSSARY OF TERMS µg Microgram ACGIH American Conference of Governmental Industrial Hygienists alkyd paint A hydrocarbon solvent (typically mineral spirits) based paint. Alkylate Bottoms A mixture of unreacted n-alkanes and benzene that remain after the production of Linear Alkyl Benzene (LAB). ATSDR Agency for Toxic Substances and Disease Registry CAA Clean Air Act CNS Central Nervous System Cycloalkane Synonymous with cycloparaffin. A saturated hydrocarbon with a ring - typically a 6-carbon single ring or a 10-carbon double ring – with unspecified branching off of the ring. EHC Environmental Health Criteria EPA Research A model house in Cary, NC where EPA conducted indoor air studies to validate House the Wall Paint Exposure Model (WPEM). IPCS International Programme on Chemical Safety IRIS Integrated Risk Information System Isoalkane Synonymous with isoparaffin. A saturated hydrocarbon with carbon branching. Kg Kilogram LAB Linear Alkyl Benzene LAS Linear Alkyl Sulfonate LOAEL Lowest Observed Adverse Effect Level mg Milligram NCEA National Center for Environmental Assessment NOAEL No Observed Adverse Effect Level n-Alkane Synonymous with n-paraffin. A straight-chained, saturated hydrocarbon, with no (Normal Alkane) branching or cyclic components. NTP National Toxicology Program OECD Organization of Economic Cooperation and Development OSHA Occupational Safety and Health Administration Paraffin Equivalent term to alkane ppb Parts Per Billion RfC Inhalation Reference Concentration RfD Oral Reference Dose SD Standard Deviation SEM Standard Error of the Mean SIAM SIDS Initial Assessment Meeting SIAR Screening Information Assessment Report SIDS Screening Information Data Set STEL Short-Term Exposure Limit TEAM Total Exposure Assessment Method TLV Threshold Limit Value TPHCWG Total Petroleum Hydrocarbon Criteria Working Group TSCA Toxic Substances Control Act TWA Time-Weighted Average VOC Volatile Organic Compound VCCEP Voluntary Children’s Chemical Evaluation Program WAGM Weighted Average Geometric Mean WHO World Health Organization n-Alkane VCCEP Submission 4 1. Executive Summary This submission covers n-decane (C10), CAS No. 124-18-5, n-undecane (C11), CAS No. 1120-21-4, and n-dodecane (C12), CAS 112-40-3, the three n-alkanes sponsored under the Tier 1 of the VCCEP Pilot Program by the American Chemistry Council n-Alkane VCCEP Consortium (the “Consortium”). As these three chemicals are very similar in chemical structure, physical and chemical properties, hazard properties, potential health effects, and exposure sources, the Consortium is considering them together as a category. These three n-alkanes were included in the VCCEP pilot program because the Total Exposure Assessment Methodology (TEAM) project detected them in indoor air and exhaled breath. They are also sponsored under the Organization for Economic Cooperation and Development (OECD) High Production Volume (HPV) Screening Information Data Set (SIDS) Program. Production and Use These three chemicals present an interesting VCCEP case because the production and use of these chemicals as pure chemicals and high-purity n-alkane process streams is quite small relative to the petroleum substances (i.e., kerosene, jet fuel, home heating oil, hydrocarbon solvents) that contain these n-alkanes as constituents. In addition, almost all (99+%) of the purified n-alkane production is not as single chemicals but as process streams that contain a range of n-alkanes, typically C10-C13, C12-C14, C12-C16, and C14-C16. These n-alkane process streams are consumed as closed-system chemical intermediates in the manufacture of linear alkylbenzenes (LABs), which are a chemical building block for the manufacture of detergents. A very small volume (estimated at less than 20,000 pounds) is produced in pure form for use as laboratory reagents. There are no known consumer product applications for pure n-decane, n-undecane, and n-dodecane. There are several different types of petroleum substances that may contain these n-alkanes, including aliphatic hydrocarbon solvents (e.g. mineral spirits) and middle-distillate fuels such as kerosene, jet fuel, diesel fuel and home heating oil. Generally these substances contain approximately 25% n-alkanes, but given their large production volumes and wide usage they were the primary source of exposure identified in the exposure assessment. Exposure The Consortium conducted an exposure assessment of n-decane, n-undecane, and n- dodecane, with emphasis on exposure to children, potential parents and the fetus. The Consortium also reviewed the TEAM and indoor air studies discussed in the VCCEP Federal Register notice (65 FR 81700, December 26, 2000). Four routes of exposure - inhalation, oral, dermal, and human milk - were considered in the exposure assessment. Of these, only inhalation was determined to be sufficiently significant to undergo detailed risk characterization. The most common exposure sources identified were fuels (particularly jet fuel, kerosene and diesel), paints, and other products containing solvents. Due to the low volatility of these compounds and the limited CNS effects, even at saturated n-Alkane VCCEP Submission 5 concentrations, solvent abuse involving decane, undecane, or dodecane is improbable and was not considered in this assessment. Based on the analyses of the available exposure data, the following scenarios were identified as being the most representative of situations where children and prospective parents are likely to have the highest potential exposure to decane, undecane, and dodecane. These scenarios are: 1. Chronic exposure of infants and children to indoor air. 2. Chronic exposure of prospective parents to indoor air. 3. Short term exposure of infants and children in a newly renovated (painted) home. 4. Short term exposure of prospective parents in a newly renovated (painted) home. 5. Prospective parents exposed occupationally in the painting trade and refueling operations at an airport. Relevant exposure concentration data for these scenarios were abstracted from the studies summarized in Appendix A and are summarized below in Table 1. These exposure concentrations are the combined exposure to decane, undecane, and dodecane since the chemicals are being considered together as a category. Table 1: Exposure Concentrations for Selected Scenarios Type of Measurement Representative Upper Bound Applicable References Concentration1 Concentration2 Scenario3 Average daily 42 µg/m3 129 µg/m3 1,2 Brown et al, household indoor air 1994; BRE, concentrations 1996; Interior painting Brown & 122 µg/m3 910 µg/m3 3,4,5 average ambient air Crump, 1998 concentrations and Wallace, 1989 personal samplers Highest exposed Air 5,061 µg/m3 16,800 µg/m3 5 Pleil et al, force fuel workers: 1 2000 hour average ambient exposures