") .., , 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(Do Not Cite 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(Do Not Cite or Quote) EPA 600/8-87/041A 

August 1994 

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. 

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 27711 
r 

DISCLAIMER 

This document is an external draft for review purposes only and does not constitute 

U.S. Environmental Protection Agency policy. Mention of trade names or commercial 

products does not constitute endorsement or recommendation for use. 

ii 
J_ .. . 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 

111 
TABLE 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 ENVIRONMENTAL LEVELS AND EXPOSURE .•....... 

3. 3.1 Chlorin.e . . . . . . . . • . . . . . . . . . . . . . . . . . . . . 

3.3.2 Hydrogen Chloride ..•................... 

REFEREN CBS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 

4. ENVIRONMENTAL FATE AND ECOLOGICAL EFFECTS · ..... . 

4.1 ENVIRONMENTAL FATE ...................... . 

4.1.1 Chlorine . . • . . . . . . . . . . . . . . . . . . . . . . . . . . 

4.1.2 Hydrogen Chloride ..................... . 

4.2 ECOLOGICAL EFFECTS ...................... . 

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

REFEREN CBS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 

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 EXPERIMENTAL ANIMALS . . . . . . . . . . . . . . . . . . . . . 

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 

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

6.1.1.3 Chronic Toxicity . . . . . . . . . . . . . . . . . . 6-9 

6.1.2 Hydrogen Chloride . . . • . . . . . . . . . . . . . . . . . . 6-10 

6.1.2.1 Acute Toxicity 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. DEVELOPMENTAL TOXICITY 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 

v 
LIST OF TABLES 

2-1 Chlorine Reactions Known To Occur in Aqueous 

Solution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-2 

4-1 The Acute Toxicity of Chlorine 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 

vi 
LIST OF FIGURES 

Number Page 

4-1 Schematic outline of chemical reactions in estuarine and 

marine waters . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4-3 

4-2 Principal.chemical pathways for reaction, degradation, and 

environmental fate of free chlorine in the aquatic 

environment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4-4 

6-1 Hydrogen chloride concentrations producing 50% mortality 

in adult male Sprague-Dawley rats versus time of exposure 

6-2 Incapacitation time as a function of hydrogen chloride 

6-13 

concentration . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . 6-19 

6-3 Survival time as a function of hydrogen chloride concentration 6-20 

vii 
PREFACE 

The Office of Health 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 of Air Quality Planning and Standards to 

support information needs on hazardous air pollutants. 

Ideally, when evaluating the health effects associated with exposure of a given 

compound and its by-products, both oral and inhalation routes of exposure are addressed; 

however, in the case of chlorine and hydrogen chloride, a relationship between the inhalation 

of these gases and the ingestion of chlorinated liquids with respect to human health effects is 

questionable. With that in mind, this document will mainly address effects resulting from the 

inhalation of chlorine and hydrogen chloride gas or aerosol. The health effects resulting from 

the ingestion of chlorinated liquids are addressed in a separate document. 

In the development of the 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 of concentration-response relationships 

are discussed, where appropriate, so that the nature of the 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 a preliminary indication of the potential 

presence of this substance in the ambient air. While the available information is presented as 

accurately as possible, it is acknowledged to be limited and dependent in many instances on 

assumptions rather than specific data. This information is not intended, nor should it be 

used, to support any conclusions regarding risk to public health. If such 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 a pungent odor, is used in the manufacture of 

inorganic and organic chemicals and plastics, bleaching of pulp and paper, and disinfection of 

wastewater and drinking water. Natural sources and photochemical processes do not 

contribute to levels of chlorine in the ambient air. There is a potential for release of small 

~ounts of chlorine during its manufacture or during loading and unloading in transportation. 

However, photodissociation in the lower atmosphere and troposphere is rapid. 

Hydrogen chloride, a colorless gas with a pungent odor; is used in the manufacture of 

inorganic and organic chemicals~ oil well acidizing, steel pickling, processing of food 

products, and mineral and metal processing. Hydrogen chloride may be found naturally in 

the atmosphere from the cooling of volcanic ash, the photolysis of chlorine, and the reaction 

of the chloride ion with methane. Anthropogenic sources {)f hydrogen chloride include the 

burning of fossil fuel and polyvinyl chloride plastics, incineration of municipal refuse, and 

solid rocket fuel exhaust. Photodegradation of hydrogen chloride in the atmosphere is slow 

because of the low atmospheric concentrations of hydroxy radicals. It is, however, diluted 

and ·tends to adsorb on aqueous aerosols and particulates. No ·data were found in the 

published literature on the levels of hydrogen 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 per kilogram of municipal and hospital waste incinerated, 

respectively. 

Both chlorine and hydrogen chloride are acutely toxic gases. The effects of acute 

inhalation exposure are primarily respiratory and range from irritation to pulmonary edema 

and death. Limited epidemiology studies indicate that chlorine is not carcinogenic. 

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

nor did it enhance the carcinogenicity of formaldehyde in rats; however, it was found to have 

an adverse effect on the reproduction potential of rats exposed to high concentrations prior to 

mating or during gestation. 

xi 

7 
AUTHORS, CONTRIBUTORS, AND REVIEWERS 

The U.S. Environm~ntal Protection Agency's Office of Health and Environmental 

Assessment (OHEA) is responsible for the preparation of this health assessment document. 

The OHEA Environmental Criteria and Assessment Office, Research Triangle Park, NC, had 

the overall responsibility for coordination and direction· of the document (Beverly M. 

Comfort, Project Manager). 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 of Health and Environmental 

Assessment 

Human Health Assessment Group 

Washington, DC 

Arthur Chin 

Office of Health and Environmental 

Assessment 

Human Health Assessment Group 

Washington, DC 

Beverly M. Comfort 

Office of Health and Environmental 

Assessment 

Environmental Criteria and Assessment 

Office 

Research Triangle Park, NC 

xiii 

Gregory Kew 

Office of Health and Environmental 

Assessment 

Exposure Assessment Group 

Washington, DC 

Charles Ris 

Office of Health and Environmental 

Assessment 

Human Health Assessment Group 

Washington, DC 

Lawrence Valcovic 

Office of Health 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 Culebra Road 

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 Service Number [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. The gas 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 of the methods used to monitor air levels of chlorine, which are based 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 of these 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 The domestic production of chlorine in 1993 was approximately 24.06 billion pounds, 

18 an increase of 0.55 billion pounds from 1992. It is manufactured by the electrolytic 

19 decomposition of brine, which is associated with the production of caustic soda or alkali. Its 

20 major uses are in the manufacture of organic and inorganic chemicals and plastics, bleaching 

21 of pulp and paper, and disinfection of wastewater and drinking water. 

22 There is a potential for release of small amounts of chlorine 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 of its reactivity, chlorine released into 

25 the atmosphere from end-use applications is not detectable. Monitoring of workplace 

26 atmospheres generally have shown concentrations of less than 0.1 ppm (0.3 mg/m3

) with very 

27 few samples exceeding the ceiling permissible exposure limit of 1 ppm (3 mg/m3) or the 8-h 

28 time-weighted average threshold limit value of 0.5 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 of up to 20% occurs. This cools the liquid to 

31 -34 oc (boiling point), and subsequent evaporation is dependel)t on the rate of heat 

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 of a spill, dangerous levels exist for only a few hours. Monitoring of a release of · 

3 approximately 70,000 kg chlorine in a train derailment several hours after the accident found 

4 levels of 3.4 to 34 ppb (10 to 100 p.g/m3), with peak values of up to 0.14 ppm (0.4 mg/m3) 

5 in the plume at a distance of 0.5 to 1 km from the accident site. Photodissociation in the 

6 lower atmosphere and troposphere is rapid in the daytime, and further atmospheric reactions 

7 produce hydrogen chloride. Chlorine released to the soil surface evaporates, and, when 

8 released into water, it may 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. It is very hygroscopic. When it dissolves in water, it is 

16 very corrosive to metals and reacts with most organic materials. It is 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, it vaporizes, 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 or potentiometric methods, using a 

22 chloride selective electrode. It can be absorbed in a solution of sodium bromate-sodium 

23 bromide, resulting in the production of bromine, which is reacted with alkaline luminal and 

24 the resulting chemiluminescence measured. Most methods of analyses 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 of chemical syntheses of chlorinated 

27 compounds. Domestic production of hydrogen 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 of inorganic and organic chemicals, oil well 

30 acidizing, steel pickling, processing of food products, mineral and metal processing, and 

31 various miscellaneous uses. 

