") .., , A f



# & EPA United States Environmental Protection Agency

Research And Development Office of Research and Development Washington, DC 20460



# Health Assessment Document for Chlorine and Hydrogen Chloride

NOTICE
This document is a preliminary draft

. It has not been formally released by EPA and should not at this stage be construed to represent Agency policy

. It is being circulated for comment on its technical accuracy and policy implications

. EPA/600/8-87/041A August 1994

0 .3



### let-- 

# Review Draft

(Do Not Cite or Quote)

### (Do Not Cite or Quote) EPA600/8-87/041A August 1994



## Health Assessment Document for Chlorine and Hydrogen Chloride

NOTICE This document is apreliminary draft. It has not been formally released by EPA and should notatthis stage be construed to represent Agency policy. It is being circulated for comment on its technical accuracy and policy implications.

Environmental Criteria and Assessment Office Office of Health and Environmental Assessment Office of Research and Development U.S. Environmental Protection Agency

Research Triangle Park, NC 27711r



### DISCLAIMER



### This document is an external draft

### for review purposes only and does notconstitute U.S. Environmental Protection Agency policy. Mention oftrade names or commercial products does not constitute endorsement orrecommendation for use.

iiJ_

.. .1

TABLE OF CONTENTS

LIST OF TABLES

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Vl 

### UST OF FIGURES

. . . . . . • . . . • . . . . . . . . . . . . . . . . . . . . . vii PREFACE

. . . . . . . . . . . . . . . . . • . . . . . . . . . . . . . . . 

### ix ABSTRA.CT

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 

### xi AUTHORS, CONTRIBUTORS, AND REVIEWERS

. . . . . . . . . . . . . . . 

### xiii

1. SUMMARY AND CONCLUSIONS

. . . . . . . . . . . . . . . . . . . . . . 1-1 1.1 BACKGROUND INFORMATION

. . . . . . . . . . . . . . . . . . 1-1 1.1.1 Chlorine

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1-1 1.1.2 Hydrogen Chloride

. . . . . . . . . . . . . . . . . . . . . . 1-2 1.2 PHARMACOKINETICS AND MECHANISM OF ACTION

. . . 1-3 1.2.1 Chlorine

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1-3 

### 1.2.2 Hydrogen Chloride

. . . . . . . . . . . . . . . . . . . . . . 1-4 

### 1.3 ANIMAL TOXICITY

. . . . . . . . . . . . . . . . . . . . . . . . . o 1-4 1.3.1 Chlorine

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1-4 

### 1.3.2 Hydrogen Chloride

. . . . . . . . . . . . . . . . . . . . . . 

### 1-6 1.4 HUMAN HEALTH EFFECTS

. . . . . . . . . . . . . . . . . . . . . 1-7 1.4.1 Chlorine

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1-7 1.4.2 Hydrogen Chloride

. . . . . . . . . . . . . . . . . . . . . . 1-8 1.5 RESEARCH NEEDS

. . . . . . . . . . . . . . . . . . . . . . . . . . . 1-9
2. PHYSICAL AND CHEMICAL PROPERTIES, QUANTIFICATION, AND ANALYSIS

. . . . . . . . . . . . . . . . . . . 2-1 2.1 PHYSICAL AND CHEMICAL PROPERTIES

. . . . . . . . . . . 2-1 

### 2.1.1 Chlorine

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 

### 2-1 2.1.2 Hydrogen Chloride

. . . . . . . . . . . . . . . . . . . . . 0 2-1 2.2 QUANTIFICATION AND ANALYSIS

.............. 0 2-2 2.2.1 Chlorine

...... 0 • • • • • • • • • • • • • • • • • • • • • • 2-2 

### 2.2.2 Hydrogen Chloride

. . . . . . . . . . . . . . . . . . . . . . 

### 2-4 REFERENCES

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-7

( 3. PRODUCTION, USE, ENVIRONMENTAL SOURCES, AND ENVIRONMENTAL LEVELS AND EXPOSURE

. . . . . . . . . . 3-1 3.1 PRODUCTION AND USE

. . . . . . . . . . . . . . . . . . . . . . . 3-1 3.1.1 Chlorine

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3-1 3.1.2 Hydrogen Chloride

. . . . . . . . . . . .·. . . . . . . . . . 3-2 3.2 ENVIRONMENTAL SOURCES

. . . . . . . . . . . . . . . . . . . . 3-2 3.2.1 Chlorine

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3-2

111TABLE OF CONTENTS 

### (cont'd)

3.2.1.1 

### Manufacturing and Transport • . . . . . . . . . . 3-2 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

. . . . . . . . . . . . . . . . . . . . . . . 3.2.2.3 

### Anthropogenic 

### Processes

............. . 3.3 ENVIRONMENTALLEVELS AND EXPOSURE .•....... 

### 3.3.1 Chlorin.e

. . . . . . . . • . . . . . . . . . . . . . . . . . . . . 3.3.2 

### Hydrogen Chloride ..•................... REFEREN CBS

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4. ENVIRONMENTAL FATEAND ECOLOGICAL EFFECTS · ..... . 4.1 ENVIRONMENTALFATE

...................... . 4.1.1 

### Chlorine

. . • . . . . . . . . . . . . . . . . . . . . . . . . . . 4.1.2 

### Hydrogen Chloride

..................... . 4.2 ECOLOGICALEFFECTS

...................... . 4.2.1 

### Chlorine

.........................**~** 

### .. . 4.2.1.1 

### Fish

. . . . . . . . . . . . . . . . . . . . . . . . . . 4.2.1.2 Invertebrates

. . . . . . . . . . . . . . . . . . . . . 4.2.1.3 Plants

........................ . 4.2.2 

### Hydrogen Chloride (Hydrochloric Acid)

......... . 4.2.2.1 

### Aquatic Organisms

................ . 4.2.2.2 Terrestrial Organisms

............... . REFERENCBS

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5. PHARMACOKINETICS AND MECHANISM OF ACTION

...... . 5.1 PHARMACOKINETICS AND METABOLISM

.......... . 5.2 MECHANISM OF ACTION AND BIOCHEMICAL EFFECTS

. 

## s

. 2.1 Chlorin.e

. . . . • . . . . . . . . . . . . . . . . . . . . . . . .. 5.2.2 

### Hydrogen Ghloride

..................... . REFERENCES

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6. TOXICOLOGY

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6.1 EXPERIMENTALANIMALS

. . . . . . . . . . . . . . . . . . . . . 6.1.1 

### Chlorine

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6.1.1.1 

### Acute Inhalation Toxicity

. . . . . . . . . . . . . 6.1.1.2 

### Subchronic Toxicity

............... .

IV 3-4 3-4 3-6 3-6 

### 3-9 3-10
4-1 4-1 4-1 4-3 4-6 4-6 4-6 4-9 4-10 4-10 4-10 4-11 4-12
5-1 5-1 5-1 5-1 

### 5-3 5-4
6-1 

### 6-1 6-1

. 6-2

. 6-6TABLE OF CONTENTS (cont'd)

6.1.1.3 Chronic Toxicity

. . . . . . . . . . . . . . . . . . 6-9 6.1.2 Hydrogen Chloride

. . . • . . . . . . . . . . . . . . . . . . 6-10 6.1.2.1 AcuteToxicity Inhalation

. . . . . . . . . . . . . 6-11 6.1.2.2 Subchronic Toxicity

........**~** . . . • . . . 6-25 6.1.2.3 Chronic Toxicity

. . . . . . . . . . . . . . . . . . 6-26 6.2 HUMAN TOXICITY

. . . . . . . . . . . . . . . . . . . . . . . . . . . 6-27 6.2.1 Chlorine

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6-27 6.2.1.1 Acute Exposure

. . . . . . . . . . . . . . . . . . . 6-27 6.2.1.2 Chronic Exposure

. . • . . . . . . . . . . . . . . . 6-40 6.2.1.3 Epidemiology Studies

. . . . . . . . . . . . . . . . 6-40 6.2.2 Hydrogen Chloride

. . . . . . . . . . . . . . . . . . . . . . .6-43 6.2.2.1 Acute Exposure

. . . . . . . . . . . . . . . . . . . 6-44 6.2.2.2 Epidemiology Studies

. . . . . . . . . . . . . . . . 6-45 REFERENCES

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6-47
7. DEVELOPMENTALTOXICITY AND REPRODUCTIVE EFFECTS

. . . . . .·. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7-1 7.1 EXPERIMENTAL ANIMALS

. . . . . . . . . . . . . . . . . . . . . 7-1 7.1.1 Chlorine

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7-1 

### 7.1.2 Hydrogen Chloride

. . . . . . . . . . . . . . . . . . . . . . 

### 7-2 7.2 HlJMAN STUDIES

........ o • • • • • • • • • • • • • • • • • • • 7-3 REFERENCES

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7-4 8. MUTAGENIC AND CARCINOGENIC EFFECTS

. . . . . . . . . . . . . 8-1 8.1 MUTAGENIC EFFECTS

. . . . . . . . . . . . . . . . . . . . . . . . 8-1 8.1.1 Chlorine

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8-1 8.1.2 Hydrogen Chloride

. . . . . . . . 0 • • • • • • • • • • • • • 8-1 8.2 CARCINOGENIC EFFECTS

. . . . . . . . . . . . . . . . . . . . . . 8-2 8.2.1 Experimental Animals

. . . . . . . . . . . . . . . . . . . . . 8-2 8.2.1.1 Chlorine

. . . . . . . . . . . . . . . . . . . . . . . 8-2 8.2.1.2 Hydrogen Chloride

. . . . . . . . . . . . . . . . . 8-2 8.2.2 Epidemiological Studies

................... .- 8-3 REFERENCES

................. o • • • • • • • • • • • • • • • • • 8-12
9. REGULATIONS AND STANDARDS

... 0 • • • • • • • • • • • • • • • • • 9-1 

### 9.1 CHLORINE

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9-1 9.2 HYDROGEN CHLORIDE

. . . . . . . . . . . . . . . . . . . . . . . 9-1 REFERENCES

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9-3

vLIST OF TABLES

2-1 Chlorine Reactions Known To 

### Occur in Aqueous 

### Solution

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-2

4-1 TheAcuteToxicity ofChlorine to Fish and Aquatic Invertebrates

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4-7 6-1 Acute Toxicity Values for Chlorine 

### in 

### Rats and Mice

. . . . . . . . . . . . 6-3 6-2 Acute Toxicity Values for Hydrogen Chloride 

### in Mice and Rats

. . . . • . . . . . . . . . . . . . . . . . . . . . . . . . . • . . . . 6-11 6-3 Acute Toxicity Values 

### in Rats Exposed to Hydrogen Chloride

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6-12 6-4 Threshold Levels for Chlorine 

### Gas 6-28

viLIST OF FIGURES 

### Number Page 4-1 Schematic outline ofchemical reactions in 

### estuarine and marine waters

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4-3 4-2 Principal.chemical pathways for reaction, degradation, and environmental fate offree 

### chlorine in 

### the aquatic environment

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4-4 

### 6-1 Hydrogen chloride concentrations producing 50% 

### mortality in 

### adult male Sprague-Dawley rats 

### versus 

### time ofexposure 6-2 Incapacitation time as 

### a function ofhydrogen chloride 6-13

concentration

. . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . 6-19 6-3 Survival time as a function ofhydrogen chloride concentration 6-20



### vii

### PREFACE



### The Office ofHealth and Environmental Assessment has prepared this health assessment to serve as a source document for U.S. Environmental Protection Agency use.**Specifi~y,** 

### this**docume~t** 

### was developed for use by the Office ofAir Quality 

### Planning and Standards to support information needs on 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 ofchlorinated liquids with respect to 

### human health effects is questionable. With that in

### mind, this document will 

### mainly address effects resulting from the inhalation ofchlorine and hydrogen chloride gas or aerosol. The health effects resulting from the ingestion ofchlorinated liquids are addressed in a separate document. In the development ofthe assessment document, the scientific literature has been inventoried through April 1994, 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 ofconcentration-responserelationships

are discussed, where appropriate, so that the nature ofthe adverse health responses is placed -in perspective with 

### observed environmental levels. Any information regarding sources, emissions, ambient air

### concentrations, and public exposure has been included only to give the reader apreliminary indication ofthe potential presence ofthis 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 assumptions rather than specific data. 

### This information is not intended, nor should itbe used, to support any conclusions regarding risk to 

### public health. Ifsuch a risk characterization is needed, considerable effort will be

### undertaken to 

### obtain appropriate information regarding sources, emissions, and ambient air

### concentrations.

ix

### ABSTRACT



### Chlorine, a noncombustible gas with apungent odor, is used in the manufacture of inorganic and organic chemicals and plastics, bleaching ofpulp and paper, and disinfection of wastewater and drinking water. Natural sources and photochemical processes do not contribute to

### levels ofchlorinein the ambient air. 

### There is

### apotential for release ofsmall**~ounts** 

### ofchlorine during its manufacture orduring loading and unloading in transportation. However, photodissociation in 

### the lower atmosphere and troposphere is rapid. Hydrogen chloride, acolorless gas with apungent odor; is used in

### the manufacture of inorganic and organic**chemicals~** 

### oil well acidizing, steel pickling, processing offood 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 ofthe chloride ion with methane. Anthropogenic sources {)fhydrogen chloride include the burning offossil fuel and polyvinyl chloride plastics, incineration ofmunicipal refuse, and solid rocket fuel exhaust. Photodegradation ofhydrogen chloride in 

### the atmosphere is slow because ofthe low atmospheric concentrations ofhydroxy radicals. It

### is, however, diluted and·tends to adsorb 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. Several studies have reported that as much as 2.11 and 5.3 g hydrogen chloride are emitted perkilogram ofmunicipal and hospital waste incinerated, respectively. Both chlorine and hydrogen chloride are acutely toxic gases. The effects ofacute inhalation exposure are primarily respiratory and range from irritation to pulmonary edema and death. Limited epidemiology studies indicate thatchlorine is not carcinogenic. In

### available animal toxicity studies, hydrogen chloride did not produce nasal tumors in rats

nor did itenhance the carcinogenicity offormaldehyde in rats; however, it was found to have

an adverse effect on the reproduction potential ofrats exposed to high 

### concentrations prior to mating or during gestation.

xi 7

### AUTHORS, CONTRIBUTORS, AND REVIEWERS

The U.S.**Environm~ntal** 

### Protection Agency's Office ofHealth and Environmental Assessment (OHEA) is responsible for the preparation ofthis health assessment document. The OHEA Environmental Criteria and Assessment Office, Research Triangle Park, NC, had the overall responsibility for coordination and direction·ofthe document (Beverly M. 

### Comfort, ProjectManager). The document

### was prepared by Dynamac Corporation. The principal author is Dr. William McLellan. Other authors are Louis Borghi and Jessup Roland.

U.S. 

### Environmental Protection Agency Reviewers and Contributors David Bayliss Office ofHealth and Environmental

Assessment Human Health Assessment Group Washington, DC Arthur Chin Office ofHealth and Environmental

Assessment Human Health Assessment Group Washington, DC Beverly M. 

### Comfort Office ofHealth and Environmental

Assessment Environmental Criteria and Assessment

Office Research Triangle Park, NC

xiii Gregory Kew Office ofHealth and Environmental

Assessment Exposure Assessment Group Washington, DC Charles Ris Office ofHealth and Environmental

Assessment Human Health Assessment Group Washington, DC Lawrence Valcovic Office ofHealth and Environmental

Assessment Human Health Effects Assessment Group Washington, DC

### External Reviewers and Contributors Craig S. 

### Barrow PPG

### Industries, Inc. 260 Kappa Drive Environmental Sciences Center Pittsburgh, PA 

### Charles R. Crane FAA, 

### CAMl, AAM-114 P.O. Box

### 25082 Oklahoma City, OK Brian Hammond Research Management Division Alberta Environment 14th Floor, Standard Life Center 10405 Jasper Avenue Edmonton, Alberta, Canada

XIV 

### Harold L. 

### Kaplan Southwest Research Institute 6220 CulebraRoad San Antonio, TX 

### Dr. Raymond Kutzman Consulting in

### Toxicology 12511 Morgans Ridge San Antonio, TX 

### Theodore B. 

### Torkelson 315 Birch Street Roscominon, MI John Withers 141 Maplewell Road Woodhouse Eaves Leicestershire, United Kindgom

### 1 

### 2 

## 1. 

## SUMMARY AND CONCLUSIONS

3 4 

### 1.1 BACKGROUND INFORMATION 5 

### 1.1.1 Cbiorine 6 Chlorine (Chemical Abstracts ServiceNumber [CAS No.]7782-50-5) is a 7 noncombustible gas with a pungent odor; for shipping or storing, the gas is compressed to a 8 liquid that vaporizes at -34 °C. Thegas is dense {1.468 at 0 °C) and soluble in 

### water, 9 forming elemental chlorine and hypochlorous acid. It is very reactive chemically with 10 organic compounds. 11 Many ofthe methods used to monitor 

### air levels ofchlorine, which arebased on 12 titrimetry, potentiometry, and colorimetry, are nonspecific and measure total chloride ion 13 rather than the diatomic gas. Ozone, sulfur dioxide, and nitrous oxides in air samples, as 14 well as chloramines and hydrochloric acid, can interfere with several ofthese analytical 15 methods. A sensitive and specific method for personal chlorine monitoring, using a chlorine 16 electrochemical sensor and a microprocessor data-logger, has been developed recently. 17 Thedomestic production ofchlorine in 

### 1993 was approximately 24.06 billion pounds, 18 an increase of0.55 billion pounds from 1992. It

### is manufactured by the electrolytic 19 decomposition ofbrine, which is associated with the production ofcaustic soda or alkali. Its 20 major uses are in the manufacture oforganic and inorganic chemicals and plastics, bleaching 21 ofpulp and paper, and disinfection ofwastewater and drinking water. 22 There is a potential for release ofsmall amounts ofchlorine during its manufacture or 23 during loading and unloading in 

### transportation. Natural sources and photochemical processes 24 do not contribute to levels in ambient air, and, because ofits reactivity, chlorine released into 25 the atmosphere from end-use applications is not detectable. Monitoring ofworkplace 26 atmospheres generally have shown concentrations ofless than 0.1 ppm (0.3 mg/m3) 

### with very 27 few samples exceeding the ceiling permissible exposure limitof 1ppm (3 mg/m3) 

### orthe 8-h 28 time-weighted average threshold limit value of0.5 ppm (1.5 mg/m3). 

### 29 When liquid chlorine, stored under high pressure and at ambient temperature, is 30 released into the atmosphere, flash evaporation ofup to 20% occurs. This cools the liquid to 31 -34

# oc (boiling point), and subsequent evaporation is dependel)t on the rate ofheat August 1994 1-1 DRAFT

- DO NOT QUOTE OR CITE \T )

1 exchange. Chlorine is rapidly diluted 

### in the atmosphere, and, except 

### in the immediate 2 vicinity ofa spill, dangerous levels exist for only a few hours. Monitoring ofa release of· 3 approximately 70,000 kg chlorine 

### in a 

### train derailment several hours after the accident found 4 levels of3.4 to 34ppb (10 to 100 p.g/m3), with 

### peakvalues ofup to 0.14 ppm (0.4 mg/m3) 

### 5 in theplume ata distance of0.5 to 1 km from the accident site. Photodissociation 

### in the 6 lower atmosphere and troposphere israpid 

### in the daytime, and further atmospheric reactions 7 produce hydrogen chloride. Chlorine released to the soil surface evaporates, and, when 

### 8 released into water, itmay evaporate to the atmosphere or form hypochlorous acid. 9 Chlorine is extremely toxic to fish, with acute 

### median lethal levels ranging from 10 0.037 to 0.65 mg/L. Aquatic invertebrates such as mollusks, crabs, and shrimp, as well as 11 phytoplankton, appear to be more sensitive than fish. 12 13 

## 1.1.2 Hydrogen Chloride 14 Hydrogen chloride (CAS No. 7647-01-0) is a colorless gas with a pungent odor that 15 produces whitish fumes in moist 

### air. Itis very hygroscopic. When it dissolves in water, it is 16 very corrosive to metals and reacts with most organic materials. Itis very soluble in water 17 (82.3 g/100 mL), and ·the aqueous solution is called hydrochloric acid. Concentrated 18 hydrochloric acid is 37.1% hydrogen chloride; at room temperature, itvaporizes, producing a 19 whitish pungent vapor. Twenty percent hydrochloric acid does not vaporize appreciably from 20 an open container. 21 Hydrogen chloride 

### can be monitored by titrimetric orpotentiometric methods, using a 22 chloride selective electrode. It

### can be absorbed 

### in a solution ofsodium bromate-sodium 23 bromide, resulting in the production ofbromine, which is reacted with alkaline luminal and 24 the resulting chemiluminescence measured. Most methods ofanalyses are no!}specific; 25 ozone, nitrous oxides, and sulfur dioxide interfere, as does any acid other than hydrochloric. 26 Hydrogen chloride is produced as a by-product ofchemical syntheses ofchlorinated 27 compounds. Domestic production ofhydrogen chloride in 1993 was approximately 28 6.45 billion pounds, compared to 7.13 billion pounds produced 

### in 1992. End uses of 29 hydrogen chloride include the manufacture ofinorganic and organic chemicals, oil well 30 acidizing, steel pickling, processing offood products, mineral and metal processing, 

### and 31 various miscellaneous uses. August 

### 1994 1-2 DRAFT

- DO NOT QUOTE OR CITE1 Because ofits captive use as a gas and its use as an aqueous solution in most 2 applications, there are little emissions in the manufacture and transport. However, end uses 3 can result in emission ofacid into waste streams with the potential ofreaching groundwater. 4 Hydrogen chloride can befound naturally in the atmosphere from the cooling of 5 volcanic ash. A photochemical source is the photolysis ofchlorine and the reaction ofthe 6 chloride ion with methane in the atmosphere. 7 Anthropogenic sources ofhydrogen chlorideinclude the burning offossil fuel and 8 polyvinyl chlorideplastics, and the incineration ofmunicipal refuse. Hydrogen chlorideis 9 also released into the lower stratosphere 

### in solid rocket fuel exhaust. 10 Photochemical degradation ofhydrogen chloride occurs, but itis a slow process because 11 ofthe low atmospheric concentrations ofhydroxy radicals. When released into the 12 atmosphere, itis diluted and tends to adsorb on aqueous aerosols and particulates. The 13 National Aeronautics and Space Administration has studied the fate of**~ydrogen** chloride in 14 rocket exhaust. Levels in the exhaust cloud are as high as 40 ppm (60 mg/m3). 15 No monitoring studies ofanthropogenic hydrogen chloride 

### in ambient air were found; 16 however, it has been reported that as much as 2.11 and 5.3 g hydrogen chloride are emitted 17 per kilogram ofmunicipal and hospital waste incinerated, regpectively. Hydrogen chloride is 18 also toxic to several plant species, with leafinjury and a decrease 

### in chlorophyll levels 19 occurring between exposure concentrations of4.3 and 18.0 ppm (6.5 and 27.0 mg/m3). 20 21 22 

### 1.2 PHARMACOKINETICS AND MECHANISM OFACTION 23 

### 1.2.1 Chlorine 24 Chlorine reacts with tissues ofthe respiratory tract but does not appear to cause 25 systemic effects. Several theories have been proposed on the mechanism ofchlorine's 26 toxicity. In a pH range of6 to 8, chlorine can combine with water from tissue to form 27 hypochlorous and hydrochloric acids. Hypochlorous acid destroys the cell structure by 28 forming N-chloro derivatives with amino groups ofproteins. Ithas been suggested that 29 hypochlorous acid can inhibit sulfhydryl-dependent enzymes by reacting with sulfhydryl 30 groups. Cell damage may also becaused by oxygen radicals generated by chlorine orby the

August 1994 1-3 DRAFr ;_ DO NOT QUOTE 

### OR CITE1 oxidation potential ofchlorine. Theinitial oxidation process is clearly harmful and other 2 secondary processes may be also. 

### 3 4 

## 1.2.2 Hydrogen Chloride 5 There is no information on the metabolism ofhydrogen chloride; however, hydrogen 6 chloride is corrosive to tissue. The corrosive action ofhydrogen chlorideis**as~iated** with 7 its high solubility in water, forming hydronium ions. Hydronium ions arereactive 

### with 8 organic molecules and produces cellular injury and necrosis. 9 10 11 

## 1.3 ANIMAL TOXICITY 12 

## 1.3.1 Chlorine 13 The exposure concentrations producing 50% mortality (LC50) in mice for a 10-min 14 exposure to chlorine range between 618 and 676 ppm (1,742 and 1,960 mg/m3). For a 15 30-min exposure, an LC50 value of 127 ppm (368 mg/m3) was determined, but similar 16 exposure ofmice to 10 ppm for 3 h caused death 

### in .8 ·of 10 animals. In one study with 17 mice, only delayed deaths (5 to 10 days) were observed; the time to 50% mortality (LT 50) 18 was 11 min with exposure to 290 ppm (841 mg/m3 ) and 

### 55 min with exposure to 170 ppm 19 (493 mg/m3). TheLC50 value for a 60-min exposure ofrats was 293 ppm (850 mg/m3). 20 In dogs exposed to chlorine for 30 min, the LC50 was 650 ppm (1,885 mg/m3). When data 21 were normalized for a 30-min exposure, the LC50 values were 256, 414, and 650 ppm (384, 22 621, and 975 mg/m3) for mice, rats, and dogs, respectively. Rabbits and guinea pigs were 23 somewhatless susceptible, butadequate LC50 values were not found. 24 Miceand rats respond to exposure to sublethal levels ofchlorineby a reflex decrease 

### in 25 respiratory rate. The level for 50% reduction in respiratory rate (RD50) in mice for a 10-min 26 · exposure is 9.3 ppm (27 mg/m3) chlorine. However, repeated expos.ure.to chlorine can 27 ind:uce tolerance to this reflex response. Repeated exposure ofrats to levels as low as 1 ppm 28 (2.9 mg/m3) caused a fourfold higher level in the RD50 value than in naive rats, and repeated 29 preexposures to higher levels caused a 20-fold increase. 30 Exposure ofrabbits to sublethal concentrations ofchlorine causes changes in lung 31 function tests. Exposure for 30 min to 50 ppm (145 mg/m3) caused no effects on August 1994 

### 1-4 DRAFT

- DO NOT QUOTE OR CITE

### 1**inspiratory~xpiratory** 

### flow rate ratios (V1

### :Vs), butexposure to 100 and 200 ppm (295**an~** 

### 2 590 mg/m3) 

### caused increases 

### in V1

### :VE, which were related to pulmonary edema. 

### Initially, 3 there was a 

### decrease in Pl!lmonary compliance in all 

### exposed animals. However, by 

### 60 days 4 postexposure, animals in the two highest exposure groups showed a 

### significantincrease in 

### 5 compliance suggestive ofemphysema. This finding was 

### confirmed by histopathological 

### 6 exanrlnation. 7 

### In subchronic studies, exposure ofrats to chlorine at9ppm (26 mglm3), 

### 6 

### h/day, 8 5 

### days/week for 6 weeks, caused inflammation ofthe upper and lower respiratory tract, with 9 necrotic lesions appearing 

### in the nasal 

### turbinates. In addition, hyperplasia and hypertrophy 10 

### occurred in 

### the epithelia ofthe bronchi and alveoli. Less severe lesions were found after 11 repeated exposure to 1or 3ppm (2.9 or 8.7 mg/m3 ). 

### When rats were exposed to chlorine 12 (0.5, 1.5, and 5.0 ppm [1.4, 4.4, and 14.5 mg/m3]) 

### for up to 62 days, there was upper 13 respiratory tract irritation in all exposed groups. Histopathological evaluation ofthe 14 respiratory tract and other major organs did not show any significant exposure-related effects; 15 however, the mean trachea pathology scores ofthe rats exposed to 0.5 and 5.0 ppm chlorine 16 were significantly greater than those ofthe control group. There was also no chlorine-related 17 effect on the reproductive potential ofeither male orfemale**expo~** 

### animals. 18 In

### a 12-mo chronic study with monkeys exposed to 0.1, 0.5, and 2.3 ppm (0.3, 1.4, 19 and 6.7 mg/m3) 

### chlorine, 6 hi

### day, 

### 5 days/week, no effects on pulmonary physiology were 20 found. Ocular irritation was noted in both sexes at 2.3 ppm. The only exposure-related 21 histopathologic change was a mild focal epithelial hyperplasia in the respiratory epithelium of 22 the nose and trachea, which was associated with a loss ofcilia and goblet cells in 

### the group 23 exposed to 2.3 ppm chlorine. Similarbut less severe changes were reported in 

### the nasal 24 passage ofboth sexes in the 0.5-ppm group and in 

### females in 

### the 0.1-ppm**gr~up.** 

### 25 Respiratory and olfactory epithelial degeneration, 

### septal fenestration, inflammation, 26 epithelial hyperplasia and squamous metaplasia, gobletcell hyperplasia/hypertrophy, and 27 secretory metaplasia ofthe transitional epithelium ofthe lateral meatus were noted in male 28 rats and male and female mice 

### exposed to 0.4, 1.0, or2.5 ppm (1.2, 2.9, or7.2 mg/m3) 

### 29 chlorine gas, 5 

### hi

### day, 5 

### days/week for 2 years. Female rats were exposed to the 

### same 30 chlorine concentrations but on 3 alternate days 

### per week over the 2-year period. 31


### August 1994 

### 1-5 DRAFr

- DO NOT QUOTE OR CITE1 

### 1.3.2 Hydrogen Chloride 2 

### The LC50 

### values for hydrogen chloride in 

### rats were 4,701 

### ppm (7,051 

### mg/m3) 

### for a 3 30-min 

### exposure and 40,989 

### ppm (61,483 

### mg/m3) 

### for a 5-min 

### exposure. In mice, the

### LC**~** 4 

### values were 

### 2,644 ppm (3,966 

### mg/m3) 

### for a 30-min 

### exposure and 13,745

### ppm 5 (20,617 

### mg/m3 ) 

### for a 5-min 

### exposure. However, no mortalities werereported in mice and 6 

### rats exposed to hydrogen chloride atlevels of410 

### and 2,078 

### ppm (615 

### and 3,117 

### mg/m3), 

### 7 

### respectively for 30 min. 

### In a recent study, rats were exposed individually and**continuou~ly.** 

### 8 

### in a rotating cage to concentrations ofhydrogen chloride varying between 2,000 

### and 9 94,000 

### ppm (3,000 

### and 141,000 

### mg/m3) 

### and**time-to-incapacitation(~)** 

### and time-to-death (td) 10 

### were recorded. At 2,000**ppm,~** 

### was 185 min, 

### whereas at 94,000**ppm,~** 

### was 5.5 

### min and 11 

### td was 6.2 

### min. The exposure-response curves were hyperbolic. The LC50 

### value for a 12 30-min 

### exposure in 

### female guinea pigs was 2,519 

### ppm (3,778 

### mg/m3). 

### 13 

### When mice were exposed to sublethal concentrations ofhydrogen chloride for 10 

### min, 14 

### most histopathologic changes were found in the upper respiratory tract. There was erosion of 15 

### the epithelium ofthe external nares at 17 

### ppm (25 

### mg/m3 ), 

### and, as the concentration was 16 

### increased, there was erosion ofmucosa more distally and damage to underlying structures, 17 

### including bone

.. Olfactory epithelia were affected at 1,973 

### ppm (29,595 

### mg/m3), 

### and, at 18 7,279 

### ppm (10,918 

### mg/m3), 

### there was total destruction ofthe upper respiratory tract and 19 

### eyes. Hydrogen chloride is less irritating than chlorine; the RD50 

### in mice was 309 ppm 20 (460 

### mg/m3) 

### compared to 9.4 

### ppm (14.1 

### mg/m3) 

### for chlorine. 21 

### In guinea pigs, sensory irritation occurred after a 6-min exposure to 320 

### ppm 22 (480 

### mg/m3) 

### and after a 1-min 

### exposure to 680 

### ppm (1",020 

### mg/m3) 

### hydrogen chloride; 23 

### pulmonary irritation occurred after a 20-min 

### exposure at 320

### ppm and in 

### less than 4 min 

### at 24 1,380

### ppm (2,070 

### mg/m3). 

### Obstructive and restrictive lung changes that**per~isted** 

### for · 25 15 

### days were seen after 30-min 

### exposures to 1,040 (1,560 

### mg/m3) 

### or 1,380

### ppm, and there 26**w~** 

### histologic tissue damage in both the airways and alveolar regions. 27 

### Exposure ofa baboon to hydrogen chloride for 5 

### min at a level of 190

### ppm 28 (285 

### mg/m3) 

### caused no irritation. A 

### level of810 

### ppm (1,215 

### mg/m3) 

### caused irritation but 29 

### no postexposure symptoms, and a level of2,780 

### ppm (4,170 

### mg/m3) 

### caused a postexposure 30 

### cough. Levels of 16,570 

### to 17,280

### ppm (24,855 

### to 25,920 

### mg/m3) 

### caused respiratory

August 1994 1-6 DRAFT

- DO NOT QUOTE OR CITE

### 1 damage and death. An 

### exposure to 

### 10,000ppm (15,000 mg/m3) 

### for 15 min caused an 2 increased respiratory rate and long-term effects on lung**functi~n.** 

### 3 Limited information is available on repeated exposures ofanimals to hydrogen chloride. 4 Exposure ofguineapigs to 0.1 ppm (0.15 mg/m3) 

### hydrogen chloride, 2 hi 

### day for 28 clays, 

### 5 produced no.effects. Repeated exposure ofguineapigs to 10ppm (14.9 mg/m3) 

### hydrogen 6 chloride for 2 blday, 

### 5 days/week for 49 days caused no changes in lung function parameters 7 orhistological changes 

### in the lungs; and exposure to 67 ppm (100 mg/m3), 

### 6 h/day for 8 5 

### days, caused no histologic changes in the respiratory system. When rats were exposed to 9 hydrogen chloride concentrations of 10, 20, or50ppm (14.9, 29.8, or 74.5 mg/m3), 

### 10 6 hlday, 

### 5 days/week for 90 days, there was minimum to mild rhinitis that was 11 concentration- and time-related. Mice exposed under the same exposure regime developed 12 eosinophilic globules in 

### the epithelial lining ofthe nasal tissues. Rhinitis, epithelial or 13 squamous hyperplasia, and squamous metaplasia were reported in rats exposed to 10 ppm 14 hydrogen chloride for 6 h/day, 

### 5 days/week for life. There was also a high incidence of 15 these lesions reported in 

### control animals. However, an increased incidence ofhyperplasia of 16 the larynx 

### and trachea ofexposed animals over that ofthe controls was noted. 17 

### 18 19 

### 1.4 HUMAN HEALTH EFFECTS 20 

### 1.4.1 Chlorine 21 In

### humans, the odor threshold ofchlorine is very broad and ranges from about 0.02 to 22 1.3 ppm (0.06 to 3.83 mg/m3). 

### Irritation ofthe eyes, nose, and throat has beenreported to 23 occur at levels as low as 1ppm (2.9 mg/m3). 

### Exposure to 100 ppm (295 mg/m3) 

### for several 24 ininutes is intolerable and incapacitating, and exposure for a few minutes to 

### levels of40 to 25 60 ppm (118 to 177 mg/m3) 

### causes severebut reversible effects on the respiratory system. 26 Controlled exposure ofhuman volunteers to 1ppm chlorine for 8 h causes transient changes 27 in pulmonary function tests. There is a slight decrease in forced vital

### ·capacity (FVC), forced 28 expiratory volume in 1 s (FEV1), 

### and peak

### expiratory flow rate; most values returned to 29 normal.within a day. Mortalities in humans have occurred after gassing ofsoldiers with 30 chlorine, in 

### catastrophic spills from accidental releases at use facilities, and from accidental 31 occupational exposures. August 1994 1-7 DRAFf- 

### DO NOT QUOTE OR CITE1 Several case reports ofacute nonlethal exposures havebeen reviewed. The immediate 2 effects ofexposure areburning ofthe eyes 

### with lacrimation, burning ofthe nose and throat, 3 rhinorrhea, salivation, coughing and choking, dyspnea, and chest pain. Pulmonary edema 4 and bronchitis may follow depending on the severity ofexposure. Within 6 to 24 h of 

### 5 exposure, abnormalities inpulmonary function may be seen that arecaused by airway 6 obstruction. There 

### is a reduction in PVC and FBV1 .• There 

### is usually a reduction of 7 pulmonary compliance and increased airway resistance. 

### Within a few weeks·ofexposure, 8 there is usually animprovement 

### in pulmonary function, but, 

### in severe cases, patients have 9 been keptunder surveillance for at least 6 mo. 10 There arelimited epidemiologic data on chlorine. From eross-sectional surveys of 11 workers potentially exposed to chlorine, it does not appear that long-term exposure results in 12 any respiratory defects and diseases or in any effects on the standard mortality rate. 13 Exposure data are sparse and unreliable, and the available 

### reports are oflimited use. 14 Adequate human or animal studies to define mutagenic, teratogenic, or carcinogenic effects in 15 humans have not been conducted. Based on the U.S. Environmental Protection Agency's 16 Guidelines for Carcinogen Risk Assessment, chlorine is classified as a Group D substance, 17 which means that the available data are inadequate to assess the carcinogenic potential. 18 19 

### 1.4.2 Hydrogen Chloride 20 There are few data in the literature on the effects ofhydrogen chloride exposure to 21 humans. Inhalation ofhydrogen chlorideresults in irritation ofthe nose, throat, and larynx, 22 and exposure to high concentrations can cause edema, emphysema, and damage to lung 23 tissue. Levels of

### 5 ppm (7.5 mg/m3) areconsidered to cause no damage, but levels between 24 10 ppm (15 mg/m3) and 35 ppm (52 mg/m3 ) can cause irritation ofthe

### .throat, and levels of 25 50to 100ppm (75 to 150

### mg/m~) are considered barely tolerable. 26 Two studies indicate that continued exposure ofworkers to hydrogen chloride may 27 cause an increase in dental erosion. However, the lack ofdata on levels ofexposure and the 28 small numbers ofworkers examined limit the usefulness ofthese data. No data are available 29 on possible mutagenic, teratogenic, or carcinogenic effects ofhydrogen chloride in**~umans.** 30 

### Based on the U.S. Environmental Protection Agency's Guidelines for Carcinogen Risk 31 Assessment, hydrogen chloride is classified as a Group D substance.
August 1994 1-8 DRAFT

- DO NOT QUOTE OR CITE**~-** ·,



### 1 

## 1.5 RESEARCH NEEDS 2 The following data are needed: 3 

### 4 • 

### conduct longitudinal studies on exposed human populations with adequately 

### 5 documented levels ofchlorine, including measurements ofpulmonary function 

### 6 parameters; 7 8 • obtain 

### additional information on the long-term effects ofchlorine and hydrogen 

### 9 chloride on 

### the respiratory system; 10 

### 11 • 

### examine the development ofolfactory tolerance and tolerance to irritation ofchlorine 12 in 

### humans; and 13 14 • 

### perform adequate studies to defme mutagenic and 

### teratogenic effects ofchlorine and 15 hydrogen chloride. 16



### August 1994 1-9 DRAFT

- DO NOT QUOTE OR CITE

### 1 

# 2. PHYSICAL AND CHEMICAL 

# PROPERTIES,. 2 

# QUANTIFICATION, AND 

# ANALYSIS 3 4 

### 5 

### 2.1 PHYSICAL AND CHEMICALPROPERTIES 6 

### 2.1.1 Chlorine 7 At ambient temperatures, chlorine is a gas 

### with a pungent odor and a greenish yellow 8 color. Its molecular weight is 70.91, and the conversion factor at 20

# oc and 760 mm.Hg is 9 1.0ppm (volume weight to volume conversion factor [v/v]) 

# =2.9 mg/m3

.

### in air or 10 1.0 mg/m3 = 

### 0.344 ppm (v/v). The freezing pointis -100.98 °C, and theboiling point is 11 -34.6 °C. Its specific gravity at 0 

# oc is 1.468 and 1.567 at -34 °C. The solubility of 12 chlorine in water is 0.73 g/100 g (20 °C) (Verschueren, 1983; Environment Canada, 1984). 13 

### In pure water, chlorine forms elemental chlorine, the chloride ion, and hypochlorous acid. 14 As the pH increases, hypochlorous acid rapidly dissociates into the hypochlorite ion. The·

. 15 term "free chlorine" refers collectively to the concentration of**el~mental** 

### chlorine, 16 hypochlorous acid, and hypochlorite ion in water. The stabilitY ofchlorine in water is 17 directly related to the chlorine concentration, pH, temperature, exposure to light, and the 18 presence ofcatalysts or organic material (National Research Council, 1980). Table 2-1 lists 19 some ofthe major chlorine reactions lmown to occur in water. 20 21 

### 2.1.2 Hydrogen Chloride 22 Hydrogen chloride (anhydrous) is a clear, colorless gas thatproduces whitish fumes in 23 moist air and has a pungent odor. Its molecular weight is 36.46, and the conversion factor at 24 20

# oc and 760 mmHg is 1.0 ppm (v/v) or 1.49 mg/m3 

### in 

### air or 

### 1.0 mg/m3

## h-t air = 

### 25 0.67ppm (v/v). The freezing point is -114.8 °C, and the boiling point is -84.9 °C. 26 Hydrogen chloride is very hygroscopic. 

