PRELIMINARY DRAFT ECAO-R-065 DO NOT QUOTE OR CITE AUGUST 1990 EXTERNAL REVIEW DRAFT HEALTH ASSESSMENT DOCUMENT FOR CHLORINE AND HYDROGEN CHLORIDE This document is a preliminary draft and is intended for internal Agency use only. It has not been formally released by the U.S. Environmental Protection Agency and should not atthis stage be construed to represent Agency policy. It is being circulated for comments on its technical merit and policy implications. ENVIRONMENTAL CRITERIA AND ASSESSMENT OFFICE OFFICEOF HEALTH AND ENVIRONMENTAL ASSESSMENT U.S. ENVIRONMENTAL PROTECTION AGENCY RESEARCH TRIANGLE PARK, NC 27711 J: DISCLAIMER This document is an external draft for review purposes only and does not constitute Agency policy. Mention oftrade names or commercial products does not constitute endorsement or recommendation for use. n CONTENTS Page vi TABLES . vii FIGURES viii PREFACE ix ABSTRACT AUTHORS, CONTRIBUTORS, AND REVIEWERS x 1. SUMMARY AND CONCLUSIONS 1-J 1.1 BACKGROUND INFORMATION 1-1 1.1.1 Chlorine x'\ 1.1.2 Hydrogen Chloride J"2 1.2 PHARMACOKINETICS AND MECHANISM OF ACTION 1-3 1.2.1 Chlorine ]"* 1.2.2 Hydrogen Chloride J-* 1.3 ANIMAL TOXICITY j** 1.3.1 Chlorine J"* 1.3.2 Hydrogen Chloride 1-5 1.4 HUMAN HEALTH EFFECTS I"7 1.4.1 Chlorine }"7 1.4.2 Hydrogen Chloride l'l 1.5 RESEARCH NEEDS 1-8 2. PHYSICAL AND CHEMICAL PROPERTIES, QUANTIHCATION, AND ANALYSIS 2-1 2.1 PHYSICAL AND CHEMICAL PROPERTIES 2-1 2.1.1 Chlorine 2-1 2.1.2 Hydrogen Chloride 2-1 2.2 QUANTIFICATION AND ANALYSIS 2-2 2.2.1 Chlorine 2-2 2.2.2 Hydrogen Chloride 2-4 2.3 REFERENCES . 2-6 3. PRODUCTION, USE, ENVIRONMENTAL SOURCES, AND ENVIRONMENTAL LEVELS AND EXPOSURE . 3-1 3.1 PRODUCTION ANDUSE 3-1 3.1.1 Chlorine ^"1 3.1.2 Hydrogen Chloride 3-2 3.2 ENVIRONMENTAL SOURCES 3-3 3.2.1 Chlorine 3"3 ill CONTENTS (continued) 3.2.1.1 Manufacturing and Transport 3-3 3.2.1.2 Natural Sources and Photochemical Processes 3-3 3.2.1.3 Anthropogenic Processes 3-3 3.2.2 Hydrogen Chloride 3-4 3.2.2.1 Manufacturing and Transport 3-4 3.2.2.2 Natural Sources and Photochemical Processes 3-4 3.2.2.3 Anthropogenic Processes 3-4 3.3 ENVIRONMENTAL LEVELS AND EXPOSURE 3-5 3.3.1 Chlorine 3-5 3.3.2 Hydrogen Chloride 3-8 3.4 REFERENCES 3-9 4. ENVIRONMENTAL FATE AND ECOLOGICAL EFFECTS 4-1 4.1 ENVIRONMENTAL FATE 4-1 4.1.1 Chlorine 4-1 4.1.2 Hydrogen Chloride . 4-5 4.2 ECOLOGICAL EFFECTS 4-6 4.2.1 Chlorine 4-6 4.2.1.1 Fish 4-7 4.2.1.2 Invertebrates 4-7 4.2.1.3 Plants 4-7 4.2.2 Hydrogen Chloride (Hydrochloric Acid) 4-11 4.2.2.1 Aquatic Organisms 4-11 4.2.2.2 Terrestrial Organisms 4-12 4.3 REFERENCES 4-13 5. PHARMACOKINETICS AND MECHANISM OF ACTION 5-1 5.1 PHARMACOKINETICS AND METABOLISM 5-1 5.2 MECHANISM OF ACTION AND BIOCHEMICAL EFFECTS ... 5-1 5.2.1 Chlorine 5-1 5.2.2 Hydrogen Chloride 5-3 5.3 REFERENCES 5-4 6. TOXICOLOGY 6-1 6.1 EXPERIMENTAL ANIMALS 6-1 6.1.1 Chlorine 6-1 6.1.1.1 Acute Toxicity Inhalation 6-2 6.1.1.2 Subchronic Toxicity 6-6 iv CONTENTS (continued) 6.1.1.3 Chronic Toxicity 6"9 6.1.2 Hydrogen Chloride f\® 6.1.2.1 Acute Toxicity Inhalation 6-10 6.1.2.2 Subchronic Toxicity 6-22 6.1.2.3 Chronic Toxicity • M4 6.2 HUMANTOXICITY <>-24 6.2.1 Chlorine fj* 6.2.1.1 Acute Exposure 6-24 6.2.1.2 Chronic Exposure 6-34 6.2.1.3 Epidemiology Studies 6-35 6.2.2 Hydrogen Chloride 6-37 6.2.2.1 Acute Exposure 6-38 6.2.2.2 Epidemiology Studies 6-39 6.3 REFERENCES • 6Al 7. DEVELOPMENTAL TOXICITY AND REPRODUCTIVE EFFECTS • 7"1 7.1 EXPERIMENTAL ANIMALS 7"1 7.1.1 Chlorine 7'\ 7.1.2 Hydrogen Chloride 7"2 7.2 HUMAN STUDIES 7"3 7.3 REFERENCES 7"3 TABLES Number Page 2-1 Chlorine Reactions Known to Occur in Aqueous Solution 2-2 4-1 The Acute Toxicity ofChlorine to Fish and Aquatic Invertebrates . 4-9 6-1 Mortality in Dogs Exposed to Chlorine for 30 Minutes 6-4 6-2 LC50 Values for Chlorine in Rats and Mice 6-4 6-3 Inhalation L<(~7Values and Minimal Lethal Concentrations for Hydrogen Chloridein Mice and Rats 6-11 6-4 Acute Toxicity Values in Rats Exposed to Hydrogen Chloride 6-12 6-5 Threshold Levels for Chlorine Gas 6-26 VI FIGURES Number EagS 4-1 Schematic outlineofchemical reactions in freshwater, estuarine, and marine waters 4-3 4-2 Principal chemical pathways for reaction, degradation, and environmental fate of free chlorine in the aquatic environment 4-4 6-1 LC50 values for hydrogen chloride exposed adult male Sprague-Dawley rats vs. time ofexposure 6-13 6-2 Incapacitation time as a function of hydrogen chloride concentration 6-17 6-3 Survival time as a function of hydrogen chloride concentration 6-18 Vll PREFACE The Office ofHealth and Environmental Assessmenthas prepared this healthassessment to serveas a source document for EPA use. Specifically this document was developed for use by the Office of Air Quality Planning and Standards