August 1994 1-2 DRAFT - DO NOT QUOTE OR CITE 
1 Because of its 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 of acid into waste streams with the potential of reaching groundwater. 

4 Hydrogen chloride can be found naturally in the atmosphere from the cooling of 

5 volcanic ash. A photochemical source is the photolysis of chlorine and the reaction of the 

6 chloride ion with methane in the atmosphere. 

7 Anthropogenic sources of hydrogen chloride include the burning of fossil fuel and 

8 polyvinyl chloride plastics, and the incineration of municipal refuse. Hydrogen chloride is 

9 also released into the lower stratosphere in solid rocket fuel exhaust. 

10 Photochemical degradation of hydrogen chloride occurs, but it is a slow process because 

11 of the low atmospheric concentrations of hydroxy radicals. When released into the 

12 atmosphere, it is 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 of anthropogenic 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 of municipal and hospital waste incinerated, regpectively. Hydrogen chloride is 

18 also toxic to several plant species, with leaf injury and a decrease in chlorophyll levels 

19 occurring between exposure concentrations of 4.3 and 18.0 ppm (6.5 and 27.0 mg/m3). 

20 

21 

22 1.2 PHARMACOKINETICS AND MECHANISM OF ACTION 

23 1.2.1 Chlorine 

24 Chlorine reacts with tissues of the respiratory tract but does not appear to cause 

25 systemic effects. Several theories have been proposed on the mechanism of chlorine's 

26 toxicity. In a pH range of 6 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 of proteins. It has been suggested that 

29 hypochlorous acid can inhibit sulfhydryl-dependent enzymes by reacting with sulfhydryl 

30 groups. Cell damage may also be caused by oxygen radicals generated by chlorine or by the 

August 1994 1-3 DRAFr ;_ DO NOT QUOTE OR CITE 
1 oxidation potential of chlorine. The initial 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 of hydrogen chloride; however, hydrogen 

6 chloride is corrosive to tissue. The corrosive action of hydrogen chloride is as~iated with 

7 its high solubility in water, forming hydronium ions. Hydronium ions are reactive 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 of mice 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 (LT50) 

18 was 11 min with exposure to 290 ppm (841 mg/m3

) and 55 min with exposure to 170 ppm 

19 (493 mg/m3). The LC50 value for a 60-min exposure of rats 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 somewhat less susceptible, but adequate LC50 values were not found. 

24 Mice and rats respond to exposure to sublethal levels of chlorine by 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 of rats 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 of rabbits to sublethal concentrations of chlorine 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), but exposure 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 significant increase in 

5 compliance suggestive of emphysema. This finding was confirmed by histopathological 

6 exanrlnation. 

7 In subchronic studies, exposure of rats to chlorine at 9 ppm (26 mglm3), 6 h/day, 

8 5 days/week for 6 weeks, caused inflammation of the upper and lower respiratory tract, with 

9 necrotic lesions appearing in the nasal turbinates. In addition, hyperplasia and hypertrophy 

10 occurred in the epithelia of the bronchi and alveoli. Less severe lesions were found after 

11 repeated exposure to 1 or 3 ppm (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 of the 

14 respiratory tract and other major organs did not show any significant exposure-related effects; 

15 however, the mean trachea pathology scores of the rats exposed to 0.5 and 5.0 ppm chlorine 

16 were significantly greater than those of the control group. There was also no chlorine-related 

17 effect on the reproductive potential of either male or female 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 of cilia and goblet cells in the group 

23 exposed to 2.3 ppm chlorine. Similar but less severe changes were reported in the nasal 

24 passage of both 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, goblet cell hyperplasia/hypertrophy, and 

27 secretory metaplasia of the transitional epithelium of the lateral meatus were noted in male 

28 rats and male and female mice exposed to 0.4, 1.0, or 2.5 ppm (1.2, 2.9, or 7.2 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 CITE 
1 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 were reported in mice and 

6 rats exposed to hydrogen chloride at levels of 410 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 of hydrogen 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 of hydrogen chloride for 10 min, 

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

15 the epithelium of the external nares at 17 ppm (25 mg/m3), and, as the concentration was 

16 increased, there was erosion of mucosa 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 of the 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 of a baboon to hydrogen chloride for 5 min at a level of 190 ppm 

28 (285 mg/m3

) caused no irritation. A level of 810 ppm (1,215 mg/m3) caused irritation but 

29 no postexposure symptoms, and a level of 2,780 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 10,000 ppm (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 of animals to hydrogen chloride. 

4 Exposure of guinea pigs to 0.1 ppm (0.15 mg/m3) hydrogen chloride, 2 hi day for 28 clays, 

5 produced no.effects. Repeated exposure of guinea pigs to 10 ppm (14.9 mg/m3) hydrogen 

6 chloride for 2 blday, 5 days/week for 49 days caused no changes in lung function parameters 

7 or histological 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, or 50 ppm (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 of the 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 of hyperplasia of 

16 the larynx and trachea of exposed animals over that of the controls was noted. 

17 

18 

19 1.4 HUMAN HEALTH EFFECTS 

20 1.4.1 Chlorine 

21 In humans, the odor threshold of chlorine is very broad and ranges from about 0.02 to 

22 1.3 ppm (0.06 to 3.83 mg/m3). Irritation of the eyes, nose, and throat has been reported to 

23 occur at levels as low as 1 ppm (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 of 40 to 

25 60 ppm (118 to 177 mg/m3) causes severe but reversible effects on the respiratory system. 

26 Controlled exposure of human volunteers to 1 ppm 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 (FEV 1), and peak expiratory flow rate; most values returned to 

29 normal.within a day. Mortalities in humans have occurred after gassing of soldiers 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 CITE 
1 Several case reports of acute nonlethal exposures have been reviewed. The immediate 

2 effects of exposure are burning of the eyes with lacrimation, burning of the nose and throat, 

3 rhinorrhea, salivation, coughing and choking, dyspnea, and chest pain. Pulmonary edema 

4 and bronchitis may follow depending on the severity of exposure. Within 6 to 24 h of 

5 exposure, abnormalities in pulmonary function may be seen that are caused by airway 

6 obstruction. There is a reduction in PVC and FBV 1.• There is usually a reduction of 

7 pulmonary compliance and increased airway resistance. Within a few weeks· of exposure, 

8 there is usually an improvement in pulmonary function, but, in severe cases, patients have 

9 been kept under surveillance for at least 6 mo. 

10 There are limited 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 of limited 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 of hydrogen chloride exposure to 

21 humans. Inhalation of hydrogen chloride results in irritation of the 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) are considered to cause no damage, but levels between 

24 10 ppm (15 mg/m3) and 35 ppm (52 mg/m3) can cause irritation of the .throat, and levels of 

25 50 to 100 ppm (75 to 150 mg/m~) are considered barely tolerable. 

26 Two studies indicate that continued exposure of workers to hydrogen chloride may 

27 cause an increase in dental erosion. However, the lack of data on levels of exposure and the 

28 small numbers of workers examined limit the usefulness of these data. No data are available 

29 on possible mutagenic, teratogenic, or carcinogenic effects of hydrogen 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 of chlorine, including measurements of pulmonary function 

6 parameters; 

7 

8 • obtain additional information on the long-term effects of chlorine and hydrogen 

9 chloride on the respiratory system; 

10 

11 • examine the development of olfactory tolerance and tolerance to irritation of chlorine 

12 in humans; and 

13 

14 • perform adequate studies to defme mutagenic and teratogenic effects of chlorine 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 CHEMICAL PROPERTIES 

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 1.0 ppm (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 point is -100.98 °C, and the boiling 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 of chlorine in water is 

17 directly related to the chlorine concentration, pH, temperature, exposure to light, and the 

18 presence of catalysts or organic material (National Research Council, 1980). Table 2-1 lists 

19 some of the major chlorine reactions lmown to occur in water. 