### Its vapor pressure is 25.5 atm at-0 °C and 41.6 atm 27 at20 °C. As an aqueous solution, concentrated hydrochloric acid is 37.1% hydrogen 28 chloride and has a specific gravity of 1.189 (15.3 °C)

..When hydrogen chloride gas absorbs 29 moisture, itis highly reactive with most metals, evolving hydrogen gas. It also reacts with 30 

### most organic materials (Verschueren, 1983; GEOMET Technologies, Inc., 1981).

August 1994 2-1 DRAFT-DO NOT QUOTE OR CITE- TABLE2-1. CHLORINEREACTIONS KNOWN TO OCCUR 

### IN AQUEOUS SOLUTION Reaction Type 

### Water

Hydrolysis Ionization Ammonia



### Substitution Oxidation Inorganic oxidation Disproportionation Decomposition Organic reactants Oxidation Addition Substitution

N-Cl bond C-CI bond

Source: Jolley and Carpenter (1983). 

### Examples

CI2 

## +**~O=HOCl** 

## + H+ 

## +

## cr HOCI

# =H+ 

## + OCr

NH3 

## + HOCI -+ NH2

### Cl 

## + H20 

### 2NHCI2 

## +**~0** 

### -+ N2 

## + HOCl 

## + 3H+ 

## + 3Cr Mn2

### + 

## + HOCI 

## + 2H2

### 0-+ MnO(OH)2 

## + 3H+ 

## + Cr 

### 30Cr-+ 

### 2Cr 

## + Cl03 2HOC1 -+ 2H+ 

### + 2Cr 

## + 02 

### RCHO 

## +HOCl -+ RCOOH 

## + H+ 

## + Cr RC=CR' 

## + HOCl-+ RC(OH)C(Cl)R' RNH2 

## + HOCl -+ RNHCl 

## + H2

### 0 RCOCH3 

## + 3HOC1 -+ RCOOH 

## + HCC13 

## + 2H2

### 0

1 

### 2.2 QUANTIFICATION AND ANALYSIS 2 

### 2.2.1 Chlorine 3 Although methods have been developed to analyze chlorine in air

### and in 

### water, they 4 lack specificity and measure total chloride ion rather than chlorine gas (World Health 5 Organization, 1982). 6 Methods based on a color change in 

### the dye o-tolidine have been used as early as 7 1913 and havebeen modified several times. Johnson and Overby (1969) developed a method 8 to improve specificity and sensitivity in which the o-tolidine reagent was stabilized with 9 bis(2-ethylhexyl) sulfosuccinate. Their method allowed the reaction to take_place at 10 

### pH 7 rather than in 

### acid media, thus miriimizing interference by chloramine, manganese, 11 

### iron, and nitrate

### ions and retarding the rapid fading ofthe colorproduced by reaction with 12 chlorine. Ablue color, resulting from oxidation ofthe dye to a semiquinone, was quantitated 13 colorimetrically. This method is not now widely used because o-tolidine has been found to 14 be carcinogenic. August 1994 2-2 

### DRAFT-DO NOT QUOTE OR CITE 

### -•

### 1 The American Public Health Association (1977) used a colorimetric method 

### in which air 

### 2 containing chlorine was passed into methyl orange, and the decrease in color caused by dye 3 oxidation was measured spectrophotometrically. The level ofdetection is 0.05 to 1.0 ppm · 4 (0.14 to 2.9 mg/m3) 

### using a 30-L sample ofair and a sampling rate of 1to 2 Umin when 

### 5 sampling is directly in methyl orange. However, the range ofthe method can.

### be extended by 6 trapping the air in sodium hydroxide and assaying an aliquot. Ozone, sulfur dioxide, and 7 nitrous oxides interfere. 8 

### Several analytical methods have been developed based on the oxidation ofpotassium 9 

### iodide to iodine in acidic solution. Wagenknecht et al. (1981) titrated the iodine with 10 thiosulfate. Nirmalchandar and Balasubiamanian (1984) reacted the iodine, which was . 11 formed with cationic dye Rhodamine 6G, and extracted the colored complex into benzene; the 12 sensitivity was between 0.1 and 0.3 ppm (0.29 and 0.87 mg/m3). 

### Apersonal monitor has 13 been developed by Hardy et al. (1979) in which the resulting bromine is reacted with 14 fluorescein to form eosin, which is determined spectrophotometrically. The sensitivity is 15 about 0.1 ppm. 16 Rigdon**~tal.** 

### (1978) used an Orion® residual chlorine electrode that develops a potential 17 based on the relative amounts ofiodine and iodide ion in 

### solution. The method was capable 18 ofdetermining water concentrations offree chlorine in the range of3 to 100 ppb (8.

### 7 to 19 29.0 p.g/m3). 

### 20 Cheplen et al. 

### (1984) developed a method capable ofdetermining low concentrations of 21 chlorine in air (0.1 ppm [0.29 mg/m3]) 

### in the presence ofammonia. Chloramine, which is 22 formed by reaction ofchlorine with ammonia, can interfere with the determination offree 23 chlorine. Air samples were collected into 100 mL ofchlorine-free water containing 15 mg 24 2,6-dimethylphenol (DMP) and three drops ofconcentrated sulfuric acid; 4-bromo-2,6-DMP 25 was added 

### as an internal standard in the gas collection impinger. The flow rate was 26 0.72 Umin, and collection was for 10 

### min. The resulting 4-Cl-2,6-DMP was extracted with 27 15 mL hexane, the organic phase was concentrated to about 1mL, and 1or 2 p.L was 28 injected into a gas chromatograph with a fused silica capillary column and a flame ionization 29 detector. A calibration curve was required because a linear response was not obtained at low 30 chlorine levels.

August 1994 2-3 DRAFT-DO NOT QUOTE OR CITE1 Langhorst and rues (1986) have described a functional, commercially available 2 continuous chlorine analyzer that uses an ion-specific electrode and a microprocessor data3 logging system. Chlorine 

### in air diffuses to a platinum electrode where it is reduced to 4 chloride; silver is oxidized atthe reference electrode, and a currentis produced. The 5 referenceelectrodeis

### in an electrolyte solution and 

### separated from the platinum electrodeby 

### 6 a porous glass frit. The sensor has a range of0.05 to 10.0

### ppm (0.15 to 29.0 mg/m3) (v/v) 7 chlorine and a precision of

## ±12%. Recovery timeis 1 to 4 min. The instrument can 8 measurepeakvalues as well as time-weighed average values (fWAs). Ithas the same 9 sensitivity as the sulfamic acid bubbler method. The latter method, however, is less 10 convenient than a 3Mdosimeterbadgebut 

### has the advantage ofcollecting continuous data 11 whereas thebadge can only measure a TWA value. A computer package is described for 12 manipulating the data selected and formatting the results. 13 Lane and Thomson (1981) have described a mobile mass spectrometer system (TAGA 8 ) 14 that has been used for continuous and instantaneous measurement ofchlorine levels in air. 15 Air is collected at a flow rate of 1L/s, and molecules are ionized by ion-molecule reactions 16 in a corona discharge. They are**~en** introduced into a quadripole mass spectrometer. 17 Chlorine produces chlorine gas and the chloride ion, which are stable in air; however, the 18 chlorine gas can befragmented to the chloride ion 

### in the mass spectrometer and selectively 19 monitored at a mass-to-charge ratio (m/z) of35. Chloride ions may also be formed from 20 chlorinated hydrocarbons; therefore, chloride ions are occasionally monitored because they 21 are more specific indicators ofchlorine gas. The deteCtion limit is about 30ppt (0.1 p.g/m3). 22 A sensitive and specific method for capturing and analyzing for chlorine 

### was reported 23 by Gaind et al. (1992). Chlorineis collected by aspiration through an aqueous impinger 24 solution of2-naphthol, and converted to 1-chloro-2-naphthol. The 1-chloro-7-naphthol is 25 quantified chromatographically using a variety ofdetection systems. The sampling and 26 analytical method has been tested in chlorine-generated atmospheres of 1.35 p.g/L, and the 27 yield ofthe reaction product under the test conditions 

### was reported to·be 75%. 28 29 

### 2.2.2 Hydrogen Chloride 30 Most ofthe methods used for monitoring hydrogen chloride have limitations. Methods 31 involving absorption in an alkali and titration orcolorimetric change ofa pH-indicator dye

August 1994 2-4 DRAFf-DO NOT QUOTE OR CITE

### 1 are nonspecific when measuring ambient air 

### or emission sources. It

### has been found that 2 considerable error can 

### beintroduced in sampling ofair

### for hydrogen chloride because the 3 

### acid in the collecting tube may interact with glass wool orthe filtering medium (Cheney and 4 Fortune, 1984). 

### 5 Drabke et al. (1982) developed a method for continuous monitoring ofairborne 6 

### hydrogen chloride (gas oraerosol) using a chloride-sensitiveflow electrode and a 7 copper-sensitive reference electrode. The absorption solution contained 10-3 

### M copper 8 

### nitrate. This method measures total chlorideion and not specifically hydrogen chloride. 9 

### mavay and Guilbault (1978) developed apiezoelectric quartz crystal detector with a 10 coating oftrimethylamine-hydrogen chloride ortriphenylamine. Moisture was removed from 11 the sampled air

### through a column ofsilica gel. Hydrogen chloride could easily bequantified 12 in the range of 1to 100 ppm (1.4 

### to 140 mg/m3) 

### with 

### aresponse time ofless than a minute. 13 The lower detection limit was stated to be at the parts-per-billion level. 14 The National Aeronautics and Space Administration has evaluated methodologies for 15 quantitating hydrogen chloride gas and aerosol in exhaust gases from space launching 16 (Gregory and Moyer, 1977). Two methods were developed and proven \.!Seful, one to 17 

### measure total hydrogen. chloride and the other to measure gaseous hydrogen chloride 18 (Sebacher et al., 1980). An inlet tube (on the nose of

### a monitoring aircraft) contained 19 sodium bromate-sodium bromide-coated alumina. When air

### containing hydrogen chloride 20 (gas or aerosol) passed through the inlet, bromine was generated and reacted with alkaline 21 

### luminol; the resulting chemiluminescence was measured (Gregory and Moyer, 1977). 

### Ozone, 22 nitrous oxide, sulfur dioxide, and chlorine will interfere with 

### the method. The instrument is 23 

### useful when interferant concentrations in the sourcebeing monitored are low (10%). 

### Gaseous 24 hydrogen chloride was monitored with an instrument that measured the**abso~tion** 

### ofinfrared 25 radiation at a narrow spectral**inte~al** 

### where the 

### spectral lines ofhydrogen chloride absorb. 26 

### Because ofthe narrow filtering, this method is quite specific. At the high flow rates used, 27 

### 0.2 ppm (0.3 

### mg/m3) 

### hydrogen chloride gas could be measured (Sebacher et al., 1980). 

### 28 A diffusion scrubber-ion chromagraphic instrument was evaluated for measurement of 29 atmospheric hydrogen chloride by Lindgren (1992). The detection limit for this method is

August 1994 2-5 DRAFf-DO NOT QUOTE OR 

### CITE

### 1 estimated to be 

### 5 ppt (0.008 p.g/m3), 

### but the design ofthe diffusion scrubber used lacks a 2 

### theoretical model for accurate prediction ofthe collection efficiency. Also, a decrease in 

### 3 collection efficiency is noted with increasing relative 

### humidity. 4



### August 1994 2-6 DRAFT-DO NOT QUOTE

## OR CITE1 

### REFERENCES 2 American Public Health Association. (1977) Tentative methods for analysis for five dichlorine content ofthe 3 atmosphere (methyl orange method). In: Katz, M., ed. ;Methods ofair sampling and analysis, 2nded. 4 Washington, DC: American Public Health Association; p. 381. 

### 5 6 Cheney, J. L.; Fortune, C. R. (1984) Improvementsin themethodology for measuring hydrochloric acid in 

### 7 combustion source emissions. J. Environ. Sci. HealthPartA 19: 337-350. 8 

### 9 Cheplen, J. M.; Barrow, C.; White, E. L. (1984) Determinationofairborne free chlorinein thepresence of 10 ammonia by capillary column gas chromatography. Anal. Chem. 56: 1194-1196. 0 11 

### 12 Drabke, P.; Kirsch, H.; Wolf, J. (1982) EineMethodezurkontinuierlichen Bestimm.ung von 13 HCl-Konzentrationen in der LuftmitHilfeeinerchloridsensitivenDurchflusselektrode [Amethod of 

### 14 continuous determination ofHClconcentrationsin the airwith theaid ofa chloride--sensitive flow 

### 15 electrode]. Z. GesamteHyg. 1hreGtenzgeb. 28: 241-243. 

### 16 17 Environment Canada. (1984) Chlorine: environmental and technical information for problem spills. Ottawa, ON, 18 Canada: Environmental Protection Service, Technical Services Branch. (EnviroTIPS manual). 

### 19 20 Gaind, V. S.; Wu, W. S.; Chai, F. (1992) Chromatographic determination oflowlevels ofchlorine in air. 

### 21 J. High Resolut. Chromatogr. 15: 840-842. 

### 22 23 GeOMETTechnologies, Inc. (1981) Hydrogen chloride: report 4, occupational hazard assessment. Cincinnati, 

### 24 OH: U.S. Department ofHealth and Human Services, National Institute for Occupational Safety and 

### 25 Health; NIOSH contract no. 210-79-0001. Available from: NTIS, Springfield, VA; PB83-105296. • 

### 26 27 Gregory, G. L.; Moyer, R. H. (1977) Evaluation ofa hydrogen chloridedetector for environmental monitoring. 

### 28 Rev. Sci. Instrum. 48: 1464-1468. 0 

### 29 30 Hardy, J. K.; Dasgupta, P. K.; Reismer, K. D.; West, P. W. (1979) A personal chlorine monitor utilizing 

### 31 permeation sampling. Environ. Sci. Techno!. 13: 1090-1093. 

### 32 33 mavay, J.; Guilbault, G. G. (1978) Detection ofhydrogen chloride gas in ambient airwith a coated piezoelectric 

### 34 quartz crystal. Anal. Chem. 50: 965-967. 

### 35 36 Johnson, J. D.; Overby, R. (1969) Stabilized neutral orthotolidine, SNORT, colorimetric method for chlorine. 

### 37 Anal. Chem. 41: 1744-1750. 

### 38 39 Jolley, R. L.; Carpenter, J. H. (1983) A review ofthechemistry and environmental fate ofreactive oxidant 40 species in chlorinated water. In: Jolley, R. L.; Bnmgs, W. A.; Cotruvo, J. A.; Cumming, R. B.; 41 Mattice, J. S.; Jacobs, V. A., eds. Water chlorination: environmental impact andhealtheffects, 42 volume 4, book 1, chemistry andwatertreatment, proceedings ofthe fourth conference; October 1981; 43 Pacific Grove, CA. Ann Arbor, MI: Ann Arbor SciencePublishers, Inc.; pp. 3-47. 44 45 Lane, D. A.; Thomson, B. A. (1981) Monitoring a chlorine spill from a train derailment. J. Air Pollut. Control 46 Assoc. 31: 122-127. 

### 47 48 Langhorst, M. L.; Illes, S. P., Jr. (1986) A portable data-logging system for industrial hygiene personal chlorine 49 monitoring. Am. Ind. Hyg. Assoc. J. 47: 78-86. 50 51 Lindgren, P. F. (1992) Diffusion scrubber-ion chromatography for the measurement oftrace levels of 52 atmospheric HCI. Atmos. Environ. Part A 26: 43-49. 53 August 1994 2-7 DRAFT-DO NOT QUOTE OR CITE1 National Rese8rch Council. (1980) Thedisinfection ofdrinking water. In: Drinking water and health: volume 2. 2 Washington, DC: National Academy Press; pp. 5-42. 3 4 Nirmalchandar, V.; Balasubramanian, N. (1984) Spectrophotometric determination ofchlorineafter fixing in 

### 5 alkali. 

## z. GesamteHyg.·IhreGrenzgeb. 30: 468-470. 

### 6 7 Rigdon, L. P.; Moody, G. J.; Frazer, J. W. (1978) Determination ofresidual chlorine inwater with computer 8 automation and a**residual~hlorine** electrode. Anal. Chem. SO: 465-468. 9 10 Sebacher, D. I.;

### Bendura, R. J.; Womom, D. E. (1980) Hydrochloric acid aerosol and gaseoushydrogen 11 chloridepartitioning ina cloudcontaminated by solidrocketexhaust. Atmos. Environ. 14: 543-547. 12 

### 13 Verschueren, K. (1983) Handbook ofenvironmental data on organic chemicals. 2nded. NewYorkNY: Van 14 NostrandReinhold; p. 44. 15 16 Wagenknecht, J. H.; Jansson, R. E. W.; Stover, F. S. (1981) Analysis ofmixtures ofchlorineandchlorine 17 dioxide. Anal. Lett. 14: 197-204. · 18 19 World Health Organization. (1982) Chlorine and hydrogen chloride. Geneva, Switzerland: World Health 20 Organization. (Environmental health criteria 21). 21

August 1994 2-8 DRAFT-DO NOT QUOTE OR CITE1 

## 3. PRODUCTION, USE, ENVIRONMENTAL 2 

## SOURCES, AND ENVIRONMENTAL 3 

## LEVELS AND EXPOSURE 4 

### 5 6 

### 3.1 PRODUCTION AND USE 7 

### 3.1.1 Chlorine 8 As ofJanuary 1, 1992, there were 25 manufacturers in the United States producing 9 

### chlorine at 48 plant sites, with an estimated total 

### domestic_production capacity of24.5 billion 10 pounds (SRI International, 1992). Chlorine production in 1992 was 23.51 billion pounds. 11 In 1993, an estimated 24.06 billion pounds ofchlorine was produced in 

### the United States 12 (Reisch, 1994). 13 In 1992, over 64% ofthe domestic chlorineproduction capacity was based on the 14 electrolytic decomposition ofbrines, usually in diaphragm cells. Chlorine is also produced 15 by oxidation or electrolysis ofhydrogen chloride, as aby-product ofpotassium nitrate and 16 magnesium metal production, and as a coproductofpotassium hydroxide production (SRI 17 International, 1992). The manufacture ofchlorine, therefore, is closely associated with the 18 production ofcaustic soda or alkali. 

### This chlor-alkali industry provides an essential feedstock 19 for anumber ofkey manufacturing activities in the industrial world, including plastics, pulp 20 and paper, rayon and cellophane, soaps and detergents, and glass. 21 Chlorine is used mainly as an intermediate in 

### the production oforganic chemicals. It

### is 22 used also in bleaching pulp and paper products; as an intermediate in 

### the production of 23 inorganic chemicals; in the treatment ofpotable, process, and wastewater streams by 24 municipalities and industry; and in the manufacture ofcleaning and sanitationproducts 25 (e.g., liquid household bleaches, swimming pool chemicals, industrial sanitizing agents) (SRI 26 International, 1984). Domestic consumption ofchlorineby end-use application is as follows: 27 production ofethylene dichloride, most ofwhich is used to produce the vinyl chloride 28 monomer; production oforganic chemicals other than chloroethanes; chloroethanes and 29 chloromethanes; pulp and paper; inorganic chemicals; water treatment; and miscellaneous 30 uses (Anonymous, 1986). 31 August 1994 3-1 DRAFT-DO NOT QUOTE OR CITE.l" \



### 1 

### 3.1.2 Hydrogen Chloride 2 Domestic production ofhydrogen chloride in 

### 1992 totaled 7.13 billion pounds. 3 In 1993, an 

### estimated 6.45 billion pounds ofhydrogen chloride was produced in 

### the United 4 States (Reisch, 1994). 

### 5 About92% ofthe domestically produced hydrogen chloride is generated as a by-product 6 in

### the manufacture ofother chemicals (e.g., vinyl chloride, benzyl chloride, phosphate esters, 7 

### ethylene dichloride, isocyanates, and fluorocarbons) and the chlorination oforganic 8 

### compounds (SRI 

### International, 1992). Hence, the supply depends largely on demand for the 9 primary products rather than on demand for hydrogen chloride. Hydrogen chloride can 

### also 10 be synthesized directly by oxidation ofhydrogen with chlorine and the reaction ofmineral 11 

### acid 

### with alkali chlorides (SRI 

### International, 1984). 12 

### Most hydrogen chloride is sold as aqueous solutions commonly lmown as muriatic acid. 13 

### Technical and food processing grades contain 28 

### to 35% 

### hydrogen chloride; the anhydrous 14 

### grade is 99.8% 

### pure (SRI 

### International, 1982). 

### 15 The largest consumption ofhydrogen chloride is by the organic chemicals industry in 16 

### the production ofethylene**dichlo~de** 

### and numerous other organic chemicals. Other end-use 17 applications include use in the manufacture ofinorganic chemicals," oil well acidizing, steel 18 pickling, processing offood products, mineral and metal processing, and miscellaneous uses 19 (SRI 

### International, 1982). 20 21 22 

### 3.2 ENVIRONMENTAL SOURCES 23 

### 3.2.1 Chlorine 24 

### 3.2.1.1 Manufacturing and Transport 

### 25 There is a potential for the release ofchlorine in its manufacture, but the amount is not 26 

### significant when compared to otherpotential sources. This may occur during process 27 sampling and in 

### maintenance ofelectrolytic cells. Most**rel~es,** 

### however, would be 28 

### expected from leaks in compressor seals or from faulty valves, or in the loading or unloading 29 oftank 

### cars (Environment Canada, 1984; World Health Organization, 1982). The**bul~** 

### of 30 chlorine is transported by rail. 

### Its shipping containers are constructed ofsteel to Department 31 

### ofTransportation (DOT) specifications and are equipped with safety devices and 

### specially August 1994 

### 3-2 DRAFT-DO NOT QUOTE OR CITE1 designed valves (Simmons etal., 1974). Likewise, cylinders to betransported are approved 2 for safety by the DOT. 3 The Chlorine Institute haspublished several documents on chlorine manufacturing, safe 4 handling, packaging and transport, and emergency measures. In addition, the Chemical 5 Manufacturers Association's CMA-CHEM-TREK operation maintains a 24-h answering 6 service for help 

### and advice in regard to transportation emergencies. 7 

### 8 3.2.1.2 Natural Sources and Photochemical Processes 9 Volcanic origins ofgaseous chlorine in the atmospherehave been postulated. However, 10 Duce (1969) indicated that this is unlikely, and Johnston (1980) has reported that the cooling 11 ofvolcanic ash releases hydrogen chloride, not chlorine. Ithas been hypothesized that 12 photolysis ofsea salt particles in clouds over the 

### ocean can produce chlorine (Duce, 1969), 13 but the primary mechanisms involved in this conversion have not been conclusively 14 demonstrated (Keene et

### al., 1990). Methods used in the past to monitor chlorine in rain or 15 ambient air detected total chloride ion and were not specific for the gas (see Chapter 2). 16 There are photochemical reactions that produce the chloride ion in the stratosphere (e.g., 17 photolysis ofnitrosyl chloride), but there is no evidence that these reactions would produce 18 chlorine gas (Prather etal., 1984). 19 20 

### 3.2.1.3 Anthropogenic Processes 21 The use ofgaseous chlorine in treatment ofdrinking water, disinfection ofswimming 22 pools, and treatment ofwastewater can result in fugitive emissions. However, the use 

### in 23 swimming pools has been replaced largely by the use ofsolid materials that generate active 24 chlorine or hypochlorite. In.general, the use ofchlorine in the treatment of<!rinkffig water is 25 more discrete 

### than in the past. Proportionately less chlorine is used in the treatment ofwater 26 (World Health Organization, 1982), but the total tonnage used worldwide probably is 27 increasing. Potential releases also occur in pulp and paper mills, where chlorine is used as a 28 bleaching agent. Theuse ofchlorine as a biocide in a recirculating cooling water system ofa 29 power plant can potentially result in release to the atmosphere in the cooling tower orrelease 30 into seawater; a typical system uses about 50 tons ofchlorine per year (Holzwarth et

### al., 31 1984).

August 

### 1994 3-3 DRAFT-DO NOT QUOTE OR CITE

### 1 

### 3.2.2 Hydrogen Chloride 2 3.2.2.1 Manufacturing and Transport 

### 3 Much ofthe hydrogen chlorideproduced as 

### aby-product ofchlorination reactions is 4 

### used captively or recycled in 

### a closed system with 

### efficientcontainment so the amount 5 

### released into the environment is not significant. However,**poten~al** 

### releases can occur from 6 

### leaking valves, pumps, or compressor seals. Anhydrous hydrogen chloride is transported in 

### 7 safety-designed cylinders (World Health Organization, 1982), and vent gases from storage 

### 8 tanks containing hydrogen chloride are normally scrubbed with alkaline aqueous solutions. 9 

### Concentrated aqueous hydrochloric acid (37.7%) has 

### a substantial vapor pressure and 

### can 10 evolve hydrogen chloride vapor, but aqueous solutions containing less than 20%**hydr~gen** 

### 11 

### chloride, 

### can be used in 

### open vessels without appreciable release ofvapor (GEO:MET 12 

### Technologies, Inc., 1981). 13 

### 14 3.2.2.2 Natural Sources and Photochemical Processes 15 

### Magma from volcanoes can 

### give rise to hydrogen chloride (Johnston, 1980). It

### was 16 

### estimated that degassing ofash from the St. Augustine volcano in 

### Alaska emitted 82 to 17 175 

### x 106 

### kg hydrogen chloride into the stratosphere. Photoehemically, chlorine 

### can form 18 the chloride ion, which reacts with methane to form hydrogen chloride (Sebacher et al., 19 1980). 

### Less than 1

### ppb (0.14 

### mg/m3) 

### hydrogen chloride was reported offthe east coast of 20 the United States during the summer of 1988. The concentration ofhydrogen chloride 21 decreased with increasing altitude and distance from the coastline (Keene et al., 1990). 22 

### Slightly higher concentrations ofhydrogen chloride have been reported in cities in southern 23 

### California. Eldering etal. (1991) reported hydrogen chloride concentrations for 24-h 24 

### averaging periods ranging from 0.39 

### to 1.25 

### ppb (0.57 

### to 1.84 p.g/m3) in

### nin~ 

### cities 25 

### monitored during 1986. The highest hydrogen chloride levels were noted in the coastal 26 cities. Decreased levels ofhydrogen chloride were noted further inland. 

### 27 28 3.2.2.3 Anthropogenic Processes 

### 29 The burning offossil.fuel (World Health Organization, 1982) 

### and the incineration of 30 

### municipal waste containing polyvinyl chloride plastics (Chan, 1984) 

### are the two major 31 

### sources ofhydrogen chloride in the 

### atmosphere. Based 

### on projected compositional change,
August 1994 3-4 

### DRAFT-DO NOT QUOTE OR CITE

### 1 plastics will 

### make up 13% 

### ofrefuse in the year 2000, compared to 2% 

### in 1970. 

### Although 2 emission controls such as electrostatic precipitators and water spraying ofexhaust gases 3 should trap most hydrogen chloride emission in an incineratorexhaust, there are still 4 substantial emissions. Allen et al. (1986) 

### analyzed stackemissions from incineration of 

### 5 hospital waste and found a hydrogen chloride air

### emissions factor of3.3 to 5.3 g/kg. 6 Hospital waste, for which no emissions controls are required, is expected to**co~tain** 

### about 7 

### four times moreplastic material than 

### municipal waste. Rollins and Homolya (1979) 

### 8 monitored the mass emission rate for two state-of-the-artincinerators ofmunicipal waste and 9 

### found 2.11 

### and 1.98 

### g hydrogen chlorideperkilogram ofrefuse incinerated, respectively. 10 

### These researchers estimated that ambient air

### levels could be as high as 30.6 

### and 22.7

### ppb 11 (42.8 

### and 31.8 

### p.g/m3) 

### at a distance of800 

### mfrom each ofthe sources studied. The 12 

### reliability ofhydrogen chloride emission estimates from the incineration ofwaste was 13 

### questioned by Johnson et al. (1992). 

### According to 

### these authors, hydrogen chloride 14**~missions** 

### from waste incineration is dependent on the nature ofthe waste, the presence of 15 

### hydrogen in

### the gas stream, and the composition ofthe surfaces in the furnace, making any 16 

### estimate ofhydrogen chloride emission unreliable. Hydrogen chloride generated from 17 

### polyvinyl chloride is also apotential toxicity problem for fire fighters (Dyer and Esch, 1976). 18 

### The main fossil fuel emitter ofhydrogen chloride is coal, and the amount ofhydrogen 19 

### chloride generated from the burning ofcoal depends on the chloride content ofthe coal. 20 

### According to Kamrin 

### (1992), 

### an estimated 1,700 

### tons ofhydrogen chloride are emitted per 21 

### year from a coal-frred powerplantburning 2 million tons/year ofbituminous coal with 

### a 22 

### chloride content of0.095%. 23 

### Exhaustproducts emitted from a space shuttle vehicle contain hydrogen chloride. Potter 24 (1978) 

### estimated that the amount emitted in the surfaceboundary area, the ti''?JX>sphere, and 25 

### the stratosphere were 24,700, 78,500, 

### and 59,700 

### kg, respectively, and the amountin the 26 

### stabilized ground cloud was 35,200

### kg. 27 

### Aqueous waste streams are a source ofhydrogen chloride released to surface waters. 28 

### Sources are over-acidified swimming pool water and waste from treatment ofmetals in steel 29 

### production·and electroplating industries (World Health·Organization, 1982). 30 31


### August 1994 3-5 DRAFT-DO NOT QUOTE OR CITE

### 1 

### 3.3 ENVIRONMENTAL LEVELS AND EXPOSURE 2 

### 3.3.1 Chlorine 3 Thereis little information in the available literature regarding ambient air concentrations 4 ofchlorine orhydrogen chloride. According to the World Health Organization (1982), the 5 presence ofmeasurable quantities ofchlorine orhydrogen chloride in ambient air

### has not 6 been demonstrated. 

### Air monitoring studies genera.lly provide 

### data only on total chloride 7 concentrations and do not differentiatebetween chlorine, hydrogen chloride, orother sources 8 ofchloride ions. The National Academy ofSciences reported that mean ambient air

### levels of 9 chloride range from 0.344 ppm (1 mg/m3) 

### to 1.27 ppm (3.7 mg/m3) 

### (National Research 10 Council, 1976). However, Applied Science Associates, 

### Inc. (1978) reported atmospheric 11 levels of0.001 ppm (2.9 p.g/m3) 

### in coastal

## areas and 0.02 ppm (58 p.g/m3) 

### in ambient air 

### 12 samples from metropolitan areas (e.g., Cincinnati and Baltimore). 13 Lane and Thomson (1981) monitored a chlorine plume that resulted from a 

### train 14 derailment at Mississauga, Ontario, in 1979. The accident was followed by an explosion and 15 fire, and it appears that about 70 ofthe 90 tons ofchlorine in a rail 

### tanker leaked out during 16 the most intense period ofthe fire. 

### A mobile mass spectrometer system using atmospheric17 pressure chemical ionization was used to analyze ground-level concentrations ofchlorine. 18 The monitoring began several hours after the accident and continued for 6 

### days until the 19 remaining chlorine had been pumped from the tanker and transported away. For the first 20 3 days, under light wind conditions (1 to 4 km/h), the maximum ground-level concentrations 21 were in the range of3.4 to 34.0 ppb (10 to 100 p.g/m3) 

### at a distance 0.5 to 1.0 km 

### from the 22 source, with briefexcursions ofup to 137 ppb (400 p.g/m3 ). 

### During the fourth day, the 23 tanker was patched, and levels decreased below the detection limit (0.29 ppb [0.1 p.g/m3]). 

### 24 Chlorine was confined to a narrow plume at ground level; it was about 1 km 

### .wide and 5 km 

### 25 from the source when measurements were made on the third day. There was no vertical 26 concentration gradient when measurements were made between ground**lev~l** 

### (0.15 m) 

### and a 27 height ofabout 4.5 m (the plume concentration was 0.1 ppm [35 

### JLg/m3]). 

### No trapped 

### 28 chlorine gas was found in low-lying 

### areas. 29 Gudiksen et al. 

### (1986) 

### used computer models to 

### estimate the surface air 

### concentrations 30 ofchlorine that would result from the release of9,500 gal ofliquid chlorine from a spill 31 covering 30m2

. 

### The nominal evaporation rate ofthis size spill was 7.2 kg/s. The steadyAugust 

### 1994 3-6 DRAFf-DO 

### NOT QUOTE 

### OR CITE**~-**



### 1 state concentration under nocturnal conditions was estimated to 

### vary from about 10,000 ppm 2 (29,000 mg/m3) 

### near the source to 60 

### ppm (174 mg/m3) 

### at a distance of5,000 munder 3 

### nighttime conditions. Under daytime conditions, the corresponding values would be 4 3,000 and 10 ppm (8,700 and 29 mg/m3). 

### These concentrations would persist for 2 to 

### 3 h. 5 It

### was reported that release of80 gal 

### over a 12-minperiod would result in

### leyels exceeding 

### 6 25 ppm (72.5 mg/m3) 

### at a distance of 115 m in

### the daytime. Similarly, release of 150 gal in 

### 7 a 1 0-min 

### period would result in 

### levels exceeding 

### 25 ppm at a distance of700 mduring the 

### 8 nighttime. 

### 9 Environment Canada (1984) constructed nomograms to predictthe rate ofrelease of 10 chlorine from an 80,000-L railroad tank 

### car with punctures on the top oron the bottom. 11 With a puncture of 100 mm in 

### diameter on the bottom, the rate ofdischarge was estimated to 12 be about 200 kg/s, and about 50% ofthe chlorine in 

### the tanker would be released in 3 

### min. 13 With a rupture .ofthe same size on the top, the rate ofrelease was estimated to be about 14 40 kg/s, and 50% was expected to be released in 

### 70 

### min. Liquid chlorine on the bottom of 15 the tank 

### car is released more rapidly than**g~eous** 

### chlorine**~at** 

### is at the top. 16 All 

### oftllese estimates have been prepared to aid the protection offire fighters and to 17 assist emergency-response planners. Although the accuracy ofthe estimates depends on 18 climatic and meteorologic conditions, the estimates indicate that releases oflarge amounts of 19 chlorine in accident scenarios result in 

### high airborne concentrations in the vicinity ofa spill 20 and rapid dilution ofthe chlorine in 

### the atmosphere so that dangerous levels do notpersist 21 except for a few hours. 22 The use ofchlorine in potable, process, and wastewater treatment has led to release of 23 the compound to surface waters and detection ofchlorine in 

### drinking water supplies. For 24 example, Moore et al. 

### (1979) reported a mean residual chlorine level of 1.3**~g/L** 

### (range 25 0.3 to 4.0 mg/L) in 

### the finished water of 19 Massachusetts communities served by water 26 treatment facilities using an average chlorine application of 15.2 mg/L (range 4.3 to 27 29.7 mg/L). The mean total residual chlorine level was 1.5 mg/L (range 0.4 to 6.0 mg/L). 28 Of80 domestic groundwater and surface water supplies tested in 

### the National Organics 29**Reconnai~sance** 

### Survey, 41% had free residual chlorine concentrations ranging from 0 

### to 30 0.4 mg/L; 19% had concentrations of0.4 to 0.8 mg/L; 4% had concentrations of0.8 to 31 1.2 mg/L; and 20% had concentrations of 1.2 to 1.6 mg/L (Symons et al., 1975). Chlorine

August 1994 3-7**DRAFf~DO** 

### NOT QUOTE 

### OR CITE1 

### was also detected in the finished drinking water supplies ofCincinnati (2.7 mg/L), Miami 2 (2.3 mg/L), Ottumwa (1.4 

### mg/L), and Philadelphia (2 mg!L)_. 

### 3 Chlorine is used by the food processing industry 

### as a general disinfectant and as a 4 

### bleaching agent for wheat flour. Chlorine-bleached cake flour was found to contain 131 

### to 

### 5 189 

### mg chlorideper 100 

### g flour as compared to 43 

### to 54 

### mg chloride for unbleached flour 6 

### (Sollars, 1961). 

### 7 Information on the exposure ofthe general public to ambient levels ofchlorine was not 8 found in the published literature. However, the National Institute for Occupational Safety 9 and Health (NIOSH) conducted a workplace survey, the National Occupational Exposure 10 

### Survey (NOES), from 1980

### to 1983 

### (National Institute for Occupational Safety and Health, 11 1984). 

### Preliminary data 

### from this survey indicate that 147,116 

### workers, including 12 11,095 

### women, were potentially exposed to chlorine in the workplace in 1980. 

### The NOES 13 estimates were based only on observations ofthe actual use ofchlorine. 14 

### The National Institute for Occupational Safety and Health (1976) 

### reviewed the available 15 

### literature concerning chlorine concentrations in 

### workplace air 

### and reported that workers are 16 generally exposed to less than 

### 1ppm (2.9 

### mg/m3) 

### chlorine during manufacturing operations 17 

### and trace amounts to 64 ppm (185.6 mg/m3) 

### during use ofthe compound in

### bleaching 18 

### operations in the pulp and paper industry. The value of64 ppm was probably the maximum 19 value found in apulp and paper factory by Ferris et al. (1967). The average value was 20 7.4

### ppm (21.5 mg/m3); 

### when analyses were performed 4 and 5 years later, the levels in the 21 

### same plant were 

### 0.5 to 1.0 ppb (1.45 to 2.9 p,g/m3). 

### Pendergrass (1964) monitored air levels 22 

### in a plant producing chlorine for a period of5

### mo and reported that levels of 

### <0.1 

### ppm 23 (0.29 

### mg/m3) 

### were found in over 91% 

### of2,785 samples and fewer than 1.2% 

### ofthe samples 24 

### exceeded 1ppm.. Patil et al. (1970) 

### report that, for 332 diaphragm cell**wor~rs** 

### in 

### a 25 chlorine-producing plant, the time-weighted average exposure mean for chlorine was 26 

### 0.15 

## ± 0.29 

### ppm (0.44 

## + 0.84 

### mg/m3 ) 

### and the range ofexposure was from 0.006 

### to 27 1.42 ppm (0.02 to 4.1 mg/m3). 

### However, the value of0.006

### ppm that was reported is 28 doubtful because it is below the analytical capability ofthe method used. Chan-Yeung et al. 29 (1980) 

### found that 

### mean**~xposure** 

### to chlorine for workers in 

### a paper mill 

### was 0.05 

### ppm 30 

### (range 0.05 to 0.1 ppm [0.15 to 0.29 mg/m3]). 

### Enarson et al. (1984) 

### analyzed 25 personal

August 1994 3-8 DRAFT-DO NOT QUOTE OR CITE

### 1 samples in 

### the bleach area ofa paperpulp plant and found a mean exposure of0.18 ppm 2 

### (0.52 mg/m3) 

### and a maximum exposure of 1.61 ppm 

### (4.7 mg/m3) 

### chlorine. 3 

### 4 

### 3.3.2 Hydrogen Chloride 5 

### There are no data 

### available relating air

### concentrations ofhydrogen chloride to a 6 

### particular source. Several studies, however, have reported 

### as much 

### as 2.11 

### and 5.3 g 7 

### hydrogen chloride emitted per kilogram ofmunicipal and hospital refuse incinerated, 8 

### respectively (see Section 3.2.2.3). 

### Also, it has been estimated that 1,700 

### tons ofhydrogen 9 

### chloride are emitted per year from one coal-fired powerplantburning 2 

### million tons/year of 10 bitutninous coal with a chloride content of0.095% (Kamrin, 

### 1992). 11 In 1980, 540,518 workers, including 114,796 women, were potentially exposed to 12 hydrogen chloride in 

### the workplace (National Institute for Occupational Safety and Health, 13 1984). 

### These NOES 

### estimates consisted only ofobservations ofthe.actual use ofhydrogen 14 chloride. 15 16 17



### August 1994 3-9 DRAFT-DO NOT QUOTE OR CITE1 

### REFERENCES 2 Allen, R. J.; Brenniman, G. R.; Darling, C. (1986) Airpollution emissions from the incineration of**h~ital** 3 waste. J. Air Pollut. Control Assoc. 36: 829-831. 4 5 Anonymous. (1986) Top SO chemicals output declined 3% last year. Chem. Eng. News 64: 13. 

### 6 7 Applied ScienceAssociates, Incorporated. (1978) Diagnosing vegetationinjury caused by airpollution. Research 

### 8 Triangle Park, NC: U.S. Environmental Protection Agency, Office ofAir Quality Planning and 

### 9 Standards; EPAreport no. EPA-450/3-78-005. Available from: NTIS, Springfield, VA; PB82-238924. 10 11 Chan, H. S. 0. (1984) Measurement ofhydrochloric acid emission from burning PVC compounds. J. Fire 12 Sci. 2: 106-122. 13 

### 14 Chan-Yeung, M.; Wong, R.; Maclean, L.; Tan, F.; Dorken, E.; Schulzer, M.; Dennis, R.; Grzybowski, S. 

### 15 (1980) Respiratory swvey ofworkers in a pulp and paper mill in Powell River, BritishColumbia. 16 Am. Rev. Respir. Dis. 122: 249-257. 

### 17 18 Duce, R. A. (1969) On the sourceofgaseous chlorine in the marine atmosphere. J. Geophys. Res. 19 74: 4597-4599. 

### 20 21 Dyer, R. F.; Esch, V. H. (1976) Polyvinyl chloride toxicity in fires: hydrogen chloride toxicity in fire fighters. 

