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ADDENDUM for THORIUM Supplement to the 1990 Toxicological Profile for Thorium

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ADDENDUM for THORIUM Supplement to the 1990 Toxicological Profile for Thorium ADDENDUM TO THE TOXICOLOGICAL PROFILE FOR THORIUM Agency for Toxic Substances and Disease Registry Division of Toxicology and Human Health Sciences Atlanta, GA 30333 October 2014 THORIUM ii CONTRIBUTORS CHEMICAL MANAGER(S)/AUTHOR(S) Sam Keith, MS, CHP ATSDR, Division of Toxicology and Human Health Sciences, Atlanta, GA David W. Wohlers, Ph.D. SRC, Inc., North Syracuse, NY THORIUM iii CONTENTS CONTRIBUTORS.......................................................................................................................... ii CONTENTS................................................................................................................................... iii LIST OF FIGURES ........................................................................................................................ v LIST OF TABLES......................................................................................................................... vi Background Statement .................................................................................................................. vii 2. HEALTH EFFECTS.................................................................................................................. 1 2.2 DISCUSSION OF HEALTH EFFECTS BY ROUTE OF EXPOSURE ......................... 1 2.2.1 Inhalation Exposure .................................................................................................. 1 2.2.1.1 Death.................................................................................................................. 1 2.2.1.7 Genotoxic Effects .............................................................................................. 2 2.2.1.8 Cancer................................................................................................................ 2 2.2.4 Other Routes of Exposure......................................................................................... 3 2.2.4.1 Death.................................................................................................................. 3 2.2.4.2 Systemic Effects. ............................................................................................... 4 2.2.4.3 Immunological Effects ...................................................................................... 5 2.2.4.4 Neurological Effects.......................................................................................... 5 2.2.4.7 Genotoxic Effects .............................................................................................. 6 2.2.4.8 Cancer................................................................................................................ 7 2.3 TOXICOKINETICS......................................................................................................... 9 2.3.2 Distribution ............................................................................................................... 9 2.3.2.1 Inhalation Exposure ......................................................................................... 10 2.3.2.4 Other Routes of Exposure................................................................................ 11 2.3.3 Metabolism ............................................................................................................. 12 2.3.4 Excretion................................................................................................................. 13 2.3.4.1 Inhalation Exposure ......................................................................................... 13 2.3.5 Physiologically Based Pharmacokinetic (PBPK)/Pharmacodynamic (PB) Models 13 2.4 RELEVANCE TO PUBLIC HEALTH.......................................................................... 26 2.6 INTERACTION WITH OTHER CHEMICALS. .......................................................... 27 2.9 METHODS FOR REDUCING TOXICITY. ................................................................. 28 2.9.2 Reducing Body Burden........................................................................................... 28 2.9.3 Interfering with the Mechanisms of Action ............................................................ 29 3. CHEMICAL AND PHYSICAL INFORMATION ................................................................. 30 3.2 PHYSICAL AND CHEMICAL PROPERTIES ............................................................ 30 4. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL .............................................. 32 4.3 Use.................................................................................................................................. 32 4.4 DISPOSAL..................................................................................................................... 33 5. POTENTIAL FOR HUMAN EXPOSURE............................................................................. 34 5.3 ENVIRONMENTAL FATE .......................................................................................... 34 5.3.1 Transport and Partitioning ...................................................................................... 34 5.4 LEVELS MONITORED OR ESTIMATED IN THE ENVIRONMENT ..................... 35 5.4.3 Soil .......................................................................................................................... 35 5.5 GENERAL POPULATION AND OCCUPATIONAL EXPOSURE ............................ 36 THORIUM iv 5.6 POPULATIONS WITH POTENTIALLY HIGH EXPOSURES .................................. 36 6. ANALYTICAL METHODS ................................................................................................... 38 6.1 BIOLOGICAL MATERIALS........................................................................................ 38 6.2 ENVIRONMENTAL SAMPLES .................................................................................. 38 7. REGULATIONS AND ADVISORIES ................................................................................... 40 8. REFERENCES ........................................................................................................................ 42 9. GLOSSARY ............................................................................................................................ 51 THORIUM v LIST OF FIGURES Figure 2-4. Respiratory Tract Compartments in Which Particles May be Deposited ……..... 15 Figure 2-5. Environmental Pathways for Potential Human Health Effects from Thorium .... 18 Figure 2-6. The Human Respiratory Tract Model: Absorption into Blood ……………….. 23 Figure 2-7. Structure of the Human Alimentary Tract Model (HATM) …………………… 25 THORIUM vi LIST OF TABLES Table 2-5. Reference Respiratory Values for a General Caucasian Population at Different Levels of Activity ..................................................................................................................................... 17 Table 2-6. Reference Values of Parameters for the Compartment Model to Represent Time- dependent Particle Transport from the Human Respiratory Tract ................................................ 19 Table 3-2. Physical and Chemical Properties of Thorium and its Compounds ……………...…31 Table 7-1. Regulations and Guidelines Applicable to Thorium .................................................. 41 THORIUM vii ADDENDUM FOR THORIUM Supplement to the 1990 Toxicological Profile for Thorium Background Statement This addendum to the Toxicological Profile for Thorium supplements the profile that was released in 1990. Toxicological profiles are developed in response to the Superfund Amendments and Reauthorization Act (SARA) of 1986 which amended the Comprehensive Environmental Response, Compensation, and Liability Act of 1980 (CERCLA or Superfund). CERCLA mandates that the Administrator of ATSDR prepare toxicological profiles on substances on the CERCLA Priority List of Hazardous Substances and that the profiles be revised “no less often than once every three years.” CERCLA further states that the Administrator will “establish and maintain inventory of literature, research, and studies on the health effects of toxic substances” [Title 42, Chapter 103, Subchapter I, § 9604 (i)(1)(B)]. The purpose of this addendum is to provide to the public and other federal, state, and local agencies a non-peer reviewed supplement of the scientific data that were published in the open peer-reviewed literature since the release of the profile in 1990. Chapter numbers in this addendum coincide with the Toxicological Profile for Thorium (1990). This document should be used in conjunction with the profile. It does not replace it. THORIUM 1 2. HEALTH EFFECTS 2.2 DISCUSSION OF HEALTH EFFECTS BY ROUTE OF EXPOSURE Many of the studies evaluating the health effects of thorium (Th) involved the intravascular injection of a 232 colloidal suspension form of ThO2 termed Thorotrast. Thorotrast was specifically prepared as an injectable contrast agent for medical x-ray imaging of the body during the period 1928-1954. Although the colloid contained different size particles, some manufacturers filtered out the large particles leaving an average size of 10 nm (Dalheimer et al. 1988), i.e., Thorotrast was a nanomaterial. Its manufacture and use ended when delayed adverse health effects were recognized and attributed to its use. These effects included bone marrow insufficiency and hemangioendothelioma (sometimes termed thorotrastosis) and cancer. Thorotrast has unique physico-chemical characteristics which enable it to distribute to bone marrow and have essentially complete retention. This, along
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