20 

21 2.1.2 Hydrogen Chloride 

22 Hydrogen chloride (anhydrous) is a clear, colorless gas that produces 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 0.67 ppm (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 at 20 °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, it is 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 
- TABLE 2-1. CHLORINE REACTIONS 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 -+ NH2Cl + H20 

2NHCI2 + ~0 -+ N2 + HOCl + 3H+ + 3Cr 

Mn2+ + HOCI + 2H20-+ MnO(OH)2 + 3H+ + Cr 

30Cr -+ 2Cr + Cl03 

2HOC1 -+ 2H+ + 2Cr + 0 2 

RCHO + HOCl -+ RCOOH + H+ + Cr 

RC=CR' + HOCl-+ RC(OH)C(Cl)R' 

RNH2 + HOCl -+ RNHCl + H20 

RCOCH3 + 3HOC1 -+ RCOOH + HCC13 + 2H20 

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 have been 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 of the color produced by reaction with 

12 chlorine. A blue color, resulting from oxidation of the 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 of detection is 0. 05 to 1. 0 ppm · 

4 (0.14 to 2.9 mg/m3) using a 30-L sample of air and a sampling rate of 1 to 2 Umin when 

5 sampling is directly in methyl orange. However, the range of the 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 of potassium 

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). A personal 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 of iodine and iodide ion in solution. The method was capable 

18 of determining water concentrations of free chlorine in the range of 3 to 100 ppb (8. 7 to 

19 29.0 p.g/m3). 

20 Cheplen et al. (1984) developed a method capable of determining low concentrations of 

21 chlorine in air (0.1 ppm [0.29 mg/m3]) in the presence of ammonia. Chloramine, which is 

22 formed by reaction of chlorine with ammonia, can interfere with the determination of free 

23 chlorine. Air samples were collected into 100 mL of chlorine-free water containing 15 mg 

24 2,6-dimethylphenol (DMP) and three drops of concentrated 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 1 mL, and 1 or 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 CITE 
1 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 at the reference electrode, and a current is produced. The 

5 reference electrode is in an electrolyte solution and separated from the platinum electrode by 

6 a porous glass frit. The sensor has a range of 0.05 to 10.0 ppm (0.15 to 29.0 mg/m3) (v/v) 

7 chlorine and a precision of ± 12%. Recovery time is 1 to 4 min. The instrument can 

8 measure peak values as well as time-weighed average values (fWAs). It has the same 

9 sensitivity as the sulfamic acid bubbler method. The latter method, however, is less 

10 convenient than a 3M dosimeter badge but has the advantage of collecting continuous data 

11 whereas the badge 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 (TAGA8 ) 

14 that has been used for continuous and instantaneous measurement of chlorine levels in air. 

15 Air is collected at a flow rate of 1 L/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 be fragmented to the chloride ion in the mass spectrometer and selectively 

19 monitored at a mass-to-charge ratio (m/z) of 35. Chloride ions may also be formed from 

20 chlorinated hydrocarbons; therefore, chloride ions are occasionally monitored because they 

21 are more specific indicators of chlorine gas. The deteCtion limit is about 30 ppt (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). Chlorine is collected by aspiration through an aqueous impinger 

24 solution of 2-naphthol, and converted to 1-chloro-2-naphthol. The 1-chloro-7-naphthol is 

25 quantified chromatographically using a variety of detection systems. The sampling and 

26 analytical method has been tested in chlorine-generated atmospheres of 1.35 p.g/L, and the 

27 yield of the reaction product under the test conditions was reported to· be 75%. 

28 

29 2.2.2 Hydrogen Chloride 

30 Most of the methods used for monitoring hydrogen chloride have limitations. Methods 

31 involving absorption in an alkali and titration or colorimetric change of a 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 be introduced in sampling of air for hydrogen chloride because the 

3 acid in the collecting tube may interact with glass wool or the filtering medium (Cheney and 

4 Fortune, 1984). 

5 Drabke et al. (1982) developed a method for continuous monitoring of airborne 

6 hydrogen chloride (gas or aerosol) using a chloride-sensitive flow electrode and a 

7 copper-sensitive reference electrode. The absorption solution contained 10-3 M copper 

8 nitrate. This method measures total chloride ion and not specifically hydrogen chloride. 

9 mavay and Guilbault (1978) developed a piezoelectric quartz crystal detector with a 

10 coating of trimethylamine-hydrogen chloride or triphenylamine. Moisture was removed from 

11 the sampled air through a column of silica gel. Hydrogen chloride could easily be quantified 

12 in the range of 1 to 100 ppm (1.4 to 140 mg/m3) with a response time of less 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 source being monitored are low ( 10%). Gaseous 

24 hydrogen chloride was monitored with an instrument that measured the abso~tion of infrared 

25 radiation at a narrow spectral inte~al where the spectral lines of hydrogen chloride absorb. 

26 Because of the 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 of the diffusion scrubber used lacks a 

2 theoretical model for accurate prediction of the 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 CITE 
1 REFERENCES 

2 American Public Health Association. (1977) Tentative methods for analysis for five dichlorine content of the 

3 atmosphere (methyl orange method). In: Katz, M., ed. ;Methods of air sampling and analysis, 2nd ed. 

4 Washington, DC: American Public Health Association; p. 381. 

5 

6 Cheney, J. L.; Fortune, C. R. (1984) Improvements in the methodology for measuring hydrochloric acid in 

7 combustion source emissions. J. Environ. Sci. Health Part A 19: 337-350. 

8 

9 Cheplen, J. M.; Barrow, C.; White, E. L. (1984) Determination of airborne free chlorine in the presence of 

10 ammonia by capillary column gas chromatography. Anal. Chem. 56: 1194-1196. 0 

11 

12 Drabke, P.; Kirsch, H.; Wolf, J. (1982) Eine Methode zur kontinuierlichen Bestimm.ung von 

13 HCl-Konzentrationen in der Luft mit Hilfe einer chloridsensitiven Durchflusselektrode [A method of 

14 continuous determination of HCl concentrations in the air with the aid of a chloride--sensitive flow 

15 electrode]. Z. Gesamte Hyg. 1hre Gtenzgeb. 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 of low levels of chlorine in air. 

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

22 

23 GeOMET Technologies, Inc. (1981) Hydrogen chloride: report 4, occupational hazard assessment. Cincinnati, 

24 OH: U.S. Department of Health 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 of a hydrogen chloride detector 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 of hydrogen chloride gas in ambient air with 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 of the chemistry and environmental fate of reactive 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 and health effects, 

42 volume 4, book 1, chemistry and water treatment, proceedings of the fourth conference; October 1981; 

43 Pacific Grove, CA. Ann Arbor, MI: Ann Arbor Science Publishers, 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 of trace levels of 

52 atmospheric HCI. Atmos. Environ. Part A 26: 43-49. 

53 

August 1994 2-7 DRAFT-DO NOT QUOTE OR CITE 
1 National Rese8rch Council. (1980) The disinfection of drinking 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 of chlorine after fixing in 

5 alkali. z. Gesamte Hyg.·Ihre Grenzgeb. 30: 468-470. 

6 

7 Rigdon, L. P.; Moody, G. J.; Frazer, J. W. (1978) Determination of residual chlorine in water 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 gaseous hydrogen 

11 chloride partitioning in a cloud contaminated by solid rocket exhaust. Atmos. Environ. 14: 543-547. 

12 

13 Verschueren, K. (1983) Handbook of environmental data on organic chemicals. 2nd ed. New York NY: Van 

14 Nostrand Reinhold; p. 44. 

15 

16 Wagenknecht, J. H.; Jansson, R. E. W.; Stover, F. S. (1981) Analysis of mixtures of chlorine and chlorine 

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 CITE 
1 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 of January 1, 1992, there were 25 manufacturers in the United States producing 

9 chlorine at 48 plant sites, with an estimated total domestic _production capacity of 24.5 billion 

10 pounds (SRI International, 1992). Chlorine production in 1992 was 23.51 billion pounds. 

11 In 1993, an estimated 24.06 billion pounds of chlorine was produced in the United States 

12 (Reisch, 1994). 