### 22 JAMAJ. Am. Mecl. Assoc. 235: 393-397. · 

### 23 24 Eldering, A.; Solomon, P. A.; Salmon, L. G.; Fall, T.; Cass, G. R. (1991) Hydrochloric acid: a regional 25 perspective on concentrations and formation in the atmosphere ofsouthern California. Atmos. Environ. 

### 26 Part A 25: 2091-2102. 

### 27 28 Enarson, D. A.; MacLean, L.; Dybuncio, A.; Chan-Yeung, M.; Grzybowski, S.; Johnson, A.; Block, G.; 

### 29 Schragg, K. (1984) Respiratory health at a pulpmill in British Columbia. Arch. Environ. Health 30 39: 325-330. 31 

### 32 Environment Canada. (1984) Chlorine: environmental and technical information for problem spills. Ottawa, ON, 33 Canada: Environmental Protection Service, Technical Services Branch. (EnviroTIPS manual). 

### 34 35 Ferris, B. G., Jr.; Burgess, W. A.; Worcester, J. (1967) Prevalence ofchronic respiratory disease in a pulp mill 

### 36 and a paper mill in the United States. Br. J. Ind. Med. 24: 26-37. 37 

### 38 GEOMETTechnologies, Inc. (1981) Hydrogen chloride: report 4, occupational hazard assessment. Cincinnati, 39 OH: U.S. Department ofHealth and Human Services, National Institute for Occupational Safety and 

### 40 Health; NIOSH contract no. 210-79-0001. Availablefrom: NTIS, Springfield, VA; PB83-105296. 41 42 Gudiksen, P.; Dickerson, M.; Chan, S.; Morris, L.; Ermak, D.; Brown, M.; Perry, J.; Vonada, M.; 43 Robinson, L. (1986) Emergencyresponse planning for potential accidental liquid chlorinereleases. 44 Livermore, CA: Lawrence Livermore National Laboratory; report no. UCRL-53685. Available from: 45 NTIS, Springfield, VA; DE86-013168. 

### 46 47 Holzwarth, G.; Balmer, R. G.; Soni, L. (1984) Thefate ofchlorine and chloramines in cooling towers: Henry's 48 law constants for flashoff. WaterRes. 18: 1421-1427. 49 50 Johnson, L. D.; Fuerst, R. G.; Logan, T. J.; Midgett, M. R. (1992) Development ofa laboratory method for 51 estimation ofhydrogen chlorideemissionpotential ofincinerator feed materials. Research Triangle Park, 52 NC: U.S. Environmental Protection Agency; EPAreport no. EPA/600/A-92/230. Availablefrom: NTIS, 53 Springfield, VA; PB93-119907. August 1994 3-10 DRAFf-DO NOT QUOTE OR CITE

### 1 Johnston, D. A. (1980) Volcanic contribution ofchlorine to the stratosphere: more significant to ozone than 

### 2 previously estimated? Science (Washington, DC) 209: 491-493. · 

### 3 4 Kamrin, M.A. (1992) Workshop on thehealth effects ofHCl ip ambient air. Regul. Toxicol. Pharmacal. 

### 5 15: 73-82. 

### 6 7 Keene, W. C.; Pszenny, A. A. P.; Jacob, D. J.; Duce, R. A.; Galloway, J. N.; Schultz-Tokos, J. J.; 8 Sievering, H.; Boatman, J. F. (1990) Thegeochemical cycling ofreactivechlorinethrough the marine 9 troposphere. Global Biogeochem. Cycles 4: 407-430. 

### 10 11 Lane, D. A.; Thomson, B. A. (1981) Monitoring a chlorinespill from a train derailment. J. AUPollut. Control 

### 12 Assoc. 31: 122-127. 

### 13 14 Moore, G. S.; Tuthill, R. W.; Polakoff, D. W. (1979) A statistical model for predicting chloroform levels in 

### 15 chlorinated surfacewater supplies. J. Am. WaterWorks Assoc. 71: 37-39. 

### 16 17 National Institute for Occupational Safety and Health. (1976) Criteria for a recommended standard ..• 

### 18 occupational exposure to chlorine. Cincinnati, OH: U.S. Department ofHealth, Education, andWelfare, 

### 19 Public Health Service; HEWpublication no. (NIOSH) 76-170. Available from: NTIS, Springfield, VA; 20 PB-266367.

. 

### 21 22 National Institute for Occupational Safety and Health. (1984) National occupational exposure survey (1980-1983) 

### 23 [data base]. Cincinnati, OH: Department ofHealth and Human Services, National Institute for 

### 24 Occupational Safety and Health. 

### 25 26 National Research Council. (1976) Chlorine and hydrogen chloride. Washington, DC: Committee on Medical**~d** 27 Biologic Effects ofEnvironmental Pollutants; EPAreport no. EPA/600/1-76-020. Available from: NTIS, 

### 28 Springfield, VA; PB-253196/0.

. 

### 29 30 Patil, L. R. S.; Smith, R. G.; Vorwald, A. J.; Mooney, T. F., Jr. (1970) Thehealth ofdiaphragm cell workers 

### 31 exposed to chlorine. Am. Ind. Hyg. Assoc. J. 31: 678-686. 

### 32 

### 33 Pendergrass, J. A. (1964) An air monitoring program in a chlorine P.lant. Am. Ind. Hyg. Assoc. J. 25: 492-495. 34 

### 35 Potter, A. E. (1978) Environmental effects ofthe space shuttle. J. Environ. Sci. 21: 15-21. 

### 36 37 Prather, M. J.; McElroy, M. B.; Wofsy, S. C. (1984) Reductions in ozone at high concentrations of 

### 38 stratospheric halogens. Nature (London) 312: 227-231. 39 

### 40 Reisch, M. S. (1994) Top SO chemicals production rose modestly last year. Chem. Eng. News 

### 41 72 (Apri111): 12-15. 

### 42 43 Rollins, R.; Homolya, J. B. (1979) Measurement ofgaseous hydrogen chloride emissions from municipal refuse 44 energy recovery systems in the United States. Environ. Sci. Techno!. 13: 1380-1383. 

### 45 46 Sebacher, D. 1.; Bendura, R. J.; Womom, D. E. (1980) Hydrochloric acid aerosol and gaseous hydrogen 47 chloridepartitioning in a cloud contaminated by solid rocket exhaust. Atmos. Environ. 14: 543-547. 

### 48 49 Simmons, J. A.; Erdmann, R. C.; Naft, B. N. (1974) Therisk ofcatastrophic spills oftoxic chemicals. 50 Los Angeles, CA: University ofCalifornia School ofEngineering and Applied Science; report no. 

### 51 UCLA-ENG-7425. 

### 52 53 Sollars, W. F. (1961) Chloride content ofcake flours and flour fractions. Cereal Chem. 38: 487-500. 54 

### August 1994 3-11 DRAFT-DO NOT QUOTE OR CITE1 SRI International. (1982) Chemical economics handbook. Menlo Park, CA: SRI International. 

### 2 §§733.4000A-733.4002J. 

### 3 4 SRI International. (1984) Chemical economics handbook. Menlo Park, CA: SRI International. 

### 5 §§733.1000A-733.1006I.· 

### 6 7 SRI International. (1992) 1992directory ofchemical producers United States ofAmerica. Menlo Park, CA: SRI 

### 8 International; pp. 527-529, 696-699. 

### 9 10 Symons, J. M.; Bellar,

## T. A.; Carswell, J. K.; DeMarco, J.; Kropp, K. L.; Robeck, G. G.; Seeger, D. R.; 

### 11 Slocum, C. J.; Smith, B. L.; Stevens, A. A. (1975) National organics reconnaisc;ance survey for 

### 12 halogenated organics. J. Am. WaterWorks Assoc. 67: 634-647. 

### 13 14 World Health Organization. (1982) Chlorine andhydrogen chloride

.. Geneva, Switzerland: World Health 

### 15 Organization. (Environmental health criteria 21). · 

### 16 17



### August 1994 3-12 DRAFf-DO NOT QUOTE OR CITE1 

### 2 

# 4. ENVIRONMENTAL FATE AND ECOLOGICALEFFECTS

3 4 

### 5 

### 4.1 ENVIRONMENTAL FATE 6 

### 4.1.1 Chlorine 7 When liquid chlorine, which is stored under high pressure and at a temperature above · 8 

### its boiling point, is released instantaneously into the atmosphere, there is flash evaporation 9 

### until the liquid has 

### cooled to -34 °C, 

### where the vapor**pr~sure**

### is 1

### atm. Simmons**e~** 

### al. 10 (1974) 

### presented a graph ofthe percent ofliquid chlorine flashed at temperatures between 11 

### -30 op 

### and 170 

### °F. 

### About 12.5 

### and 20% 

### ofthe liquid flashes at 40 op 

### (4 °C) 

### and 80 op 12 (27 °C), 

### respectively. Subsequent to this flashing, there is vaporization at a rate dependent 13 

### on heat absorption. They reported that the rate ofvaporization ofliquid chlorine from a flat 14 

### surface in sunlight was 

### 5 to 

### 6 lb/tt2/h. Because chlorine is a heavy gas (density 

## = 1.5), it 15 

### has been found to move laterally and fails to disperse from low-lying areas. 16 The atmospheric chemistry 

### ofchlorine was reviewed by Sebacher et al. 

### (1980). The 17 

### following reactions were presented: 18 19 20 21 

### 22 23 24 

### 25 26 27 

### 28 29 

### 30 (1) CI2 

### + (2) cr 

### + (3) cr 

## + (4) cr 

## + (5) cr 

## + hv**(A~** 475 

### nm)

CH4 OH H20 CH20 2cr, HCH3- 

### + HCl, 

## o- + HCI, HO- 2 

### + HCl, Hco- 

### + HCl.

31 

### Photodissociation (Reaction 1) 

### is rapid in the lower atmosphere and troposphere. 32 

### Reaction 2 

### is the main reaction that produces hydrogen chloride. The photoexcitation rate of 33 

### chlorine was estimated by Zafiriou (1974) 

### to be 0.0027 

### quanta/molecule/s, and this indicates

August 1994 4-1 DRAFT-DO NOT QUOTE OR CITE1 that, in sunlight, molecular chlorine is not the principal species ofthe gaseous element, and 2 the chlorinepresent in ambient 

### air is not elemental diatomic chlorine. 3 Prather etal. (1984) expressed concern that an increase of "inorganic chlorine" in the 4 stratosphere to levels comparable to that ofreactive nitrogen oxides could result in reduction 

### 5 ofozone levels in the lower stratosphere (20 to 30

### km). Inorganic chlorine consists of 

### 6 chlorine, nitrosyl chloride, hypochlorous acid, hydrogen chloride, and chlorine monoxide. 7 Themajor sources ofthese species would 

### be expected to 

### be carbon tetrachloride, 8 trichloroethane, trichlorofluoromethane, and dichlorofluoromethane, and notchlorine

### gas. 9 Ifchlorine is released in water, it is expected that much ofit

### will eventually find its 10 way into the atmosphere. The Bureau ofMines (Murphy etal., 1970) carried out studies in 11 which liquid chlorine (5 or 10 gal) was spilled on the surface ofa pond, and gaseous or 12 liquid chlorine was released underwater; evaporation and atmospheric dispersion were 13 followed. When 5 gal were released under 4ftofwater, the denser chlorine was buoyed up 14 by the vapor generated by reaction atthe chlorine-water interface, and essentially all ofthe 15 chlorine was released to the atmosphere. When chlorine was spilled on the surface, the rate 16 ofvaporization was_accelerated, possibly by facilitation ofheat transfer, and essentially all 17 was vaporized. 

### It was concluded that only in slow leakage or after small spills would a 18 significant fraction ofthe chlorinebe solubilized 

### in water. 19 When chlorine is used as an antifouling agent in recirculating cooling water systems of 20 powerplants, there is a potential for release offree chlorine into the atmosphere. The 21 chlorine is present in the water as hypochlorous acid. Holzwarth etal. (1984) have 22 demonstrated that 10 to 15% ofthe hypochlorous acid is volatilized from a cooling tower on 23 each passage. Because the uncharged species hypochlorous acid is volatile whereas the 24 hypochlorite ion is not, the "flashoff" offree chlorine is markedly dependent on the pH of 25 the water and would be 10 times faster atpH 6 

### than at pH 8.5. 26 

### In aqueous environments, chlorine occurs as elemental chlorine, hypochlorous acid, and 27 hypochlorite ion. However, the fate ofchlorine in natural waters is not well defined. The 28 primary chemical reactions ofchlorine in saltwater and freshwater are illustrated in 29 Figure 4-1, and a more detailed illustration ofthereactions involving chlorine and chlorinated 30 compounds in the aquatic environment is given in Figure 4-2. Factors such as reactant·

August 1994 4-2 DRAFT-DO NOT QUOTE OR CITE0 c: 0

## ~ Q) 

### a: "'C

### ~ a:

## ~ 0 

### :E Most Important In Freshwater**---------A-------~** I**~** 

### Free Chlorine Br· Cl2 

### (aq)



### Ht0

2 • 

# t

.. _Br HOCI4

.. OCt·+ H



### , Most Important in Seawater 

# ______ ./ '------ 1 

### Free Bromine BrCI



# t H

2

### 0 

## +

. + HOBr4

.. OBr+ H

, B{



### ........·....·.... ... Bromamines Slow Chloramlnes

Chloro-Organic Compounds, 

## crand Oxidation Products Bromo-OrganicCompounds, Br·and Oxidation Products

Figure 4-1. Schematic outline ofchemical reactions in

### estuarine andmarine waters.
Source: Sugam and Helz (1980).



### 1 concentrations, pH, temperature, salinity, and exposure to light control the extent ofthese 2 reactions (Jolley and Carpenter, 1983). 

### 3 4 

## 4.1.2 Hydrogen Chloride · 5 

### Hydrogen chloride can be removed from the atmosphere by the following reaction: 6 hydrogen chloride plus hydroxy ions yields waterplus chloride ions. However, the 7 concentration ofhydroxy ions in the troposphere and stratosphere is low, which leads to 

### a 8 relatively long residence time for hydrogen chloride (Sebacheretal., 1980). Because ofits 9 solubility in 

### water, it would be expected that hydrogen chloride will be absorbed in aqueous 10 aerosols and will be removed from the troposphere by rainfall. It 

### is also expected that its August 1994 4-3 DRAFT-DO NOT QUOTE OR CITEI I I I I I I \ \

### ' \ \' \

### ' ' \

# , Nz ' \ \ \\\

\ \**~ ~**  

# i .----...:..t

____ , __ 

# ' + Br-Organlcs Oxidized Organics 

### ero· s 

### c10; NHBrCf \\\\\**~**

Nz N2 , N0 3I I I I I I I I I I I I I I qt-Organics Oxidized Organics 

# '

Figure 4-2. Principal chemical pathways for reaction, degradation, and environmental fate offree chlorine intheaquatic environment. Presumed pathways (not yet proven) are shownby dashed arrows. Compounds formed at different places inthereaction scheme are depicted with superscripts

### a and 

### b to assist in

### understanding interrelationships. Halides (chlorine and bromine) are not depicted but areproducts ofmany ofthechemical pathways.

Source: Sugam and Helz (1980).



### 1 deposition velocity would be at least as high as that ofsulfur dioxide, which is on the order 2 of 1cm/s (Cocks and McElroy, 1984). Potter (1978) and Pellett et 

### al. (1983) reported 3 incidences involving acid rain from hydrogen chloride emitted in exhaust during solid rocket 4 firing. The amount ofhydrogen chloride generated by the ammonium perchlorate propellant 5 in launching a space shuttle is approximately 35,200 kg. This could result in 

### rain ofpH 

### < 1 6 at a distance of4 to 19 mi, depending on meteorologic conditions (Potter, 1978). Sebacher 7 et al. 

### (1980) measured the partitioning ofhydrogen chloride between gaseous hydrogen

August 1994 4-4 DRAFT-DO NOT QUOTE OR CITE1 chloride and hydrochloric acid aerosol in a tropospheric cloud contaminated by exhaust.from 2 launching ofa Titan

## mrocket. The monitoring devices were capable ofmonitoring total 3 airbornehydrogen chloride and airborne gaseous hydrogen chloride. An**~craft** with 4 sampling and measuring equipmentpassed through a ground cloud containing the rocket 

### 5 exhaust and measured gaseous and 

### total hydrogen chloride at several intervals (2 to 

### 5 min 6 apart) from about4 

### to 40 

### min postlaunch. The

### peaktotal hydrogen chloride**(g~s** plus 7 aerosol) concentration was 15 ppm (21 mg/m3) on the first pass; its decrease to about 8 2.4ppm (3.4 mg/m3) by the sixth pass indicates the rapidity ofdilution with the surrounding 9 atmosphere. Aerosol hydrochloric acid was several times higher than gaseous hydrogen 10 chloride during the first pass. Relative humidity greater than 90% and temperatures below 11 20

# oc favored the fonnation ofaerosol hydrochloric acid. The measurements agreed with 12 values predicted from calculations. 13 Morerecent workby the National Aeronautics and Space Administration (Cofer et al., 14 1985) measured hydrogen chloride in aerosol/gas from space shuttle launchings. 15 Concentrations ofhydrogen chloride in the exhaust cloud were as high as 40 ppm (60 mg/m3) 16 and**decr~ed** about an order ofmagnitude in an hour

.. Early after the launch, most 17 hydrogen chloride was 

### in the aqueous phase.**Howe~er,** within 40 to 60 min, the amount of 18 gaseous hydrogen chloride exceeded that in the aqueous phase. This was due to evaporation 19 from the aerosol as well as a measured increase in hydrogen chloride in largerparticles, 20 which suggests extensive aerosol fallout. Prevailing meteorology will strongly determine the 21 fate ofhydrogen chloride 

### in the atmosphere. 22 No information was found on the fate ofhydrochloric acid spilled into the ocean or 23 ponds orentering the soil. Ifhydrogen chloride is spilled into the ocean, however, it would 24 be diluted rapidly and would no longer be a strong acid. Hydrochloric acid**~pilled** on soil 25 might find its way into groundwater, butthere would be extensive evaporation atthe surface, 26 and, as hydrochloric acid percolated through the soil, it would be neutralized to some extent 27 by carbonates in the soil. 28 

### 29 30

August 1994 

### 4-5 DRAFT-DO NOT QUOTE OR CITE1 

## 4.2 ECOLOGICAL EFFECTS 2 

## 4.2.1 Chlorine 3 Theextensive use ofchlorine as a biocide in 335 of550 steam electric generating plants 4 that use once-through cooling systems has yielded substantial information on the toxicity of 

### 5 chlorine to aquatic organisms (Federal Register, 1980)

.. Many aquatic organisms, particularly 

### 6 larval and otherpianktonic forms, are entrained 

### in cooling water systems and other chlorine7 containing effluents, where they areexposed to various combinations ofstressors. 8 The toxicity ofchlorine to aquatic organisms depends mainly on three environmental 9 factors: temperature,**e~posure** time, and available form ofchlorine orother halogen 10 compounds (Capuzzo et

### al., 1977). The assessment ofchlorine toxicity to freshwater and 11 marine organisms is very complex because ofthe complex chemistry ofchlorine in water. 12 Theparticular halogen compound formed during seawater chlorination, for example, varies 13 with therelative levels ofbrol:llide, organic matter, ammonia, and other nitrogenous 14 compounds. 15 Chlorine added to seawater may remain in a free form (hydrochlorous acid or 16 hypochorite ion) orcombine with residual ammonium ions and organic matter, yielding 17 mono-, di-, and.trichloramines ororganochlorine compounds (Capuzzo et al., 1977). 18 Chlorine generally decays rapidly (in minutes orhours) to lower residual levels. Typically, 19 the toxicant effect is measured as total residual chlorine (TRC) orthe sum ofthe 20 concentrations offree and combined residuals, usually determined by amperometric titration 21 analyses. 

### A more detailed discussion ofthe effects ofchlorine on aquatic organisms is 22 addressed 

### in the Ambient Water Criteria Document for Chlorine-1984 (U.S. Environmental 23 Protection Agency, 1985). 24 25 

### 4.2.1.1 Fish 26 The acute toxicity ofchlorine to marine and freshwater fishes is sumr_narized 

### in 27 Table 4-1. Median lethal levels range from 0.037 to less than 0.65 mg/L TRC. There is 28 little apparent difference in toxicity between marine and freshwater fish. 29 Other trends in fish toxicity are apparent for some species. Toxicity sometimes 30 increases with ambient temperature as well as duration and pattern ofexposure. Toxicity is 31 often lower during the egg stage and then increases during larval development August 1994 4-6 DRAFT-DO NOT QUOTE OR CITETABLE4-1. THEACUTETOXICITY OF**CHLO~** TO FISH AND AQUATIC INVERTEBRATES Exposure Median Lethal Level Conditions Organism (mg/LTRC)• (hours) Reference FISH-MARINE and ESTUARINE

Alosa aestivalis (Bluebackhening)

egg 0.3 180 Morgan and Prince (1977) 2-day larvae 0.25 48 Morgan and Prince (19?7)

. Cymalogasteraggregata (Shinerperch)

1-3 mo old 0.23 TROb 1 at 20 °C Stoberet al. (1980) 0.31 1**~t** 13 °C Fundulus heteroclitus (Killifish) <0.65 0.5 at 25 °C Capuzzo et al. (1977)

juvenile <0.25 0.5 at 30

### oc Capuzzo et al. (1977) Gobiosoma bosci (Naked goby)

unspecified age 0.08 96 Roberts et al. (1975) Leiostomusxanthurus (Spot)

juvenile 0.13

### cpoc: 6 Middaugh et al. (1980) 0.37 1.5 Menidia beryllina (Tidewater silversides)

egg (2 to 24 h old) 0.21-0.32 48 Morgan and Prince (1977) egg (2 to 3 h old) 0.23-0.26 24 Morgan and Prince (1977) Menidia menidia (Atlantic silversides)

egg 0.3 48 Morgan and Prince (1977) juvenile 0.037 96 Roberts et al. (1975) Morone americana (Whiteperch)

egg 0.27 76 Morgan and Prince (1977) larvae 0.31 24 Morgan and Prince (1977) 25-day larvae 0.25 (46% died) 4 Hallet al. (1979b) 0.2 (41% died) 4 Hall et al. (1979b) 0.28 (21%died) 1 Hall et al. (1979b) Morone soxatilis (Striped bass)

egg (>40hold) 0.36 24 Morgan and Prince (1977) egg (

### <40·h old) 0.2-0.22 48 Morgan and Prince (1977) 1- to 3-day larvae 0.2 24 Morgan and Prince (1977) 22-day larvae 0.14 96 Hall et al. (1982) 60-dayjuveniles 0.19 96 Hall et al. (1982) 388-dayjuveniles 0.23 96 Hall et al. (1982)
August 1994 4-7 DRAFT-DO NOT QUOTE OR CITE

### TABLE4-1 (cont'd). THEACUTE TOXICITY OFCHLORINETO FISH AND AQUATIC INVERTEBRATES Exposure MediumLethal Level Conditions Organism (mg!L TRC)• (hours) Reference FISH-MAIUNEand ESTUARINE (cont'd)

Oncorhynchus ldsutch (Coho salmon)

1year old 0.13 TRO 1 at 20 °C Stoberetal. (1980) 0.21 1 at 13 °C Stoberetal. (1980) Pseudopleuronectes americanus (Winterflounder)

juvenile 0.55 (100% died) 0.5 Capuzzo etal. (1977)

Stenotomus versicolor (Scup)

juvenile 0.65 (100% died) 0.5 Capuzzo et al. (1977) Syngnathusfuscus (Northern pipefish)

unspecified age 0.27 96 Roberts et al. (1975) FISH-FRESHWATER

Lepomis macrochirus (Bluegill)

juvenile 0.44 96 Wildeet al. (1983) Pimephalespromelas (Fathead minnow)

juvenile 0.08 96 Wildeet al. (1983) adult 0.35 96 Wildeet al. (1983) Gambusia affinis (Mosquito fish)

unspecified age 1.59 0.5 Matticeet al. (1981) 0.84 1 Mattice et al. (1981) INVERTEBRATE-MARINE

Acartia tonsa (Copepod)

unspecified age <0.05 48 Roberts et al. (1975) Callinectes sapidus (Blue crab)

juvenile >0.3 

## - d Hall et al. (1979a) Crassostrea virginica (Oyster)

larvae <0.005 48 Roberts et al. (1975)

August 1994 

### 4-8 DRAFf-DO NOT QUOTE OR CITE

### TABLE4-1 (cont'd). THEACUTE TOXICITY OF CHLORINE TO FISH AND AQUATIC INVERTEBRATES Exposure Median Lethal Level Conditions Organism (mg/LTRC)• (hours) Reference INVERTEBRATE-MARINE (cont'd)

Mercenaritl mercenaria (Hard clam)

larvae <0.005 48 Roberts etal. (1975) Palaemonetespugio (Grass shrimp)

unspecified age 0.22 96 Roberts etal. (1975) unspecified age 0.38 24 Roberts et al. (1975) adult 0.3 (53% died) 2 at 28 °C Hall et al. (1979a) adult 0.15 (43% died) 4 at 24 °C Hall et al. (1979a) INVERTEBRATE-FRESHWATER

Daphnia magna (Water flea)

unspecified age 0.097 0.5 Mattice et al. (1981) 0.063 1 Mattice et al. (1981)

-Tests were done under continuous-flow orconstant-addition conditions using measured levels oftotal residual chlorine (TRC) unless otheJWise stated. b-J'RO 

### = Total residual oxidants. CCPO = Total chlorine-prOduced oxidants. dData not available.



### 1 (e.g., metamorphosis in striped bass). Age-related trends in 

### chlorine tolerance, however, are 2 not consistent for all species. Some fish show increasing toxicity, others show decreasing 3 

### toxicity, and still others show no trend in 

### toxicity with age; this may be an artifact ofthe 4 specific ages studied (Hallet

### al., 1982, 1981). 5 

### 6 4.2.1.2 Invertebrates 7 

### Chlorine is toxic to aquatic invertebrates at acute exposures comparable to or lower than · 8 

### those for fish (see 

### Table 4-1). 

### Ofthe five invertebrate species 

### described in Table 4-1, 

### larvae 9 

### oftwo molluscan species (oyster and clam) were substantially more sensitive than any ofthe 10 

### fish.

August 1994 4-9 DRAFT-DO NOT QUOTE OR CITE1 As with some fish, the interaction ofchlorine, temperature, and exposure conditions has 2 been studied for some invertebrates. Halletal. (1979a) exposed the blue crab and grass 3 shrimp to TRC levels of0, 0.15, and 0.3 mg/L at 2, 6, or 10 

# oc above ambient 4 temperatures for 0.08, 2.0, and 4.0 h, respectively. Mortality in the shrimp increased with 5 increased chlorine level, temperature, and exposure duration; the blue crab did not exhibit a 

### 6 similareffect. 7 

### 8 4.2.1.3 Plants 9 Theonly toxicity data for aquatic vascularplants were for

### Myriophyllum spicatum 10 (Eurasian water milfoil). Continuous exposure ofplants to concentrations as low as 11 0.05 mg/LTRC resulted in a 30% reduction 

### in dry weight ofshoots and total biomass and a 12 16% reduction in shoot length when compared to controls. At a concentration of0.1 mg/L, 13 chlorophyll levels were reduced 25%. Plants exposed intermittently for three 2-h periods 14 daily for 96 h were more resistant to chlorine, showing no lethality at concentrations below 15 1 mg/L (Watkins and Hammerschlag, 1984). 16 Phytoplankton (floating algae) may be more sensitive to chlorine**th~** M. 

### spicatum. 17 Watkins and Hammerschlag (1984) cited studies with phytoplaruaon showing 50% inhibition 18 ofradiolabeled carbon dioxide uptake at chlorine levels as low as 0.01 mg/L and inhibition of 19 nitrate uptake at chlorine levels of0.03 mg/L. 20 21 

### 4.2.2 Hydrogen Chloride (Hydrochloric Acid) 22 

### 4.2.2.1 Aquatic Organisms 23 The toxic effects ofhydrochloric acid on aquatic organisms are due to the acid's effect 24 on.hydrogen ion concentration (Rose etal., 1977). Aquatic organisms in their natural 25 environments often exhibit a broad range ofpH tolerance. DeGraeve et al. (1979), for 26 example, concluded that aquatic organisms generally exhibit no deleterious effects at a 27 pH range of6 to 9. For freshwater fish, few adults are harmed directly at pH 5 to 9, but 28 increases in acidity or alkalinity within this pH range may raise the toxicity ofvarious 

### 29 common pollutants (European Inland Fisheries Advisory Commission, 1968). Many 30 freshwater organisms show no deleterious effects atpH 3 to 4 or 10 to 11.

August 1994 4-10 DRAFr-DO NOT QUOTE 

### OR CITE

### 1 In marine waters, the pH varies less (generally, the pH is about 8) because ofincreased 2 

### buffering capacity. However, there may be substantial diurnal variation, as in fresh waters, 3 

### where photosynthesis is rapid (DeGraeve et al., 1979). 4 

### 5 4.2.2.2 Terrestrial Organisms 6 

### Laboratory studies have shown that 20-min 

### exposures ofa variety ofplants to 

### levels of 7 

### hydrogen chloridebetween 4.6

### and 19.3 

### ppm (6.5 

### and 27.0 

### mg/m3) 

### caused visible leafinjury 8 and decreased chlorophyll levels (Endress et al., 1982; Granett and Taylor, 1981; Lerman 9 etal., 1976). 

### Field studies on 50

### plant species growing 

### near an anhydrous aluminum· 

### 10 chloride manufacturing plantindicated that the more sensitive species were American elm, 11 buroak, eastern white pine, basswood, red ash, and several bean species. Foliarinjury of 12 

### the more sensitive species was usually associated with concentrations ofchloride ion 13 

### exceeding 0.2% 

### ofwhole-leafdry weight. Hydrogen chloride-tolerant species showed no leaf 14 

### toxicity despite foliar concentrations ofchloride ion up to 5%. 

### Both plantinjury and leaf 15 chloride concentrations declined as the distance from the source increased; no effects were · 16 

### reported beyond 300m 

### (Harper and Jones, 1982).



### August 1994 4-11 DRAFT-DO NOT QUOTE OR CITE

### 1 

### REFERENCES 2 Capuzzo, J. M.; Davidson, J. A.; Lawrence, S. A.; Libni, M. (1977) Thedifferential effects offree and 

### 3 combined chlorineonjuvenilemarine fish. Estuarine Coastal Mar. Sci. 5: 733-741. 4 5 Cocks, A. T.; McElroy, W. J. (1984) The absorption ofhydrogen chlorideby aqueous aerosols. Atmos. 

### 6 Environ. 18: 1471-1483. 7 

### 8 Cofer, W. R., ill; Bendura, R. J.; Sebacher, D. I.; Pellett, G. L.;.Gregory, G. L.; Maddrea, G. L., Jr. (1985) 

### 9 AirbomemeasUrements ofspace shuttleexhaust constituents. AlAA J. 23: 283-287. 10 11 DeGraeve, G. M.; Blogoslawski, W. J.; Bnm.gs, W. A.; Fava, J. A.; Finlayson, B. J.; Frost, T. P.; Kriscban, 12 T. M.; Meldrim, J. W.; Michaud, D. T.; Nakatani, R. E.; Seegert, G. L. (1979) Chlorine. In: 13 Thurston, R. V.; Russo, R. C.; Fetterolf, C. M., Jr.; Edsall, T. A.; Barber, Y. M., Jr., eds. A review 14 oftheEPA red book: quality criteriaforwater. Bethesda, MD: American Fisheries Society; pp. 67-75. 

### 15 16 Endress, A. G.; Suarez, S. J.; Taylor, 0. C. (1982) Photosynthetic andrespiratory consequences ofhydrogen 17 chloride gas exposures ofPhaseolus vulgaris L. andSpinacea oleracea L. Environ. Pollut. Ser. 18 A 29: 13-26.

. 

### 19 20 European Inland Fisheries Advisory Commission. (1968) Waterquality criteria for European freshwater fish: 

### 21 report on extremepH values and inland fisheries. Rome, Italy: Food and Agriculture Organization ofthe 22 United Nations; ElF AC technical paper no. 4. 23 

### 24 Federal Register. (1980) Effluent limitations guidelines, pretreatment standards and new sourceperformance 

### 25 standards under CleanWaterAct; steamelectric power generating point source category. F. R. 26 (October 14) 45: 68328-68356. 

### 27 28 Granett, A. L.; Taylor, 0. C. (1981) Diumal and seasonal changes insensitivity ofplants to short exposures of 29 hydrogen chloride gas. Agric. Environ. 6: 33-42. · 30 31 Hall, L. W., Jr.; Burton, D. T.; Margrey, S. L. (1979a) Chlorine, temperature, and exposure duration effects of 32 powerplant effluents onjuvenilebluecrabs Callinectes sapidus and grass shrimpPalaemonetespugio. 

### 33 J. Toxicol. Environ. Health 5: 749-757. 34 35 Hall, L. W., Jr.; Burton, D. T.; Margrey, S. L. (1979b) Theeffects ofchlorine, elevated temperature and 

### 36 exposure duration ofpowerplant effiuents on larval whiteperchMorone americana (Gmelin). Water 37 Resour. Bull. 15: 1365-1373. 

### 38 39 Hall, L. W., Jr.; Burton, D. T.; Richardson, L. B. (1981) Comparison ofozone and chlorinetoxicity to the 40 developmental stages ofstriped bass, Morone**saxat~lis.** Can. J. Fish. Aquat. Sci. 38: 752-757. 41 42 Hall, L. W., Jr.; Graves, W. C.; Burton, D. T.; Margrey, S. L.; Hetrick, F. M.; Roberson, B. 

## s: (1982) 43 A comparison ofchlorine toxicity to three life stages ofstripedbass (Morone saxatilis). Bull. Environ. 

### 44 Contam. Toxicol. 29: 631-636. 45 46 Harper, D. S.; Jones, R. D. (1982) Therelative sensitivity offifty plant species to chronic doses ofhydrogen 47 chloride. Phytopathology 72: 261-262. 48 

### 49 Holzwarth, G.; Balmer, R. G.; Soni, L. (1984) The fate of**chlorin~** and chloramines in cooling towers: Henry's 50 law constants for flashoff. Water Res. 18: 1421-1427. 51



### August 1994 4-12 DRAFT-DO NOT QUOTE OR CITE1 Jolley, R. L.; Carpenter, J. H. (1983) A review ofthe chemistry and environmental fate ofreactive oxidant 2 species inchlorinated water. In: Jolley, R. L.; Brungs, W. A.; Cotruvo, J. A.; Cumming, R. B.; 

### 3 Mattice, J. S.; Jacobs, V. A., eds. Waterchlorination: environmental impact andhealth effects, 

### 4 volume 4, book 1, chemistry and watertreatment, proceedings ofthe fourth conference; October 1981; 

### 5 Pacific Grove, CA. Ann Arbor, MI: AnnArbor Science Publishers, Inc.; pp. 3-47. 

### 6 

### 7 Lerman, S.; Taylor, 0. C.; Darley, E. F. (1976) Phytotoxicity ofhydrogen chloride gas with a short-term 

### 8 exposure. Atmos. Environ. 10: 873-878. 

### 9 10 Mattice, J. S.; Burch, M. B.; Tsai, S. C.; Roy, W. K. (1981) A toxicity testing system for exposing small 

### 11 invertebrates and fish to short square-waveconcentrations ofchlorine. WaterRes. 15: 923-927. 12 

### 13 Middaugh, D. P.; Burnett, L. E.; Couch, J. A. (1980) Toxicological andphysiological responses ofthe fish, 14 Leiostomusmnthurus, exposed to chlorineproduced oxidants. Estuaries 3: 132-141. 15 16 Morgan, R. P., ll; Prince, R. D. (1977) Chlorinetoxicity to eggs and larvae offive Chesapeake Bay fishes. 

### 17 Trans. Am. Fish. Soc. 106: 38Q-38S.

. . 18 

### 19 Murphy, J. N.; Burgess, D. S.; Harris, M. E.; Lang, H.; Mattes, R.; Grainger, H.; Slomski, W. B.; 

### 20 Albaugh, W. (1970) Hazards ofmarine transportation ofliquid chlorine. Pittsburgh, PA: U.S. 21 Department ofthe Interior, Bureau ofMines; PMSRC report no. S-4158. Available from: NTIS, 22 Springfield, VA; AD-750068. 23 24 Pellett, G. L.; Sebacher, D. 1.; Bendura, R. J.; Womom, D. E. (1983) HCl in rocket exhaust clouds: 

### 25 atmospheric dispersion, acid aerosol characteristics, and acid rain deposition. J. Air. Pollut. Control 26 Assoc. 33: 304-311. · 

### 27 28 Potter, A. E. (1978) Environmental effects ofthe space shuttle. J. Environ. Sci. 21: 15-21. 

### 29 30 Prather, M. J.; McElroy, M. B.; Wofsy, S. C. (1984) Reductions in ozone at high concentrations of 31 stratospheric halogens. Nature (London) 312: 227-231. 32 

### 33 Roberts, M. H., Jr.; Diaz, R. J.; Bender, M. E.; Huggett, R. J. (1975) Acute toxicity ofchlorine to selected 34 estuarine species. J. Fish. Res. Board Can. 32: 2525-2528. 

### 35 36 Rose, C. D.; Williams, W. G.; Hollister, T. A.; Parrish, P. R. (1977) Method for determining acute toxicity of 37 an acid waste and limiting permissible concentration at boundaries ofan oceanic mixing zone. Environ. 38 Sci. Technol. 11: 367-371. 39 40 Sebacher, D. 1.; Bendura, R. J.; Womom, D. E. (1980) Hydrochloric acid aerosol and gaseous hydrogen 41 chloride partitioning ina cloud cm:-taminated by solid rocket exhaust. Atmos. Environ. 14: 543-547. 42 43 Simmons, J. A.; Erdmann, R. C.; Naft, B. N. (1974) The risk ofcatastrophic spills oftoxic chemicals. Los 44 Angeles, CA: University ofCalifornia School ofEngineering and Applied Science; report no. 45

. UCLA-ENG-7425. 

### 46 47 Stober, Q. J.; Dinnel, P. A.; Hurlburt, E. F.; DiJulio, D. H. (1980) Acute toxicity and behavioral responses of 48 coho salmon (Oncorhynchus kisutch) and shiner perch (Cymatogaster aggregata) to chlorine inheated 49 sea-water. Water Res. 14: 347-354. 50 51 Sugam, R.; Helz, G. R. (1980) Seawater chlorination: a description ofchemical speciation. In: Jolley, R. L.; 

### 52 Brungs, W. A.; Cumming, R. B.; Jacobs, V. A., eds. Water chlorination: environmental impact and 

### 53 health effects, volume 3, proceedings ofthe third conference; October-November 1979; Colorado 54 Springs, CO. Ann Arbor, MI: Ann Arbor Science Publishers, Inc.; pp. 427-433.
August 1994 4-13 DRAFT-DO NOT QUOTE OR CITE

### 1 U.S. Environmental Protection Agency. (1985) Ambient waterquality criteria for chlorine-1984. Washington, 

### 2 DC: Office ofWater Regulations and Standards, Criteria and Standards Division; EPA report no. EPA 

### 3 440/5-84-030. Available from: NTIS, Springfield, VA;**PB85-2274~9.** 4 5 Watkins, C. H.; Hammerschlag, R. S. (1984) Thetoxicity ofchlorine to a common vascular aquatic plant. Water 

### 6 Res. 18: 1037-1043. 

### 7 

### 8 Wilde, E. W.; Soracco, R. J.; Mayack, L.A.; Shealy, R. L.; Broadwell, T. L.; Steffen, R. F. (1983) 

### 9 Comparison ofchlorine and chlorinedioxide toxicity to fathead minnows andbluegill. WaterRes. 

### 10 17: 1327-1331. 

### 11 12 Zafiriou, 0. C. (1974) Photochemistry ofhalogens in the marine atmosphere. J. Geophys. Res. 79: 2730-2732. 

### 13

August 1994 4-14 DRAFT-DO NOT QUOTE OR CITE1 

### 2 3 4 

## 5. PHARMACOKINETICS AND MECHANISM OF ACTION

5 

### 5.1 PHARMACOKINETICS AND METABOLISM 6 The respiratory pharmacokinetics ofchlorineand hydrogen chloride have notbeen 7 examined thoroughly. There are data that suggestthat these compounds ortheir reaction 8 products are absorbed from the respiratory tractby the finding ofliver and/or kidney effects 9 in animals exposed to 

### high levels ofboth compounds. However; these effects may have been 10 the result ofa disturbance in the acid-base metabolism or a decrease in blood oxygen levels 11 due to excessive pulmonary damage. Under normal breathing oflow levels ofchlorine or 12 hydrogen chloride, there is no evidence that suggests that much of**~ither** 

### compound enters the 13 bloodstream (see Chapter 6). 14 No information has been found addressing the oral pharmacokinetics ofchlorine and 

### 15 hydrogen chloride. There is a limited amount ofinformation addressing the oral 16 pharmacokinetics ofchlorine-related compounds (derived from water chlorination) that 17 demonstrates that these compounds are absorbed from the gastrointestinal tract. Once 18 absorbed, the chlorine molecule apparently reacts with organic molecules in the body to 19 produce a wide variety ofchlorinated compounds. Chlorine is eliminated via urine and feces 20 as the chloride ion (Abdel-Rahman et al., 

### 1983; Abdel-Rahman et al., 1982; Mink et al., 21 1983). 22 23 24 

### 5.2 MECHANISM OFACTION AND BIOCHEMICALEFFECTS 25 

### 5.2.1 Chlorine 26 Several theories have been proposed on the mechanism ofchlorine's toxicity. One 27 theory suggests that atphysiologic pH (pH range of6 to 

### 8), chlorine reacts with water from 28 moist tissue, forming hypochlorous acid and hydrochloric acid. The hypochlorous acid is 29 very reactive and rapidly dissipates, liberating hydrochloric acid and nascent oxygen 30 (Cl2 

### + H2

### 0 

### > 2HC1 

## + Ot) (Kramer, 1967; World Health Organization, 1982;

August 1994 5-1 DRAFf-DO NOT QUOTE OR CITE1 Colardyn et al., 1976). The major portion ofthe damage to tissues would then be caused by 2 thepotent oxidizing action ofthe nascent oxygen, which is a strong protoplasmic poison 3 (Adelson and Kaufman, 1971; Colardyn etal., 1976). Superimposed on the primary trauma 4 is the secondary irritation produced by the hydrochloric acid (Adelson and Kaufman, 1971). 