to support decision makingregarding possible regulation ofchlorineand hydrogenchloride as hazardous air pollutants. Ideally when evaluating the health effects associated with exposure ofa given compound and its by-products both oral and inhalation routes ofexposure are addressed; however, in the case ofchlorine and hydrogen chloride, a relationship between the inhalation ofthese gases and the ingestion of chlorinated liquids with respect to human health effects is questionable. With that in mind, this document will mainly address effects resulting from the inhalationof chlorineand hydrogen chloride gas or aerosol. The health effects resulting from the ingestion ofchlorinated liquids will be addressed in a separate document. In the development of the assessment document, the scientific literature has been to inventoried through April 1929, key studies have been evaluated, and summary/conclusions have been prepared so that the chemicals* toxicity and related characteristics are qualitatively identified. Observed effect levels and other measures of concentration-response relationships are discussed, where appropriate, so that the nature of the adverse health responses is placed in perspectivewith observed environmental levels. Any information regarding sources, emissions, ambient air concentrations, and public exposure has been included only to give the reader a preliminary indication of the potential presence of this substance in the ambient air. While the available information is presented as accurately as possible, it is acknowledged to be limited and dependent in many instances on assumption ratherthan specific data. This information is not intended, nor should it be used, to support any conclusions regarding risk to public health. If a review ofthe healthinformation indicates that the Agency should consider regulatory action for these substances, considerable effort will be undertaken to obtain appropriate information regarding sources, emissions, and ambientair concentrations. Such data will provide additional information for drawing regulatory conclusions regarding the extent and significance of public exposure to these substances. viii ABSTRACT Chlorine, anoncombustible gas with a pungent odor, is used in the manufacture of inorganic and organic chemicals and plastics, in the bleaching ofpulp and paper, and in the disinfection of wastewater and drinking water. Natural sources and photochemical processes do not contribute to levels of chlorine inthe ambient air. There isa potential for release of small amounts of chlorine during its manufacture or during loading and unloading in transpor tation. However, photodissociation in the lower atmosphere and troposphere israpid. Hydrogen chloride, acolorless gas with apungent odor, is used in the manufacture of inorganic and organic chemicals, oil-well acidizing, steel pickling, processing of food products, and mineral and metal processing. Hydrogen chloride may be found naturally in the atmosphere from the cooling ofvolcanic ash, the photolysis ofchlorine, and the reaction 0\> of(£l» with methane. Anthropogenic sources ofhydrogen chloride include the burning of fossil fuel, the incineration of municipal refuse, the burning of polyvinyl chloride plastics, and solid rocket fuel exhaust. Photodegradation of hydrogen chloride in the atmosphere is slow because of the low atmospheric concentrations of hydroxy radicals. It is, however, diluted and tends to absorb on aqueous aerosols and particulates. No data were found in the published literature on the levels ofhydrogen chloride in air from either natural or anthropogenic sources. Howcvois several studies have reported that as much as 2.11 and 5.3 ghydrogen chloride are emitted/kg ofmunicipal and hospital waste incinerated, respectively. Both chlorine and hydrogen chloride are acutely toxic gases. The effects of acute inhalation exposure are primarily respiratory and range from irritation to pulmonary edema and death. Limited epidemiology studies indicate that cMorme is not carcinogenic. In available animal toxicity studies hydrogen chloride did not produce nasal tumors in rats nor did it enhance the carcinogenicity of formaldehyde in rats; however, it was found to have an adverse effect on the reproduction potential of rats exposed to high concentrations prior to mating or during gestation. ix AUTHORS, CONTRIBUTORS, AND REVIEWERS The Environmental Protection Agency's Office ofHealth and Environmental Assessment (OHEA) is responsible for the preparation ofthis health assessment document. The OHEA Environmental Criteriaand Assessment Office (ECAO-RTP) had the overall responsibility for coordination and direction ofthe document (Beverly M. Comfort, Project Manager).