13 In 1992, over 64% of the domestic chlorine production capacity was based on the 

14 electrolytic decomposition of brines, usually in diaphragm cells. Chlorine is also produced 

15 by oxidation or electrolysis of hydrogen chloride, as a by-product of potassium nitrate and 

16 magnesium metal production, and as a coproduct of potassium hydroxide production (SRI 

17 International, 1992). The manufacture of chlorine, therefore, is closely associated with the 

18 production of caustic soda or alkali. This chlor-alkali industry provides an essential feedstock 

19 for a number of key 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 of organic 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 of potable, process, and wastewater streams by 

24 municipalities and industry; and in the manufacture of cleaning and sanitation products 

25 (e.g., liquid household bleaches, swimming pool chemicals, industrial sanitizing agents) (SRI 

26 International, 1984). Domestic consumption of chlorine by end-use application is as follows: 

27 production of ethylene dichloride, most of which is used to produce the vinyl chloride 

28 monomer; production of organic 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 of hydrogen chloride in 1992 totaled 7.13 billion pounds. 

3 In 1993, an estimated 6.45 billion pounds of hydrogen chloride was produced in the United 

4 States (Reisch, 1994). 

5 About 92% of the domestically produced hydrogen chloride is generated as a by-product 

6 in the manufacture of other chemicals (e.g., vinyl chloride, benzyl chloride, phosphate esters, 

7 ethylene dichloride, isocyanates, and fluorocarbons) and the chlorination of organic 

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 of hydrogen with chlorine and the reaction of mineral 

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 of hydrogen chloride is by the organic chemicals industry in 

16 the production of ethylene dichlo~de and numerous other organic chemicals. Other end-use 

17 applications include use in the manufacture of inorganic chemicals," oil well acidizing, steel 

18 pickling, processing of food 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 of chlorine in its manufacture, but the amount is not 

26 significant when compared to other potential sources. This may occur during process 

27 sampling and in maintenance of electrolytic 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 of tank cars (Environment Canada, 1984; World Health Organization, 1982). The bul~ of 

30 chlorine is transported by rail. Its shipping containers are constructed of steel to Department 

31 of Transportation (DOT) specifications and are equipped with safety devices and specially 

August 1994 3-2 DRAFT-DO NOT QUOTE OR CITE 
1 designed valves (Simmons et al., 1974). Likewise, cylinders to be transported are approved 

2 for safety by the DOT. 

3 The Chlorine Institute has published 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 of gaseous chlorine in the atmosphere have been postulated. However, 

10 Duce (1969) indicated that this is unlikely, and Johnston (1980) has reported that the cooling 

11 of volcanic ash releases hydrogen chloride, not chlorine. It has been hypothesized that 

12 photolysis of sea 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 of nitrosyl chloride), but there is no evidence that these reactions would produce 

18 chlorine gas (Prather et al., 1984). 

19 

20 3.2.1.3 Anthropogenic Processes 

21 The use of gaseous chlorine in treatment of drinking water, disinfection of swimming 

22 pools, and treatment of wastewater can result in fugitive emissions. However, the use in 

23 swimming pools has been replaced largely by the use of solid materials that generate active 

24 chlorine or hypochlorite. In. general, the use of chlorine in the treatment of <!rinkffig water is 

25 more discrete than in the past. Proportionately less chlorine is used in the treatment of water 

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. The use of chlorine as a biocide in a recirculating cooling water system of a 

29 power plant can potentially result in release to the atmosphere in the cooling tower or release 

30 into seawater; a typical system uses about 50 tons of chlorine 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 of the hydrogen chloride produced as a by-product of chlorination reactions is 

4 used captively or recycled in a closed system with efficient containment 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 of vapor (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 of ash 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 off the east coast of 

20 the United States during the summer of 1988. The concentration of hydrogen chloride 

21 decreased with increasing altitude and distance from the coastline (Keene et al., 1990). 

22 Slightly higher concentrations of hydrogen chloride have been reported in cities in southern 

23 California. Eldering et al. (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 of hydrogen chloride were noted further inland. 

27 

28 3.2.2.3 Anthropogenic Processes 

29 The burning of fossil.fuel (World Health Organization, 1982) and the incineration of 

30 municipal waste containing polyvinyl chloride plastics (Chan, 1984) are the two major 

31 sources of hydrogen 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% of refuse in the year 2000, compared to 2% in 1970. Although 

2 emission controls such as electrostatic precipitators and water spraying of exhaust gases 

3 should trap most hydrogen chloride emission in an incinerator exhaust, there are still 

4 substantial emissions. Allen et al. (1986) analyzed stack emissions from incineration of 

5 hospital waste and found a hydrogen chloride air emissions factor of 3.3 to 5.3 g/kg. 

6 Hospital waste, for which no emissions controls are required, is expected to co~tain about 

7 four times more plastic material than municipal waste. Rollins and Homolya (1979) 

8 monitored the mass emission rate for two state-of-the-art incinerators of municipal waste and 

9 found 2.11 and 1.98 g hydrogen chloride per kilogram of refuse 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 of 800 m from each of the sources studied. The 

12 reliability of hydrogen chloride emission estimates from the incineration of waste was 

13 questioned by Johnson et al. (1992). According to these authors, hydrogen chloride 

14 ~missions from waste incineration is dependent on the nature of the waste, the presence of 

15 hydrogen in the gas stream, and the composition of the surfaces in the furnace, making any 

16 estimate of hydrogen chloride emission unreliable. Hydrogen chloride generated from 

17 polyvinyl chloride is also a potential toxicity problem for fire fighters (Dyer and Esch, 1976). 

18 The main fossil fuel emitter of hydrogen chloride is coal, and the amount of hydrogen 

19 chloride generated from the burning of coal depends on the chloride content of the coal. 

20 According to Kamrin (1992), an estimated 1,700 tons of hydrogen chloride are emitted per 

21 year from a coal-frred power plant burning 2 million tons/year of bituminous coal with a 

22 chloride content of 0.095%. 

23 Exhaust products emitted from a space shuttle vehicle contain hydrogen chloride. Potter 

24 (1978) estimated that the amount emitted in the surface boundary area, the ti''?JX>sphere, and 

25 the stratosphere were 24,700, 78,500, and 59,700 kg, respectively, and the amount in the 

26 stabilized ground cloud was 35,200 kg. 

27 Aqueous waste streams are a source of hydrogen chloride released to surface waters. 

28 Sources are over-acidified swimming pool water and waste from treatment of metals 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 There is little information in the available literature regarding ambient air concentrations 

4 of chlorine or hydrogen chloride. According to the World Health Organization (1982), the 

5 presence of measurable quantities of chlorine or hydrogen 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 differentiate between chlorine, hydrogen chloride, or other sources 

8 of chloride ions. The National Academy of Sciences 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 of 0.001 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 of the 90 tons of chlorine in a rail tanker leaked out during 

16 the most intense period of the fire. A mobile mass spectrometer system using atmospheric17 pressure chemical ionization was used to analyze ground-level concentrations of chlorine. 

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 of 3.4 to 34.0 ppb (10 to 100 p.g/m3) at a distance 0.5 to 1.0 km from the 

22 source, with brief excursions of up 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 of about 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 of chlorine that would result from the release of 9,500 gal of liquid chlorine from a spill 

31 covering 30m2. The nominal evaporation rate of this 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 of 5,000 m under 

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 of 80 gal over a 12-min period 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 of 700 m during the 

8 nighttime. 

9 Environment Canada (1984) constructed nomograms to predict the rate of release of 

10 chlorine from an 80,000-L railroad tank car with punctures on the top or on the bottom. 

11 With a puncture of 100 mm in diameter on the bottom, the rate of discharge was estimated to 

12 be about 200 kg/s, and about 50% of the chlorine in the tanker would be released in 3 min. 

13 With a rupture .of the same size on the top, the rate of release 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 of tllese estimates have been prepared to aid the protection of fire fighters and to 

17 assist emergency-response planners. Although the accuracy of the estimates depends on 

18 climatic and meteorologic conditions, the estimates indicate that releases of large amounts of 

19 chlorine in accident scenarios result in high airborne concentrations in the vicinity of a spill 

20 and rapid dilution of the chlorine in the atmosphere so that dangerous levels do not persist 

21 except for a few hours. 