### 5 Another theory suggests that because chlorine is a more potent sensory irritant

### than 6 hypocbloric acid, the observed response is due to hypochlorous acid (Barrow etal., 1977). 7 Thehypochlorous acid penetrates the cell and forms N-chloro derivatives with amino groups 8 ofproteins, which damage cell structure (National Research Council, 1976). 9 Hypochlorous acid has been shown to inhibit enzymatic reactions inliving cells. 10 Pereiraetal. (1973) demonstrated that hypochlorous acid can convert several amino acids 11 into a mixture ofcorresponding nitriles and aldehydes. It has been theorized that the chlorine 12 irreversibly inhibits glucose metabolism at thepoint ofthiosephosphoric acid oxidation to 13 phosphoglyceric acid {Green and Stumpf, 1946), and thatthe inhibition_ ofglucose 14 metabolism was the result ofchlorine reacting with sulfhydryl groups (Knox et al., 1948). 15 However, Dodd et al. {1980) did not find 

### an effect on lung total protein ornonprotein 16 sulfhydryl

### levels~ rats exposed to 12 ppm (35 mg/m3) chlorine (6 hlday for 1, 5, or 17 10 days) during the exposure period. In a more recent study," McNulty etal. (1983) found a 18 decrease in total sulfhydryl content in the respiratory tract mucosa but not the olfactory nasal 19 mucosa ofrats exposed to 5 or 10 ppm (14.5 or 29.0 mg/m3) chlorine for 6 h. Based on 20 these results, itis not likely that the oxidation of

### total sulfhydryl content in the lung is 21 playing a major role in the respiratory tract toxicity ofchlorine, since the toxic effects of 22 chlorine

### occur at concentrations below those required to alter the total sulfhydryl content. 23 However, whether chlorine exerts its toxicity by negatively impacting selected sulfhydryl 24 compounds, present as a relatively low portion ofthe sulfhydryl content, is**n~t** lmown. 25 Ithas 

### also been demonstrated that hypochlorous acid 

### can react with the.nucleotidebases 26 ofdeoxyribonucleic acid (DNA) and ribonucleic acid (RNA). Patton et al. (1972) found that 27 when one equivalent ofhypochlorous acid was added to cytosine, 4-N-chlorocytosine was 28 obtained. The addition oftwo equivalents ofhypochlorous acid to cytosine yielded a 29 precipitateidentified as a mixture of4-N-chlorocytosiile and 4-N-5-dichlorocytosine. 30 Hypochlorous acid has been reported to form labile intermediates and stable end products 

### 31 when reacted with purine and pyrimidinebases (Hoyano et al., 1973).

August 1994 5-2 DRAFT-DO NOT QUOTE

### OR CITE1 

### 5.2.2 Hydrogen Chloride 2 The mechanism ofhydrogen chloride's toxicity has been described in two parts: 3 (1) 

### molecular and elementary biochemical effects and (2) 

### disturbed function. In water, 4 

### hydrogen chloride dissociates almost completely, yielding hydronium and chlorine ions 

### 5 (HCl 

## + H20**~** H30 

## + Cl). The hydronium ion donates a proton with catalytic 6 properties capable ofcleaving organic molecules (World Health 

### Organization,**~982).** 

### Ithas 

### 7 also

### been suggested thatthe hydrolysis ofpeptides and esters plays a significantrole in the 8 

### injury produced by hydronium ions since they are components ofthe cell wall. 

### Other 

### 9 reactions produced by the**hydro~um** 

### ion include hydroxylation ofcarbonyl groups and 10 polymerization and depolymerization oforganic molecules. Once the cell wall 

### has been 11 

### damaged, the cell 

### may be depleted ofcytoplasmic components and 

### die (National Research 12 Council, 1976). 13 14 

### 15 16

August 1994 5-3 DRAFf-DO NOT QUOTE OR CITE1 

### REFERENCES 2 Abdel-Rahman, M. S.; Berardi, M. R.; Bull, R. J. (1982) Effect ofchlorine and monochloramine in drinking 3 water on the developing rat fetus. J. Appl. Toxicol. 2: 156-159. 4 5 Abdel-Rahman, M. S.; Waldron, D. M.; Bull, R. J. (1983) A comparative kinetics study ofmonochloramine and 

### 6 hypochlorous acid inrat. J. Appl. Toxicol. 3: 175-179. 7 8 Adelson, L.; Kaufman, J. (1971) Fatal chlorinepoisoning: report oftwo cases with clinicopathologic correlation. 

### 9 Am. J. Clin. Pathol. 56: 430-442. 10 11 Barrow, C. S.; Alarie, Y.; Wanick, J. C.; Stock, M. F. (1977) Comparison ofthe sensory irritation response in 

### 12 mice to chlorine andhydrogen chloride. Arch. Environ. Health 32: 68-76. 13 

### 14 Colardyn, F.; vander Straeten, M.; Tasson, J.; van Egmond, J. (1976) Acute chlorine gas intoxication. Acta 15 Clin. Bel g. 31: 70-77. 16 17 Dodd, D. E.; Bus, J. S.; Barrow, C. S. (1980) Lung sulfhydryl changes inrats following chlorine inhalation. 

### 18 Toxicol. Appl. Pharmacal. 52: 199-208. 

### 19 20 Green, D. E.; Stumpf, P. K. (1946) The mode ofaction ofchlorine. J. Am. WaterWorksAssoc. 

### 21 38: 1301-1305. 22 23 Hoyano, Y.; Bacon, V.; Summons, R. E.; Pereira, W. E.; Halpern, B.; Duffield, A.M. (1973) Chlorintaion 24 studies. IV. The reaction ofaqueous hypochlorous acid withpyrimidine and purinebases. Biochem. 25 Biophys. Res. Commun. 53: 1195-1199. 

### 26 27 Knox, W. E.; Stumpf, P. K.; Green, D. E.; Auerbach, V. H. (1948) Theinhibition ofsulfhydryl enzymes as the 28 basis ofthebactericidal action ofchlorine. J. Bacterial. 55: 451-458. 

### 29 30 Kramer, C. G. (1967) Chlorine. J. Occup. Med. 9: 193-196. 31 32 McNulty, M. I.; Chang, J. C. F.; Barrow, C. S.; Casanova-Schmitz, M.; Heck, H. d'A. (1983) Sulfhydryl 33 oxidation in rat nasal mucosal tissues after chlorine inhalation. Toxicol. Lett. 17: 241-246. 

### 34 35 Mink, F. L.; Coleman, W. E.; Munch, J. W.; Kaylor, W. H.; Ringhand, H. P. (1983) Invivo formation of 36 halogenated reaction products following peroral sodiumhypochlorite. Bull. Environ. Contam. Toxicol. 37 30: 394-399. 

### 38 39 National Research Council. (1976) Chlorine and hydrogen chloride. Washington, DC: Committee on Medical and 40 Biologic Effects ofEnvironmental Pollutants; EPAreport no. EPA/600/1-76-020. Available from: NTIS, 41 Springfield, VA; PB-253196/0. 42 43 Patton, W.; Bacon, V.; Duffield, A. M.; Halpern, B.; Hoyano, Y.; Pereira, W.; Lederberg, J. (1972) 

### 44 Chlorination studies. I. Thereaction ofaqueous hypochlorous acid with cytosine. Biochem. Biophys. 45 Res. Commun. 48: 880-884. 

### 46 47 Pereira, W. E.; Hoyano, Y.; Summons, R. E.; Bacon, V. A.; Duffield, A. M. (1973) Chlorination studies: 48 ll. thereaction ofaquecius hypochlorous acid with ?-amino acids and dipeptides. Biochem. Biophys. Acta 49 313: 170-180.

. . . 50 51 World Health Organization. (1982) Chlorine and hydrogen chloride. Geneva, Switzerland: World Health 52 Organization. (Environmental health criteria 21). 53
August 1994 5-4 DRAFT-DO NOT QUOTE OR CITE

### 1 2 

### 3 

# 6. TOXICOLOGY

4 

### 6.1 EXPERIMENTALANIMALS 5 

### 6.1.1 Chlorine 6 The experimental animal toxicity studies for chlorine evaluate the effect ofacute, 7 subchronic, orchronic inhalation ofchlorine gas or aerosol. These studies indicate that · · 8 

### inhaled chlorine can attack the respiratory tract, producing irritation, pulmonary edema, and, 9 in somecases, death. Experimental animal studies utilizing chlorine 

### in an aqueous medium 10 (usually as hypochlorous acid or sodium hypochlorite) not containing ammonia or other 11 nitrogen-containing compounds or 

### in food commodities, while limited, demonstrate that the 12 ingestion ofchlorine does not produce serious adverse effects 

### in animals. Cunningham 13 (1980) reported no signs oftoxicity in male rats that drank water containing hypochlorite 14 (calculated as 0, 20, 40, or 80 mg/L chlorine) for 6 weeks or 

### in guinea pigs that consumed 15 50 mg/L available chlorine for 5

### weeks. A similar lack oftoxicity also has been reported in 16 mice that drank 

### highly chlorinated drinking water (Blabaum and Nichols, 1956). ·In a study 17 designed to evaluate the effect ofconsuming chlorine-treated ground beef, Kotula et al. 18 (1987) fed rats ground beefcontaining 0, 50, 200, or 600 ppm chlorine for 92 days; no 19 clinical orhematological abnormalities were reported. However, there have been several 20 reports ofincreased ordecreased organ weights 

### in experimental animals given cake diets 21 made from chlorinated flour. Fisher et al. (1983a) reported a decrease 

### in spleen weight in 22 female rats given a cake diet containing 0, 1,250, or 2,500 ppm available chlorine for 23 104 weeks. In

### another study, a dose-related increase 

### in kidney weight (males) and liver 24 weight (both sexes) was seen in rats that consumed chlorinated cake containing 0, 1,257, or 25 2,506ppm available chlorine for 28 days (Fisher et al., 1983b). Female mice experienced a 26 dose-related increase in heart and liver weights and a decrease 

### in uterus weight after 27 consuming chlorinated cake containing either 0, 1,250, or2,500 ppm available chlorine for 28 73 weeks. Nonexposure-related amyloidosis involving the spleen, liver, and heart was also 29 noted in 

### these cake-fed animals (Ginocchio et al., 1983). It was suggested that the increase 30 in 

### organ weights may represent a physiological adaptation to the nature ofthe diet (Fisher 31 et al., 1983b). In the long-term studies, increased mortality was reported in 

### the cake-fed

. . 

### August 1994 

### 6-1 DRAFr-DO NOT QUOTE OR CITE

### 1 animals compared to control animals fed a stockdiet (Ginocchio et al., 1983; Fisher et al., 2 1983a). It

### is thought that this**in~eased** 

### mortality is due to 

### the'cake diet and not to chlorine 3 per se (Fisher et

### al., 1983a). 4 

### 5 6.1.1.1 Acute Inhalation

### Toxicity 

### 6 Withers and Lees (1985a) have reviewed the early work conducted between 1887 and 7 1918 that examined the toxicity ofchlorine in animals. The studies were conducted 

### in 8 Germany, Britain, Russia, and France, primarily in response to the use ofchlorine as a "war 9 gas" in World War 

### I. The authors concluded that these dataarenot very useful because of 10 inadequate reporting and deficiencies in experimental design. 11 Underhill (1920) summarized work done by the U.S. 

### War Department on the toxicity of 12 chlorine, phosgene, and chloropicrin (war gases). Dogs were gassed with chlorine in 

### 13 a continuous flow chamber (with some variability offlow) for 30 min. Withers and Lees 14 (1985b) have reanalyzed Underhill's data, using the Litchfield and Wilcoxon method of 15 probits and converting the concentrations ofchlorine to parts per million at 25 °C 

### rather than 16 at 0 oC 

### as in the original work.**~e** 

### concentration producing**50~** 

### mortality (LC50) 

### was 17 determined to be 650 ppm (1,885 mg/m3). 

### 18 Weedon etal. 

### (1940) exposed groups offour mice or eight rats (age, sex, and strain not 19 specified) to 16, 63, 250, or 1,000

### ppm (46, 183, 725, or 2,900 mg/m3) 

### chlorine for 1, 

### 4, 20 15, 60, 240, or960 

### min oruntil they died. The LC50 

### values in mice were 1,000, 250, and 21 63 ppm for exposure times of53, 440, and >960 min, respectively. These values are 22 somewhat inexactbecause some animals died during exposure and were scored as having 23 been exposed for the entireperiod. 24 Table 6-1 summarizes LC50 

### toxicity data for chlorine in rats and mice.

.Schlagbauer 25 and Renschler (1967) exposed groups of 10 female 

### NMRI mice to between 55.3 and 26 178.8 ppm (160 and 516 mg/m3) 

### chlorine for a period of30 min. Exposure to 55.3 ppm 27 caused no deaths. TheLC50 

### was 127 ppm (368 mg/m3) 

### (106 to 

### 152 ppm [307 to 28 441 mg/m3], 

### 95% confidence limit). All 

### deaths occurred by Day 4. A 

### single exposure at 29 10 ppm (29 mg/m3) 

### for 3 h caused death in 8 of 10 mice and for 5 h 

### caused death in 9 

### of 30 10 mice; exposure for 3 h at 

### 22 ppm 

### (64 mg/m3) 

### caused 

### 100% mortality within 

### 2 days." The 31 cause ofdeath was bronchial spasm and lung damage. Thirty-minute exposures to 

### levels

August 1994 6-2 DRAFT-DO NOT QUOTE OR CITE

### TABLE 6-1. ACUTE TOXICITY VALUES FOR CHLORINEIN**~TSANDMICE** Exposure ObseiVation Concentration Time Period Lc 50

• Species Strain (ppm [mg/m 3]) (minutes) (days) (ppm [mg/m 3]) Reference Mice NMRI 55-179 30 4 127 (368) Schlagbauerand (159-519) Renschler (1967) Mice CF-1 _b 60 137 (397) Vemot**~** al. (1977) Mice 10 3 (h) 302 (876) Withers and Lees (198Sa) Mice 31Q-2,3S7 10 10 628 (1,821) Lipton and Rotariu (899-6,83S) (1941)cS Mice 252-1,139 10 10 618 (1,792) Silver and McGrath (731-3,303) (1942) Mice 379-890 10 10 676 (1,960) Silveret al. (1,099-2,S81) (1942) Mice 290 11e 30 290 (841) Bitron and Aharonson (841) (1978) Mice 170 

## sse 30 170 (493) Bitron and Aharonson (493) (1978) Rats Sprague- 1,748-2,203 10 14 1,941 (S,630) Zwart et al. (1990)c Dawley (5,070-6,390) Rats Sprague- 6S9-507 30 14 700 (2,030) Zwart et al. (1990)c Dawley (1,910-2,190) Rats Sprague- 472-534 

## so 14 503 (1,460) Zwart et al. (1990)c Dawley (1,37Q-l,SSO) Rats Sprague- 60 293 (8SO) Vemot et al. (1977) Dawley

•LC50 = Lethal concentration producing SO% mortality in exposed animals. bData not available.**~utes** ofexposure causing SO% mortality**(LT~.** dAs cited inWithers andLees (1985a).**~ted** values.

1 above 120 ppm (348 mg/m3) caused an increase in the water content ofthe lung (edema). 2 Inmice that died, histologic fmdings werenecrotic injury to the tracheal mucosal membrane, 3 desquamation ofthe epithelium ofbronchi and bronchioles, and inflammation of**th~** atveolar 4 epithelium.

August 

### 1994 6-3 DRAFf-D.O NOT QUOTE OR CITE1 Bitron and Aharonson (1978) exposed groups of 14 male albino mice (about 1 mo old) 2 in a tight-fitting cylindrical glass chamber with an airflow of 1 Umin. Thelevels of 3 exposure were 170 or290 ppm (348 or 841 mg/m3) chlorine and the time ofexposure was 4 varied from 5 to 30

### min atthehigh level and 15 to 160 

### min at the lower level. The animals 5 wereobserved for 30days afterexposure. Most deaths were delayed, occurring between 6 5 and 10 days. Theduration ofexposure causing 50% mortality was 11 min exposure at 7 290ppm and 55 

### min at 170ppm. All mice (28) exposed at 290 ppm for 6 min survived. 8 Withers and Lees (1985b) utilized the data on acute toxicity ofchlorine to adjust for a 9 common exposure

### period of30

### min. Thelethal load function (L) best fitting data where the 10 concentration (C) was held constant and time (T) varied was 

### L 

# =cr0·5• Omitting

### d~ta that 11 were incomplete, they obtained LC50 values for 30-min exposures ofmice, rats, and dogs of 12 256, 414, and 650 ppm (742, 1,201, and 1,885 mg/m3), respectively. 13 There were no adequate data on mortality in cats, rabbits, and guineapigs exposed to 14 chlorine. Rabbits appeared to be less susceptible than mice orrats, since a 30-min exposure 15 to levels of50, 100, and 200 ppm (145, 290, and 580 mg/m3) caused no mortality, but 16 range-finding studies indicated death 

### within an hour ofa similar exposure to 1,000**pp~** 17 (2,900 mg/m3) and 2 days after exposure to 500ppm (1,450 mg/m3) (Barrow and Smith, 18 1975). 19 Cralley (1942) studied the effect ofchlorine gas on ciliary activity in excised tracheal 20 preparations ofrabbits. Chlorine was passed over the tissue at a rate comparable to that of 21 breathing by the animal. Exposure to chlorine at 30 ppm (87 mg/m3) for

### 5 min or at 18 to 22 20ppm (52 to 58 mg/m3) for 10 min caused a cessation ofciliary activity. Control tissue 23 samples showed no effect on ciliary activity after exposure to circulated humid air for more 24 than 15 min. 25 Since acute exposure to high concentrations ofchlorine can damage the airway epithelial 26 cells, possibly disrupting the mucosal exclusion barriers that protect the host from an inhaled 27 antigen, O'Neil (1991) examined the effects ofa 

### 60-min exposure to 150 or 200 ppm (435 or 28 580 mg/m3) chlorine on immune function in BALB/c mice (sex not specified). Mice were 29 exposed by nose to aerosolized bovine serum albumin for 30 min a day for 

### 5 consecutive 30 days immediately or 1, 3, 7, or 30 days following the chlorine exposure by inserting conical 31 tubes with the ends removed, in the exposure chamber. There was an increase in circulating

August 1994 

### 6-4 DRAFT-DO NOT QUOTE OR CITE1 immunoglobulin G, butonly in the sera ofmice exposed to the antigen immediately following 2 exposure to 200 ppm chlorine. Chlorine exposureproduced no effects on immunoglobulin A 3 in sera orbronchoalveolar lavage fluid in any of

### the tested groups. 4 5 

### F.lfects 

### on Pulmo111lTY**~n.** Barrow etal. (1977) studied the sensory irritation 6 responses to chlorinein male Swiss-Webster miceexposed at concentrations**be~een** 0.7 and 7 38.4ppm (2.1 to 113.3 mg/m3). Concentration curves were plotted using percentdecrease 8 in respiratory rate. The 10-min concentration that causes a 50% reduction in respiratory rate 9 (RD50 value) was 9.3 ppm (27 mg/m3), and the no-measurable-effect level was 0.9 ppm 10 (2.6 mg/m3); chlorine was 33 times morepotent than hydrogen chloride gas (RD50 

## = 11 309 ppm). 12 Barrow and Steinhagen (1982) investigated the development ofa tolerance to sensory 13 irritation by male Fischer 344 rats exposed to chlorine gas at 0, 1, 5, or 10 ppm 14 (0, 2.9, 14.7, or 29.5 mg/m3) for 6 h/day, 5days/week for 2 weeks as a pretreatment. 15 Sixteen to 24 h following the pretreatmentperiod, rats were exposed to chlorine gas for 16 10 min at concentrations ranging from 1to 760 ppm (2.9 to 2,242.7 mg/m3). The 17 RD50 value in naive rats was 25.4 ppm (75.9 mg/m3 ), whereas chlorine pretreatments of 18 1, 5, or 10 ppm increased the RD50 values to 90, 71, and 454 ppm (265.5, 209.5, and 19 1,339.7 mg/m3), respectively. 20 Chang and Barrow (1984) reported that exposure

## tO 10 ppm (29.5 ·mg/m3) chlorine gas 21 for 1, 4, or 10 days induced tolerance in male Fischer 344 rats.. After 1 day ofexposure, the 22 RD50 value was 35.9 ppm (105.9 mg/m3), compared to 10.9 ppm (32.1 mg/m3) 

### in naive 23 rats. Pretreatments of4 and 10 days resulted in a 20-fold increase in the RD50 (225 ppm 24 [663.9 mg/m3]) over that ofthe naive animals. 25 Barrow and Smith (1975) studied changes 

### in pulmonary function in rabbits exposed to 26 sublethal levels ofchlorine. Groups offour rabbits (strain not specified) ofboth sexes were 27 exposed to chlorine gas at 0, 50, 100, or200 ppm (0, 145, 290, or580 mg/m3 ) for 30 min. 28 One rabbit from each group was tested for changes inpulmonary function 30 min and 3, 14, 29 and 60 days after exposure. Lung function was evaluated using capacitance respirometry in 30 which volume-pressure relationship (V-P) and inspiratory-expiratory flow rate ratios (V1:Vw 31 were measured. At 100 and 200 ppm, V1:VE increased about 40% after 30 min ofexposure.
August 1994 6-5 DRAFf-DO NOT QUOTE OR CITE

### 1 2 3 4 

### 5 

### 6 7 8 9 

### 10 At 200 ppm, V1:VE

### increased 67% after 3days; no effects were seen at 50 ppm. The**ra~os** 

### returned to normal after 

### 60 days for both the 100- and 200-ppm exposure groups. Pulmonary compliance decreased 25 to 

### 50% at all exposurelevels from 0.5 h to 3 days after exposure. After 14 and 60 days ofrecovery, compliance returned to normal in the rabbits exposed at 50 ppm 

### but was significantly increased in

### rabbits exposed at 100 or 200 ppm. Correlations


### were madebetween functional changes and postmortem findings. The V1:VE

### ratio quantitatively related to the degree ofimpairmentresulting from pulmonary edema, whereas V-P 

### changes indicated emphysema-likechanges and loss ofelastic properties. Recovery time

' . 

### was related to 

### the level ofchlorine exposure and the extent ofpulmonary damage.

11 6.1.1.2 Subchronic Toxicity 

### 12 Buckley et al. (1984) exposed groups of 16 to 24 Swiss-Webster mice to chlorine at the 13 RD50 

### concentration of9.34 ppm (27.5 mg/m3), 

### 6 h/day for 

### 5days. The effects on the 14 respiratory and olfactory epitheliaofthe upper respiratory tract were similar to those 15 previously found in 

### the same laboratory at 9.1 ppm (26.4 mg/m3) 

### chlorine, 6 h/day for 16 

# ?days (Jiang et al., 1983). Lesions ofthe trachea were described as mild to 

### moderate 17 epithelial exfoliation, hyperplasia, and squamous metaplasia. 

### In the.lungs, there was 18 moderately severe terminal bronchiolitis with occlusion ofthe affected bronchioles by 19 serocellular exudate. Barrow et al. (1979a) exposed groups often 6- to 8-week-old Fischer 20 344 rats ofboth sexes to chlorine gas at0, 1, 3, or 9 ppm (0, 2.9, 8.7, or 26.0 mg/m3) 

### for 21 6 h/day, 5 days/week for 6 weeks. Clinical signs oftoxicity were recorded daily, and body 22 weights were recorded 3**tim~** 

### a week. Prior to sacrifice, blood and urine were collected for 23 hematology and urinalysis. After sacrifice, blood was obtained for clinical chemistry 24 determination, a complete gross examination was performed, organs were**we~ghed,** 

### and 25 tissues were fixed-for histopathologic evaluation. At 1ppm, there were occasionaJ slight 26 signs ofupper respiratory irritation, and at 3 and 9ppm, lacrimation and hyperemia ofthe 27 conjunctiva occurred; nasal discharge and salivation were seen throughout the study. 28 Gasping, lung rales, and mouth breathing were observed at 9ppm. All groups ofexposed 29 rats had urinary staining ofthe perineal fur. 

### One control male and three high-dose females 30 died during the study. There were significant (p 

## < 0.05) reductions in body weight gains in 31 both males and females exposed at 3 or9ppm when compared to controls. In

### both males

August 1994 6-6 DRAFT-DO NOT QUOTE OR CITE1 and females exposed at 9 ppm, there were significant (p 

### < 0.05) increases in segmented 2 neutrophils and increases in blood urea nitrogen (BUN) and serum gamma-glutamyl 3 transpeptidase. Significant (p 

### < 0.05) increases 

### in serum alkaline phosphatase were also 4 observed in the groups ofmales and females exposed at 3 and 9 ppm. There was also an 

### 5 increase in serum glutamic oxaloacetic 

### transaminase in females exposed at9 ppm compared 6 to controls. The specific gravity ofurine tended to increasein 

### all exposed groups. 7 Histopathologic examination ofthe rats exposed to chlorine at9 ppm 

### indicated 8 inflammation ofthe upper and lower respiratory tract (Barrow etal., 1979a). There was 9 focal-to-multifocal mucopurulent inflammation ofthe nasal 

### turbinates with increased secretory 10 material and necrotic lesions. The tracheobronchial region showed epithelial hyperplasia and 11 hypertrophy ofthebronchiolar and alveolar duct epithelia, an increase ofalveolar 12 macrophages, and focal areas ofnecrosis. In rats exposed to 

### 1or 3 ppm, similar but less 13 severe lesions were noted. At 9 ppm, the histologic changes correlated with increased 14 absolute and relative lung weights. Kidneys ofboth males and females exposed at 

### 9ppm 15 showed some congestion and changes in the.renal tubules;**th~e** changes correlated with the 16 increased 

### BUN values. There were increases in hepatocellular vacuolization in the liver of 17 males and females exposed to 3 or 9 ppm when compared to controls. Thehistologic 18 changes in the liver correlated with increased actiyity ofserum enzymes. There was also 19 focal erosion ofthe gastric mucosa, but only in the animals exposed to 9 ppm. The authors 20 believed that the results ofthis study may have been affected by the presence ofchloramines 21 produced by the reaction ofchlorine with excreta. Barrow and Dodd (1979) detected 22 ammonia and chloramines in inhalation chambers ofrats exposed to chlorine, and they 23 showed that chloramines are produced by the reaction ofchlorine with excreta. Ammonia 24 concentrations 

### in a 99-L chamber with an airflow of26 Umin and an animal_loading of3.1% 25 reached 1.6ppm (4.7 mg/m3) after 

### 6 h (no chlorine exposure). The 6-h time-weighted 26**av~rage** (fWA) for 

### an animal load of 1.4% exposed to chlorine at 

### 2 ppm (5.8 mg/m3) in a 27 chamber with an airflow of26 L/min was 0.13 ppm for chloramines. 28 Jiang etal. (1983) exposed groups ofnine orten 8-week-old male Fischer 344 rats and 29 6-week-old male Swiss-Webster mice to chlorine gas ata concentration of9.1 ppm 30 (26.4 mg/m3), 6 hlday for 

### 1, 3, or

### 5 days. Theexposure concentration was close to the 31 RDso value (9.3 ppm [27 mg/m3]) (Barrow etal., 1977). After 1, 3, and 5days, groups of

August 1994 6-7 DRAFf-DO NOT QUOTE OR CITE1 animals were sacrificed for histologic examination ofthe respiratory tract. Five levels ofthe 2 nasal passage and the nasopharynx, larynx, trachea, and

### lung~ were examined by light 3 microscopy. Lesions were found in the 

### nasal passages ofexposed animals, with less severe 4 changes noted 

### in the nasopharynx, larynx, trachea, and lungs. Nasal lesions involved both 

### 5 olfactory

### an~ respiratory epithelia. Incontrast to Day 1, after Days 3 and 

### 5 ofexposure, the 6 lesions became more severeand were moreposteriorly extended. There was epithelial 7 degeneration, erosion, and ulceration after 1to 3 days and neutrophil infiltration and 8 squamous metaplasia at

### 5days. Themost severelesions were found in the olfactory 9 epithelium covering the middle third ofthe dorsal meatus inboth mice and rats. There was 10 some degeneration ofthe olfactory nerves 

### in mice. Electron microscopy indicated complete 11 loss ofcilia in extensive areas and cellular exfoliation ofthe naso- and maxilloturbinates. 12 In a subchronic inhalation study conducted by the National Toxicology Program 13 (Kutzman, 1983), male and female Fischer 344 rats were exposed to 0, 0.5, 1.5, or5.0ppm 14 (0, 1.4, 4.3, or 14.5 mg/m3) chlorine, 6 h/day, 

### 5 days/week for 62 days. All animals were 15 observed daily, weighed weekly, and sacrificed after exposure was terminated. Histologic 16 sections wereprepared ofthe respiratory tract, heart, liver, kidneys, spleen, and testes. 17 Pulmonary function tests wereperformed on 24 anesthetized rats from each exposure group. 18 Animals in the 5-ppm exposuregroup had 

### nasal discharge, excessive salivation, and 19 lacrimation. Similarbutless severe symptoms were noted 

### in the rats exposed to 1.5 ppm 20 chlorine. No outward signs ofirritation were noted 

### in the animals exposed to 0.5 ppm 21 chlorine. None ofthe pulmonary function parameters examined demonstrated a statistically 22 significant change in pulmonary function in exposed animals. However, the difference in 23 expiratory flow rate at25% ofthe vital capacity (VC), a measure ofthe degree ofconvexity 24 orconcavity ofthe effort-independent limb ofthe maximum expiratory flow yolume curve, 

### 25 was significantly reduced (p = 0.04, analysis ofvariance) 

### in chlorine-exposed animals, 26 indicating some degree ofsmall airway involvement, butthere was no exposure-related 27 relationship observed among the exposed groups. Histopathological evaluation ofthe trachea 28 ofexposed animals showed a loss ofepithelium and cilia. Thesechanges were not severe 29 · and were similar to those findings in thecontrol animals, butthe mean trachea pathology 30 scores ofthe 0.5 and 5.0ppm chlorine-exposed animals, using Kruskal-Wallis nonparametric 31 test and the multiple comparisons techniques ofDunn and Miller, were significantly greater

August 1994 6-8 DRAFr-DO NOT QUOTE OR CITE1 than those ofthe control group. Histopathological evaluation ofother organs showed no 2 exposure-related effects. There was also a significant increase in the lung collagen content 

### in 3 rats exposed to 1.5 and 5.0ppm chlorine. The elastin content in thelungs ofchlorine4 exposed animals was not significantly different from that ofcontrol animals. The authors 5 also reported mean concentrations of0.0395, 0.466, and 0.585 ppm chloramines, 6 respectively, in the cages ofchlorine-exposed animals. 7 

### 8 6.1.1.3 Chronic Toxicity 9 In a 12-mo chronic study, groups offour male and four female young adultrhesus 10 monkeys were exposed to chlorine at concentrations of0.1, 0.5, or2.5 ppm (0.29, .1.45, or 11 7.25 mg/m3) for 

### 6 h/day, 

### 5 days/week for 1year (Ulrich, 1984). The actual monitored 12 concentrations were 0.1, 0.5, and 2.3 ppm (0.29, 1.45, 6.67 mg/m3) (total chlorine); the 13 concentrations ofchloramine were 0.04, 0.14, and 0.13 ppm in the·low, middle, and high 14 exposure chambers. Animals were observed daily for toxic signs, body weight, and food 15 consumption throughout the study. Pulmonary physiology was evaluated three times prior to 16 study initiation and**~onthly** thereafter, with measurement ofnitrogen washout and pulmonary 17 diffusing capacity. Electrocardiography evaluations, hematology (hematocrit, hemoglobin 18 concentration, erythrocytecount, leukocyte count, reticulocyte count, mean corpuscular 19 volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration), 20 clinical biochemistry (alanine aminotransferase, aspartate aminotransferase, gamma 21 glutamyltransferase, blood urea, nitrogen, calcium, phosphorus, total bilirubin, and total 22 protein), and urinalyses (volume, color, sediment, specific gravity, pH, protein, glucose, 23 occultblood, nitrites, bilirubin, ketones, and urobilinogen) wereperformed on all animals 24 prior to initiation and monthly during the study; arterial blood 

### gases were alsQ measured. 25 At the end of 1year, the monkey.s were sacrificed, selected organs were weighed, and all 26 tissues were examined grossly and histologically. 27 There were no deaths, and the only toxic sign was overt ocular irritation in the 2.3-ppm · 28 chlorine-exposed group. Opthalmologic examination at 12 mo showed that irritation involved 29 the conjunctiva but not the cornea. There were·no effects on clinical chemistry or · 30 hematologic orurinary parameters, and pulmonary function parameters did not differ 31 significantly from the control values at any interval.

August 1994 6-9 DRAFT-DO NOT QUOTE OR CITE1 Theonly exposure-related histopathologic change was a mild focal epithelial hyperplasia 2 in the respiratory epithelium ofthe nose and trachea, which was associated with a loss ofcilia 3 and goblet cells. These lesions wtTe induced in both sexes exposed to 2.3 ppm chlorine. 4 Similarbutless distinct changes werepresent only in the nasal passage ofboth sexes of 5 animals in the 0.5-ppm group and

### in females in the 0.1-ppm group (Ulrich, 1984). Moderate 6 to severe granulomatous rhinitis and pulmonary lesions typical ofacariasis were reported in 7 tlle monkey population

### as the result ofa nematode and 

### mite infestation. However, according 8 to the authors, the histopathological changes produced by the parasites were separate and 9 distinct from those changes caused by the chlorine exposure (Klonne et

### al., 1987). 10 In a 2-year chronic inhalation study, male Fischer 344 rats and male and female 

### 11 B6C3Fl 

### mice were exposed to 0. 0.4, 1.0, or 2.5 ppm 

### (0, 1.2, 2.9, or7.2 mg/m3) chlorine 12 gas 5 hlday, 

### 5 days/week for 2 years. Female Fischer 344 rats were exposed to the same 13 chlorine concentrations but on 3 alternate days per week over the 2-year period. All 14 chlorine-exposed animals had respiratory and olfactory epithelial degeneration, septal 15 fenestration, inflammation, epithelial hyperplasia and squamous metaplasia, goblet 

### cell 16 hyperplasia/hypertrophy, and secretory metaplasia ofthe transitional epithelium ofthe lateral 17 meatus. Most ofthese lesions, restricted to the nasal passages·ofthe chlorine-exposed 18 animals, were concentration-dependent; however, epithelial hyperplasia and secretory 19 fenestration occurred to a similar degree 

### in all chlorine-exposed mice. There was also 20 intracellular accumulation ofeosinophilic proteinaceous material involving the respiratory, 21 transitional, and olfactory epithelia, and, in some instances, the squamous epithelium ofthe 22 nasal vestibule (Gross et al., 1993). 23 24 

## 6.1.2 Hydrogen Chloride 25 Most ofthe experimental animal studies for hydrogen chloride evaluate the effects of 26 acute inhalation ofthe gas and are concerned with sensory irritation, respiration, 27 incapacitation, lethality, pulmonary function, and respiratory/pulmonary tract pathology. 28 Subchronic and 

### repeated exposure studies are

### limited in number, and the only chronic studies 29 evaluate the carcinogenic effects ofhydrogen chloride and formaldehyde. 30 31
August 1994 6-10 DRAFT-DO NOT QUOTE OR CITE1 

### 6.1.2.1 Acute Toxicity Inhalation 2 0 

### ,'\j Darmer et al. (1974) reported the acute LC50 values for hydrogen chloride 

### in male 3

### c.\/ CF-1 

### mice and CFErats (Table 6-2). Groups of 10 to 15 animals were exposed to various 4 concentrations ofhydrogen chloride gas or aerosol for 

### 5or 30

### min. About 93% ofthe 

### 5 particle 

### size ofthe aerosol droplets was 

### in the range of 1to 2 I'm. No mortalities occurred 6 

### in 

### mice exposed for 30

### min to410 ppm (615 mg/m3 ) or 

### in rats exposed

### forth~ same 7 duration to 2,078 ppm (3,117 mg/m3) hydrogen chloridegas. Deathpatterns observed were 8 similar for both the gas and the aerosol. Most deaths occurred 

### in 1to 2 days, but some 9 deaths occurred up to 8 days after exposure. Hydrogen chloride was extremely irritating to 10 the eyes, mucous membranes, and exposed areas ofthe skin, such as the scrotum. Corneal 11 erosion and clouding occurred 

### inboth species. According to the authors, theprimary 12 pathological lesions observed 

### in the respiratory tract were alveolar emphysema, atelectasis, 13 and edemaofthe lungs, as well as severeinjury to the epithelium ofthe nose and trachea. 14 15 TABLE 6-2. ACUTE TOXICITY VALUES FORHYDROGEN CHLORIDE .IN MICEAND RATS

. Minimal Exposure Lethal Number of

Time 

## * Coneentration Deaths LCso Species (minutes) (ppm [mg/m3]) (ppm [mg/m1) Observed 

### Gas

Mice 

### 5 13,745 (20,618) 3,200 (4,800) 1/10 Rats 

### 5 40,989 (61,483) 32,255 (48,532) 1/10 

### Mice 30 2,644 (3,966) 1,134 (1,701) 2/15 Rats 30 4,701 (7,051) 2,676 (4,017) 1/10 Aerosol



### Mice 

### 5 11,238 (16,857) 9,058 (13,587) 3/10 Rats 

### 5 31,008 (46,512) 19,312 (28,968) 1/10 Mice 30 2,142 (3,213) 1,204 (1,-806). 2/10 Rats 30 5,666 (8,499) 2,910 (4,365) 1/10

LC50 

### = Lethal concentration producing 50% mortality in exposed animals. Source: Danner et al. (1974).

August 1994 6-11 DRAFT-DO NOT QUOTE OR CITE

### 1 Morerecently, Hartzell et al. 

### (1985) determined LC50 

### values for hydrogen chloride_for 2 exposure times of5, 10, 15, 22.5, 30, and 60 min. 

### Groups ofsix to eight adult male 3 Sprague-Dawley rats were.exposed to atleast**fiv~** 

### concentrations ofhydrogen chloride for 4 

### each ofthe exposure times, followed by a 14-day observation period. Table 6-3 presents the 5 LC50

### values. Agraph ofLC50 

### versus time ofexposure is shown in 

### Figure 6-1. Thereis a 6 

### discrepancy in

### the LC50

### value reported 

### by Hartzell et

## 31. (15,900 ppm [23,850 mg/m3]) 

### and 7 Danneretal. (40,989 ppm [61,483 mg/m3]) 

### for a 5-min exposure. This emphasizes the fact 8 that LC50

### values may vary considerably. 9 

### 10 TABLE 6-3. ACUTE TOXICITY VALUES IN RATS EXPOSED TO HYDROGEN CHLORIDE Exposure Time (minutes) 5 10 15 27.5 30 60 15,900 (11,540-21,890)c 8,370 (7,770-9,010) 6,920 (5,380-8,900) 5,920 (3,455-10,145) 3,715 (2,540-4,435) 2,810 (2,250,3,510)

•Lcso 

### = Lethal concentrationproducing 50% mortality in exposed animals. 

### L(Ct)sob 

### (ppm-minute) 79,500 83,700 103,800 133,200

° 

### 111,450 168,600**~Ct)so** = Lethal concentration X exposure timeproducing 50% mortality in exposed animals. VJ'he 95% confidence limits are inparentheses.
Source: Hartzell et al. (1985).

# ~~~~**~** 

### 1 Anderson and Alarie (1980)

### ~rted an LC50 

### value (30-min exposure, 3 h . 2 postexposure) for hydrogen chloride of 10,137 ppm (15,104 mg/m3) 

### in normal mice and 3 1,095 ppm (1,632 mg/m3) 

### in trachea-cannulated mice. Based 

### on these findj.ngs, Alarie 4 (1985) theorized that a safety factor of7to 10 should be applied in extrapolating the acute 

### 5 lethal effects ofhydrogen chloride in 

### mice to 

### humans to compensate for the effective 6 absorption ofthe gas in the nasal passages ofmice. However, this theory is not consistent 7 with observations oflower respiratory tract damage in animals only at very high 8 concentrations ofhydrogen chloride. August 1994 6-12 DRAFT-DO NOT QUOTE ORCITE

## i :; .5 

### g 

# I

0 CD

## ~**0~----~----~------------~----~~----~----~** 0 4 8 12 16 20 LC50 HOI (ppm x 1**~)** Figure 6-1. Hydrogen chloride concentrations producing 50% mortality in adultmale Sprague-Dawley rats versus time ofexposure.
Source: Hartzell et al. (1985).

## ~f(__-1'{01....-- 1 Higgins et al. (1972) investigated the effects ofexposure to CO on the acute lethality of 2 a 5-min exposure to hydrogen chloride in mice and rats. The concentration ofCO in mice 3 (1,500 ppm) and rats (2,100 ppm) was sufficient to produce 25% carboxyhemoglobin. The 4 7-day LC50 values for hydrogen chloride, 13,745 ppm (20,618 mg/m3) for mice and 

### 5 40,989 ppm (61,483 mg/m3) for rats, were not significantly different from those for 6 hydrogen chloride and carbon monoxide combined (10,663 and 39,010ppm [15,994 and 7 58,515 mg/m3] for mice and rats, respectively). In a later study, Hartzell etal. (1987) 

### 8 suggested that the acute lethal effects ofhydrogen chloride and carbon monoxide may be 9 additive but did not provide evidence for the interaction. 10 

### (f'.'Y Lucia et al. (1977) reported the histopathologic changes in theupper respiratory tract of 11ct"' male Swiss-Webster mice following acute exposure to hydrogen chloride. Mice were exposed August 1994 6-13 DRAFf-DO NOT QUOTE OR CITE

### 1 to concentrations ranging from 17 to 7,279 ppm (25 to 10,918 mg/m3) 

### for 10 min;.

### 24 h after 2 the exposure, four transverse sections ofthe nose, 1.5 to 2.0 mm apart, beginning at the 

### 3 external nares to the lateral canthi 

### ofthe eyes, were examined histologically. At 17 ppm, -

## pul\-~<- 4 small superficial ulcerations occurred only in the respiratory epithelium atits junction with 5 

### the squamous epithelium. As the concentration was increased, 

### the mucosal ulceration 6 increased 

### in a contiguous fashion, gradually extending up the sides and the septum ofthe 7 nasal 

### cavity. At 723 ppm (1,084 mglm3), 

### more than 

### the lower two-thirds ofthe upper 8 respiratory tract was damaged, 

### and the entire mucosa was destroyed at 1,973 ppm 9 (2,954 mglm3). 

### A concentration of493 ppm (739 mg/m3) 

### completely destroyed the 10 squamous epithelium ofthe external nares. At 1,088 ppm (1,632 mg/m3), 

### the underlying 11 support structures were damaged; the cartilage ofthe nasal epithelium was necrotic, and the 12 bone ofthe maxilloturbinate was eroded. At concentrations of 1,973 ppm or above, portions 13 ofthe squamous, respiratory, and olfactory epithelium were all affected. At 7,279 ppm 14 (10,918 mg/m3), 

### total destruction ofthe mucosa and support structures, along with total 

### 15 destruction ofthe eyes, was observed in all animals. 16

### c'v~3**'r'** Barrow et al. (1979b)

### compar~ the acute inhalation

### to~city ofhydrogen chloride and 17 the thermal decomposition products ofpolyvinyl chloride (PVC). 

### Groups offour male 18 19 20 21 22 23 24 25 26 27 28 29 30 31 Swiss-Webster mice were exposed to hydrogen chloride at concentrations ranging from 20 to 20,000 ppm (30 to 30,000 mg/m3) 

### for 10 min. Mortality occurred at concentrations between 8,276 to 20,000ppm (12,414 to 30,000 mg/m3) 

### hydrogen chloride compared to 20,690 to 27,586 ppm (31,035 to 41,379 mg/m3) 

### PVC 

### products. Histopathologic examination revealed that both hydrogen chloride and PVC 

### products produced changes in

### the upper respiratory tract and the eyes similar to those reported in the study by Lucia etal. (1977). There was also passive congestion 

### in the lungs, intestine, liver, and kidney with both 

### hy9fogen chloride and PVC 

### products; however, it was not clear at which exposure levels these changes occurred. Based 

### on the theoretical amount ofhydrogen chloride evolved from PVC, 

### it was indicated by the authors that the acute toxicity ofPVC 

### was**d~e** 

### primarily to the hydrogen chloride evolved in

### the thermal decomposition. 

### -::)IJ.f!JA 

## t1/'4/i_ The acute inhalation toxicities ofhydrogen

## chi~ and methyltrichlorosilane were compared in male and female rats by Kolesar et al. 

### (1993). Rats 

### were exposed to 

### either 1,500 or 3,000 ppm (2,235 or4,470 mg/m3) 

### hydrogen chloride for 1

### h by nose-only

August 1994 6-14 DRAFf-DO NOT QUOTE OR CITE

### 1 exposure. Hydrogen chloride-exposed animals were then sacrificed 24 or48 h, or 7 or 2 24 days postexposure and examined for changes 

### in organ weights and gross and 3 histopathological tissue changes. The most severe**tteatment-rela~** 

### effects were reported to 

### 4 be 

### in the nostril portion ofthe nasal 

### cavity. Hydrogen chloride was not only toxic to the 5 surface epithelium lining fl:le nasal cavity but also produced severe necrosis and ulceration 6 involving the underlying softtissues and cartilage, especially in 

### thehighest exposed group. 7 By 

### Day 14 postexposure, the authors reported that the mucosalining ofthe respiratory 

### tree 8 had been restored; however, the ulcers had 

### been replaced by 

### scar tissue. 9 Studies conducted in the 1930s with guineapigs and rabbits showed that single 10 exposures to hydrogen chloride gas at concentrations less than 

### 200 ppm (300 mg/m3) 

### for up 11 to 6 h were tolerated without any aftereffects orwith slight aftereffects, while exposure at 12 300 ppm (450 mg/m3) 

### for 6 h caused slight ocular 

### and respiratory irritation in

### both species. 13 Exposure to 1,350 ppm (2,025 mg/m3) 

### for 90 

### min caused severe irritation, while exposure to 

### 14 3,400 ppm (5,100 mg/m3) 

### for the same duration caused death in 

### 2 to 6 days. The authors 15 stated that guinea pigs were, in 

### general, more sensitive than cats and rabbits (World Health 16 Organization, 1982). 17

### cL..olol Machle et 

### al. (1942) exposed groups ofthree guineapigs and 

### three rabbits to hydrogen 18 chloride gas concentrations of33 to 13,667 ppm (50 to 

### 20,500 mg/m3). 

### Exposure to 19 3,685 ppm (5,500 mg/m3) 

### for 5 min 

### caused no deaths, whereas exposure to 4,288 ppm 20 (6,500 mg/m3) 

### for 30 min 

### orto 670.PPm (1,000 mg/m3) 

### for 2 to 6 h resulted in 100% 21 mortality 

### in both species. Guinea pigs were more severely affected, with deaths occurring in 

### 22 22 of57 animals 6 days after exposurebecause ofhistological changes 

### in the liver 23 (parenchymal edema, congestion, necrosis, and hemorrhage) and lungs ofanimals exposed to 24 high levels ofhydrogen chloride. Cirrhotic sclerosis was noted in

### the liver**o~** 

### some animals 25 

### in the high-exposure groups for months after exposure. There were also histological changes 26 in the kidneys and heart ofexposed animals, butit was not indicated at what exposure 27 concentrations these effects were seen. Exposure to high concentrations induced necrosis of 28 the tracheal, bronchial, and alveolar epithelia, and necrosis was accompanied by pulmonary 29 edema, atelectasis, and emphysema (Machle et 

### al., 1942). It

### is difficult to determine whether 30 the effects noted in the liver, heart, and kidney are toxic effects ofhydrogen chloride 31 exposure in the absence·ofhematological and clinical analyses, orthe result ofrespiratory

August 1994 6-15 DRAFT-DO 

### NOT QUOTE OR CITE

### 1 2 

### 3 4 

### 5 6 7 

### 8 9 10 11 12 13 14 15 16 

### 17 18 

### 19 20 21 22 23 

### 24 25 

### 26 27 

### 28 

### 29 30 31 failure, because respiratory failure orinadequacies are known to

### affect various organs and systems. Differences in hydrogen chloride-induced histopathological changes in the respiratory tract ofmouth- and nose-breathing maleFischer 344 rats were reported 

### by Stavertetal. 

## CL-crry (1991). Seventy rats were divided into four groups (nosebreathet:s, mouth breathers [fitted 

### with a mouthpiece with an attached silastic endotracheal tube], and two air-exposed control groups) and 

### exposed to 1,300 ppm (1,937 mglm3) 

### hydrogen chloride for 30**~in** 

### a partial 

### body flow plethysmograph attached to an exposure chamber. Following hydrogen chloride exposure, the animals were exposed to 

### air 

### for 15 

### min prior

### tO removal from the plethysmographs. The animals were sacrificed 24 hfollowing exposure. Nose-breathjng animals exposed to

### hydrogen chloridehad severe, necrotizing rhinitis with full 

### thiclmess necrosis ofthe turbinates, thrombosis ofvessels ofthe nasal submucosa, and fibrinous pseudomembrane formation in the anteriorportion ofthe nasal 

### cavity. The trachea ofsome hydrogen chloride-exposed nose breathers showed a mild suppurative inflammatory reaction in the proximal mucosa that was quantitatively insignificant. There were no histopathological changes noted in the lungs ofthese animals. The nasal cavities ofrats fitted with mouthpieces were generally unaffected by the hydrogen chloride exposure, with the exception ofan occasional**find~g** 

### ofblood and/or exudates in the nasal turbinates. Severe, diffuse, ulcerative tracheitis with necrosis ofthe

mucosa and submucosa with fibrin membrane formation covering the ulcerated lumen ofthe trachea was noted in the mouth-breathing animals exposed to hydrogen chloride. Polymorphonuclear leukocytes (PMNs) were observed in the submucosa, between the tracheal rings, and in the connective tissues around the trachea. Necrosis ofthe largerbronchi was
seen in some mouth-breathing, hydrogen chloride-exposed animals, but theselesions were not significantly greater than 

### those reported 

### in mouth-breathing, air-exposed animals. In 

### some lungs, there were significantly elevated numbers ofPMNs in alveoli surrounding some terminal bronchioles. However, whether the increase in PMNs was the result ofa hydrogen chloride-induced inflammatory response by the alveoli**o~ ~ge**  

### airway injury was not [t:i.tt-1

### rJ.~fx 

# I"**(~flGA...** 

## "fjR**~~·** /Cf

## 86 determined. (Stavert etal., 1991). ,... CL-o«tl'tj' 

# c L

### -o'('

## 7 Kaplan et al. 

### (1984) and Kaplan (1987) exposed ninejuvenile male baboons (Papio cynocephalus) 

### for 5

### min to

### various levels ofhydrogen chloride between 190 and

August 1994 6-16 DRAFT-DO NOT QUOTE OR CITE

### 1 17,290 ppm (285 and 25,935 mg/m3) 

### and evaluated their ability to

### escape. The animals had 2 been pretrained to operate a lever to open a door and exit from the chamber in response to 3 audio and visual cues. There was no significantincrease in 

### escape time at any exposure 4 level; itwas 7.39 

# ±4.26 s in 

### exposed baboons, and thepretest average was 6.54 

## + 1.37 s. 5**,~** 

### ppm hydrogen chloride, there were no reactions and no postexposure symptoms.

# 6N°At~els of810, 890, and 940 ppm (1,215, 1,335, and 1,410

# mg/m~~~f\... 7 agitation, salivation, and frothing atthe mouth butno significantpostexposure symptoms. 8 Atlevels of2,780 and 11,400 ppm (4,170 and 17,100 

### mgliii3), 

### there was

## imm~--;------~f-'G 9 

### 10 11 12 13 14 15 16 17 18 19 20 21 22 23 

## 24 25 26 27 28 29 30 31 coughing and choking, copious salivation, and eye irritation. ·At 2,780 ppm, there were no significantpostexposure symptoms, except a dry

### cough; at 11,400 ppm, there was coughing and frothing from the nose and mouth that, according to the authors, responded to treatment

_ in 3 to 4 days (Kaplan et al., 1984).- {

# q&) 

# 5**aw...~ J..f~**  

# · At levels of 16,570 and 17,290 ppm (24,855 and 25,920

# mg/m**)(SYnii)to~fct~ring** exposure were more severe (Kaplan et al., 1984). There were severe postexposure dyspnea and respiratory difficulties at these levels, and death occurred at 18 days and 76 days. There

was obliteration ofthe normal mucosa, tracheitis, and pneumonia in 

### the animal that died at

. . 

### Day 18, whereas the an?.mal that died at day 76 had pwmonary edema and hemorrhage, bronchopneumonia, erosion ofthe epitheliaofthe trachea, and hepatocellular degeneration. These authors also studied escape impairment in male Sprague-Dawley**~ts.** 

### Exposure to



## . . -F levels ofhydrogen chloridebetween 11,800 and 76,730 ppm (17,700,..an 115,095 mg/m3) 

### did not affect the escape time appreciably. Exposure to 87,660.ppm (131,490 mg/m3) 

### resulted in collapse ofthe animal after about 4 min 

### ofexposure, with death approximately 1 min 

### later. However, there were severe**to~f**

### E_£ects at all 

### levels, and mortality occurred at 

### levels above 14,410ppm (21,615 mg!m3}htdrogen chloride.

. (' The incapacitating potential ofhydrogen 

### chloride was reported 

### by 

### Ctane et

### al. 

### (1985). 

## L'O.r6'C) Male Sprague-Dawley rats were exposed to hydrogen chloride gas at target levels between 2,000 and 100,000 ppm (3,000 and 150,000 mg/m3) 

### while the anim3Is Yiere enclosed singly in

# acylindrical cage similar

### to an exercise wheel rotating at 6 rpm. When the animal could

no longer walk in a coordinated fashion in 

### the cage; the time to incapacitation (tj) 

### was noted and rotation was stopped. Observation was continued until respiration ceased, and the time to death (td) was recorded. The two end points measured, 1j 

### and td, 

### were equated to measured

August 1994 6-17 DRAFT-DO NOT QUOTE OR CITE

### 1 hydrogen chloride concentration (integrated over the duration ofthe exposure) by**statisti~y** 

### 2 derived regression equations. The observed 

## !i ranged from 5.5 

### min at 94,000ppm 3 (141,000 mg/m3) to 

### 185 min at 2,000 ppm. When the regression equations were fitted to 4 each data setusing a nonlinear least squares technique, the resulting response equations were 

### 5 as follows: 

### 6 

### 7 

## !i = 3 

### + 336/(HCl

- 0.3) for incapacitation, and 8 td = 3 

## + 411/(HCl

- 0.4) for lethality, 9 

### 10 where 

## !i and td are in minutes, and hydrogen chloride concentrations are in parts per 11 thousand. The relationship between responsetime and hydrogen chloride concentration is 12 shown in 

### Figure 6-2 for the incapacitation end point and in

### Figure 6-3 for lethality. The 13 constants 0.3 and 3.0in the equation suggestthatthe threshold for an infinitely long exposure 14 would be 300 ppm (450 mg/m3), 

### and the shortest

## !i at infinite exposure concentration would 15 be 3 min. The authors suggested that the results indicate that hydrogen chloride was not 16 nearly as incapacitating as had been previously thought. However, guineapigs appear to be 17 far more sensitive to hydrogen chloride exposure and exercise than rats. 18**)'\~o'V**

### According to

### Malek and Alarie (1989), there was 100% mortality in male guinea pigs 19 

### (!:>"exposed to 586 ppm (879 mg/m3) hydrogen chloride beginning 10 min into a55-min exercise 

### 20 regime. The guineapigs exposed to 

### 586 ppm became incapacitated in less than 1 min



### ·21 (0.65 min) 

### and died within 3 min. Guinea pigs exposed to 140 and 162 ppm (210 and 22 243 mg/m3) 

### hydrogen**chlorid~** 

### during the exercise also were incapacitated within 16.5 and 23 1.3 min, respectively; however, no deaths occurred as a result ofthe exposure. Animals 24 exposed to 107 ppm (161 mg/m3 ) 

### hydrogen chloride were able to complete tl!e 55-min 25 exercise regime. Mild irritation, however, was reported in 

### that group. 26 1 ':- 

### u.:tv. Cralley (1942) studied the effect ofchlorine and hydrogen chloride gas on ciliary 27 activity in excised tracheal preparations ofrabbits. The gases were passed over the tissue at a 28 rate comparable to that ofbreathing by the experimental animal. 

### Exposure to hydrogen 29 chloride at 60 ppm (90 mg/m3) 

### for 5

### min or at 30 ppm (45 mg/m3

### ).for 10 min**ca~sed** 

### 30 cessation ofciliary activity with no recovery when the tissue was exposed to air. Exposure to 31 chlorine at 30 ppm (87 mg/m3) 

### for 5

### min or at 18 to 

### 20 ppm (52 to 58 mg/m3) 

### for 10 min

August 1994 6-18 DRAFf-DO NOT QUOTE OR CITE220



### 200

180

160

(i' 

### 140

## ~ c 

# ·e 120 '-""' G) 

### E 

### i= 100 

### c 0 

## 1a



# ... 80**-~**

# ~ eo .5

40



### 20

0 0 10 20 30 40 50

. 60 70 

### 80 90 

### 100 

### HCI Concentration (ppt)



### Figure 6-2. Incapacitationtime 

### as a function ofhydrogen chloride concentration. Regression parameters: correlationcoefficient 

# =0.96; standarderrorof estimate 

### = 11.2; and 95% confidence interval for the constant, 336, is 

### 314 to 358.

Source: Crane et al. (1985).

August 1994 

### 6-19 DRAFT-DO NOT QUOTE OR CITE

### 240

220

200



### 180

180 

### -;;; 

### m '5140 c 

# g CD 

### E 120 

### I=**~100 ·~**  ::::t 

### en 80

60

40

20 0 0



### 0 0 

### 10 20 30 40 50 60 70 80 90 

### 100 

### HCI Concentration (ppt)

Figure 

### 6-3. Survivaltime as a function ofhydrogen chloride concentration. Regression parameters: correlation coefficient

# =0.92; 

### standarderrorof estimate 

# =22.0; 

### and 95% 

### confidence interval for the constant, 411, 

### is 364 

### to 374.

Source: Crane et al. (1985).



### August 1994 6-20 DRAFT-DO NOT QUOTE OR CITE

### 1 2 

### 3 4 5 

### 6 7 

### 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 

### 23 24 25 26 27 28 29·· 30 31 also caused cessation ofciliary activity. Controls showed no effect on ciliary activity after exposure to circulated humid air 

### for more than 

### 15 min.**(L-0{~0** Flfects 

### on Pubno1Ul1YFunction. 

### Barrow etal. (1977) compared the sensory irritation responses in mice exposed to chlorine and hydrogen chloride gas. Male Swiss-Webster mice

were exposed for 10 min to 

### concentrations ranging from 40 to 943 ppm (60 to 1,404 mglm3) 

### hydrogen chloride, and concentration-response curves were plotted using percent decrease in 

### respiratory rate. The 10-min RD50

### value for hydrogen chloride was 309 

### ppm (463 mg/m3), 

### and the no-measurable-effectlevel was 3ppm (4 

### mg/m3). 

### Chlorine, with an RD50 

### value of9.3 ppm (27 mg/m3), 

### was shown to be 33 times more potentthan hydrogen chloride. 

## C.

## l- 0**~**

## 3

# 7 Burleigh-Flayer etal. (1985) expoSed groups offour male English**smooth-~W~inea** 

### pigs in head-only chambers to 0, 320, or 680 ppm (0, 480, or 1,020 mg/m3)

### Clry hydrogen chloride in 

### air and groups ofeight guineapigs to 1,040 or 1,380 ppm**~1,560** 

## OL_et}f-L 2,070 mg/m3 ) 

### for a 30-min exposure. Sensory irritation was characterized by a decrease in respiratory rate and a lengthened expiratory phase; pulmonary irritation was evaluated by a change in wave pattern characterized by an initial 

### increased respiratory rate and followed by a decrease caused by apause after each expiration. Sensory irritation occurred within a minute at 680, 1,040, or 1,380 ppm and after 6 min 

### at 320 ppm. Aconcentration-response relationship was noted for pulmonary irritation. At 1,380 ppm, it occurred in less than 4 min, but at 320 ppm it took about 20 min to produce pulmonary irritation. At 1,040 ppm, two animals died after the exposure, whereas at 1,380 ppm, two died during exposure and

one after exposure. The ventilatory response to breathing 10% carbon dioxide in 20% oxygt;n/70% nitrogen

was measured prior to hydrogen chloride exposure and at various intervals thereafter. Carbon dioxide is sometimes used to cause hyperventilation. Maximal respiratory frequency during carbon dioxide challenge was lower in the hydrogen chloride-exposed animals than in controls; this effect was seen at 0.5 h at all 

### concentrations and persisted for 15 days in 

### the groups at the two highest exposure levels (1,040 and 1,380 ppm). Tidal volume**w~** 

### not affected. Lungs ofthe animals in the 1,040-ppm group were examined histologically at 2 and 15 days postexposure. There was tissue damage in both 

### the airways and alveolar
August 1994 6-21 DRAFT-DO NOT QUOTE OR CITE1 regions. At 2 days, there was multifocal alveolitis and mild hemorrhaging in the alveolar 2 regions, and squamous metaplasia, loss ofcilia, and acute inflammation in the larger airways. 

### 3 At 15 days, residual hyperplastic and inflammatory changes were still apparent 

### in the alveoli 4 and bronchi (Burleigh-Flayer etal., 1985). 

### 5 Male Fischer 

### 344 rats 

### fitted with mouthpieces with attached**~ilastic** endotracheal tubes 

### 6 and exposed to 1,300ppm (1,937 mg/m3 ) hydrogen chloride for 30 min havebeen reported 

### 7 to exhibit

### an 8% increase 

### in minute volume overthat ofexperimental animals**fi~** with the 8 mouthpiece butallowed to breath air. Nose-breathing animals exposed to hydrogen chloride 9 under the sameexposure regime demonstrated an overall decrease 

### in minutevolume (6%) 10 over that ofanimals exposed to air. The decrease in minute volume in nose-exposed**~mals** 11 was likely the result ofstimulation ofthe trigeminal nerve endings present in the nasal 12 mucosa. Theincrease (mouth breathers) and decrease (nose breathers) in minute volume was 13 attributed to an increase (10% for mouth breathers) and decrease (7% f9r nose breathers) in 14 tidal volume in hydrogen chloride-exposed rats that was not seen 

### in air-exposed animals 15

# Pt..'-~sm.vert et

### al., 1991). A discussion ofthe anatomical sites ofinjuryproduced by hydrogen 16c..v chloride exposure appears in Section 6.1.2.1. (..,{._

...

### 0

### "'1.

# b 

# 7
17 Theeffect ofhydrogen

## chlo~monary function and blood gases was 18 reported by Kaplan et al. (1988). Four**~~oups** ofthree anaesthetized malebaboons were**t-ta~** .AE.L..**~(.,.** 19 exposed to air or to 500, 5,000, or 10,000ppm (750, 7,500, or 15,000 mg/m3) hydrogen 20 chloride for 15 min using head-only exposure. Measured average concentrations were 

### within 21 20% ofthe target hydrogen chloride concentrations, except for one animal 

### in the 22 5,000-ppm-exposed group. Pulmonary function tests were taken during the week prior to 23 exposure and 3 days and 

### 3 mo postexposure. During exposure to hydrogen chloride, there 24 was a rapid increase in respiratory frequency in all exposed groups, butthe it}crease was 25 statistically significant 

### in the two highest exposure groups. There was 

### also an exposure26 related increase 

### in minute volume in hydrogen chloride-exposed animals, butthe increase was 27 only significant in the

# 10,000-pp~e,~posed group. Blood pH and arterial partial pressure for 28 oxygen (Pa02) were reduced, and arterial partial pressure for carbon dioxide (PaC02) was 29 increased at the two higher concentrations. There were no significant changes in pulmonary 30 function or morphology in the hydrogen chloride group for up to 1 year following exposure, 

### 31 except in animals exposed to 10,000ppm. In animals exposed to 10,000 ppm hydrogen

August 1994 6-22 DRAFT-DO NOT QUOTE OR CITE1 

### 2 3 4 

### 5 

### 6 7 8 9 

### 10 11 

### 12 13 14 15 16 17 18 19 20 21 22 23. "24 

### 25 26 

### 27 28 

### 29 30 31 

### chloride, there was chronic nasal 

### obstruction, mouth breathing, hypoxemia, changes 

### in pulmonary function, and, in one animal, focal pulmonary fibrosis at 1year after exposure (Anzueto 

### et al., 1987).**~**

# ~~ IntratrachealExposures. 

### The effects ofintratracheal instillation ofhydrochloric acid have been studied in dogs and goats. Greenfield et al. 

### (1969) gave intratracheal instillation of 1, 2, or 3 mUkg 

### of0.1 

### N hydrochloric acid to 

### mongrel dogs and sacrificed the animals at various time intervals up to

### 48 h. When instilled with 1mUkg, dogs exhibited hyperventilation, increases in pH and Pa02, 

### and a decrease in PaC02; 

### no deaths occurred. Instillation of2 or 3 mL/kg 

### hydrochloric acid resulted in a rapid fall in Pa02 

### and pH with an increase in PaC02, 

### followed by death. Increases in 

### lung weights and hematocrits were similar for all 

### groups, and early decreases in pulmonary surfactants were observed regardless ofdosage. At the 3 mL/kg level, hemodynamic changes observed included a marked**~crease** in 

### pulmonary vascular resistance and a fall in 

### cardiac output and systemic pressure. Air

### pressure-volume curves confirmed thepresence ofaltered mechanical properties ofthe

.. lung, principally a reduction in surfactant. Electron microscopy revealed extensive damage to

. . 

### the alveoli and capillaries and severe degenerative changes in the Type

### I and

## ncells. Four adult New Zealand white male rabbits that received intratracheal injections of hydrochloric acid (pH 1.5, 2 mL/kg body weight) and were sacrificed 4 h later exhibited a few red-brown patches ofcompression atelectasis in the lungs (Dodd et·al., 1976). Microscopic examination revealed a severe exudative necrotizing bronchitis, bronchiolitis, and alveolitis. Intra-alveolar hemorrhage and edema were also observed. Electron microscopic examination indicated folds, projections, and focal swellings ofType

### I cells lining the alveoli. A morphometric study showed 69% ofthe parenchyma to

### be normal, 26% edematous, and 5% 

### hemorrhagic; 58% ofthe epithelium in 

### the airways was damaged. In 

### mongrel dogs, instillation of2**~** 

### 0.1 

### N hydrochloric acid produced pulmonary edema that was caused, at leastin part, by increased vascular permeability (Grimbert et al., 1981). In

### goats, instillation of2.5 mUkg

### 0.1 

### N hydrochloric acid reduced the total lung capacity (TLC) from 39 to 

### 21 mUkg

### at 4 h (using a transpulmonary pressure of35 em of water). Th_e TLC returned to nearly control value after 48 h. The decrease in TLC was attributed to pulmonary edema and airway obstruction (Winn etal., 1983).

August 1994 6-23 DRAFT-DO NOT QUOTE OR CITE

## ··-

1 Demial Toxicity. 

### Vernot etal. (1977) tested the effects ofhydrochloric acid on the skin 2 ofshaved rabbits. ·The test solution (0.5 mL) 

### was applied to 

### the back, and the area was 3 covered with 

### apatch and latex film, and then washed after 4 h. A 17% solution was 4 corrosive, whereas a 15% solution was not. In another study with rats, a 1-min contact with 5 concentrated hydrochloric acid caused minorbums, a 2-min contactproduced lesions that 6 healed in 

### 15 to 

### 19-days, and a 5- to 

### 7-min contactproduced more serious burns that required 7 26 days to

### heal (GEO:MET Technologies, Inc., 1981). 8 

### 9 Ocular Toxidty. 

### Danneretal. 

### (1974) noted corneal clouding and erosion in the eyes of 10 rats and mice after 5- or 3Q-min exposures to 

### hydrogen chloride gas or aerosol; however, it 11 was not stated ifthose effects occurred at all the levels tested (2,000 to 30,000ppm [3,000 to 12 45,000 mg/m3 ]). 

### 13 Burleigh-Flayeret al. 

### (1985) found corneal opacity in four ofsix guineapigs exposed 14 for 30 min 

### to 1,040 ppm (1,560 mg/m3 ) 

### hydrogen chloride and in five offive exposed to 15 1,380 ppm (2,070 mg/m3) 

### but not in animals similarly exposed to 320 or 680 ppm (480 or 16 1,020 mg/m3). 

### 17 In another study, mice were exposed to hydrogen chloride**va~r** 

### for 10 min 

### and the 18 following.oculareffects were noted: at 490 ppm (730 mg/m3) 

### moderate to 

### marked PMN 19 infiltration ofthe palpebral and global conjunctiva; at 1,074 ppm (1,600 mg/m3) 

### necrosis of 20 the exposed cornea and marked PMN infiltration ofthe eyelids; at 1,946ppm (2,900 mg/m3) 

### 21 necrosis ofthe margins ofthe eyelids and extensive damage ofthe globes; and at 3,188 ppm 22 (4,750 mg/m3) 

### rupture ofthe globes (GEOMET Technologies, Inc., 1981). 23 Guidry et al. (1957) found eye burns in New Zealand white rabbits after instillation of 24 1.0 N hydrochloric acid for 1min. ThepH rapidly returned to normal by**th~** 

### natural 25 buffering mechanism ofthe eye. Hydration ofthe corneal tissue increased unti1120 h, 26 followed by a decrease and return to normal 168 hafter onset ofinjury. Glycolysis and 27 

### oxygen intake were markedly inhibited immediately after the injury. The inhibition of 28 metabolism was due to the denaturation ofglycolytic enzymes. 

### 29 30

August 1994 6-24 DRAFI'-DO NOT QUOTE OR CITE

### 1 

### 6.1.2.2 SubchronicToxicity 2 Very little information was found on the effects ofhydrogen chloride gas in animals 3 following repeated 

### exposure. No mortalities occurred in three rabbits orthree guineapigs 4 exposed to hydrogen chloride at 67 ppm (100 mg/m3), 

### 6 hlday for 

### 5 days nor in three 

### 5 rabbits, three guineapigs, oronemonkey exposed to 33.5 ppm (50 mg/m3), 

### 6 hi day, 6 

### 5 days/week for 4 weeks (Machle et

### al., 1942). No evidence oftoxic damage was noted 7 when the animals were 

### sacrificed several months later. The concentrations used were 8 irritating to 

### theeyes and mucous membranes. TheWorld Health Organization (1982) 9 reported eye and nasal irritation and slight respiratory difficulty 

### in rabbits and guinea pigs 10 exposed. to 

### hydrogen chloride at 100ppm (149 mg/m3), 

### 6·hfday for 

### 5 days. 11 In 

### a 90-day inhalation study using B6C3F1

### mice and Sprague-Dawley and Fischer 344 12 rats, groups of31 males and 21 females ofeach species/strain were exposed to 

### hydrogen 13 chloride at levels of

### 0, 10, 20, or50ppm (0, 15, 30, or 75 mg/m3 ), 

### 6 hi 

### day, 

### 5 days/week 14 for 90 days. Several animals died during the study; however, the deaths did not appear to be 15 exposure-related. There was a slightbut significant decrease. 

### in body weight gain 

### in male and 16 female mice and in male Fischer 344 rats 

### in the 50-ppm groups. There was no effect on 17 hematology, clinical chemistry, orurinalysis. Histologic examination showed minimum to 18 mild rhinitis in both strains ofrats. Lesions occurred in the anteriorportion ofthe nasal 19 cavity and were concentration- and time-related. In 

### mice exposed to 50 ppm there was 20 cheilitis and accumulation ofmacrophages in the perioral tissues after 90days. Mice 

### in all 

### 21 exposure groups developed eosinophilic globules in the epithelial lining ofthe nasal tissues 22 (Toxigenics Incorporated, 1984). 23 Kirsch and Drabke 

### (1982) macroscopically examined the respiratory tract ofguinea pigs 24 exposed to 

### hydrogen chloride at0.1 ppm (0.15 mg/m3), 

### 2 hlday, 5

### days/week for 28 days 25 and found no effects from the hydrogen chloride·exposure. Oddoy et

### al. (1982) exposed 26 23 guineapigs (mean weight, 385 g) to hydrogen chloride at 10 ppm (15 mg/m3), 

### 2 hlday, 27 

### 5 days/week for 7 weeks. From the 

### fifth day ofexposure, lung function parameters such as 28 tidal 

### volume, respiratory resistance, minute volume, and compliance were measured. 29 No effects were found when mean values were compared to results with 15 controls. 30 

### In addition, there were no effects on blood gases and no histologic changes in the lungs.

August 1994 6-25 DRAFT-DO NOT QUOTE OR CITE

### ..

1 Buckley et al. 

### (1984) found that damage to the upper respiratory tract was more severe 

### 2 in 

### Swiss-Webster mice exposed to 

### hydrogen chloride 

### 6hlday.for 

### 3 days at the 3 RD50

### concentration (304 

### ppm [426 mg/m3

, 

### TWA]) than in 

### mice similarly exposed to chlorine 4 

### for 

### 5 days at the RD50 

### concentration (9.7

### ppm [13.6 

### mglm3

, TWA]). 

### Body weights !n 

### mice 5 

### exposed to**~ydrogen** 

### chloride were decreased 10 to 

### 25%, and a1124 exposed mice were 

### 6 found dead ormoribund by the end ofthe third exposure. There was severe exfoliation, 7 

### erosion, ulceration, and necrosis ofthe respiratory epithelium 

### ofthe nasal 

### cavity, 

### but no 

### 8 squamous metaplasia. Ulceration and necrosis ofthe olfactory epithelium were less severe 9 after 

### exposure to hydrogen chloride than afterexposure to chlorine, and there were no lesions 10 in

### the trachea orlungs. 11 Krishnan and Rao (1981) studied the effect ofhydrogen chloride on the lung surfactant, 12 a

### lipoprotein complex with high phospholipid contentthat functions to maintain alveolar 13 

### stability via 

### lowering surface tension. Male albino rats 

### were exposed to 400

### ppm 14 (600 

### mg/m3) 

### hydrogen chloride, 

### 5 h/day for 1, 2, 3, 

### or 4 

### weeks; control animals were 15 

### exposed to filtered air. 

### The animals were sacrificed, and the surfactant material in the lungs 16 

### was removed by lavage. The surface tension and phospholipid content ofthe washes were 17 

### determilted. Exposure to 400

### ppm hydrogen chloride for up to 2 

### weeks caused no effects, 18 whereas a significant decrease in surface tension was noted after 3 

### or 4

### weeks. The decrease 19 was accompanied by a decrease in 

### total phospholipid, phosphatidyl choline, and phosphatidyl 20 ethanolamine. 21 

### 22 6.1.2.3 Chronic Toxicity 23 The only studies found on the effects ofchronic exposure to 

### hydrogen chloride 24 (discussed in 

### Section 8.2.1.2) evaluate the ability ofhydrogen chloride to·**e~ce** 

### the 25 potential offormaldehyde to produce nasal tumors in 

### rats. In these studies, hydrogen 26 chloride was not found to enhance the carcinogenicity potential offormaldehyde. Additional 27 studies are needed to adequately define the effects ofchronic exposure to hydrogen chloride. 28 

### 29 30

August 1994 6-26 

### DRAFf-DO NOT QUOTE OR CITE1 

## 6.2 HUMAN TOXICITY 2 

## 6.2.1 Chlorine 3 The toxicity ofchlorine to humans as well as to otherhigher living organisms is 4 primarily a function ofits chemical form. Forexample, chlorine gas is toxic, affecting the 

### 5 respiratory tract. Chlorine in 

### an aqueous medium not containing ammonia or other nitrogen6 containing compounds is basically nontoxic; however, chlorine in an aqueous. medium 7 containing ammonia oranother nitrogen-containing compound may lead to the formation of 8 chloramines. 9 10 

### 6.2.1.1 Acute Exposure 11 ControlledHuman Studies. 

### Experimental studies on chlorine in 

### humans have been 12 

### limited to the detection ofthe odor, the irritation threshold, and pulmonary function tests in 13 

### volunteers exposed to low levels. TheWorld Health Organization (1982) 

### cited a 1969 14 

### doctoral dissertation by Beckindicating that in 

### 2 of 10 

### subjects the**odo~** 

### threshold was 15 0.04 

### ppm (0.13 

### mg/m3) 

### and in 10 

### of 10 

### subjects the odor threshold was 0.26 

### ppm 16 

### (0.09 mg/m3). 

### There was a loss ofodorperception after 1to 24 

### min ofexposure. 17 

### Leonardos et al. (1969) 

### reported an odor threshold of0.3 

### ppm (0.8 

### mg/m3). 

### Trained odor 18 

### specialists capable ofanalyzing character and intensity ofodor were used for the studies, and 19 

### the threshold was defined as the level perceived by all 

### four panelists. Rupp and Renschler 20 (1967) 

### studied a group ofchemistry students (18 

### to 20) 

### and found the threshold for 50% 

### was 21 0.02 

### (lowest concentration tested) to 0.05 

### ppm (0.06 

### to 0.15 

### mg/m3). 

### In a double-blind 22 

### study, Dixon and lkels (1977) 

### found that 0.08 

### ppm (0.23 

### mg/m3) 

### was perceived by 50% 

### of 23 

### the subjects in

### at least 50% 

### ofthe trials. The World Health Organization (1982) 

### cites a 24 

### number ofother studies with.wider ranges, but the chemical purity and laboratory conditions 25 

### ofthese studies may have caused ·the wide scatterin the data. Table 6-4 lists some ofthe 26 

### threshold levels for chlorine gas. 27 

### The sensory irritation threshold (pain 

### and discomfort) is probably very close to the odor 28 

### threshold. However, a review ofliterature values and standard toxicology sources cited 29 ··irritation values of3 to 6 ppm (8.7 

### to 17.4 

### mg/in3) 

### and as high as 14 ppm (40.6 mgim3) 

### 30 31 

### August 1994 6-27 DRAFT-DO NOT QUOTE OR CITETABLE 

### 6-4. THRESHOLDLEVELS FOR CHLORINE GAS

Effect Odorperception Sensory irritation

Intolerable

Chronaxie/visual adaptation changes

Source: World Health Organization (1982). 11tneshold !Jevel (ppm [mg/m3]) 0.02-1.3 (0.06-3.8) 0.02-2.3 (0.06-8.7)

1.0-4.0 (2.3-11.6) 0.52 (1..5)

1 (Withers and Lees, 1985a). In a study by Rotman et al. (1983}, the irritation threshold was 2 found to be 1ppm (2.9 mg/m3), and 0.5 ppm (1.5 mg/m3) was not irritating. 3 The effects ofexposure to low levels ofchlorine on respiratory function in human 4 volunteers have been studied by Rotman et al

..(1983). Eight**~onsmoking** male subjects, 

### 5 19 to 33 years ofage, with no history ofrespiratory disease, were exposed to 0.5 or 1.0 ppm 6 (1.5 or2.9 mg/m3) chlorine for 4 or 8 h. The subjects exercised for 15 min every hour 7 during the exposure so that the heartbeat reached 100 beats/min. Pulmonary function tests 8 wereperformed prior to exposure and after4 h ofexposure; the subjects were then exposed 9 for an additional4 h, and pulmonary function tests were performed immediately after 10 exposure, 2 and 24 h postexposure, and daily until all values returned to normal. Sham 11 exposures were also carried out. Theparameters measured included forced vital capacity 12 (FVC), forced expiratory volume in 1 s (FEV1), 

### peak expiratory flow rate (PEFR}, forced 13 expiratory flow rate at50% and 25% (FEF50 and FEF25) ofvital capacity, residual volume 14 (RV), 

### TLC, airway resistance 

### <Raw}, and diffusing capacity for carbon monoxide 

### (DLc0). 15 Subjects experienced itchy eyes, runny nose, and mild burning ofthe throat at 1.0ppm 16 (2.9 mg/m3) but no subjective symptoms at0.5 ppm (1.5 mg/m3). One subject who had a 17 history ofallergic rhinitis experienced severe distress during exposure, and shortness of 18 breath and wheezing forced him to exitthe chamberbefore the full 8 h ofexposure to 19 1.0ppm chlorine. Values for the pulmonary function tests were compared longitudinally August 1994 6-28 DRAFT-DO NOT QUOTE OR CITE

### 1 (to preexposure values) and also were compared to sham controls to correct for any 2 differences in thepreexposure data from one day to the next. When the 0.5-ppm exposure 3 was compared with 

### the sham controls, only minor changes were seen in 

### pulmonary function 4 tests. Total lung capacity was less in subjects before the 0.5-ppm chlorine exposure than 5 

### before the sham**exposur~,** 

### and DLco

### was smaller 24 h 

### afterchlorine exposure than 

### after the 

### 6 sham 

### exposure. When subjects were exposed to 

### 1.0 ppm 

### chlorine, there was a significant 7 (p 

### < 0.05) decrease in FVC, FEV1, PEFR, 

### FEF50, 

### FEF25, 

### and 

## Raw after 8 h

### ·when 8 compared to sham 

### exposure using paired t tests. After 

### the 4-h 

### exposure to 1.0ppm, there 9 

### was a decrease in FEV1, 

### PEFR, FEF50, 

### FEF25, 

### and TLC. 

### The testresults for the one 10 subject with allergic rhinitis were markedly reduced after 4 h 

### exposure at 1.0ppm (FVC, 

### 11 FEV, PEFR, FEF25, FEF50, RV, 

### and TLC), 

### but the effects were also transient. When the 12 values for the pulmonary function tests were compared longitudinally, there were decreases in 