22 The use of chlorine in potable, process, and wastewater treatment has led to release of 

23 the compound to surface waters and detection of chlorine 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 Of 80 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 of 0.4 to 0.8 mg/L; 4% had concentrations of 0.8 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 CITE 
1 was also detected in the finished drinking water supplies of Cincinnati (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 chloride per 100 g flour as compared to 43 to 54 mg chloride for unbleached flour 

6 (Sollars, 1961). 

7 Information on the exposure of the general public to ambient levels of chlorine 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 of the actual use of chlorine. 

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 1 ppm (2.9 mg/m3

) chlorine during manufacturing operations 

17 and trace amounts to 64 ppm (185.6 mg/m3) during use of the compound in bleaching 

18 operations in the pulp and paper industry. The value of 64 ppm was probably the maximum 

19 value found in a pulp 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 of 5 mo and reported that levels of < 0.1 ppm 

23 (0.29 mg/m3) were found in over 91% of 2,785 samples and fewer than 1.2% of the samples 

24 exceeded 1 ppm .. 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 of exposure was from 0.006 to 

27 1.42 ppm (0.02 to 4.1 mg/m3). However, the value of 0.006 ppm that was reported is 

28 doubtful because it is below the analytical capability of the 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 of a paper pulp plant and found a mean exposure of 0.18 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 of hydrogen 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 of municipal and hospital refuse incinerated, 

8 respectively (see Section 3.2.2.3). Also, it has been estimated that 1, 700 tons of hydrogen 

9 chloride are emitted per year from one coal-fired power plant burning 2 million tons/year of 

10 bitutninous coal with a chloride content of 0.095% (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 of observations of the .actual use of hydrogen 

14 chloride. 

15 

16 

17 

August 1994 3-9 DRAFT-DO NOT QUOTE OR CITE 
1 REFERENCES 

2 Allen, R. J.; Brenniman, G. R.; Darling, C. (1986) Air pollution 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 Science Associates, Incorporated. (1978) Diagnosing vegetation injury caused by air pollution. Research 

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

9 Standards; EPA report no. EPA-450/3-78-005. Available from: NTIS, Springfield, VA; PB82-238924. 

10 

11 Chan, H. S. 0. (1984) Measurement of hydrochloric 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 of workers in a pulp and paper mill in Powell River, British Columbia. 

16 Am. Rev. Respir. Dis. 122: 249-257. 

17 

18 Duce, R. A. (1969) On the source of gaseous 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 JAMA J. 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 of southern 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 of chronic respiratory disease in a pulp mill 

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

37 

38 GEOMET Technologies, Inc. (1981) Hydrogen chloride: report 4, occupational hazard assessment. Cincinnati, 

39 OH: U.S. Department of Health and Human Services, National Institute for Occupational Safety and 

40 Health; NIOSH contract no. 210-79-0001. Available from: 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) Emergency response planning for potential accidental liquid chlorine releases. 

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) The fate of chlorine and chloramines in cooling towers: Henry's 

48 law constants for flashoff. Water Res. 18: 1421-1427. 

49 

50 Johnson, L. D.; Fuerst, R. G.; Logan, T. J.; Midgett, M. R. (1992) Development of a laboratory method for 

51 estimation of hydrogen chloride emission potential of incinerator feed materials. Research Triangle Park, 

52 NC: U.S. Environmental Protection Agency; EPA report no. EPA/600/A-92/230. Available from: NTIS, 

53 Springfield, VA; PB93-119907. 

August 1994 3-10 DRAFf-DO NOT QUOTE OR CITE 
1 Johnston, D. A. (1980) Volcanic contribution of chlorine 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 the health effects of HCl 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) The geochemical cycling of reactive chlorine through the marine 

9 troposphere. Global Biogeochem. Cycles 4: 407-430. 

10 

11 Lane, D. A.; Thomson, B. A. (1981) Monitoring a chlorine spill from a train derailment. J. AU Pollut. 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 surface water supplies. J. Am. Water Works 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 of Health, Education, and Welfare, 

19 Public Health Service; HEW publication 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 of Health 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 of Environmental Pollutants; EPA report 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) The health of diaphragm 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 of the 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 of gaseous 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 chloride partitioning 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) The risk of catastrophic spills of toxic chemicals. 

50 Los Angeles, CA: University of California School of Engineering and Applied Science; report no. 

51 UCLA-ENG-7425. 

52 

53 Sollars, W. F. (1961) Chloride content of cake flours and flour fractions. Cereal Chem. 38: 487-500. 

54 

August 1994 3-11 DRAFT-DO NOT QUOTE OR CITE 
1 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) 1992 directory of chemical producers United States of America. 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. Water Works Assoc. 67: 634-647. 

13 

14 World Health Organization. (1982) Chlorine and hydrogen chloride .. Geneva, Switzerland: World Health 

15 Organization. (Environmental health criteria 21). · 

16 

17 

August 1994 3-12 DRAFf-DO NOT QUOTE OR CITE 
1 

2 

4. ENVIRONMENTAL FATE AND 

ECOLOGICAL EFFECTS 

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 of the percent of liquid chlorine flashed at temperatures between 

11 -30 op and 170 °F. About 12.5 and 20% of the 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 of vaporization of liquid 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 of chlorine 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 CITE 
1 that, in sunlight, molecular chlorine is not the principal species of the gaseous element, and 

2 the chlorine present in ambient air is not elemental diatomic chlorine. 

3 Prather et al. (1984) expressed concern that an increase of "inorganic chlorine" in the 

4 stratosphere to levels comparable to that of reactive nitrogen oxides could result in reduction 

5 of ozone 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 The major sources of these species would be expected to be carbon tetrachloride, 

8 trichloroethane, trichlorofluoromethane, and dichlorofluoromethane, and not chlorine gas. 

9 If chlorine is released in water, it is expected that much of it will eventually find its 

10 way into the atmosphere. The Bureau of Mines (Murphy et al., 1970) carried out studies in 

11 which liquid chlorine (5 or 10 gal) was spilled on the surface of a pond, and gaseous or 

12 liquid chlorine was released underwater; evaporation and atmospheric dispersion were 

13 followed. When 5 gal were released under 4ft of water, the denser chlorine was buoyed up 

14 by the vapor generated by reaction at the chlorine-water interface, and essentially all of the 

15 chlorine was released to the atmosphere. When chlorine was spilled on the surface, the rate 

16 of vaporization was_ accelerated, possibly by facilitation of heat transfer, and essentially all 

17 was vaporized. It was concluded that only in slow leakage or after small spills would a 

18 significant fraction of the chlorine be solubilized in water. 

19 When chlorine is used as an antifouling agent in recirculating cooling water systems of 

20 power plants, there is a potential for release of free chlorine into the atmosphere. The 

21 chlorine is present in the water as hypochlorous acid. Holzwarth et al. (1984) have 

22 demonstrated that 10 to 15% of the 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" of free chlorine is markedly dependent on the pH of 

25 the water and would be 10 times faster at pH 6 than at pH 8.5. 

26 In aqueous environments, chlorine occurs as elemental chlorine, hypochlorous acid, and 

27 hypochlorite ion. However, the fate of chlorine in natural waters is not well defined. The 

28 primary chemical reactions of chlorine in saltwater and freshwater are illustrated in 

29 Figure 4-1, and a more detailed illustration of the reactions 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 CITE 
0 

c: 

0 

~ Q) 

a: 

"'C 

~ a: 

~ 0 

:E 

Most Important In Freshwater 

I ---------A-------~ ~ 

Free Chlorine Br· 

Cl2 (aq) 

Ht 0 2 • t .. _Br 

HOCI4 .. OCt·+ H 

, 

______ 

Most Important in Seawater ./ '------

1 

Free Bromine 

BrCI 

t 

H20 

+ . + HOBr4 .. OBr+ H 

, 

B{ ........ · .... ·.... . .. Bromamines 

Slow Chloramlnes 

Chloro-Organic Compounds, 

cr and Oxidation Products 

Bromo-Organic Compounds, 

Br· and Oxidation Products 

Figure 4-1. Schematic outline of chemical reactions in estuarine and marine waters. 

Source: Sugam and Helz (1980). 