### 13 FEV1, PEFR, FEF50, FEF25, TLC, 

### functional residual capacity (FRC), DLc0 , 

### and the 14 expiratory reserve volume and an increase in

## Raw in 

### subjects exposed to 0.5 ppm chlorine. 15 Exposure to 1.0ppm chlorine caused decreases in PVC, FEV1, PEFR, FEF50, 

### and FEF25 • 

### 16 and increases inTLC 

### and

## Raw· These changes were**~ore** 

### significant and longer lived. The 17 authors concluded that exposure to even low levels ofchlorine·can 

### produce adverse effects on 18 pulmonary function, and that the magnitude ofthe changes is related to the level ofexposure. 19. 20 

### Case Repons. The acute toxic effects ofchlorine gas in humans were realized during 21 World War I 

### when chlorine was used as a war gas. According to several historical reports, 22 chlorine was used only on a few occasions and accounted for less than 3% ofthe casualties 23 from gassing (World Health Organization, 1982). Withers and Lees 

### (1985a) reported that, in 

### 24 the battle ofYpres, there were 685 British casualties treated at a field station_after soldiers 25 were exposed from a gas cloud attack with chlorine; 120 ofthe 685 examined were 26 considered severe and ofthese, 33 died. Twenty-nine ofthe 33 died within 36 h 

### ofexposure 27 and 4 

### during the following 3 days. Postmortem examination of 10 ofthe.deceased confrrmed 28 that

### the acute deaths involved pulmonary edema. Other mortalities caused by chlorine were 29 probably soldiers who died in 

### the field (90) 

### and those admitted to ambulances (58). The 30 immediate symptoms were choking, coughing, and gasping for air, 

### smarting ofthe eyes, 31 burning ofthe throat, and, in many, retching and 

### vomiting; these symptoms were followed

August 1994 6-29 DRAFf-DO NOT QUOTE OR CITE1 by pain behind the sternum and in thechest, weakness, and collapse. Delayed deaths**we~e** 2 probably dueto bronchial infection and pneumonia. 3 Mortality 

### has occurred from several accidental releases ofchlorine from storage tanks, 

### 4 

### railroad cars, barges, pipelines, and cylinders. Simmons etal. (1974) have tabulated 

### 5 significant accidental chlorinereleases that wererecorded by the Chlorine Institute.between 

### 6 1926 and 1972. 

### IIi five incidents 

### (France, United States, Romania, Finland, and Germany) 7 where storagetanks failed and released 15 to 30tons ofchlorine, approximately 117 deaths 8 were

### reported. Bightrailroad car accidents wererecorded between 1934 and 1967 in the 9 

### United States and 

### Canada, involving releases of9 to 

### 55 tons;·several persons were gassed but 10 only onedeath was reported. Four incidences 

### occurring between 1920 and 1954 involving 11 150-lb cylinders accounted for seven deaths. · 12 One ofthe earliest accounts in which the clinical course ofvictims exposed to chlorine 13 was well documented concerned an accident 

### in Brooklyn, NY (Chasis et al., 1947). 14 A cylinder containing approximately 100 lb ofchlorine leaked through 

### an orifice about 15 1/8 inch in diameter for 17 min. Thedense gas found its way into ventilation grates leading 16 to the subway. No deaths occurred, but418 persons were examined ateighthospitals, and 17 208 were admitted for observation and therapy. Of 133 persons admitted to Cumberland 18 Hospital, 33 were hospitalized for 1 to 2 weeks and are the basis ofthe published description. 19 Few persons on the street at the time ofthe accident were affected; when the site ofexposure 20 was recorded on the 

### medical charts, the location of 102 of 104 persons was inthe subway. 21 Theimmediate effects were burning ofthe eyes with lacrimation, burning ofthe nose and 22 throat, rhinorrhea and**salivati~n,** and coughing and choking. Substernal pain and frequent 23 nausea, vomiting, and headache were experienced within 2 h. Loss ofconsciousness was 24 recorded for 8 of 115 persons. Most ofthe symptoms except substernal pain, cough, and 25 respiratory distress subsided 

### within 24 h. In six persons, respiratory distress persisted for 26 4 days to 3 weeks. Substernal soreness and cough were presentin every exposed person for 27 about a week. 28 Tracheobronchitis developed in all 33 patients within 2 to 4 days and generally subsided 29 in 5to 

### 7 days. Cough increased in the admitted patients after about 3 days and became 30 productive ofthick mucus; cough disappeared in all patients after 14 days. Pulmonary edema 31 was observed in 23 patients, and pneumonia developed in 14. Chest X-ray findings were not



# . August 1994 6-30 DRAFf-DO NOT QUOTE OR CITE

## ·-

1 remarkable on first examination, but when they were examined serially for each individual, a 2 sequence ofabnormal changes was recognized (mottling, irregular densities, and differences 3 in the degree ofaeration ofrespiratory fields). However, when thepatients were discharged 4 from the hospital, the X rays were normal orreturning to normal. These changes were 

### 5 interpreted aspneumonia and emphysema. Respirograms were made on eight.patients 6 48 h after exposure. The VC and 1-min maximum breathing capacity were markedly reduced 7 butprogressively returned to normal in 2 to 3 days. Eleven ofthe patients were**observ~ f~r**  8 16 mo after discharge. There was no evidence ofpulmonary 

### disease orany residual 9 symptoms related to the chlorine exposure. 10 Approximately 100 persons were treated for various degrees ofexposure to chlorine 11 when approximately 30 tons ofliquid chlorine was released from a tank car 

### in a derailment 

### in 12 1951 near Morganza, MS (Joyner and Durel, 1962). Seven hours after the accident, levels of 13 400 ppm (1,160 mg/m3) were found 75 yards from the wreck and levels of 10 ppm 14 (29 mg/m3) atthe fringe ofthe area. Ofthe 75 people treated at a local hospital, 17 were 15 hospitaHred, and an infant in a house near the wreck died. Ten ofthe hospitalized victims 16 developed pulmonary edema. Most symptoms had cleared 12 days after the exposure. 17 Weill etal. (1969) followed 12 ofthese subjects 3 and 7 years after the exposure and 18 detected no appreciable effects on VC, TLC, RV, FEV1, orDLco· This was based on 19 observed values being within two standard deviations ofthe predicted value. However, it 20 could not bedetermined ifthe standard values were corrected for age, sex, orweight factors. 21 The authors concluded thatpermanent lung damage did not result from acute exposure to 22 chl9rine gas. 23 In 1961, 156 longshoremen in Baltimore, MD, exposed to chlorine when a valve 

### 24 snapped offa cylinder that was being 

### unloaded, were examined 

### in local**hosp~tals.** Kowitz 25 etal. (1967) followed 11 of 17 ofthe most serious cases serially for 2 years. Inaddition, 26 59_subjects, who had notbeen hospitalized, were examined 18 to 35 mo after the exposure. 27 There were no fatalities. Functional residual capacity, VC, RV, FEV1, PEFR, pulmonary 28 compliance, blood gases, and DLco were measured. Seven ofthe 11 who were hospitalized 29 had severe respiratory distress. Exertional dyspnea; ·fatigue, and cough were still noted 30 3 weeks after exposure; other symptoms had disappeared. Pulmonary function tests 31 performed 4 to 6 weeks after exposure showed decreased lung volumes (TLC, RV, FRC, and

August 1994 6-31 DRAFT-DO NOT QUOTE OR CITE1 VC) and DLco and increased airway resistance. At 6, 14, and 24 mo, there was some 2 repair, butthere were still residual abnormalities. Inthe 59**~ubjects** who were examined 3 later, there were similar functional deficits that indicated slight, butpermanent lung damage. 4 However, these findings are not exact, especially in the group studied after 18 mo, because 5 there were**~o** continuous data and nopreexposure data for comparison; controls may not 6 have

### been well matched with regard to age, sex, color, or smoking habits. 7 Adelson and 

### Kaufman (1971) reported two fatalities that occurred when chlorine 8 accidentally leaked because ofa malfunction in a water filtration plant. Theincident also 9 resulted 

### in approximately 35 nonfatal exposures. Chlorineleaked into a house while 10 a husband and wife were sleeping. They were admitted to a hospital within 15 min of 11 exposure, their level ofexposureunknown. They were alertbut were coughing, dyspneic, 12 and cyanotic. Moistrales developed. Thehusband was given oxygen and remained without 13 severe respiratory distress for about 10 h; then he became hypertensive and tachypneic 14 (respiratory rate, 50) and had respiratory acidosis. He died 25 h after exposure. On autopsy, 15 the lungs were congested and edematous. Thrombi werepresent 

### in thepulmonary blood 16 vessels, and there was capillary occlusion. After 24 h on oxygen therapy, when her 17 respiratory distress, cyanosis, and moist rales had improved, the wife became acutely 18 dyspneic and coughed up a frothy, bloody fluid. A tracheostomy was performed, and 19 mechanical ventilatory assistance was instituted. At 57 h she became cyanotic and comatose, 20 and blood drawn did not clot. The wife died 75 h after exposure. Autopsy findings were 21 similarto those for the husband. In addition, the trachea and bronchi were ulcerated, and 22 their vasculature was occluded with thrombi. Hemorrhagic lesions were also found in the 23 brain and glomeruli ofthe kidneys. 

### In the 35 survivors ofthis accident, transient minor 24 reductions 

### in DLco and moderate degrees ofairway obstruction were**observ~** and were 25 reversed within a month ofexposure. 26 Chester etal. (1977) reported two siblings who had been accidentally exposed to 27 chlorine in the same room. Both had reduced FEV1 and TLC when examined, and the values 28 returned to normal ranges within a month. However, abnormalities in gas exchange persisted 29 for 

### 55 mo 

### in onepatient. 30 Beach etal. (1969) presented casereports ofseven persons who had been accidentally 31 exposed to chlorine gas for 3 to 10 min duration in separate accidents. Symptoms ofcough,

August 1994 6-32 DRAFT-DO NOT QUOTE OR CITE

### 1 dyspnea, and chest pains started 10 min after exposure and lasted 2 to 8 days. In 

### one severe 2 

### case, there was cyanosis, rapid and shallow breathing, pulmonary edema, and lung 

### 3 consolidation. The .symptoms and lung changes usually cleared within a week, except in 

### the 4 

### most severe case 

### where they persisted for 10 

### weeks. No residual effects were found after 

### 5 2 mo, and lung function tests were normal, except in 

### the most severe case 

### where PVC, FEV, 6 

### and DLco

### were still depressed. 7 

### Ploysongsang etal. (1982) performed pulmonary function tests in four healthy young 

### 8 men, ages 18 to 

### 33 years old, accidentally exposed to 

### chlorine gas leaking from a container at 

### 9 apublic swimming pool. The level ofexposure 

### was not known, but the length ofexposure 10 was 2 

### to 5 

### min. The subjects were admitted to 

### a hospital with symptoms ofeye irritation, 11 irritation ofthe upper respiratory tract, cough, tightness ofthe chest, and shortness ofbreath. 12 All showed some degree ofarterial hypoxemia. Chest X rays appeared normal. 13 Pulmonary function tests were conducted 14 to 16 h after exposure as well as 1mo after 14 

### exposure. Vital capacity, FRC, 

### and TLC 

### were within 

### the normal range at 14 

### to 16 

### h after 15 exposure, but, at retesting after 1mo, these values were increased when compared to normal. 16 Forced expiratory volume in 1

### sand FEF25

_ 75 

### were slightly lower than the normal range 17 

### after the exposure (a nonsignificant decrease) but were normal at 1 

### mo. Carbon monoxide 18 diffusing capacity was significantly increased (p 

### < 0.01) at 1mo as compared to 19 

### immediately after exposure. The results ofthese tests suggest some obstruction ofthe small 20 

### airways, impaired gas transfer, mild pulmonary edema, and stifflung. No residual injury 21 was found in two subjects tested 3 mo after exposure. The other two subjects refused further 22 testing. 23 Hasan et al. (1983) also evaluated subjects accidentally exposed to chlorine for 24 pulmonary dysfunction. Twenty-eight subjects were exposed, and 18 (14**fe~es** 

### and 25 4 males) with respiratory signs and symptoms were admitted to a hospital for observation. 26 Airway obstruction was evident in all 

### subjects 1day after exposure (lowered FEV1, FEF25, 

### 27 and FEF50). 

### Subjects were separated into groups based on chiefcomplaint (cough or 28 dyspnea). Abnormal expiratory flow rates returned to normal in 

### the cough group by 7 days 29 postexposure, but were still diminished in 

### the dyspnea group at 2 weeks. Although the 30 variable rate ofresolution ofthe obstructive abnormalities may have been associated with 31 smoking habits, the number ofsubjects was too small to draw a conclusion.

August 1994 

### 6-33 DRAFT-DO NOT QUOTE OR CITE

### 1 Charan etal. (1985) reported an industrial accident in which a large volume ofchlorine 2 gas was released, rose along the walls ofabuilding, and settled on the roofwhere · 3 20 construction workers were exposed for a few seconds to a few minutes. All but one were 4 admitted to 

### a hospital for 24 to 48 h ofobservation; they were examined physically, had 5 chest 

### Xrays and arterial blood gas measurements, and received pulmonary function 

### tests 6 

### within 24 h. Pulmonary function tests were done atintervals up to 2 years on 11 ofthe 7**~ubjects.** 

### 8 None ofthe subjects developed pulmonary edema. The ratio ofFEV1

### /VC was le8s than 

### 9 75% ofthe expected value in 

### 10 of 19 patients at 24 h, suggesting airflow obstruction. After 10 700 days, this finding was present in·3 of 11 subjects; however, 2 ofthe 3 affected were 11 heavy smokers. Residual volume was 

### >120% ofthe predicted value in 13 of 19 subjects; it 12 progressively dropped and, by day 30, was less than 80% ofthe predicted value in 4 ofthe 13 13 that were examined. 14 Twelve years after the industrial accident reported by Charan et al. (1985), 

### in which 15 20 construction workers were exposed to high concentrations ofchlorine, Schwartz et al. 16 (1990) reevaluated 13 ofthe original construction workers. The authors reported that the 17 only notable finding in the 13 subjects was the initial elevation in 

### RV that was followed by a 18 persistent decrease in RV. The prevalence ofindividuals with RV of 

### <80% ofthe predicted 19 value increased over the 12-yearperiod, suggesting that the chlorine-induced initial injury 20 may have resulted in 

### chronic stiffening ofthe airways. There was also 

### a high prevalence of 21 airflow obstruction throughout the observation period; however, the mean loss in FEV1

### was 22 not less than the expected 25 mL/year. 23 Jones et al. (1986) carried out a 6-year longitudinal follow-up study on 20 of23 people 24 hospitalized, 21 of25 people not hospitalized but having respiratory injury,**~d** 

### 53 uninjured 25 people exposed to chlorine that had been released during a train derailment in Florida in 26 1978. Pulmonary function tests (FVC, FEV1, 

### FEF25

_ 75, 

### TLC, RV, and DLco> were 27 conducted at 3 weeks, 9 mo, and annually for the 6-year period. No pulmonary function 28 values were available for this group prior to or immediately following chlorineexposure. 29 In the absence ofvalid estimates ofexposure, mean annual lung function changes were 30 evaluated based on smoking status, severity ofinjury, and distance from the site ofchlorine

August 1994 6-34 DRAFT-DO NOT QUOTE OR 

### CITE

### ·-

1 release. The severity ofinjury was based on theoccurrence ofwheeze, rhonchi, bloody 2 sputum, expiratory obstruction, 

### arterial blood gas values, and radiography findings. 3 Current smokers, former smokers, and individUals who had never smoked were 4 distinguished in the study results. Hospitalized and nonhospitalized individuals with 

### 5 respiratory tractinjury werecompared to exposed persons who appeared normal. 6 Preexposurepulmonary function measurements were not taken; general**populati~n** values 7 wereused comparatively. Three weeks after thechlorine release, mean lung function indices 8 did not show a consistentpattern ofabnormality based on severity.ofinjury immediately 9 following chlorineexposure ordistance from therelease, but there were somedifferences 10 according to smoking category. Overthe first year, lower respiratory tract symptoms 11 (cough, wheeze, and dyspnea) declined from 90 to 64%, and even inconsistent relationships 12 to severity ofinjury ordistance from release werereported to disappear. Two years 13 following exposure, the mean annual pulmonary function indices werereported to be 14 decreased in exposed current smokers when compared to fonner smokers, never smokers, and 15 the general population; FVC and FEV1were significantly (0.01 

### < p 

### < 0.05) decreased. · 16 There were no significant differences associated with severity**o~**pulmonary injury ordistance 17 from chlorine release, although there were some**spor~dic** changes between indices for these 18 groups. Longitudinal change in lung function over 6 years displayed a similar smoking effect 19 (significantly [0.05 

### < p 

### < 0.10 and 0.01 

### < p 

### < 0.05] decreased FVC and FEV1 20 and FEF25

_ 75); however, minimal effect was found relating distance or apparent severity of 21 injury. The average annual change in FEV1 over 6 years was 

### -34 rnUyear in smokers and 22 

### -18 mUyear in former and never smokers. There was no evidence ofa persisting abnormal 23 rate ofdecline in pulmonary function; however, evidence for a permanent loss oflung 24 function, notreflected in rates ofannual change, was not discerned from this.study. 25 Preexposure measurements for the exposed cohort would benecessary to comparatively 26 discern changes ofthis type. The authors concluded that the long-term prognosis following 27 acute chlorine injury was favorable. 28 ·Reactive Airways Dysfunction Syndrome, an acute dramatic asthma-like illness after a 29 single high exposure to an irritant gas, fume, orvapor, was diagnosed in a 30-year-old male 30 6 years after an accidental exposure to chlorine gas when a cylinder containing the gas 31 exploded. The subject immediately began experiencing shortness ofbreath following

August 1994 6-35 DRAFT-DO NOT QUOTE OR CITE1 exposure, and an examination revealed bilateral wheezes and a reduction in peak flow to**~0%** 2 ofthe predicted value. Twelve months following exposure, the subject reported experiencing 3 breathlessness and wheeze.during exerciseand atnight. Pulmonary ventilatory studies 4 showed a significantobstructive airflow defect 

### with a majorreversible component following 5 the use ofbronchodilators. Symptoms ofnocturnal and exercise-induced wheeze persisted, 6 despite regular use·ofbronchodilators, overthenext 5 years (Donnelly and FitzGerald, 

### 7 1990). 8 Eighty-two patients were treated ata hospital after accidental exposure to chlorine gas 9 from a leaking industrial unit (Abhyankar etal., 1989). All patients suffered from watering 10 eyes, sneezing, cough, retrostemal burning, sputum, and dyspnea. Of82persons treated, 11 62 underwent spirometry and 56underwent flexible fiber-optic bronchoscopy on Days 12 2 through 7 postexposure. Ina follow-up study of 14 ofthe chorine-exposed victims, 13 nonsmokers were asymptomatic 2 weeks postexposure. Smokers continued to have excess 14 sputum and dyspnea 6 mo after the exposure. There was also a greater obstructive ratio 15 (FEV1/FVC [62.2 

# ± .10.55% versus 78.55 

## ± 5.24%]) 6 mo following exposure in smokers 16 versus nonsmokers. However, according to the authors, these patients werenot 17 symptomatically worse, nor was it likely that they suffered additional lung damage because 18 they had preexisting lung disease. Itwas estimated that the subjects were exposed to 30ppm 19 (87 mg/m3) chlorine. Thelength ofthe exposure was not given. 20 Givan et al. (1989) reported on a 3-mo-old, previously healthy, female child who was 21 exposed to chlorine when an industrial accident occurred near her home. Thechild had mild 22 respiratory distress with**audibl~** wheezing 30 min postexposure. Chest X ray on admission to 23 the hospital was normal. Approximately 2 h after arrival, the child became agitated and 24 tachypneic and began coughing up clear, foamy sputum. Thepatient's**condi~on** improved 25 following treatment. However, 1 year after exposure, a chest radiograph showed'mild 26 hyperinflation, and she remained under treatment because ofreoccurring coughing and 27 wheezing episodes. Theauthors concluded that chlorine exposure in infants results in acute 28 respiratory illness that appears to resolve very slowly. 29 Pherwani et al. (1989) reported on changes 

### in pulmonary function in school children 30 14 to 15 days following exposure to chlorine from an accidental release. Eighty-four 31 children, ages 9 to 17 (60 males and 24 females), were examined for changes in VC, FVC,

August 1994 

### 6-36 DRAFT-DO NOT QUOTE OR CITE1 FEV1, FEV1/FVC, maximum mid-expiratory flow rate (MMEF),**P~R,** and FEF25

_ 75• 2 Eighty-four age-, sex-, and height-matched children from an ongoing study ofpulmonary 3 function measurements in normal children served as controls. There was a statistically 4 significant (p 

### > 0.005) decreasein VC, FVC, FEV1, PEFR, and FEF75 in the chorine

### 5 exposed children. Theresearchers reported another gas leakon theday of**th~** study; 6 however, details ofthat chlorineleakwerenot reported. 7 Acutehypoxemic respiratory failure was reported in a 12-year-old male accidentally 8 exposed to chlorine gas while chlorinating a swimming pool. Thirty minutes following 9 exposure, the subjectbecamelethargic. Over the next 30 min, hebecame tachypneic and 10 developed retractions and wheezing. The subject suddenlybecame comatose and cyanotic, 11 requiring intubation and mechanical ventilation. Arterial blood gas results werepH 7.25; 12 PaC02, 54 mm Hg; and Pa02, 43 mm Hg. One month following exposure, pulmonary 13 function tests were normal (Heidemann and Goetting, 1991). 14 In another case ofaccidental exposure to chlorine gas, 88 people, ages 21 to 

### 60 years, 15 were admitted to the hospital with dyspnea, .coughing, irritati_on ofthe throat and eyes, 16 headaches,**gi~diness,** chestpain, and abdominal discomfort after being exposed to 17 approximately 66ppm (191.4 mg/m3) chlorine for almost 

### 1h. Pulmonary function test 18 48 h postexposurerevealed respiratory incapacitation in 62 ofthe exposed individuals. 19 Beginning on Day 

### 5 postexposure, 

### 56 ofthe exposed were subjected to bronchoscopy. 20 Ofthe

### 56 individuals examined, 12 showed signs ofchronic bronchitis, 28 had scattered 21 hemorrhagic spots under thebronchial mucosa, and 7 showed signs ofbronchial erosion 22 (Shroffet al., 1988). 23 Cytopathologic features from bronchial brushing were determined on 28 patients, 

### 5 days 24 postexposure (Shroffetal., 1988). According to the authors, the most**signi~cant** finding 25 was that termed "irritation forms" ofbronchial epithelial cells. Thesecells had a rounding of 26 thecytoplasmic borders 

### with a hint of

### terminal end plates bearing cilia, the nuclei had 27 evidence ofchromatolysis, dense nuclear membranes, and pseudonucleoli. In 15 smears, 28 therewere multinucleated syncytial respiratory epithelial cells with terminal end plates with 29 degenerating cilia. Nonpigmented alveolar macrophages (AMs) with vacuolated cytoplasm in 30 sheets were noted in nine smears. Varying degrees of basal-cell and goblet cell hyperplasia 31 with PMNs, AMs, and erythrocytes in thebackground were noted. Proliferating fibroblasts

August 1994 6-37 DRAFT-DO NOT QUOTE OR CITE1 and capillary fragments exhibiting endothelial lining were seen in seven smears from mucosal 2 erosions. 3 Bronchial brushings were obtained from seven patients with persistent cough and 4 

### respiratory distress 15 days postexposure. Therewere abundant PMNs, erythrocytes, and 

### 5 pigmented**~d** nonpigmented AMs against a necrotic background. There were also fragments 6 ofproliferating**fibrob~** and hyperplastic basal 

### cells and few columnarepithelial and goblet 7 cells. Bronchialbrushings obtained from these samepatients 25 days postexposure showed 8 occasional fibrotic fragments, mononuclear cells, pigmented and nonpigmented AMs, and 9 

### ciliated columnar and goblet epithelial cells. Theauthors hYPothesized that these patients are 10 atrisk ofdeveloping obliterative bronchiolitis at a later date as a result ofthe chlorine 11 exposure (Shroffet

### al., 1988). 12 Ofthepatients exposed, 16 were followed for 1 year following the chlorine exposure. 13 Persistent cough was noted in four ofthe patients for 4 to 6 weeks following exposure. 14 A repeat bronchoscopy indicated that the mucosal erosion, originally noted in 2 ofthe 15 16patients following chlorine exposure, showed healing. There were no residual symptoms 16 in any ofthesepatients 1

### year after the chlorine exposure and the chest X rays and 17 pulmonary function tests were normal (Moulick etal., 1992). 18 Cases ofaccidental exposure to chlorine havebeen reported due to mixing ofbleach and 19 toiletbowl cleaner (Jones, 1972; Bernardini etal., 1990; Mrvos et al., 1993) orbleach and 20 phosphoric acid cleaners (Anonymous, 1991; Mrvos etal., 1993). Accidental exposure to 21 household cleaning agent fumes containing 55% chlorine, 36% hydrochloric acid, and 9% 22 chloramine has resulted in dyspnea, cough, and retrostemal pain (Gapany and Tirosh, 1984). 23 Voluntary exposure (self-abuse) to chlorine released from mixing industrial cleaners has 24 resulted in conjunctival irritation, cyanosis, edema, ascites, and right heart**en~argement;** upon 25 cessation ofthe self-abuse, heart size returned 

### to normal, but pulmonary hypertension 26 persisted (Rafferty, 1980). 27 Chlorine will probably beperceived at all levels that are injurious, butitis generally 28 considered that levels ofchlorinethat can cause 

### frank toxicity·or mortality in humans will be 29 intolerable and cause persons to withdraw from the contaminated atmosphere. However, 30 a report by Dewhurst (1981) suggests that inhalation oftolerable levels ofchlorine for a· short 31 period oftime may result in injury that is not immediately apparent. In the first case,

August 1994 6-38 DRAFT-DO NOT QUOTE OR CITE

### 1 17 students required hospital treatment after inhaling chlorine from a glassjar. In the second 2 incident, a technician suffered from chlorine inhalation and had to be hospitalired for sevefal 3 days after mixing two industrial cleaners. The technician had made no attempt to leave or 4 ventilate the room. Also, a reportby Dixon and Drew (1968) suggests that there is 

### 5 apossibility that occasional exposure to low concentrations of**chlo~e** 

### may result in 

### 6 development ofa tolerance. An 

### incident occurred 

### in 

### a chlorine-producing factory where 7 

### chlorine was released into the atmosphere when a valve for a tank

### being 

### filled was closed 8 before the valve to 

### the next tank 

### was opened. cannisterrespirators were available and were 9 

### used by all

### but one ofthe six men. He was exposed to the chlorine cloud for about 30 min 10 without using the respirator and reported to 

### theplant "Surgery" where he was given oxygen 11 and discharged. He died 3.0 to 3.5 h after the exposure. Postmortem examination indicated 12 pulmonary edema as 

### well as coronary insufficiency. The chemical operators who used the 13 respirators had only minor ill

### effects. 14 Conner et al. 

### (1962) described four phases ofchemical injury to the respiratory tract of 15 fire fighters due to acute massive inhalation ofa commercial solvent. In a review ofeffects 16 ofirritating gases, Summer and 

### Haponik (1981) stated that acute massive inhalation exposure 17 to 

### chlorine, as 

### well**~** 

### to phosgene, ammonia, sulfur dioxide, and oxides ofnitrogen, results 18 in similarpathophysiological effects as a response to direct respiratory mucosal injury. The 19 phases are described as follows. In

### Phase I (0 to 6 h), choking and coughing are observed. 20 Oropharyngeal and pulmonary edema, exudative inflammatory bronchitis with plugging ofthe 21 small and medium bronchi, and atelectasis are common findings during Phase ll 

### (6 h to 22 8days). A 

### reduction in VC and pulmonary compliance and increased Raw 

### are also seen 23 during this phase. Improvements in pulmonary function occur during Phase 

## m (1 to 

### 24 4 weeks); however,**coughin~** 

### may persistthroughout this period. During**Ph~e** IV 

### (after 25 4 weeks), airway obstruction**con~ues** to 

### improve, and lung volumes, diffusing capacity, and 26 arterial blood 

### gases return to normal (Summer and 

### Haponik, 1981). 27 The levels and time ofexposure to 

### cause adverse effects in humans are ill-defined. 28 Standard reference sources give variable values ofexposure that cause irritation, that are 29 dangerous to humans, orthat are intolerable orlethal (Withers and Lees 

### 1985b). It

### is 30 considered that inhalation of4 ppm (11.6 mg/m3) 

### chlorine causes irritation,

### inhalati~n of 31 14 to 21 ppm (40.6 to 60.9 mg/m3) 

### or40 to 

### 60 ppm (116 to 174 mg/m3) 

### for a 0.1 to
August 1994 6-39 DRAFT-DO NOT QUOTE OR CITE1 1.0 his dangerous, 100ppm (290 mg/m3) is intolerable and incapacitating, and even a short 2 exposure to 1,000ppm (2,900 mg/m3) is lethal. However, there are many factors

### th~t may 3 determine the degree ofresponse and whether there is complete recovery or residual effects 4 (i.e., the respiratory health ofthe victim, predisposition to asthma, age, smoking habits, 5 degree ofrespiratory damage, and specific care and therapy). 

### 6 7 6.2.1.2 Chronic Exposure 8 Faure et

### al. (1983) and Barret and Faure (1984) haverecorded their experience over 9 a span of20years with 186 subjects occupationally exposed to chlorine. Pulmonary edema 10 developed in about 4% ofthe cases. Forty-three of 129 ofthe workers that underweQt 11 spirometric measurements had abnormal tests: an obstructivepattern in 27 cases, a restrictive 12 pattern in 13 cases, and mixed syndrome in 3 cases. In 21 of79**~** studied, DLco was 13 abnormal; most ofthe subjects (11 of 13) with restrictive ·syndrome had abnormal DLco· 14 The 56 subjects who had at least three acute episodes ofexposure in the previous 5years 15 were compared to 197 controls; there were no long-term effects on FEV1, VC, or FEV1/VC 16 ratio when exposed and nonexposed groups were corrected for age, height, or smoking 17 habits. 18 19 

### 6.2.1.3 

### Epidemiology Studies 20 Patil et al. (1970) conducted a retrospective cohort study on 600 diaphragm cell workers 21 and 382 controls from 25 plants. There may have been selection bias, because the 22 examinations took place only in cooperating plants; furthermore, laboratory data, other than 23 chlorine levels, 

### may nothavebeen evaluated in a standardized way. Chest X rays were taken 24 and evaluated blind, and chlorine levels were assayed bimonthly using a standardized 25 protocol. The study population ranged in age from 19 to 69 years, with the mean age ofthe 26 two groups being 31.2 

## + 11.0 years. The average number ofchlorine exposure years was 27 10.9 

## + 2.8 years. Time-weighted average exposures to chlorine ranged from 0.006 to 28 1.42ppm (0.02 to 4.12 mg/m3) with a mean of0.15 

## ± 0.29 ppm (0.43 

## + 0.84 mg/m3). 29 Practically all exposures were less than the American Conference.ofGovernmental Industrial 30 Hygienists threshold limit value of 1 ppm (2.9 mg/m3) (only 2% were greater than 1ppm). 31 Exposure data were obtained from only 332 of600 workers; hence, the useful population was

August 1994 

### 6-40 DRAFT-DO NOT QUOTE OR CITE1 332 workers. Theparameters examined included oropharyngeal disturbances (tooth decay), 2 cardiorespiratory system, and blood and urine studies. Several pulmonary function 3 parameters (VC, TLC, and FEV1) were measured. ·with the exception ofa positive 4 correlation between exposure and increased tooth decay (p = 0.025) and between exposure 

### 5 and leukocytosis (p 

### = 0.05), no otherparameters were affected. Pulmonary function tests 6 revealed normal values in the vast majority ofworkers, including controls and those exposed 7 to chlorine. 8 

### A cross-sectional study of 139 workers atriskin a chlorine gas plant was conducted 9 over a 3-day period (Chester et al., 1969). The workers were polled by questionnaire on 10 smoking history and chlorine exposure. Significantexposure was defined as severe enough to 11 have been treated with oxygen; 

### 55 ofthe 139 workers had been so exposed at least once 12 during their employment. All others were considered to be exposed to less than 1ppm. 13 (2.9 mg/m3) chlorine gas; in continuous 8-h air sampling, 99% ofthe samples had less than 14 1ppm chlorine. Duration ofworker exposure was notpresented. Postanterior lung X-ray 15 films were normal in 82 subjects and abnormal in 56 (data for one subject were lost). 

### Only 16 oneofthe 56 workers with abnormal findings on X ray had abnormal respiratory function. 17 Regardless ofchlorine exposure, 75% ofthe workers denied cough or sputum production. 18 Differences in FEV0.5, among other function tests, did not correlatewith cough and sputum 19 production orabnormal chest films. The study showed a decreased FEV1 and FVC for 20 smokers compared to nonsmokers (in agreement with other studies) and·a decrease in MMEF 21 between no smoke/no chlorine and smoke/chlorine. Although few effects were noted in this 22 study, the major deficiencies are small numbers ofworkers and uncontrolled potentially 23 confounding variables. 24 Ferris etal. (1979) reported on the follow-up ofa 1963 mortality and**~orbidity** study 25 with pulp and paper workers who werepotentially exposed to chlorine, sulfurdioxide, 26 chlorine dioxide, and/or hydrogen sulfide in Berlin, NH. This was a prospective cohort 27 study of200 subjects (271 in 1963), which indicated that the number.ofobserved deaths were 28 greater than expected (i.e., 33 versus 26.1 for a standardized mortality ratio [SMR] of 1.26 29 [not significant] based on age-specific death rates ofU.S. white males, excluding Hawaii and 30 Alaska). This discrepancy is due probably to an excess in the paper exposure category only; 31 the SMR of71 workers identified in 1963 as being exposed to chlorine was 99 (9 deaths

August 1994 6-41 DRAFT-DO NOT QUOTE OR CITE

### 1 observed, 9.06 expected). There were no increases in specific causes ofdeath. There were 2 no differences in respiratory symptoms orprevalence ofchronic nonspecific respiratory 3 diseases in the pulp orpaper mill 

### when 

### data were not adjusted for smoking. When data 

### were 4 standardized for smoking and values compared for the general population ofBerlin, NH, 

### 5 there was not much difference in relative risk 

### for developing chronic respiratory disease in 6 pulp workers; however, currentcigarette smokers and pipe smokers (combined) had an 7 increased relative risk. Thechronic nonspecific respiratory effects ofchlorine exposure could 8 notbe separated from the resultspresented. There was no chlorine-related effecton 9 pulmonary function in 

### 27 actively employed chlorine-exposed workers. Two deficiencies of 10 this study are the use·ofthe general population as controls, which may have underestimated 11 relative risk, and the self-selection ofworkers·remaining at the mill in 

### the chlorine or sulfur 12 dioxide groups because those workers were more tolerant. With these limitations noted, the 13 authors concluded that long-term, low-level exposure to chlorine did not increase the 14 incidence ofmortality ormorbidity. 15 Enarson et al. (1984) evaluated the respiratory health of392 workers at a pulpmill and, 16 for the purpose ofcomparison, studied a cohort of310 workers in 

### arailroad maintenance 17 yard approximately 10 

### mi distant. Potential exposures in the**pulp~** 

### were to chlorine, 18 sulfur dioxide, hydrogen sulfide, and methylmercaptan. Several sites in the pulpmill were 19 surveyed for these contaminant gases. 

### In the bleach area, the mean 8-h-TWA for chlorine 20 was 0.18 ppm (0.52 mg/m3), 

### and the maximum level was 1.61 ppm (4.67 mg/m3). 

### Levels 21 ofchlorine were low, below the currentpermissible concentration, but detectable in the 22 machine room and office area, but not detectable 

### in other areas. Chest tightness was the 23 most common symptom in pulpmill workers, especially for those working in the bleach plant, 24 butthe increase was not significantly different. Cough, phlegm, wheeze, an4 dyspnea did 25 not differ among any groups when analyzed after standardization for age and smoking habits. 26 Spirometric values were compared using a multiple regression model adjusted for age, height, 27 and age-group interactions. The individuals most affected appeared to be 

### younger 28 nonsmokers who worked in the bleach area where the likely exposure would have been to 29 chlorine. These workers had lower MMEF, FEF25

_ 75, 

### and FEV1

### /FVC ratio; the older 30 workers 

### in this group had higher values when compared to the rail 

### repair yard workers. This 31 difference may have been due to older workers leaving employment. Thenumber ofworkers

August 1994 

### 6-42 DRAFT-DO NOT QUOTE OR CITE

## .. ·"

1 in the bleach 

### area ofthe plant was only 15, and 4 were nonsmokers;.the small numbers in 2 this group weaken the conclusions ofthe authors. 3 Salisbury etal. (1991) evaluated changes in lung function 

### in malepulpmill workers 4 exposed to chlorine/chlorine dioxide between 1981 and 1988. 

### Exposed subjects were divided 5 into two groups; lifetimenonsmokers (13) and continuous smokers (24). The workers were 

### 6 individually matched for age, years ofemployment, and pack-years ofsmoking to men who 7 did not

### report chlorine exposure overthe same time period. A statistically significant 8 reduction in MMEF and FEV1/FVC ratio was noted in thechlorine/chlorine dioxide-exposed 9 subjects overthe nonexposed subjects for the 8-yearperiod for both smokers and 10 nonsmokers. 11 Savad (1982) reported a 1980 outbreak of

### tooth enamel erosion in users ofa public 12 swimming pool that was chlorinated by gassing with chlorine. Prindle etal. (1983) reported 13 a cross-sectional study ofenamel erosion in competitive swimmers. Using a questionnaire 14 mailed to swim club members (747 respondents), they quantified exposure by number oflaps 15 swum per day. Ofthe452 frequent swimmers, 69 (15%) reported enamel erosion (or 16 symptoms), whereas only 9 ofthe 295 infrequent ornonswimmers reported symptoms (3%). 17 In addition, ofthe 59 members on the swim team, 23 (39%) reported signs oftooth erosion, 18 compared to 15% ofall frequent swimmers (p 

### < 0.001). Confirmation ofrandomly selected 19 

### cases and controls was conducted by an oralpathologist. However, the author suggested that 20 dental erosion may have been an effect ofthe acidity ofthe water rather than chlorine per se. 21 22 

### 6.2.2 Hydrogen Chloride 23 Only limited information was found in theprimary literature on the inhalation toxicity 24 ofhydrogen chloride gas oraerosol 

### in humans, and this information has been.largely 25 restricted to the detection ofodor and irritation thresholds. 

### It is known, however, that 26 hydrogen chloride is a strong irritant, and because ofits high water solubility the major 27 effects ofacute inhalation exposure are thought to belimited to the upper respiratory tract 28 (National Research Council, 1976). 29 30

August 1994 6-43 DRAFT-DO NOT QUOTE OR CITE1 

### 6.2.2.1 Acute Exposure 2 Threshold levels for hydrogen chlorideodorperception**~ave** been**repo~** to be as low 3 as 0.07ppm (0.1 mg/m3) and as high as 306 ppm (459 mg/m3). Under laboratory 4 conditions, however, the threshold level 

### is likely to beabout 0.2ppm (0.3 mg/m3 ) (World 

### 5 Health**Org~tion,** 1982). Leonardos et

### al. (1969) reported an odor threshold of 10 ppm 6 (15 mg/m3). Trained odor 

### specialists capable ofanalyzing character and intensity ofodor 7 wereused for the studies, and the threshold was defined as the level perceived by all four 8 panelists. Inhalation ofirritating levels ofhydrogen chloride has resulted incoughing, pain, 9 inflammation, and edema ofthe 

### nasal passages and larynx (National Research Council, 1976; 10 World Health Organization, 1982). 11 GEOMET Technologies, Inc. (1981) reported that sustained inhalation ofhigh 12 concentrations ofhydrogen chloridecauses edema, emphysema, and damage to pulmonary 13 blood vessels. Malevolunteers exposed to hydrogen chloride gas found concentrations of 14 50 to 100 ppm (75 to 150 mg/m3) barely tolerable for 1 h; 35 ppm (52 mg/m3) caused throat 15 irritation onbriefexposures; 10 ppm (15 mg/m3) was considered acceptable for prolonged 16 exposure; and concentrations below 5 ppm (I mg/m3) produced no lasting effects (Stokinger, 17 1981). nieWorld Health Organization (1982) reported that inhalation ofapproximately 18 35 ppm (52 mg/m3) can induce sneezing, laryngitis, chestpain, hoarseness, and a feeling of 19 suffocation. 20 Ingestion ofhydrochloric acid results 

### in severe corrosion ofthe mouth, throat, and 21 stomach followed by vomiting with loss ofblood; kidney damage may also occur during 22 acute intoxication. Ingestion ofa corrosive dose 

### will causepain in the mouth, destruction of 23 tissue, salivation, and severe gastroenteric distress (GEOMET Technologies, Inc., 1981). 24 Skin contact with concentrated hydrochloric acid causes tissue irritation**~d** necrosis. 25 GEOMET Technologies, Inc. (1981) reported that 1 N hydrochloric acid (3.6%) induced 26 severe changes and inflammation 

### inhuman epidermal cells. 

### In one study, application of 27 1.4 N hydrochloric acid (3%) to human skin in patch tests produced inflammatory responses 28 butdid not alter therate ofcell mitosis, and another study showed that topical application of 29 0.001 N hydrochloric acid (0.0036%) did not producepain or itching. 30

August 1994 6-44 DRAFf-DO NOT QUOTE OR CITE

### 1 Case

### Repon: In 

### one report, a 41-year-old male with a history ofmild asthma, 2 experienced a rapid and severe bronchospasm after being exposed to a pool-cleaning product 3 containing hydrochloric acid. Thepatient was treated with bronchodilators and steroids. One 4 

### year later, while still on bronchodilators and steroids, he still was experiencing marked 5 symptoms ofasthma triggered by exposure to mild irritants orminimal exercise. Healso 6 experienced frequent episodes ofnocturnal 

### asthma. Airway obstruction was completely 7 

### reversed by albuterol; however, a progressive decline ofmore 

### than 20% 

### in FEV1

### was 8 observed 4 h after inhalation. No effect on DLco

### was noted (Boulet, 1988). 9 

### Soni et al. 

### (1985) reported the death ofa

### 44-year-old man 

### 5 days afterintentional 10 

### ingestion of200 mL

### ofmuriatic acid (27% 

### hydrochloric acid). On 

### arriving at the hospital, 11 hehad severe epigastric pain, was sweating profusely, and was agitated. One hour later, 12 blood tests showed hemolysis, and coagulation studies showed abnormal values. 13 A 

### gastroscopy performed 18 h later showed a white slough throughout the esophagus, and the 14 stomach was coated with a thick black coagulum. Laparotomy revealed gross necrosis ofthe 15 esophagus, along with total gastric and duodenal necrosis and large areas ofnecrosis through 16 the small and largebowels. Extensive areas ofburnt tissue on the liver surface and 17 mesentery were found; suggesting extensive leakage ofthe acid. The massive extent of 18 damage precluded surgical repair; his condition deteriorated, and he died. 19 

### 20 6.2.2.2 Epidemiology Studies 21 Two epidemiology studies showed that continued exposure ofworkers to hydrogen 22 chloride may cause an increase in dental erosion. In 

### a cross-sectional**inv~tigation,** 

### with 23 a prospectivephase, ten Bruggen Cate (1968) studied the incidence ofindustrial dental 24 erosion 

### in a total of555 acid.workers in 48 plants over**~** 

### period of2 years. .The workers 25 were exposed to a number ofacids including hydrochloric acid. The selection ofthe control 26 group was questionable. Unskilled workers from acid-free departments were used, but they 27 were younger than the skilled workers who were exposed to the acids. Theincidence and 28 

### severity ofdental erosion 

### in the teeth ofexposed workers increased over theperiod ofthe 

### 29 study. Only the anterior teeth were affected; cuspids and molars, which areprotected by the 30 

### cheeks, were not. Grading oferosion severity was as 

### follows: Grade 1, loss ofenamel only; 31

August 1994 6-45 DRAFf-DO NOT QUOTE OR CITE

### 1 Grade 2, loss ofenamel with involvement ofdentine; and Grade 3, loss ofenamel and 2 dentine with exposure ofsecondary dentine. 3 Exposure measurements were qualitative and varied for many ofthe 48 plants and 4 

### 555 workers involved. The major exposures occurred in the pickling and galvanizing 5 operations, which correspond 

### with the more severe erosion ofthe labial surfaces ofthe 6 incisors. However, theincidence ofmild erosion 

### increased in 

### the controlpopulation as 7 a function ofyears ofservice; after 15 years ofservice, the incidence in controls and 8 lower-exposed group was similar 

### (approximately 35% ofworkers). The results ofthe 9 prospectivephase ofthe study (several examinations ofthe same workers over a 2-year 10 period) support the conclusions ofthe cross-sectional phase that continued exposure 11 exacerbates the lesions. Interestingly, the exposed workers had no perceived orreported 12 pain. Periodontal disease appeared 

### to bemore prevalent in 

### the exposed workers, but the 13 incidence was not statistically significant. 14 Remijn et

### al. (1982) examined a cohort ofapproximately 60 workers potentially 15 exposed to hydrochloric acid, zinc chloride, and zinc oxide at a two-shift, hot-dip galvanizing 16 plant in 

### the Netherlands. The investigation involved quantification ofexposure and dental 17 erosion, which was assessed in 38 workers. The remaining workers had dentures or refused 18 examination. These authors supported and expanded upon the conclusion often Bruggen 19 Cate (1968). Based 

### on their results, Remijn and co-workers concluded that inhalation of 20 hydrochloric acid first affects the "incisal one-third to one-halfofthe surfaces ofthe incisor 21 

### teeth," and that 90% ofthe workers had at least a Grade 1erosion; no cases of 22 Grade 3 erosion were diagnosed. The monitoring study leads to the conclusion that the 23 piclders worked approximately 27% ofthe time 

### with concentrations ofhydrochloric acid 24 greater than 

### the maximum allowable concentration-ceiling (MAC-C) value of.5 ppm 25 (7 

### mg/m3). 

### Theprobability ofzinc levels exceeding the MAC-C was 1%. Upon 26 examination, the picklers showed the greatest incidence and severity ofdental erosion. 27 Because ofthe small number ofworkers, multivariate analysis ofthe data as a function of 28 age, exposure time, and exposure level was notpossible. Acontrol cohort was not included 29 in the study.

August 1994 6-46 DRAFf-DO NOT QUOTE 

### OR CITEI



### 1 

### REFERENCES 2 Abhyankar, A.; Bhambure, N.; Kamath, N. N.; Pajankar, S. P.; Nabar, S. T.; Shrenivas, A.; Shah, 

### 3 A. C.; Deshmukh, S. N. (1989) Six month follow-up offourteen victims with short-termexposure 4 tochlorine gas. J. Soc. Occup. Med. 39: 131-132. 

### 5 6 Adelson, L.; Kaufman, J. (1971) Fatal chlorinepoisoning: report oftwo cases with clinicopathologic correlation. 

### 7 Am. J. Clin. Pathol. 56: 430-442. 

### 8 9 Alarie, Y. (1985) The toxicity ofsmokefrompolymeric materials during thermal decomposition. Annu. Rev. 

### 10 Pharmacol. Toxicol. 25: 325-347. 

### 11 

### 12 Anderson, R. C.; Alarie, Y. (1980) Acutelethal effects ofpolyvinylchloride thermal decomposition products in 

### 13 normal and cannulated mice. Soc. Toxicol. Meet., p. A3. 

### 14 

### 15 Anonymous. (1991) Chlorine gas toxicity frommixtureofbleach with othercleaning products-California.



### . 16 Morb. Mortal. Wkly Rep. 40: 619-621, 627-629. 

### 17 18 Anzueto, A.; Switzer, W. G.; Kaplan, H. L.; Hinderer, R. K. (1987) Long-term effects ofhydrogen chloride on 

### 19 pulmonary function and morphology innonhuman primates. Toxicologist 7: 192. 

### 20 21 Barret, L.; Faure, J. (1984) Chlorinepoisoning. Lancet (8376): 561-562. 

### 22 23 Barrow, C. S.; Dodd, D. E. (1979) Ammoniaproduction in inhalation chambers and its relevance to chlorine 

### 24 · inhalation studies. Toxicol. Appl. Pharmacol. 49: 89-95. 

### 25 26 Barrow, R. E.; Smith, R. G. (1975) Chlorine-induced pulmonary function changes in rabbits. Am. Ind. Hyg. 

### 27 Assoc. J. 36: 398-403. · 

### 28 

### 29 Barrow, C. S.; Steinhagen, W. H. (1982) Sensory irritation tolerance development to chlorine in F-344 rats 

### 30 following repeated inhalation. Toxicol. Appl. Pharmacal. 65: 383-389. 

### 31 32 Barrow, C. S.; Alarie, Y.; Warrick, J. C.; Stock, M. F. (1977) Comparison ofthe sensory irritation response in 

### 33 mice to chlorine and hydrogen chloride. Arch. Environ. Health 32: 68-76. 

### 34 35 Barrow, C. S.; Kociba, R. J.; Rampy, L. W.; Keyes, D. G.; Albee, R. R. (1979a) An inhalation toxicity study 

### 36 ofchlorine in Fischer 344 rats following 30days ofexposure. Toxicol. Appl. Pharmacal. 49: 77-88. 

### 37 

### 38 Barrow, C. S.; Lucia, H.; Alarie, Y. C. (1979b) A comparison ofthe acute inhalation toxicity ofhydrogen 

### 39 chloride versus the thermal decomposition products ofpolyvinylchloride. J. Combust. Toxicol. 6: 3-12. 40 

### 41 Beach, F. X. M.; Jones, E. S.; Scarrow, G. D. (1969) Respiratory effects ofchlorine gas. Br. J. Ind. Med. 

### 42 26: 231-236. 

### 43 44 Bernardini, P.; Castellino, N.; Sabatelli, G.; Magalini, S. I.; DeGiacomo, M.; Addario, C. (1990) Domestic 45 chlorinepoisoning inItaly 

### froin mixing household cleaners. In: Indoor air '90:**p~gs** ofthe 5th 

### 46 international conference on indoor air quality and climate, volume 1, human health, comfort and 

### 47 performance; July-August; Toronto, ON, Canada. Ottawa, ON, Canada: International Conferenceon 48 Indoor Air Quality and Climate, Inc.; pp. 407-411. 

### 49

.. 50 Bitron, M. D.; Aharonson, E. F. (1978) Delayed mortality ofmice following inhalation ofacute doses ofCH20, 

### 51 S02, Cl2, and Br 2• Am. Ind. Hyg. Assoc. J. 39: 129-138. 

### 52

August 1994 6-47 DRAFT-DO NOT QUOTE OR CITE

### 1 Blabaum, C.**J~;** Nichols, M. S. (1956) Effect ofhighly chlorinated drinking wateronwhite mice. J. Am. Water 

### 2 Works Assoc.**4~:** 1503-1506. 3 4 Boulet, L.-P. (1988) Increases in airway responsiveness following acuteexposureto respiratory irritants: reactive 

### 5 airway dysfunction syndrome oroccupational asthma? Chest 94: 476-481. 

### 6 7 Buckley, L.A.; Jiang, X. Z.; James, R. A.; Morgan, K. T.; Barrow, C. S. (1984) Respiratory tract lesions 

### 8 inducedby sensory irritants at the RD50 concentration. Toxicol. Appl. Pharmacol. 74: 417-429. 

### 9 

### 10 Burleigh-Flayer, H.; Wong, K. L.; Alarie, Y. (1985) Evaluation ofthepulmonaryeffects ofHCl using C02 

### 11 cballcmges in guineapigs. Fundam. Appl. Toxicol. 5: 978-985. 12 

### 13 Chang, J. C. F.; Barrow, C. S. (1984) Sensory initationtolerance andcross-tolerance in F-344 rats exposed to 

### 14 chlorineorformaldehyde gas. Toxicol. Appl. Pharmacol. 76: 319-327. 

### 15 16 Charan, N. B.; Lakshminarayan, S.; Myers, G. C.; Smith, D. D. (1985) Effects ofaccidental chlorine inhalation 

### 17 onpulmonary function. West. J. Med. 143: 333-336. · 

### 18 19 Chasis, H.; Zapp, J. A.; Bannon, J. H.; Whittenberger;J. L.; Helm, J.; Doheny, J. J.; MacLeod, C. M. (1947) 

### 20 Chlorine accident in Brooklyn. Occup. Meci. 4: 152-176. 21 

### 22 Chester, E. H.; Gillespie, D. G.; Krause, F. D. (1969) Theprevalence ofchronic obstructive pulmonary disease 23 inchlorine gas workers. Am. Rev. Respir. Dis. 99: 365-373. 

### 24 25 Chester, E. H.; Kaimal, P. J.; Payne, C. B., Jr.; Kohn, P. M. (1977) Pulmonary injury following exposure to 26 chlorine gas: possible beneficial effects ofsteroid treatment. Chest 72: 247-250. 

### 27 28 Conner, E. H.; DuBois, A. B.; Comroe, J. H., Jr. (1962)**Ac~te** chemical injury ofthe airway and lungs: 

### 29 experiencewith six cases. Anesthesiology 23: 538-547. 

### 30 31 Cralley, L. V. (1942) Theeffect ofirritant gasesupon therate ofciliary activity. J. Ind. Hyg. Toxicol. 32 24: 193-198. 33 34 Crane, C. R.; Sanders, D. C.; Endecott, B. R.; Abbott, J. K. (1985) Inhalation toxicology: IV. times to 

### 35 incapacitation and death for rats exposed continuously to atmospheric hydrogen chloride gas. Washington, 

### 36 DC: Federal Aviation Administration; FAAreport no. FAA-AM-85-4. 

### 37 38 Cunningham, H. M. (1980) Effect ofsodiumhypochlorite on the growth ofrats and guinea pigs. Am. J. Vet. 39 Res. 41: 295-297. · 

### 40 41 Darmer, K. 1., Jr.; Kinkead, E. R.; DiPasquale, L. C. (1974) Acute toxicity inrats and miceexposed to 42 hydrogen chloride gas and aerosols. Am. Ind. Hyg. Assoc. J. 35: 623-631. 43 44 Dewhurst, F. (1981) Voluntary chlorine inhalation. Br. Med. J. 282: 565-566. 

### 45 46 Dixon, W. M.; Drew, D. (1968) Fatal chlorine J)?isoning. J. Occup. Med. 10: 249-251. 47 48 Dixon, G. A.; lkels, K. G. (1977) Olfactory threshold ofchlorine inoxygen. Brooks AirForceBase, TX: USAF 49 School ofAerospace Medicine; reportno. SAM-TR-77-22. Available from: DefenseTechnical 50 Information Center, Alexandria, VA; ADA046015. · 51 52 Dodd, D. C.; Marshall, B. E.; Soma, L. R.; Leatherman, J. (1976) Experimental acid-aspiration pneumonia in 

### 53 the rabbit: a pathologic and morphometric study. Vet. Pathol. 13: 436-448. 

### 54
August 1994 6-48 DRAFT-DO NOT QUOTE OR CITE1 Donnelly, S. C.; FitzGerald, M. X. (1990) Reactive aitways dysfunction syndrome (RADS) due to chlorine gas 

### 2 exposure. Ir. J. Med. Sci. 159: 275-277. 

### 3 4 Enarson, D. A.; MacLean, L.; Dybuncio, A.; Chan-Yeung, M.; Grzybowski, S.; Johnson, A.; Block, G.; 

### 5 Schragg, K. (1984) Respiratory healthat a pulpmill in British Columbia. Arch. Environ. Health 

### 6 39: 325-330. 

### 7 8 Faure, J.; Arsac, Ph.; Bouissou, X.; Barret, L. (1983) Intoxication parles vapeurs de chlore. Suites immediates 

### 9 et tardives [Chlorine gas exposure: early and late sequelae]. Toxicol. Bur. Res. 5: 207-210. 10 11 Ferris, B. G., Jr.; Puleo, S.; Chen, H. Y. (1979) Mortality and morbidity in a pulp and a papermillin the 12 United States: a ten-year follow-up. Br. J. Ind. Med. 36: 127-134. 13 14 Fisher, N.; Hutchinson, J. B.; Berry, R.; Hardy, J.; Ginocchio, A. V. (1983a) Long-term toxicity and 15 carcinogenicity studies ofcakemade from chlorinated flour: 1. studies inrats. Food Chem. Toxicol. 16 21: 427-434. 

### 17. 18 Fisher, N.; Berry, R.; Hardy, J. (1983b) Short-term toxicity study in rats ofchlorinated cake flour. Food Chem. 19 Toxicol. 21: 423-426. 

### 20 21 Gapany, M.; Tirosh, M. (1984) Exposure to domestic lung irritants. Harefuah 107: 147-149, 164. 

### 22 23 GEOMET Technologies, Inc. (1981) Hydrogen chloride: report 4, occupational hazard assessment. Cincinnati, 24 OH: U.S. Department ofHealth and Human Services, National Institute for Occupational Safety and 

### 25 Health; NIOSH contract no. 210-79-0001. Available from: NTIS, Springfield, VA; PB83-105296. 26 

### 27 Ginocchio, A. V.; Fisher, N.; Hutchinson, J. B.; Berry, R.; Hardy, J. (1983) Long-term toxicity and 

### 28 carcinogenicity studies ofcakemade from chlorinated flour: 2. studies in mice. Food Chem. Toxicol. 29 21: 435-439. 

### 30 31 Givan, D. C.; Eigen, H.; Tepper, R. S. (1989) Longitudinal evaluation ofpulmonary function in an infant 

### 32 following chlorine gas exposure. Pediatr. Pulmonol. 6: 191-194. 33 34 Greenfield, L. J.; Singleton, R. P.; McCaffree, D. R.; Coalson, J. J. (1969) Pulmonary effects ofexperimental 35 graded aspiration ofhydrochloric acid. Ann. Surg. 170: 74-86. 

### 36 37 Grimbert, F. A.; Parker, J. C.; Taylor, A. E. (1981) Increased pulmonary vascular permeability following acid 

### 38 aspiration. J. Appl. Physiol.: Respir. Environ. Exercise Physiol. 51: 335-345. 

### 39 40 Gross, E. A.; Wolf, D. C.; Barrow, C. S.; Morgan, K. T.; Moss, 0. R.; Popp, J. A. (1993) Chronic inhalation 41 study ofchlorinein B6C3F1 mice and F344 rats [abstract]. Toxicologist 13: 150. 42 43 Guidry, M. A.; Allen, J. H.; Kelly, J. B. (1957) Some biochemical characteristics ofhydrochloric-acid injury of 44 the cornea:

## n. carbohydrate metabolism. Am. J. Ophthalmol. 44: 243-248. 

### 45 46 Hartiell, G. E.; Packham, S. C.; Grand, A. F.; Switzer, W. G. (1985) Modeling oftoxicological effects offire 

### 4 7 gases:

## m. quantification ofpost-exposure lethality ofrats from exposure to HCI atmospheres. J. FireSci. 48 3: 195-207. 

### 49 50 Hartzell, G. E.; Gnmd, A. F.; Switzer, W. G. (1987) Modeling oftoxicological effects offire gases: VI. further 51 studies on the toxicity ofsmoke containing hydrogen chloride. J. Fire Sci. 5: 368-391. 

### 52 53 Hasan, F. M.; Gehshan, A.; Fuleihan, F. J.D. (1983) Resolution ofpulmonary dysfunction following acute 54 chlorine exposure. Arch. Environ. Health 38: 76-80. August 1994 6-49 DRAFT-DO NOT QUOTE OR CITE1 Heidemann, S. M.; Goetting, M.G. (1991) Treatment ofacute hypoxemic respiratory failure caused by chlorine 2 exposure. Pediatr. Emerg. Care 7: 87-88. 3 

### 4 Higgins, E. A.; Fiorca, V.; Thomas, A. A.; Davis, H. V. (1972) Acute toxicity ofbriefexposures to HF, HCl, 

### 5 N02 and HCN with and without CO. FireTechnol. 8: 120-130. 

### 6 7 Jiang, X. Z.; Buckley, L. A.; Morgan, K. T. (1983) Pathology oftoxic responses to theRDSO concentration of 8 chlorinegas in thenasal passages ofrats and mice. Toxicol. Appl. Pharmacol. 71: 225-236. 

### 9 

### 10 Jones, F. L., Jr. (1972) Chlorinepoisoning from mixing household cleaners. JAMAJ. Am. Med. Assoc. 

### 11 222: 1312. 

### 12 13 Jones, R. N.; Hughes, J. M.; Glindmeyer, H.; Weill, H. (1986) Lung function afteracutechlorine exposure. 

### 14 Am. Rev. Respir. Dis. 134: 1190-1195. 

### 15 16 Joyner, R. E.; Durel, E. G. (1962) Accidental liquid chlorine spill ina rural community. J. Occup. Med. 

### 17 4: 152-154. 

### 18 19 Kaplan, H. L. (1987) Effects ofirritant gases on avoidance/escape performance and respiratory response ofthe 

### 20 baboon. Toxicology 47: 165-179. 

### 21 22 Kaplan, H. L.; Grand, A. F.; Rogers, W. R.; Switzer, W. G.; Hartzell, G. E. (1984) A research study ofthe 

### 23 assessment ofescape impairment by irritant combustion gases inpostcrash aircraft fires. Atlantic City 

### 24 Airport, NJ: U.S. Department ofTransportation, Federal Aviation Administration; report no. 

### 25 DOT/FAA/CT-84/16. Available from: NTIS, Springfield, VA; AD-A146484. 

### 26 27 Kaplan, H. L.; Anzueto, A.; Switzer, W. G.; Hinderer, R. K. (1988) Effects ofhydrogen chloride onrespiratory 

### 28 response and pulmonary function**o~**thebaboon. J. Toxicol.**Env~n.** Health 23: 473-493. 

### 29 30 Kirsch, V. H.; Drabke, P. {1982) ZurBeurteilung biologischer Wirkungen von Chlorwasserstoff [Assessing the 

### 31 biological effects ofhydrogen chloride]. Z. Gesamte Hyg. Ihre Grenzgeb. 28: 107-109. 

### 32 33 Klonne, D. R.; Ulrich, C. E.; Riley, M.G.; Hamm, T. E., Jr.; Morgan, K. T.; Barrow, C. S. {1987) One-year 34 inhalation toxicity study ofchlorine inrhesus monkeys (Macaca mulatta). Fundam. Appl. Toxicol. 

### 35 9: 557-572. 36 37 Kolesar, G. B.; Crofoot, S. D.; Sibert, G. J.; Siddigui, W. H. {1993) A comparison ofthe acute inhalation 

### 38 toxicity ofmethyltrichlorosilane and gaseous hydrogen chloride in the rat. Toxicologist 13: 151. 

### 39 40 Kotula, A. W.; Emswiler-Rose, B. S.; Cramer, D. V. (1987) Subacute study ofrats fed groundbeeftreated with 

### 41 aqueous chlorine: hematologic and clinical pathology. J. Toxicol. Environ. Health20: 401-409. 

### 42 43 Kowitz, T. A.; Reba, R. C.; Parker, R. T.; Spicer, W. S., Jr. (1967) Effects ofchlorine gasupon respiratory 44 function. Arch. Environ. Health 14: 545-558. 

### 45 46 Krishnan, B.; Rao, A. S. {1981) Surface activity & phospholipid content ofsaline extract from control 47 & hydrogen chlorideexposed lungs. IndianJ. Exp. Bioi. 19: 637-639. 

### 48 49 Kutzman, R. S. {1983) A study ofFischer-344 rats subchronically exposed to 0, 0.5, 1.5, or5.0ppmchlorine 

### 50 [informal report]. Upton, NY: Brookhaven National Laboratory; Interagency agreement no. 51 222-YOl-ES-9-0043. 

### 52 53 Leonardos, G.; Kendall, D.; Barnard, N. {1969) Odor threshold determinations of53 odorant chemicals. J. Air 54 Pollut. Control Assoc. 19: 91-95. 

### August 1994 

### 6-50 DRAFT-DO NOT QUOTE OR

## CITE1 Lipton, M. A.; Rotariu, G. J. (1941) In: Geiling, E. M. K.; McLean, F. C., eds. Progress report on toxicity of 2 chlorine gas for mice. Washington, DC: U.S. National Defense Committee, Office ofScientific Research 

### 3 and Development; report no. 286. [As cited in: Withers and Lees, 1985). 4 

### 5 Lucia, H. L.; Barrow, C. S.; Stock, M. F.; Alarie, Y. (1977) A semi-quantitative method for assessing anatomic 

### 6 damage sustained by theupper respiratory tract ofthe laboratory mouse, Mus musculis. J. Combust. 

### 7 Toxicol. 4: 472-486. 

### 8 9 Machle, W.; Kitzmiller, K. V.; Scott, E. W.; Treon, J. F. (1942) Theeffect ofthe inhalation ofhydrogen 10 chloride. J. Ind. Hyg. Toxicol. 24: 222-225. 

### 11 12 Malek, D. E.; Alarie, Y. (1989) Ergometerwithin a whole-body plethysmograph to evaluateperformanceof 

### 13 guinea pigs under toxic atmospheres. Toxicol. Appl. Pharmacol. 101: 340-355. 

### 14 

### 15 Moulick, N. D.; Banavali, S.; Abhyankar, A. D.; Borkar, S.; Aiyengar, J.; Kapadia, N. M.; Khokhani, R. C. 

### 16 (1992) Acute accidental exposure to chlorinefumes: a study of82 cases. IndianJ. Chest Dis. Allied Sci. 

### 17 34: 85-89. 18 

### 19 Mrvos, R.; Dean, B. S.; Krenzelok, E. P. (1993) Home exposures to chlorine/chloraminegas: review of 

### 20 216 cases. South. Med. J. 86:**65~57.** 

### 21 22 National Research Council. (1976) Chlorine and hydrogen chloride. Washington, PC: Committee on Medical and 

### 23 Biologic Effects ofEnvironmental Pollutants; EPAreport no. EPA/60011-76-020. Available from: NTIS, 24 Springfield, VA; PB-253196/0. 

### 25 26 O'Neil, C. E. (1991) Immune responsiveness in chlorine exposed rats. Cincinnati, OH: U.S. Department of 

### 27 Health and Human Services, National Institute for Occupational Safety and Health. Available from NTIS, 

### 28 Springfield, VA; PB92-124478.

. 

### 29 30 Oddoy, A.; Drabke, P.; Feigner, U.; Kirsch, H.; Lachmann, B.; Merker, G.; Robertson, B.; Vogel, J. (1982) 

### 31 DerEinfluss einer intermittierenden Chlorwasserstoffexposition aufdie Lungenfunktion des 

### 32 Meerschweinchens [The effect ofintermittent hydrogen chloride gas exposure on the lung function ofthe 

### 33 guinea pig]. Z. Erler. Atmungsorgane 158: 285-290. 

### 34 35 Patil, L. R. S.; Smith, R. G.; Vorwald, A. J.; Mooney, T. F., Jr. (1970) Thehealth ofdiaphragm cell workers 

### 36 exposed to chlorine. Am. Ind. Hyg. Assoc. J. 31: 678-686. 

### 37 38 Pherwani, A. V.; Khanna, S. A.; Patel, R. B. (1989) Effect ofchlorine gas leak onthe pulmonary functions of 

### 39 school children. IndianJ. Pediatr. 56: 125-128. 

### 40 41 Ploysongsang, Y.; Beach, B. C.; DiLisio, R. E. (1982) Pulmonary function changes after acute inhalation of 42 chlorine gas. South. Med. J. 75: 23-26. · 43 44 Prindle, R. A.; Elzay, R. P.; Armstrong, C. W.; Funkhouser, L. S.; Miller, G. B., Jr. (1983) Erosion ofdental 

### 45 enamel among competitive swimmers-Virginia. Morb. Mortal. Wkly. Rep. 32: 361-362. 

### 46 47 Rafferty, P. (1980) Voluntary chlorine inhalation: a new form ofself-abuse? Br. Med. J. 281: 1178-1179. 48 49 Remijn, B.; Koster, P.; Houtbuijs, D.; Boleij, J.; Willems, H.; Brunekreef, B.; Biersteker, K.; van Loveren, C. 50 (1982) Zinc chloride, zinc oxide, hydrochloric acid**~xposure** and dental erosion in a zinc galvanizing 51 plant in The Netherlands. Ann. Occup. Hyg. 25: 299-307. 52

August 1994 6-51 

### DRAFf-DO NOT QUOTE OR CITE

### 1 Rotman, H. H.; Fliegelman, M. J.; Moore, T.; Smith, R.. G.; Anglen, D. M.; Kowalski, C. J.; Weg, J. G. 

### 2 (1983) Effects oflowconcentrations ofchlorineonpulmonary function inhumans. J. Appl. 

### 3 Physiol.: Respir. Environ. ExercisePhysiol. 54: 1120-1124. 4 

### 5 Rupp, H.; Henschler, D. (1967) Wirkungengeringer Chlor- und Bromkonzentrationen aufden Menschen [Effects 

### 6 oflowchlorine andbromineconcentrationsonman]. Int. Arch. Gewerbepathol. Gewerbehyg. 23: 79-90. 7 8 Salisbury, D. A.; Enarson, D. A.; Chan-Yeung, M.; Kermedy, S. M. (1991) First-aidreports ofacute chlorine 

### 9 gassing amongpulpmillworkers aspredictors ofbmg health consequences. Am. J. Ind. Med. 20: 71-81. 

### 10 11 Savad, E. N. (1982) Enamel erosion ••• multiplecaseswith a common cause(?) J. N.J. Dent. Assoc. 12 53: 32, 35-37, 60. 

### 13 14 Schlagbauer, M.; Renschler, D. (1967) Toxicitaetvon ChlorundBrombei einmaliger undwiederholter 15 Inhalation [Toxicity ofchlorineandbromineafter single andrepeated inhalation]. Int. Arch. 16 Gewerbepathol. Gewerbehyg. 23: 91-98. 

### 17 18 Schwartz, D. A.; Smith, D. D.; J.aksbminarayan, S. (1990) Thepulmonary sequelae associated with acCidental 19 inhalation ofchlorine gas. Chest 97: 820-825. 

### 20 21 Shroff, C. P.; Kbade, M. V.; Srinivasan, M. (1988) Respiratory cytopathology .in chlorine gas toxicity: a study 22 in28 subjects. Diagn. Cytopathol. 4: 28-32. 23 24 Silver, S. D.; McGrath, F. P. (1942) Chlorine. Median lethal concentration for mice. Edgewood Arsenal,· 25 MD: War Department, Chemical Warfare Service; report no. E.A.T.R. 351. Available from: Defense 

### 26 Technical Information Center, Alexandria, VA; ADB955268. 

### 27 28 Silver, S. D.; McGrath, F. P.; Ferguson, R. L. (1942) Chlorine. Median lethal concentration for mice. 

### 29 Edgewood Arsenal, MD: War Department, Chemical Warfare Center; report no. E.A.T.R. 373. 30 Available from: DefenseTechnical Information Center, Alexandria, VA; ADB955266. [As cited in: 

### 31 Withers andLees, 1985]. 32 

### 33 Simmons, J. A.; Erdmann, R. C.; Naft, B. N. (1974) The risk ofcatastrophic spills oftoxic chemicals. Los 34 Angeles, CA: University ofCalifornia School ofEngineering and Applied Science; report no. 35 UCLA-ENG-7425. 

### 36 37 Soni, N.; O'Rourke, I.; Pearson, I. (1985) Ingestion ofhydrochloric acid. Med. J. Aust. 142: 471-472. 

### 38 39 Stavert, D. M.; Archuleta, D. C.; Behr, M. J.; Lehnert, B. E. (1991) Relative acute toxicities ofhydrogen 40 fluoride, hydrogen chloride, and hydrogenbromide in nose- and pseudo-mouth-breathing rats. Fundam. 

### 41 Appl. Toxicol. 16: 636-655. 42 

### 43 Stokinger, H. E. (1981) Chlorine, Cl2• In: Clayton, G. D.; Clayton, F. E., eds. Patty's industrial hygiene and 44 toxicology: volume 2B, toxicology. 3rdrev. ed. New York, NY: John Wiley & Sons; pp. 2954-2965. 45 

### 46 Summer, W.; Haponik, E. (1981) Inhalation ofirritant gases. Clin. Chest Med. 2: 273-287. 

### 47 48 ten Bruggen Cate, H. J. (1968) Dental erosion in industry. Br. J. Ind. Med. 25: 249-266. 49 50 Toxigenics Incorporated. (1984) 90-day inhalation toxicity study ofhydrogen chloride gas in B6C,F1 mice, 51 Sprague-Dawley rats and Fischer-344 rats. Research Triangle Park, NC: Chemical Industry Institute of 52 Toxicology; CIIT docket no. 20915. 

### 53

August 1994 6-52 DRAFT-DO NOT QUOTE OR CITE

### 1 Ulrich, C. E. (1984) Chlorine: chronic inhalation toxicity study on chlorine in non-human primates. Mattawan, 2 MI: International Research and Development Corporation; unpublished; CIIT docket no. 12484. · 

### 3 4 Underhill, F. P. (1920) The lethal war gases: physiology and**e~perimental** treatment. New Haven, CT: Yale 

### 5 University Press. 

### 6 

### 7 Vemot, E. H.; MacEwen, J. D.; Haun, C. C.; Kinkead, E. R. (1977) Acute toxicity and skin corrosion data for 

### 8 some organic and inorganic compounds and aqueous solutions. Toxicol. Appl. Pharmacol. 42: 417-423. 9 

### 10 Weedon, F. R.; Hartzell, A.; Setterstrom, C. (1940) Toxicity ofammonia, chlorine, hydrogen cyanide, hydrogen 

### 11 sulphide, and sulphurdioxide gases. V. Animals. Contrib. Boyce Thompson lnst. 11: 365-385. 

### 12 13 Weill, H.; George, R.; Schwarz, M.; Ziskind, M. (1969) Late evaluation ofpulmonary function afteracute 

### 14 exposure tochlorine gas. Am. Rev. Respir. Dis. 99: 374-379. 

### 15 16 Wiun, R.; Stothert, J.; Nadir, B.; Hildebrandt, J. (1983) Lung mechanics following aspiration of 

### 17 0.1 N hydrochloric acid. J. Appl. Physiol.: Respir. Environ. Exercise Physiol. 55: 1051-i056. 

### 18 

### 19 Withers, R. M. J.; Lees, F. P. (1985a) Theassessment ofmajorhazards: the lethal toxicity ofchlorine; 

### 20 part 1, review ofinformation on toxicity. J. Hazard. Mater. 12: 231-282. 

### 21 22 Withers, R. M. J.; Lees, F. P. (1985b) The assessment ofmajorhazards: the lethal toxicity ofchlorine; 

### 23 part 2, model oftoxicity to man. J. Hazard. Mater. 12: 283-302. 

### 24 25 World Health Organization. (1982) Chlorine and hydrogen chloride. Geneva, Switzerland: World Health 

### 26 Organization. (Environmental health criteria 21). 

### 27 28 Zwart, A.; Arts, J. H. E.; Klokman-Houweling, J. M.; Schoen, E; D. (1999) Determination of 

### 29 concentration-time-mortality relationships to replace LCSO values. Inhalation Toxicol. 2: 105-117.

August 1994 6-53 DRAFT-DO NOT QUOTE OR CITE

### 1 2 

## 7. 

# DEVELOPMENTAL TOXICITY AND 

# REPRODUCTIVE EFFECTS.
3 4 5 

### 7.1 EXPERIMENTAL ANIMALS 6 

### 7.1.1 Chlorine 7 A number ofstudies have addressed the teratological and reproductive effects of 8 ingested chlorine and the by-products ofwater chlorination (hypochlorous acid and 

### 9 hypochlorite). Forthe most part, chlorine and theby-products ofwater chlorination were not 10 found to affect reproduction in mice (Les,**19~8;** Chernoffet al., 1979; Staples etal., 1979) 11 orrats (Carlton et al., 1986; Druckrey, 1968; Abdel-Rahman et al., 1982). There was, 12 however, an increase in the number of sperm head abnormalities 

### in mice given sodium 13 hypochlorite in drinking water (Meier et al., 1985). A significant increase in the number of 14 soft tissue anomalies has also been reported in rats treated with 100 mg/Lhypochlorous acid 15 for 2.5 mo prior to mating and throughout gestation, but the results ofthis experiment were 16 limited by the small numbers ofanimals tested and the fmding ofa higher rate ofsoft tissue 17 anomalies in the control group compared to the low-exposure group (10 mg/mL) (Abdel18 Rahman et

### al., 1982). 19 Only limited information was found on the reproductive and/or teratological effects of 20 the inhalation ofchlorine gas by experimental animals. 

### In the study by Kutzman (1983), 21 male and female Fischer 344 rats were exposed to 0, 0.5, 1.5, or5.0ppm 

### (0, 1.4, 4.3, or 22 14.5 mg/m3) chlorine gas for 

## 6h/day, 5 days/week for 62 days. Six days after termination 23 ofexposure, 

### 8 male and 10 female rats from each exposure group were mated with 24 unexposed**animals~** Female rats were then sacrificed on Day 19 ofgestation. Analysis of 25 the number ofviable embryos, late and early reabsorptions, and corpea lutea did not show a 26 chlorine-related effect on the reproductive potential ofeither male or female animals. 27 The only other study on the teratological orreproductive effects ofchlorine inhalation 28 was a study by Skljanskaja and Rappoport (1935), as reported by the World Health· 29 Organization (1982). In that study, eight rabbits were exposed to chlorine gas at 30 concentrations of

### 0.6 to 

### 1.5 ppm 

### (1.7 to 4.3 mg/m3 ), 5h/day, every other day for 

### 1to 31 

### 9 mo. Only one rabbit served as a control. The animals were said to have delivered healthy, August 1994 7-1 DRAFT-DO NOT QUOTE OR CITE

### 1 well-developed fetuses except for macerated fetuses in the abdomen oftwo exposed rabbits. 2 The rabbits were reported to have exhibited nasal irritation, sneezing, and labored breathing. 3 Histopathological examination ofthe respiratory tract showed catarrhal inflammation ofthe· 4 upper respiratory tract, metaplasia ofthe bronchi, suppurative bronchitis and pneumonia, 5 pleuritis, emphysema, and atelectasis. There were also granulomas in the brain and other 

### 6 organs and necrosis ofthe liver. Theauthors believe that all 

### ofthe changes noted in the 7 exposed rabbits were the directresult ofthe toxic action ofchlorine; however, the**Worl~** 

### 8 Health Organization (1982) reported that lesions ofthe nature noted in the exposed rabbits are 9 typical ofseveral infectious diseases 

### common to rabbits. 10 11 

### 7.1.2 Hydrogen Chloride 12 Only two reports were found in the published literature on developmental toxicity and 13 reproductive effects ofinhaled hydrogen chloride. In the first ofthese studies, Pavlova 14 (1976) exposed two groups of8 to 15 female Wistar rats to 302 ppm (450 mg/m3) 

### hydrogen 15 chloride gas for 1h; one group was exposed 12 days prior to mating and the other group on 16 Day 9 ofgestation. In

### both groups, signs ofsevere dyspnea and cyanosis were noted, and 17 mortality occurred in one-third ofthe animals. Lungs revealed congestion, edema, and 18 hemorrhage. 

### In addition, exposure lowered blood oxygen saturation, increased absorption of 19 vital dye by lung tissue, and disturbed kidney (increased chloride and protein in urine) and 20 liver functions (Quick-Pytel test). Fetal mortality was significantly {p 

### < 0.05) higher in rats 21 exposed during pregnancy. When the progeny were subjected to an additional exposure of 22 35 ppm (52 mg/m3) 

### at the age of2 to 3 mo, functionai abnormalities in the organs ofthe 23 progeny were similar to those found in 

### the mothers. Progeny ofdams exposed before 24 pregnancy were affected more severely than were progeny ofthose exposed during 25 pregnancy. 

### In both groups, the male offspring were more sensitive than the females. The 26 author concluded that hydrogen chloride-induced changes 

### in organs in pregnant rats disturbed 27 embryogenesis, producing functional abnormalities in the same organs in the progeny. The 28 severity ofthese abnormalities in

### progeny ofmothers exposed to hydrogen chlorideprior to 29 conception is thought to be the result ofconception taking place in spite ofthe maternal organ 30 damage.

August 1994 7-2 DRAFT-DO NOT QUOTE OR CITE1 Inthe other study, female Wistarrats and mixed-strain rats were exposed to 302 ppm 2 (450 mg/m3) hydrogen chloride for 1 h prior to mating. Exposure killed 30% ofWistar and 3 20% ofthe mixed-strain rats. Inrats surviving 6 days after exposure, a decrease 

### in blood 4 oxygen saturation was noted, as was kidney, liver, and spleen damage. In addition, treatment 5 altered the**~trous** cycles. In rats mated 12 to 16 days postexposure and 

### killed on Day 21 of 6 pregnancy, fewer live fetuses, a decrease in fetal weight, and an increasein relative lung 7 weights ofthe fetUses were observed (GBOMET Technologies, Inc., 1981). 

### 8 

### 9 10 

### 7.2 HUMAN STUDIES 11 No adequate human studies were found 

### in the literature on developmental toxicity or 12 reproductive effects ofeither chlorine or hydrogen chloride. However, Skljanskaja et al. 13 (1935) followed the pregnancies of 15 female workers who had been exposed for 6 h/day to 14 levels ofchlorinebetween 0.9 to 1.8ppm (2.5 and 

### 5 mg/m3). Although 2 of 15 had 15 spontaneous abortions, the authors concluded that these were not related to chlorine exposure. 16 The small number ofpregnancies**~d** the lack ofa control group preclude any conclusions 17 based on this study. 18 19 20

August 1994 7-3 DRAFf-DO NOT QUOTE OR CITE1 

### REFERENCES 2 Abdel-Rahman, M. S.; Berardi, M. R.; Bull, R. J. (1982) Effect ofchlorine and monochloramine in drinking 3 water on the developing rat fetus. J. Appl. Toxicol. 2: 156-159. 4 

### 5 Carlton, B. D.; Barlett, P.; BaSaran, A.; Colling, K.; Osis, 1.; Smith, M. K. (1986) Reproductive effects of 6 alternative disinfectants. Environ. Health Perspect. 69: 237-241. 