1 concentrations, pH, temperature, salinity, and exposure to light control the extent of these 

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 water plus chloride ions. However, the 

7 concentration of hydroxy ions in the troposphere and stratosphere is low, which leads to a 

8 relatively long residence time for hydrogen chloride (Sebacher et al., 1980). Because of its 

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 CITE 
I 

I 

I 

I 

I 

I 

I 

\ 

\ 

' \ 

\ 

' \ 

' ' 

, \ 

Nz 

' \ 

\ 

\ 

\ 

\ 

\ 

\ 

~ 

~ 

i .----...:..t ____ , __ 

' + Br-Organlcs Oxidized Organics 

ero· s 

c10; 

NHBrCf \ 

\ 

\ 

\ 

\ 

~ 

Nz 

N2 , N03 I 

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 of free chlorine in the aquatic environment. Presumed pathways (not 

yet proven) are shown by dashed arrows. Compounds formed at different 

places in the reaction scheme are depicted with superscripts a and b to 

assist in understanding interrelationships. Halides (chlorine and bromine) 

are not depicted but are products of many of the chemical pathways. 

Source: Sugam and Helz (1980). 

1 deposition velocity would be at least as high as that of sulfur dioxide, which is on the order 

2 of 1 cm/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 of hydrogen chloride generated by the ammonium perchlorate propellant 

5 in launching a space shuttle is approximately 35,200 kg. This could result in rain of pH < 1 

6 at a distance of 4 to 19 mi, depending on meteorologic conditions (Potter, 1978). Sebacher 

7 et al. (1980) measured the partitioning of hydrogen chloride between gaseous hydrogen 

August 1994 4-4 DRAFT-DO NOT QUOTE OR CITE 
1 chloride and hydrochloric acid aerosol in a tropospheric cloud contaminated by exhaust. from 

2 launching of a Titan m rocket. The monitoring devices were capable of monitoring total 

3 airborne hydrogen chloride and airborne gaseous hydrogen chloride. An ~craft with 

4 sampling and measuring equipment passed 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 about 4 to 40 min postlaunch. The peak total hydrogen chloride (g~s plus 

7 aerosol) concentration was 15 ppm (21 mg/m3

) on the first pass; its decrease to about 

8 2.4 ppm (3.4 mg/m3) by the sixth pass indicates the rapidity of dilution 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 of aerosol hydrochloric acid. The measurements agreed with 

12 values predicted from calculations. 

13 More recent work by the National Aeronautics and Space Administration (Cofer et al., 

14 1985) measured hydrogen chloride in aerosol/gas from space shuttle launchings. 

15 Concentrations of hydrogen chloride in the exhaust cloud were as high as 40 ppm (60 mg/m3) 

16 and decr~ed about an order of magnitude 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 larger particles, 

20 which suggests extensive aerosol fallout. Prevailing meteorology will strongly determine the 

21 fate of hydrogen chloride in the atmosphere. 

22 No information was found on the fate of hydrochloric acid spilled into the ocean or 

23 ponds or entering the soil. If hydrogen 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, but there would be extensive evaporation at the 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 CITE 
1 4.2 ECOLOGICAL EFFECTS 

2 4.2.1 Chlorine 

3 The extensive use of chlorine as a biocide in 335 of 550 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 other pianktonic forms, are entrained in cooling water systems and other chlorine7 containing effluents, where they are exposed to various combinations of stressors. 

8 The toxicity of chlorine to aquatic organisms depends mainly on three environmental 

9 factors: temperature, e~posure time, and available form of chlorine or other halogen 

10 compounds (Capuzzo et al., 1977). The assessment of chlorine toxicity to freshwater and 

11 marine organisms is very complex because of the complex chemistry of chlorine in water. 

12 The particular halogen compound formed during seawater chlorination, for example, varies 

13 with the relative levels of brol: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) or combine with residual ammonium ions and organic matter, yielding 

17 mono-, di-, and.trichloramines or organochlorine compounds (Capuzzo et al., 1977). 

18 Chlorine generally decays rapidly (in minutes or hours) to lower residual levels. Typically, 

19 the toxicant effect is measured as total residual chlorine (TRC) or the sum of the 

20 concentrations of free and combined residuals, usually determined by amperometric titration 

21 analyses. A more detailed discussion of the effects of chlorine 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 of chlorine 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 of exposure. Toxicity is 

31 often lower during the egg stage and then increases during larval development 

August 1994 4-6 DRAFT-DO NOT QUOTE OR CITE 
TABLE 4-1. THE ACUTE TOXICITY OF CHLO~ TO FISH 

AND AQUATIC INVERTEBRATES 

Exposure 

Median Lethal Level Conditions 

Organism (mg/L TRC)• (hours) Reference 

FISH-MARINE and ESTUARINE 

Alosa aestivalis 

(Blueback hening) 

egg 0.3 180 Morgan and Prince (1977) 

2-day larvae 0.25 48 Morgan and Prince (19?7) . 

Cymalogaster aggregata 

(Shiner perch) 

1-3 mo old 0.23 TROb 1 at 20 °C Stober et 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) 

Leiostomus xanthurus 

(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 

(White perch) 

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 (>40 hold) 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-day juveniles 0.19 96 Hall et al. ( 1982) 

388-day juveniles 0.23 96 Hall et al. (1982) 

August 1994 4-7 DRAFT-DO NOT QUOTE OR CITE 
TABLE 4-1 (cont'd). THE ACUTE TOXICITY OF CHLORINE TO FISH 

AND AQUATIC INVERTEBRATES 

Exposure 

Medium Lethal Level Conditions 

Organism (mg!L TRC)• (hours) Reference 

FISH-MAIUNE and ESTUARINE (cont'd) 

Oncorhynchus ldsutch 

(Coho salmon) 

1 year old 0.13 TRO 1 at 20 °C Stober et al. (1980) 

0.21 1 at 13 °C Stober et al. (1980) 

Pseudopleuronectes americanus 

(Winter flounder) 

juvenile 0.55 (100% died) 0.5 Capuzzo et al. (1977) 

Stenotomus versicolor 

(Scup) 

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

Syngnathus fuscus 

(Northern pipefish) 

unspecified age 0.27 96 Roberts et al. (1975) 

FISH-FRESHWATER 

Lepomis macrochirus 

(Bluegill) 

juvenile 0.44 96 Wilde et al. (1983) 

Pimephales promelas 

(Fathead minnow) 

juvenile 0.08 96 Wilde et al. (1983) 

adult 0.35 96 Wilde et al. (1983) 

Gambusia affinis 

(Mosquito fish) 

unspecified age 1.59 0.5 Mattice et 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 
TABLE 4-1 (cont'd). THE ACUTE TOXICITY OF CHLORINE TO FISH 

AND AQUATIC INVERTEBRATES 

Exposure 

Median Lethal Level Conditions 

Organism (mg/L TRC)• (hours) Reference 

INVERTEBRATE-MARINE (cont'd) 

Mercenaritl mercenaria 

(Hard clam) 

larvae <0.005 48 Roberts et al. (1975) 

Palaemonetes pugio 

(Grass shrimp) 

unspecified age 0.22 96 Roberts et al. (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 or constant-addition conditions using measured levels of total 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 of the 

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). Of the five invertebrate species described in Table 4-1, larvae 

9 of two molluscan species (oyster and clam) were substantially more sensitive than any of the 

10 fish. 

August 1994 4-9 DRAFT-DO NOT QUOTE OR CITE 
1 As with some fish, the interaction of chlorine, temperature, and exposure conditions has 

2 been studied for some invertebrates. Hallet al. (1979a) exposed the blue crab and grass 

3 shrimp to TRC levels of 0, 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 similar effect. 

7 

8 4.2.1.3 Plants 

9 The only toxicity data for aquatic vascular plants were for Myriophyllum spicatum 

10 (Eurasian water milfoil). Continuous exposure of plants to concentrations as low as 

11 0.05 mg/L TRC resulted in a 30% reduction in dry weight of shoots and total biomass and a 

12 16% reduction in shoot length when compared to controls. At a concentration of 0.1 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 of radiolabeled carbon dioxide uptake at chlorine levels as low as 0.01 mg/L and inhibition of 

19 nitrate uptake at chlorine levels of 0.03 mg/L. 