### 7 8 Chemoff, N.; Rogers, E.; Carver, B.; Kavlock, R.; Gray, E. (1979) Thefetotoxic potential ofmunicipal 9 drinking water inthe mouse. Teratology 19: 165-169. 

### 10 11 Dnlckrey, H. (1968) Chloriertes Trinkwasser, Toxmtaets-Pruefungen anRatten ueber sieben Generationen 

### 12 [Chlorinated drinking water, toxicity studies in seven generations ofrats]. Food Cosmet. Toxicol. 

### 13 6: 147-154. 14 

### 15 GEOMETTechnologies, Inc. (1981) Hydrogen.chloride: report 4, occupational ha7Md assessment. Cincinnati, 16 OH: U.S. Department ofHealth and Human Services, National Institute for Occupational Safety and 17 Health; NIOSH contract no. 210-79-0001. Available from: NTIS, Springfield, VA; PB83-105296. 

### 18 19 Kutzman, R. S. (1983) A study ofFischer-344 rats subchronically exposed to 0, 0.5, 1.5, or5.0ppmchlorine 

### 20 [informal report]. Upton, NY: Brookhaven National Laboratory; Interagency agreement no. 

### 21 222-Y01-ES-9-0043. 

### 22 23 Les, E. P. (1968) Effect ofacidified-chlorinated water onreproduction in C3H/HeJ and C57BL/6J mice. Lab. 

### 24 Anim. Care 18: 210-213. · 

### 25 26 Meier, J. R.; Bull, R. J.; Stober, J. A.; Cimino, M. C. (1985) Evaluation ofchemicals**~ed** for drinking water 

### 27 disinfection for production ofchromosomal damage and sperm-head abnormalities in mice. Environ. 

### 28 Mutagen. 7: 201-21.1. 

### 29 

### 30 Pavlova, T. E. (1976) Disturbance ofdevelopment oftheprogeny ofrats exposed to hydrogen chloride. Bull. 

### 31 Exp. Bioi. Med. 82: 1078-1081. 32 33 Skljanskaja, R. M.; Rappoport, J. L. (1935) Experimentelle Studienueberchronische Vergiftung von Kaninchen 34 mit geringen Chlorkonzentrationen unddie Entwicklung derNachkommenscbaft derchlorvergifteten 

### 35 Kaninchen [Experimental studies onchronic poisoning and'the development the offspring of 

### 36 chlorine-poisoned rabbits]. Naunyn-Schmiedebergs Arch. Exp. Pathol. Pharmakol. 177: 276-287. 37 

### 38 Skljanskaja, R. M.; Klaus, L. M.; Ssidorowa, L. M. (1935) Ueber dieEinwirkung des Chlors aufden 39 weiblichen Organismus [On the effect ofchlorine on the female organism]. Arch. Hyg. Bakteriol. 

### 40 114: 103-114. 

### 41 42 Staples, R. E.; Worthy, W. C.; Marks, T.. A. (1979) Influence ofdrinking water-tap versus purified-on 43 embryo and fetal development inmice. Teratology 19: 237-243. 44 45 World Health Organization. (1982) Chlorineand hydrogen chloride. Geneva, Switzerland: World Health 46 Organization. (Environmental health criteria 21). 

### 47

August 1994 7-4 DRAFf-DO NOT QUOTE OR CITE1 

# 8. MUTAGENIC AND CARCINOGENIC EFFECTS 2 3 4 

## 8.1 MUTAGENIC EFFECTS 5 

## 8.1.1 Chlorine 6 Chlorine is a highly reactive compound, and, consequently, the determination ofthe 

### 7 direct mutagenic potential ofchlorine is a difficult undertaking. Forinstance, 

### a number of 

### 8 the chlorinereaction products, chlorinated organic and inorganic compounds formed during 

### 9 thetreatment ofdrinking water and waste water, havebeen shown to possess mutagenic 10 potential in various test systems (Meier et al., 1983; Dolara etal., 1981; Mickey and 11 Holden, 1971; Cumming, 1978; Shih and Lederberg, 1976; Zoeteman etal., 1982; Stover 12 etal., 1983; 

### Rannug et al., 1981; Douglas et al., 1982; 

## Lee et al., 1981). Ithas also been 13 reported that dry seeds, treated with chlorine gas for 25 hand sprouted, developed 14 chlorophyll mutations at twice the frequency observed in untreated plants (Ehrenberg etal., 15 1956). However, there is no indication that chlorineper se is mutagenic in humans orother 16 mammals (National Research Council, 1976). 

### In fact, analysis ofmetaphase cells ofbone

. 17 marrow and peripheral blood lymphocytes for sister chromatid exchange in rats 18 subchronically exposed to up to 

### 5ppm (14.5 mg/m3) chlorine showed no significant effects. 19 There were also no effects reported on cellular proliferation ofbone marrow cells, the 20 frequency ofchromosomal aberrations in peripheral blood lymphocytes, or the morphology of 21 sperm cells 

### in the chlorine-exposed rats 

### (see Section 6.1.1.2) (Kutzman, 1983). 

### 22 23 

## 8.1.2 Hydrogen Chloride 24 No information was found in the published literature on the mutagenic potential of 25 hydrogen chloride.

August 1994 8-1 DRAFT-DO NOT QUOTE 

### OR CITE1 

### 8.2 CARCINOGENIC EFFECTS 2 

### 8.2.1 Experimental Animals 3 8.2.1.1 Chlorine 4 Only one study was found that evaluated the inhalation carcinogenicity ofchlorine. 

### 5 MaleFischer 344 rats and male and female B6C3F1 mice were exposed to 0, 0.4, 1.0, or 6 2.5 ppm (0, 1.2, 2.9, or7.2 mg/m3) chlorine gas 6 h/day, 

### 5 days/week for a period of 7 

### 2 years. FemaleFischer

### 344 rats wereexposed to the same chlorine gas concentrations but 8 for 

### 3 alternate days perweek for the 2-yearperiod. Complete histopathology was performed 9 on all control animals and animals in the highest exposure group, and target organs were 10 ex-edin animals in the two lowest exposed groups. No exposurerelated neoplasms were 11 found in any ofthe animals examined (Grosset al., 1993). Also, no increased**inciden~** of 12 malignant tumors was reported in 236 BD IIrats given highly chlorinated water (containing 13 100 mg/L free chlorine) over seven generations (Druckrey, 1968) orin rats fed a cake diet 14 containing 1,250 or 2,500ppm chlorine for 104 weeks (Fisher etal., 1983). 15 16 

### 8.2.1.2 Hydrogen Chloride 17 No standard carcinogenicity bioassays for hydrogen chloride were found. However, 18 Albert et al. (1982) conducted a study designed to assess the carcinogenic response ofmale 19 Sprague-Dawley rats following combined and separate**e~posures** to formaldehyde and 20 hydrogen chloride. The rationale was that**bis(chlorome~hyl)ether,** a compound demonstrated 21 to becarcinogenic in mice, rats, and humans, may be formed by the gas-phase reaction of 22 hydrogen chloride and formaldehyde. Exposure to hydrogen chloride at 10.2ppm 23 (14.3 mg/m3), 

### 6 hlday, 5 days/week for 382 exposures over 588 days did not induce any 24 

### nasal tumors. Theaddition ofhydrogen chloride gas (10 ppm [14 mg/m3]) to formaldehyde 25 (14 ppm) did notenhance the carcinogenic response offormaldehyde. When hydrogen 26 chloride and formaldehyde werepremixed at high concentrations to**m~mize** the formation 27 ofbis(chloromethyl)ether and then diluted 75-fold to give chamber concentrations of 10ppm 28 hydrogen chloride and 14 ppm formaldehyde, there was no clear increase in the carcinogenic 29 response. Theauthors concluded that under the conditions ofthe study, hydrogen chloride 30 was not carcinogenic, and that formaldehyde accounted for most ifnot all ofthe carcinogenic 31 activity ofthe mixture.
August 1994 8-2 DRAFT-DO NOT QUOTE OR CITE1 In siriillar studies, Sellakumar etal. (1985) concluded that hydrogen chloride did not 2 appreciably influence the nasal carcinogenicity offormaldehyde. Groups of 100 male 3 Sprague-Dawley rats were_exposed to filtered 

### air, 14 ppm formaldehyde, or 10 ppm 4 (14 mg/m3) hydrogen chloride or to formaldehyde and hydrogen chloride at the above levels, 

### 5 6 hlday, 

### 5 days/week for life. In rats exposed to hydrogen chloride, there were no serious 6 irritating effects

### inthenasal epithelium, nor were there anypreneoplastic orneoplastic 7 lesions. Lesions found in the

### nasal mucosa ofrats exposed to hydrogen chloride included 8 rhinitis (81 of99 exposed compared to 72 of99 controls), epithelial or squamous hyperplasia 9 (62 of99 exposed compared to 51 of99 controls), and·squamous metaplasia (9 of99 exposed 10 compared to 5of99 controls). There was also hyperplasia ofthe 

### larynx (22 of99 exposed 11 compared to 2 of99 controls) and trachea (26 of99 exposed compared to 2 of99 controls). 

### 12 13 

### 8.2.2 Epidemiological Studies 14 Itmust bekept in mind that, when chlorine is used as a disinfectant in drinking water, 15 ithas thepotential to form chloroform from the reaction oforganic compounds that persist 16 through the purification process. Chloroform has been shown to bea carcinogenic substance 17 and reported as such by the U.S. Environmental Protection Agency (EPA) (1985). The 18 overall weight ofevidence classification for chloroform has been determined by the EPA to 19 be "B2", meaning there is adequate evidence to classify chloroform as

# an animal carcinogen 20 butinadequate evidence 

### in humans. 21 With respect to chlorine itself, the evidence 

### again is not convincing 

### in humans. The 22 following studies appear to 

### be .the only epidemiologic studies where there may have been 23 exposure to chlorine orhydrogen chloride. 24 A cohort mortality study (Reeve etal., 1983) was performed on some**1~666** white male 25 employees ofa Texas-based chemical company. These employees constituted a 5% 26 systematic sample ofan alphabetized list oftheproduction and nonproduction work force 27 from 1940 to 1977. The chiefcause ofdeath ofinterest to the researchers was malignant 28 neoplasms ofthe brain, becauseprevious studies seem to indicate that employees ofthe 29 petroleum refining and chemical industry are subject to a higher risk ofbrain cancer. Other 30 causes ofdeath were not considered. A further restriction imposed by theresearchers on this 31 cohort involved geography and residence (i.e., observed deaths due to a brain tumor were
August 1994 8-3 DRAFr-DO NOT QUOTE OR CITE

## ..

1 confined to those who were residents ofa four-county area surrounding theTexas plant). 2 This led the researchers to generate three sets ofexpected rates from which to calculate 3 expected deaths. The first (method A) involved the assumptions that none ofthe cohort 4 members had moved from the four-county area and that each was atrisk ofdeath from a 

### 5 brain tumor from the time offirst exposurethrough theend ofthe exposureperiod orhis 6 death, whichever came first (person-years). Two other estimates considered that the subjects 7 had migrated outside ofthe four-county area. Inthe first oftheseestimates (method B),

. . 8 person-years wereassumed to cease accumulating on the last day ofemployment. In the 9 second case (method C), expected deaths, calculated in four distinct lengths ofemployment 10 categories, wereobtained by multiplying the expected deaths, determined by method A, by 11 the fraction ofthe number ofthose persons with malignant neoplasms residing only in the 12 four-county study area to the total number ofmalignant neoplasms found in all members of 13 the cohort. 14 Altogether, 25 brain tumor deaths were found in this cohort. Included with these deaths 15 were both benign and malignant (nature unspecified) neoplasms ofthe brain and central 16 nervous system. Only five deaths fell into the latter two categories (methods B and C). 17 Presumably, the"rates that were used to calculate expected deaths must also have included 18 deaths in these two categories as well, although not explicitly stated. Using the three 19 methods described above, 43.0, 19.7, or 22.9 brain tumor deaths, respectively, would have 20 been expected. Although adjustment method A failed to show any trend, adjustment 21 methods B and C revealed an increased riskofbrain tumors with increasing employment for 22 the segment ofthe cohort thatbegan workpriorto 1945. No statistical analyses were done 23 because ofthe authors' uncertainty regarding the handling ofa sample cohort from a much 24 larger population. Under adjustment method 

### B, standard mortality ratios (SMRs) were 65, 25 175, 86, and 214 for persons employed under 1 year, 1 to 4 years, 

### 5 to 19 years, and 26 20years or more, respectively. In the group employed for 20 or more years, there were 27 16 observed deaths compared to 9.4 expected using method B. Because these excesses were 28 confined mostly to a period ofemploymentprior to 1945, the authors concluded that those 29 hired before 1945 wereprobably subject to an**incr~ed** risk ofbrain cancer, although no 30 statistical analyses were run because the authors did not know how to calculate significance 31 based on sample data.

August 1994 

### 8-4 DRAFf-DO NOT QUOTE OR CITE1 Apparently, the authors' 

### main purpose was to demonstrate the efficacy ofa variation in 2 a rather well-established methodological design, and made no .effort to identify any likely 3 occupational exposure as the cause ofthe slight suggested excesses ofbrain cancer. The 4 authors' only reference to any possible exposure is a general statement thatpopulations 

### 5 employed 

### in .the petroleum refining and chemical industries may beatincreased risk of 6 developing brain tumors, without identifying any possible etiologic agents. 7 Theauthors could have avoided the wholeproblem ofsmall numbers in the study 8 results 

### ifthey 

### had been morejudiciousin their selection ofmethodologies. Reducing the size 9 ofa cohort to manageableproportions is laudable; however, rather well-established methods 10 ofreducing the cohort 

### size have

### been developed by the National Institute for Occupational 11 Safety and Health (NIOSH). Taking a systematic random sample ofall employees who ever 12 worked attheplant implies thattheresearcher intends to make inferences about the 13 population as a whole concerning certain health conditions that might exist in the plant. But, 14 ifthepurpose is to identify 

### certain agents orplantdepartments, itmight bebetter to look for 15 commonalities in the individual cases and then define a cohort consisting ofonly those who 16 have greatest potential for exposureto those commonalities. The approach utilized by these 17 authors is inappropriate to identify single agents responsible for an excess in the risk ofa 18 

### disease. As a result, this paper falls shortin its ability to identify any department or agent 19 responsible for the suggested excess ofbrain lesions. 20 A second study (Bond et

### al., 1983) was undertaken as a sequel to the study that 21 identified an excess number ofbrain tumors in the chemical plant in.Texas (Reeve et al., 22 1983). Bond and associates examined thebrain tumors identified in the study by Reeve and 23 co-workers, refined thecase definition, conducted a more vigorous case ascertainment, and 24 increased the total number ofnet cases of "primary intercranial neoplasms"**fr~m** 25 to 28. 25 They then conducted a case-control study ofbrain tumors utilizing two matched**comp~son** 26 groups; thepurpose ofwhich was to identify a likely etiologic agent, but nothing specific. 27 Control group A (four controls pereach case) was selected from all white male noncancer 28 deaths known to the company. They were matched on the ba8is ofage at death and year of 29 death. The second control group (group B) was selected from white male members ofthe 30 5% sample for all eligiblecohort employees that formed the basis ofthe original cohort ·

August 1994 8-5 DRAFT-DO NOT QUOTE OR CITE1 mortality study (Reeve etal., 1983). Cases were matched with controls on the basis ofage 2 and duration ofemployment atthe plant. 3 Theauthors found that the agents to which both cases and controls had the greatest 4 potential for exposure werechlorine, hydrogen chloride, and sulfurdioxide. Although the 

### 5 riskofbrain tumors from exposureto all three ofthese agents was elevated when compared 6 to the first control group (A), none was statistically significant. When the second control 7 group (B) was utilized, not even the suggestion ofan elevated riskappeared. One 8 explanation for thenonsignificant elevated risk seen in control group A is the lack oftest 

### 9 sensitivity because itwas based upon small numbers. 

### Ifall cases ofbrain cancer had been 10 enumerated from theplant sample, company records, deaths recorded in the four-county area 11 surrounding theplant, and unsolicited reports to the NIOSH, itmay havebeen possible to 12 increase thepower ofthe study enough to detect a risk. On the other hand, as was 

### pointed 13 outby the authors, duration ofemployment at the plant may have been a confounder that 14 produced an excess when not adequately controlled for 

### in the analysis. In fact, when the 15 authors evaluated the length ofemployment in control group A (employees from the 5% 16 sample), they found that the mean length ofemployment was an average·of41 man-months 17· longer than that ofthe cases. They attribute this to a bias introduced from inclusion of 18 greaternumbers ofskilled laborers 

### in control group A, whojusthappened to have much 19 longer service (

## >20 years) with the company. These workers were located mainly in the 20 magnesium department, and, consequently, an odds ratio of 1.93 (borderline significant) was 21 found for this department. 22 Inaddition to controlling for length ofemployment, a minimum latentperiod also 23 should havebeen specified 

### in the evaluation ofbrain cancer deaths. Ofnote is the large 24 number ofcases (17) listed whose minimum lapse oftime since initial emploY.ment was over 25 20 years. Exposure variable comparisons ofcases with matched controls should have been 26 done for those with 20 or more years oflatency. In fact, 24 ofthe 28 cases were diagnosed 27 with brain cancer more than 10 years after initial employment. 28 Besides the problem with latency, there is the problem with the small sample sizes 29 introduced by taking only a 5% sample ofthose·who worked there. As a possibly**b~tter** 30 approach to keep the cohort size manageable, a minimum length ofemployment should have 31 been specified for an employee to be included in the cohort. This also would have insured

August 1994 8-6 DRAFT-DO NOT QUOTE OR CITE

### 1 that only the maximally exposed employees be studied. This study fails to implicate an 2 etiologic agent because ofthe deficiencies outlined above, and, also fails to evaluate ·mortality 3 for other site-specific cancers from exposure to

### chlorine orhydrogen chloride. 4 In

### a later case-control study, Bond et al. (1985b) identified 26 cases ofrenal cancer in 5 

### former employees ofthe same Texas petrochemical plant**previou~ly** 

### studied by Bond et

### al. 6 (1983) and Reeve etal. (1983). Only five ofthe renal cancer deaths occurring in this group 

### 7 were found 

### as part

### ofthe 5% 

### sample discussed in 

### the earlier studies. The**re~g** 

### 21 

### cases 8 were found 

### as the result of

### an intensive effort on thepart ofthe company by matching·the 

### 9 mortality files ofthe Texas Bureau ofVital Statistics and the

### M. D. Anderson Hospital 

### and 10 Tumor Institutein the five-county area surrounding the plant. 11 As in

### the earlier study by Bond et al. (1983), two control groups were selected for 12 comparison purposes similar to the control groups ofthe earlier study ofbrain cancer with 13 certain differences as follow. 

### In control group A, referents were selected from all white male 14 decedents who were part ofthe same random sample that was chosen earlier minus those who 15 died from cancer. Four controls were matched on the basis ofdate ofbirth and duration of 16 employment. A total of92 decedents was chosen in 

### this manner. 17 The second control group (group B) 

### was selected from the same 5% 

### sample but without 18 restrictions on vital status. Matching was four to one on thebasis ofdate ofbirth, date of 19 hire, and date oftermination. A 

### total of98 

### individuals was chosen this way. In neither 20 control group was four-to-one matching possible for every case, however. 21 A 

### statistically significant odds ratio (OR) 

### was found to be associated with a history of 22 employmentin the chlorine production work area when compared to control group A 

### 23 (OR 

# =3.80). The risk was also elevated with respect to 

### control group B, but not 24 significantly (OR 

# =2.34). When the analysis was restricted to only**those~** 

### and controls 25 who worked 1year or longer in the chlorine work area, the risk ofrenal cancer was 26 enhanced significantly when compared to both control group A (OR 

# =5.27) and control 27 group B (OR = 

### 6.00). This was based on five cases. The authors indicated that chlorine 28 production consisted ofsix 

### separate chlorine production and chlorine cell 

### maintenance areas. 29 The elevated risks were for employment in the cell maintenance area ofchlorine production 30 (i.e, caustic solution and asbestos, but not chlorine). The authors indicated that this is an 31 

### entry-leveljob that does 

### not involve actual exposure to chlorine. It involves the preparation

August 1994 8-7 DRAFT-DO NOT QUOTE OR CITE1 ofan asbestos slurry in a caustic orwater solution into which the chlorine cell is**dip~.** 2 These five workers were also exposed to asbestos, phenol-formaldehyde resins, tung oil, cell 3 putty, Cab-0-Sil,., benzene-sulfonyl chloride, trichloroacetic vinyl-ester**r~in,** and methyl 4 ethyl ketone-peroxide. Hence, itwould be impossible 

### to determine which ofthe agents above 

### 5 was theonethatcaused the excess 

### in renal cancer. 

### 6 This study 

### has several problems, one ofwhich is the 

### likelihood that notall 

### cases of 

### 7 renal cancer 

### in thisplantpopulation areenumerated 

### in the 24 

### cases studied by the author due 

### 8 to the unusual manner in which renal cancer cases were identified. More ofthem may 9 remain unidentified simply because unconventional methods for determining vital status were

· 10 followed. Furthermore, a simple cohort mortality study might havebeen the more

11 appropriate choice ofa methodology to beutilized, rather than thecase-control method. That 12 this is probably thebetterprocedure has been recognized by Bond and co-researchers. 13 

### In summary, itappears that the excess ofrenal cancer 

### in the employees who worked in 14 the cell maintenance area ofchlorine production ofthis company cannotbe attributed to 15 exposure to chlorinebecause ofthe likelihood ofmultiple chemical exposures occurring in · 16 workers 

### in that area. As a result, this study does not provide convincing evidence ofa causal 17 relationship between exposure to chlorine and an excess risk ofrenal cancer. 18 Another cohort mortality study (Bond et al., 1985a) was completed on the 5% 19 systematic random sample ofall present and past white male employees ofthepetrochemical 20 plant 

### in Texas that was suspected ofbeing associated with a high risk ofbrain cancer. The 21 initial purpose ofthe sample was to provide an estimate ofthe extentofbrain cancer to be 22 found 

### in this plant, butlater this sample also was used for determining directions for 23 additional research on cause-specific mortality. Ultimately, this baseline data sourceprovided 24 the material from which several

### case control studies (Reeve et

### al., 1983;**Bon~** etal., 1983; 25 Bond et

### al., 1985b) were derived. 26 Cause-specific mortality was analyzed by duration ofemployment and date ofhire. 

### " 27 These data provided the basis for developing a surrogate for exposure. Significant excess 28 risks ofmortality were found due to total cancer (71 observed, 55.5 expected), ill-defined 29 conditions (8 observed, 3.3 expected), and all external causes ofdeath (57 observed, 30 40.7 expected). In addition, excess cancer mortality was primarily due to significant excess 31 cancer risks ofkidney cancer (5 observed, 1.4 expected) and lung cancer (29 observed,

August 1994 8-8 DRAFT-DO NOT QUOTE OR CITE

### 1 17 expected) and a nonsignificant excess risk ofpancreatic cancer 

### (7 observed, 3**expec~).** 2 When the analysis was narrowed to only those who had achieved a minimum of 15 years 3 follow-up, only lung cancerremained statistically significant (26 observed, 14.8 expected). 4 With the added requirement that a minimum of 15 years service must beachieved, cancerof 5 the kidney and lung cancerremained statistically significant as follows: 2 persons died with 6 kidney cancerbutonly 0.3 wereexpected, and 6 former employees with lung cancer died, 7 whereas only 2.3 were expected. 8 Theauthors mentioned that many chemical agents werepresent in this plantduring its 9 operation (i.e., chlorine, caustic, ethylene, ethylene glycol, ethylene dichloride, ethylene 10 dibromide, carbon tetrachloride, styrene, perchlorethylene, plus many organic and inorganic 11 chemicals). Apparently some40,000 persons.had been employed in this plant from 1940 to 

### 12 1977. 13 A majorproblem with this study is the fact that itis a random sample ofthe total 14 employed population at this plant in Texas. This limits its utility for identifying causes of 15 death because the power to detect significant cause-specific mortality is reduced. 16 Approximately 45.6% ofthe sample consisted ofemployees with a duration ofemployment 

### 17 less than 

### 1 year. Theauthors concluded that it

### was beyond the**sco~** ofthe study to lookfor 18 cause-specific agents responsible for theexcesses that were seen. They do speculate, 19 however, that certain confounders (i.e, smoking and/or region ofresidence) may have had an 20 influence. "Region ofresidence" comprises regional differences in health care delivery, 

### 21 death certification practices, lifestyle factors, orother environmental exposures. 22 In conclusion, there**ap~s** to be a suggestion ofan association ofcertain cause23 specific mortality with employment atthis plant, but that it is not possible to determine from 24 this study whether itis due to confounders or to some agent in the workplace= This study is 25 inadequate to conclude that either chlorine orhydrogen chloride is responsible. 26 Bond et al. (1991) reported on a case-control study oftrachea, bronchus, and lung 

### 27 cancer occurring from 1940 through 1980 in a cohort of 19,608 male employees exposed to a 28 variety ofchemicals at the Dow Chemical Company's Freeport, TX, facility. The case group 29 consisted of308 cancer decedents. Two control groups of308 males each, individually

August 1994 8-9 DRAFT-DO NOT QUOTE OR CITE1 matched to cases by race, year ofbirth (within 

### 5 years), and year ofhire, were chosen; one 2 was 

### a decedent series and the other living. Ofthe cohort, 41.9% ofthe subjects in the case 3 groups and 41.6% ofthe controls werejudged to have been exposed to hydrogen chloride. · 4 Smoking histories wereobtained for 70.8% oftheexposed and 75.5% ofthe controls. 5 A pack-years index was calculated for each subject to.permit control for potential 6 confounding by the smoking. Latency was evaluated byexcluding all exposures 

### within 7 15 years ofdeath. 8 Exposure to hydrogen chloride occurred in 

### areas where hydrogen chloride was a 9 by-product ofan electrochemical reaction orin 

### areas where hydrogen chloride was used as a 10 raw material in a reaction. Based on available monitoring·data and the amount oftime 11 required to be spent in the respectivejob, 8-h time-weighted average \fWA) exposure 12 estimates for hydrogen chloride were 0, 0.2 to 0.3, 0.9 to 2.0, and 2.2 to 5.1 ppm 

### (0, 0.3 to 13 0.4, 1.3 to 3.0, and 3.3 to 7.6 mg/m3). Workers who held assignments as supervisors, 14 engineers, orclerical workers were assigned to the lowest exposure group, foremen and 15 utility workers were in the moderately exposed group, and operators and cell maintenance 16 personnel OCCJJpied thehighest exposure group. 17 The duration ofhydrogen chloride exposure was calculated by adding the time spent on 18 thejobswith TWAs above zero. A cumulative exposure score was derived for each subject 19 by multiplying the time spent on eachjob by the midpoint ofthe TWA range for thatjob 20 (0, 0.25, 1.5, and 3.75) and summing across alljobs. 

### Based on an examination ofthe 21 distribution ofall subjects, four categories ofcumulative exposure were chosen for analysis 22 (0, 0.1 to 3.9, 4.0 to 12.4, and**~12.5** ppm-years [0, 0:15 to 5.8, 6.0 to 18.5, and 23

### ~18.6 mg/m3-years]). Because oftoo few subjects 

### in the mid-exposed group, subjects from 24 that group were combined with the lowest exposed group. 25 The authors reported that there was no indication that an increased incidence oflung 26 cancer was associated with exposure to hydrogen chloride under theconditions ofthis study. 27 Therewas no relationship between lung cancer and the duration ofexposure, nor was there a 28 relationship between the highest average hydrogen chloride exposure and lung cancer. 29 Allowing for the 15-yearlatency period**betw~n** exposure to hydrogen chloride and death 30 slightly lowered the risk estimate (Bond et al., 1991).

August 1994 8-10 DRAFr-bO NOT QUOTE OR CITEJ



### 1 Because there are no adequate epidemiological studies or animal 

### carcinogenicity studies 2 for chlorine and hydrogen chloride in 

### thepresent data

### base,**~ese** 

### compounds are classified as 3 Group D, "not classifiable as to human carcinogenicity," based on the weight-of-evidence 4 

### approach in 

### the EPA 

### guidelines for carcinogen risk assessment.

August 1994 8-11 DRAFf-DO NOT QUOTE OR CITE

### 1 

### REFERENCES 2 Albert, R. E.; Sellakumar, A. R.; Laskin, S.; Kuschner, M.; Nelson, N.; Snyder. C. A. (1982) Gaseous 

### 3 formaldehyde andhydrogen chlorideinduction ofnasal cancer in therat. JNCIJ. Natl. Cancer Inst. 

### 4 68: 597-603. 5 

### 6 Bond, G. G.; Cook, R. R.; Wight, P. C.; Flores, G. H. (1983) A case-control study ofbrain tumor mortality at 

### 7 a Texas chemical plant. J. Occup. Mecl. 25: 377-386. 8 

### 9 Bond, G. G.; Reeve, G. R.; Ott, M.G.; Waxweiler, R. J. (1985a) Mortality among a sample ofchemical 

### 10 company employees. Am. J. Ind. Mecl. 7: 109-121. 

### 11 12 Bond, G. G.; Shellenberger, R. J.; Flores, G. H.; Cook, R. R.; Fishbeck, W. A. (198Sb) A case-control study 13 ofrenal cancermortality at a Texaschemical plant. Am. J. Ind. Med. 7: 123-139. 14 

### 15 Bond, G. G.; Flores, G. H.; Stafford, B. A.; Olsen, G. W. (1991) Lung**~cer** andhydrogen chlorideexposure: 16 results from a nested case-amtrol study ofchemical workers. J. Occup. Mecl. 33: 958-961. 

### 17 18 Cumming, R. B. (1978) Thepotential forincreased mutagenic risk to thehuman population dueto theproducts 19 ofwater chlorination. In: Jolley, R. L., ed. Waterchlorination: environmental impact andhealth effects, 20 volume 1, proceedings ofthe conference; October 1975; Oak Ridge, TN. Ann Arbor, MI: Ann Arbor 

### 21 SciencePublishers, Inc.; pp. 229-241. 

### 22 23 Dolara, P.; Ricci, V.; Burrini, D.; Griftini, 0. (1981) Effect ofozonation andchlorination on the mutagenic 

### 24 potential ofdrinking water. Bull. Environ. Contam. Toxicol. 27: 1-6. 25 

### 26 Douglas, G. R.; Bell, R. D. L.; Liu, V. W.; Kamra, 0. P. (1982) Mutagenic activity ofchlorination-stagepulp 

### 27 andpaper mill effluents in a battery ofmammalian mutagenicity assays. Environ. Mutagen. 4: 397-398. 

### 28 

### 29 Dmckrey, H. (1968) Chloriertes Trinkwasser, Toxizitaets-Pmefungen an Ratten ueber sieben Generationen 30 [Chlorinated drinking water, toxicity studies in seven generations ofrats]. Food Cosmet. Toxicol. 31 6: 147-154. 

### 32 33 Ehrenberg, L.; Gustafsson, A.; Lundqvist, U. (1956) Chemically induced mutation and sterility inbarley. Acta 

### 34 Chem. Scand. 10: 492-494. 

### 35 36 Fisher, N.; Hutchinson, J. B.; Berry, R.; Hardy, J.; Ginocchio, A. V. (1983) Long-termtoxicity and 37 carcinogenicity studies ofcake JD&4e from chlorinated flour: 1. studies inrats. Food Chem. Toxicol. 38 21: 427-434. 

### 39 40 Gross, E. A.; Wolf, D. C.; Barrow, C. S.; Morgan, K. T.; Moss, 0. R.; Popp, J. A. (1993) Chronic inhalation 41 study ofchlorine inB6C3Fl miceandF344rats [abstract]. Toxicologist 13: 150. 

### 42 43 Kutzman, R. S. (1983) A study ofFischer-344 rats subchronically exposed to 0, 0.5, 1.5, or5.0ppmchlorine 44 [informal report]. Upton, NY: Brookhaven National Laboratory; Interagency agreementno. 

### 45 222-Y01-ES-9-0043. 

### 46 47 Lee, E. G-H.; Mueller, J. C.; Walden, C. C.; Stich, H. (1981) Mutagenic properties ofpulp mill effluents. Pulp 48 Pap. 

### Can:· 82: T149-T154. 49 

### 50 Meier, J. R.; Lingg, R. D.; Bull, R. J. (1983) Formation ofmutagens following chlorination ofhumic acid: 

### 51 a model for mutagen formation during drinking water treatment. Mutat. Res. 118: 25-41. 52

August 1994 

### 8-12 DRAFT-DO NOT QUOTE OR CITE1 Mickey, G. H.; Holden, H., Jr. (1971) Chromosomal effects ofchlorine on mammaliancells in vitro. EMS 2 Newsl. 4: 39-41. 3 4 National Research Council. (1976) Chlorine and hydrogen chloride. Washington, DC: Committee on Medical and 

### 5 Biologic Effects ofEnvironmental Pollutants; EPA reportno. EPA/60011-76-020. Available from: NTIS, 

### 6 Springfield, VA; PB-253196/0. 

### 7 8 Rannug, U.;Jenssen, D.; Ramel, C.; Eriksson, K.-E.; Kringstad, K. (1981) Mutagenic effects ofeffiuents from 9 chlorinebleaching ofpulp. J. Toxicol. Environ. Health7: 33-47. 10 11 Reeve, G. R.; Bond, G. G.; Uoyd, J. W.; Cook, R. R.; Waxweiler, R. J.; Fishbeck, W. A. (1983) An 12 investigation ofbraintumors among chemicalplantemployees using a sample-based cohort method. 13 J. Occup. Mecl. 25: 387-393. 

### 14 15 Sellakumar, A. R.; Snyder, C. A.; Solomon, J. 1.; Albert, R. E. (1985) Carcinogenicity offormaldehyde and 16 hydrogen chloride in rats. Toxi9(>1. Appl. Pharmacol. 81: 401-406. 17 18 Shih, K. L.; Lederberg, J. (1976) Effects ofchloramine onBacillus subtilis deoxyribonucleic acid. J. Bacteriol. 

### 19 125: 934-945. 

### 20 21 Stover, E. L.; Cumming, R. B.; Lee, N. E.; Jolley, R. L. (1983) Chlorine vs ozone at Marlborough, 22 Massachusetts: disinfection and mutagenic activity screening. In: Jolley, R. L.; Brungs, W. A.; Cotruvo, 

### 23 J. A.; Cumming, R. B.; Mattice, J. S.; Jacobs, V. A., eds. Waterchlorination: environmental impact 24 andhealth effects, volume 4, book 2, environment, health, and risk, proceedings ofthe fourth 

### 25 conference; October 1981; Pacific Grove, CA. Ann Arbor, MI: Ann Arbor Science Publishers, Inc.; 26 pp. 1249-1260. 

### 27 28 U.S. Environmental Protection Agency. (1985) Health assessment document for chloroform. Research Triangle 

### 29 Park, NC: Office ofHealth and Environmental Assessment, Environmental Criteria and Assessment 

### 30 Office; EPA report no. EPA-600/8-84-004F. Available from: NTIS, Springfield, VA; PB86-105004. 31 

### 32 Zoeteman, B. C. J.; Hmbec, J.; de Greef, E.; Kool, H. J. (1982) Mutagenic activity associated with by-products 33 ofdrinking water disinfection by chlorine, chlorine dioxide, ozone and UV-irradiation. Environ. Health 

### 34 Perspect. 46: 197-205.



### August 1994 8-13 DRAFT-DO NOT QUOTE OR CITE1 2 

# 9. REGULATIONS AND STANDARDS

3 4 

### 9.1 CHLORINE 5 TheNational Institute for OcCupational Safety and Health (1976) recommended a 6 15-min ceiling concentration of0.5 ppm (1.5 mg/m3) for chlorine in workplace air. The 7 Occupational Safety and Health Administration 

### (OSHA) established a ceiling permissible 8 exposurelimit of 1ppm (3 mg/m3) for the gas. The

### American Conference ofGovernmental 9 Industrial Hygienists (ACGIH) recommended a tentative 8-h time-weighted average 

### \fW A) 10 threshold limitvalue (TLV) of0.5 ppm (1.5 mg/m3) and a 15-min short-term exposure TLV 11 of 1ppm (3 mg/m3) for chlorine (American Conference ofGovernmental Industrial 12 Hygienists, 1987). Theserecommendations were based on chronic effects noted 

### in the lung 13 and digestive system (American Conference ofGovernmental Industrial Hygienists, 1986). 14 TheTWA value 

### in Switzerland is 0.5 ppm (1.5 mg/m3), and the minimum inhibitory 15 concentration value 

### in the U.S.S.R. is 0.3 ppm (1 mg/m3) (International Labour Office, 16 1980). The National Research Council (NRC) panel on chlorine set short-te(lll public 17 exposure limits (STPLs) of 1ppm (3 mg/m3) for 10·min and 0.5 ppm (1.5 mg/m3) for 18 30 

### min; these were based on minimum irritation and not

### health hazard. The same committee 19 setpublic emergency limits (PELs) of3 ppm (0.9

### mg/m~) for a 10-min.exposure and 2 ppm 20 (5.8 mg/m3) for a 30- or 

### 60-min exposure. These levels were based on strong odor and 21 irritation ofmucous membranes (National Research Council, 1973). 22 23 24 

### 9.2 HYDROGEN CHLORIDE 25 The OSHA established a ceiling permissibleexposurelimit for hydrogen chloride of 26 5ppm (7 mg/m3). The ACGIH also recommended a TL V of5 ppm, the.concentration 27**pr~umed** to be the borderline for severe irritation effects yet sufficiently low to prevent toxic 28 injury from exposure (American Conference ofGovernmental Industrial Hygienists, 1987). 29 TheNRC Subcommitteeon Hydrogen Chloride recommended STPLs of4 ppm (6 mg/m3) 30 for 10 min and 2 ppm (3 mg/m3) for 30 or 

### 60 

### min. Similarly, PELs of7 ppm (10 mg/m3)

August 1994 9-1 DRAFT-DO NOT QUOTE OR CITE

### 1 for 10 

### min and 3 ppm (5 mg/m3) 

### for 30 or 60 

### min have been established (GEOMET 2 Technologies, Inc., 1981). 3 The U.S. Environmental Protection Agency has developed an inhalation reference 4 concentration (RfC) for hydrogen chloride of7E-3 mg/m3• 

### The RfC is an estimate (with 5 uncertainty spanning perhaps an orderofmagnitude) ofcontinuous exposure concentration to 6 the human population (including sensitive subgroups) that is likely to be without appreciable 7 risk 

### ofdeleterious noncancer effects over a lifetime exposure (U.S. Environmental Protection 8 Agency, 1993). See Chapter 6 for a discussion ofthe effects ofchronic hydrogen chloride 9 exposure on experimental animals. 10 

### 11

August 1994 9-2 DRAFT-DO NOT QUOTE OR CITE

# • l



### 1 2 3 4 5 

### 6 

### 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 

### REFERENCES
American Conference ofGovernmental Industrial Hygienists. (1986) Documentation ofthethreshold limit values andbiological exposureindices. Sth ed. Cincinnati, OH: American Conference ofGovernmental Industrial Hygienists, Inc.; pp. 117, 313.
American Conference ofGovernmental Industrial Hygienists. (1987) TLVs: threshold limit values and biological exposure indices for 1987-1988. Cincinnati, OH: American.Conference ofGovernmental Industrial Hygienists; pp. 23, 40.
GEOMETTechnologies, Inc. (1981) Hydrogen chloride: report4, occupational hazard assessment. Cincinnati, OH: U.S. Department ofHealth andHuman Services, National Institute for Occupational Safety and Health; NIOSH contractno. 210-79-0001. Availablefrom: NTIS, Springfield, VA; PB83-10S296.
International Labour Office. (1980) Occupational exposurelimits for airborne toxic substances. Geneva, Switzerland:**~temational** Labour Office; pp. 66, 128. (Occupational safety and health series no. 37). IRIS, Integrated Risk Information System [database]. (1993) [Printout ofreference dose for inhalation; acute toxicity; and ambient waterquality criteria for aquatic organisms for hydrogen chlorideas ofMarch 11]. Cincinnati, OH: U.S. Environmental Protection Agency, OfficeofHealth and Environmental Assessment, Environmental Criteria and assessment Office. Available from: TOXNET, National Library ofMedicine, Rockville, MD.
National Institute for Occupational Safety and Health. (1976) Criteria for a recommended standard

...occupational exposure to chlorine. Cincinnati, OH: U.S. Department ofHealth, Education, and Welfare, NIOSH publication no. 76-170. Available from: NTIS,**~pringfield,** VA;**PB~266367/2.** National Research Gouncil. (1973) Guides for short-termexposures ofthepublic to airpollutants. VID. Guide for chlorine. Washington, DC: U.S. Environmental Protection Agency; reportno. NAS/ACTIP-628.9. Available from: NTIS, Springfield, VA; PB-244339.

August 1994 9-3 DRAFf-DO NOT QUOTE OR CITE