20 

21 4.2.2 Hydrogen Chloride (Hydrochloric Acid) 

22 4.2.2.1 Aquatic Organisms 

23 The toxic effects of hydrochloric acid on aquatic organisms are due to the acid's effect 

24 on .hydrogen ion concentration (Rose et al., 1977). Aquatic organisms in their natural 

25 environments often exhibit a broad range of pH tolerance. DeGraeve et al. (1979), for 

26 example, concluded that aquatic organisms generally exhibit no deleterious effects at a 

27 pH range of 6 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 of various 

29 common pollutants (European Inland Fisheries Advisory Commission, 1968). Many 

30 freshwater organisms show no deleterious effects at pH 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 of increased 

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 of a variety of plants to levels of 

7 hydrogen chloride between 4.6 and 19.3 ppm (6.5 and 27.0 mg/m3) caused visible leaf injury 

8 and decreased chlorophyll levels (Endress et al., 1982; Granett and Taylor, 1981; Lerman 

9 et al., 1976). Field studies on 50 plant species growing near an anhydrous aluminum· 

10 chloride manufacturing plant indicated that the more sensitive species were American elm, 

11 bur oak, eastern white pine, basswood, red ash, and several bean species. Foliar injury of 

12 the more sensitive species was usually associated with concentrations of chloride ion 

13 exceeding 0.2% of whole-leaf dry weight. Hydrogen chloride-tolerant species showed no leaf 

14 toxicity despite foliar concentrations of chloride ion up to 5%. Both plant injury 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) The differential effects of free and 

3 combined chlorine on juvenile marine fish. Estuarine Coastal Mar. Sci. 5: 733-741. 

4 

5 Cocks, A. T.; McElroy, W. J. (1984) The absorption of hydrogen chloride by 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 Airbome measUrements of space shuttle exhaust 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 

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15 

16 Endress, A. G.; Suarez, S. J.; Taylor, 0. C. (1982) Photosynthetic and respiratory consequences of hydrogen 

17 chloride gas exposures of Phaseolus vulgaris L. and Spinacea oleracea L. Environ. Pollut. Ser. 

18 A 29: 13-26. . 

19 

20 European Inland Fisheries Advisory Commission. (1968) Water quality criteria for European freshwater fish: 

21 report on extreme pH values and inland fisheries. Rome, Italy: Food and Agriculture Organization of the 

22 United Nations; ElF AC technical paper no. 4. 

23 

24 Federal Register. (1980) Effluent limitations guidelines, pretreatment standards and new source performance 

25 standards under Clean Water Act; steam electric 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 in sensitivity of plants 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 power plant effluents on juvenile blue crabs Callinectes sapidus and grass shrimp Palaemonetes pugio. 

33 J. Toxicol. Environ. Health 5: 749-757. 

34 

35 Hall, L. W., Jr.; Burton, D. T.; Margrey, S. L. (1979b) The effects of chlorine, elevated temperature and 

36 exposure duration of power plant effiuents on larval white perch Morone americana (Gmelin). Water 

37 Resour. Bull. 15: 1365-1373. 

38 

39 Hall, L. W., Jr.; Burton, D. T.; Richardson, L. B. (1981) Comparison of ozone and chlorine toxicity to the 

40 developmental stages of striped 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 of chlorine toxicity to three life stages of striped bass (Morone saxatilis). Bull. Environ. 

44 Contam. Toxicol. 29: 631-636. 

45 

46 Harper, D. S.; Jones, R. D. (1982) The relative sensitivity of fifty plant species to chronic doses of hydrogen 

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 CITE 
1 Jolley, R. L.; Carpenter, J. H. (1983) A review of the chemistry and environmental fate of reactive oxidant 

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6 

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

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9 

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

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12 

13 Middaugh, D. P.; Burnett, L. E.; Couch, J. A. (1980) Toxicological and physiological responses of the fish, 

14 Leiostomus mnthurus, exposed to chlorine produced oxidants. Estuaries 3: 132-141. 

15 

16 Morgan, R. P., ll; Prince, R. D. (1977) Chlorine toxicity to eggs and larvae of five Chesapeake Bay fishes. 

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18 

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

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23 

24 Pellett, G. L.; Sebacher, D. 1.; Bendura, R. J.; Womom, D. E. (1983) HCl in rocket exhaust clouds: 

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27 

28 Potter, A. E. (1978) Environmental effects of the 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 

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32 

33 Roberts, M. H., Jr.; Diaz, R. J.; Bender, M. E.; Huggett, R. J. (1975) Acute toxicity of chlorine 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 of an 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 in a 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 of catastrophic spills of toxic chemicals. Los 

44 Angeles, CA: University of California School of Engineering 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 in heated 

49 sea-water. Water Res. 14: 347-354. 

50 

51 Sugam, R.; Helz, G. R. (1980) Seawater chlorination: a description of chemical 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 of the 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 water quality criteria for chlorine-1984. Washington, 

2 DC: Office of Water 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) The toxicity of chlorine 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 of chlorine and chlorine dioxide toxicity to fathead minnows and bluegill. Water Res. 

10 17: 1327-1331. 

11 

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

13 

August 1994 4-14 DRAFT-DO NOT QUOTE OR CITE 
1 

2 

3 

4 

5. PHARMACOKINETICS AND MECHANISM 

OF ACTION 

5 5.1 PHARMACOKINETICS AND METABOLISM 

6 The respiratory pharmacokinetics of chlorine and hydrogen chloride have not been 

7 examined thoroughly. There are data that suggest that these compounds or their reaction 

8 products are absorbed from the respiratory tract by the finding of liver and/or kidney effects 

9 in animals exposed to high levels of both compounds. However; these effects may have been 

10 the result of a disturbance in the acid-base metabolism or a decrease in blood oxygen levels 

11 due to excessive pulmonary damage. Under normal breathing of low levels of chlorine 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 of chlorine and 

15 hydrogen chloride. There is a limited amount of information addressing the oral 

16 pharmacokinetics of chlorine-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 of chlorinated 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 OF ACTION AND BIOCHEMICAL EFFECTS 

25 5.2.1 Chlorine 

26 Several theories have been proposed on the mechanism of chlorine's toxicity. One 

27 theory suggests that at physiologic pH (pH range of 6 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 + H20 > 2HC1 + Ot) (Kramer, 1967; World Health Organization, 1982; 

August 1994 5-1 DRAFf-DO NOT QUOTE OR CITE 
1 Colardyn et al., 1976). The major portion of the damage to tissues would then be caused by 

2 the potent oxidizing action of the nascent oxygen, which is a strong protoplasmic poison 

3 (Adelson and Kaufman, 1971; Colardyn et al., 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 et al., 1977). 

7 The hypochlorous acid penetrates the cell and forms N-chloro derivatives with amino groups 

8 of proteins, which damage cell structure (National Research Council, 1976). 

9 Hypochlorous acid has been shown to inhibit enzymatic reactions in living cells. 

10 Pereira et al. (1973) demonstrated that hypochlorous acid can convert several amino acids 

11 into a mixture of corresponding nitriles and aldehydes. It has been theorized that the chlorine 

12 irreversibly inhibits glucose metabolism at the point of thiosephosphoric acid oxidation to 

13 phosphoglyceric acid {Green and Stumpf, 1946), and that the inhibition_ of glucose 

14 metabolism was the result of chlorine reacting with sulfhydryl groups (Knox et al., 1948). 

15 However, Dodd et al. {1980) did not find an effect on lung total protein or nonprotein 

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 et al. (1983) found a 

18 decrease in total sulfhydryl content in the respiratory tract mucosa but not the olfactory nasal 

19 mucosa of rats exposed to 5 or 10 ppm (14.5 or 29.0 mg/m3

) chlorine for 6 h. Based on 

20 these results, it is not likely that the oxidation of total sulfhydryl content in the lung is 

21 playing a major role in the respiratory tract toxicity of chlorine, 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 of the sulfhydryl content, is n~t lmown. 

25 It has also been demonstrated that hypochlorous acid can react with the .nucleotide bases 

26 of deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). Patton et al. (1972) found that 

27 when one equivalent of hypochlorous acid was added to cytosine, 4-N-chlorocytosine was 

28 obtained. The addition of two equivalents of hypochlorous acid to cytosine yielded a 

29 precipitate identified as a mixture of 4-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 pyrimidine bases (Hoyano et al., 1973). 

August 1994 5-2 DRAFT-DO NOT QUOTE OR CITE 
1 5.2.2 Hydrogen Chloride 

2 The mechanism of hydrogen 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 of cleaving organic molecules (World Health Organization, ~982). It has 

7 also been suggested that the hydrolysis of peptides and esters plays a significant role in the 

8 injury produced by hydronium ions since they are components of the cell wall. Other 

9 reactions produced by the hydro~um ion include hydroxylation of carbonyl groups and 

10 polymerization and depolymerization of organic molecules. Once the cell wall has been 

11 damaged, the cell may be depleted of cytoplasmic components and die (National Research 

12 Council, 1976). 

13 

14 

15 

16 

August 1994 5-3 DRAFf-DO NOT QUOTE OR CITE 
1 REFERENCES 

2 Abdel-Rahman, M. S.; Berardi, M. R.; Bull, R. J. (1982) Effect of chlorine 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 of monochloramine and 

6 hypochlorous acid in rat. J. Appl. Toxicol. 3: 175-179. 

7 

8 Adelson, L.; Kaufman, J. (1971) Fatal chlorine poisoning: report of two 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 of the sensory irritation response in 

12 mice to chlorine and hydrogen chloride. Arch. Environ. Health 32: 68-76. 

13 

14 Colardyn, F.; van der 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 in rats following chlorine inhalation. 

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

19 

20 Green, D. E.; Stumpf, P. K. (1946) The mode of action of chlorine. J. Am. Water Works Assoc. 

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 of aqueous hypochlorous acid with pyrimidine and purine bases. Biochem. 

25 Biophys. Res. Commun. 53: 1195-1199. 

26 

27 Knox, W. E.; Stumpf, P. K.; Green, D. E.; Auerbach, V. H. (1948) The inhibition of sulfhydryl enzymes as the 

28 basis of the bactericidal action of chlorine. 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) In vivo formation of 

36 halogenated reaction products following peroral sodium hypochlorite. 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 of Environmental Pollutants; EPA report 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. The reaction of aqueous 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. the reaction of aquecius 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 EXPERIMENTAL ANIMALS 

5 6.1.1 Chlorine 

6 The experimental animal toxicity studies for chlorine evaluate the effect of acute, 

7 subchronic, or chronic inhalation of chlorine gas or aerosol. These studies indicate that · · 

8 inhaled chlorine can attack the respiratory tract, producing irritation, pulmonary edema, and, 

9 in some cases, 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 of chlorine does not produce serious adverse effects in animals. Cunningham 

13 (1980) reported no signs of toxicity 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 of toxicity 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 of consuming chlorine-treated ground beef, Kotula et al. 

18 (1987) fed rats ground beef containing 0, 50, 200, or 600 ppm chlorine for 92 days; no 

19 clinical or hematological abnormalities were reported. However, there have been several 

20 reports of increased or decreased 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 2,506 ppm 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, or 2,500 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 of the 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 stock diet (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 of chlorine in animals. The studies were conducted in 

8 Germany, Britain, Russia, and France, primarily in response to the use of chlorine as a "war 

9 gas" in World War I. The authors concluded that these data are not 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 of flow) 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 of chlorine to parts per million at 25 °C rather than 

16 at 0 o C as in the original work. ~e concentration producing 50~ mortality (LC50) was 

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

18 Weedon et al. (1940) exposed groups of four 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, or 960 min or until they died. The LC50 values in mice were 1,000, 250, and 

21 63 ppm for exposure times of 53, 440, and >960 min, respectively. These values are 

22 somewhat inexact because some animals died during exposure and were scored as having 

23 been exposed for the entire period. 

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 of 30 min. Exposure to 55.3 ppm 

27 caused no deaths. The LC50 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 of death 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 CHLORINE IN 

~TSANDMICE 

Exposure ObseiVation 

Concentration Time Period Lc50• 

Species Strain (ppm [mg/m3

]) (minutes) (days) (ppm [mg/m3

]) Reference 

Mice NMRI 55-179 30 4 127 (368) Schlagbauer and 

(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) Silver et 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 of exposure causing SO% mortality (LT~. 

dAs cited in Withers and Lees (1985a). 

~ted values. 

1 above 120 ppm (348 mg/m3) caused an increase in the water content of the lung (edema). 

2 In mice that died, histologic fmdings were necrotic injury to the tracheal mucosal membrane, 

3 desquamation of the epithelium of bronchi and bronchioles, and inflammation of th~ atveolar 

4 epithelium. 

August 1994 6-3 DRAFf-D.O NOT QUOTE OR CITE 
1 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. The levels of 

3 exposure were 170 or 290 ppm (348 or 841 mg/m3) chlorine and the time of exposure was 

4 varied from 5 to 30 min at the high level and 15 to 160 min at the lower level. The animals 

5 were observed for 30 days after exposure. Most deaths were delayed, occurring between 

6 5 and 10 days. The duration of exposure causing 50% mortality was 11 min exposure at 

7 290 ppm and 55 min at 170 ppm. All mice (28) exposed at 290 ppm for 6 min survived. 

8 Withers and Lees (1985b) utilized the data on acute toxicity of chlorine to adjust for a 

9 common exposure period of 30 min. The lethal 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 of mice, 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 guinea pigs exposed to 

14 chlorine. Rabbits appeared to be less susceptible than mice or rats, since a 30-min exposure 

15 to levels of 50, 100, and 200 ppm (145, 290, and 580 mg/m3

) caused no mortality, but 

16 range-finding studies indicated death within an hour of a similar exposure to 1 ,000 pp~ 

17 (2,900 mg/m3) and 2 days after exposure to 500 ppm (1 ,450 mg/m3) (Barrow and Smith, 

18 1975). 

19 Cralley (1942) studied the effect of chlorine gas on ciliary activity in excised tracheal 

20 preparations of rabbits. 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 20 ppm (52 to 58 mg/m3) for 10 min caused a cessation of ciliary 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 of chlorine 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 of a 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 CITE 
1 immunoglobulin G, but only in the sera of mice exposed to the antigen immediately following 

2 exposure to 200 ppm chlorine. Chlorine exposure produced no effects on immunoglobulin A 

3 in sera or bronchoalveolar lavage fluid in any of the tested groups. 

4 

5 F.lfects on Pulmo111lTY ~n. Barrow et al. (1977) studied the sensory irritation 

6 responses to chlorine in male Swiss-Webster mice exposed at concentrations be~een 0.7 and 

7 38.4 ppm (2.1 to 113.3 mg/m3). Concentration curves were plotted using percent decrease 

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 more potent than hydrogen chloride gas (RD50 = 

11 309 ppm). 

12 Barrow and Steinhagen (1982) investigated the development of a 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, 5 days/week for 2 weeks as a pretreatment. 

15 Sixteen to 24 h following the pretreatment period, rats were exposed to chlorine gas for 

16 10 min at concentrations ranging from 1 to 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 of exposure, 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 of 4 and 10 days resulted in a 20-fold increase in the RD50 (225 ppm 

24 [663.9 mg/m3]) over that of the naive animals. 

25 Barrow and Smith (1975) studied changes in pulmonary function in rabbits exposed to 

26 sublethal levels of chlorine. Groups of four rabbits (strain not specified) of both sexes were 

27 exposed to chlorine gas at 0, 50, 100, or 200 ppm (0, 145, 290, or 580 mg/m3

) for 30 min. 

28 One rabbit from each group was tested for changes in pulmonary 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 of exposure. 

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 3 days; 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 exposure levels from 0.5 h to 3 days after exposure. 

After 14 and 60 days of recovery, 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 made between functional changes and postmortem findings. The V1:VE ratio 

quantitatively related to the degree of impairment resulting from pulmonary edema, whereas 

V-P changes indicated emphysema-like changes and loss of elastic properties. Recovery time ' . was related to the level of chlorine exposure and the extent of pulmonary 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 of 9.34 ppm (27.5 mg/m3), 6 h/day for 5 days. The effects on the 

14 respiratory and olfactory epithelia of the 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 of the 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 of the affected bronchioles by 

19 serocellular exudate. Barrow et al. (1979a) exposed groups of ten 6- to 8-week-old Fischer 

20 344 rats of both sexes to chlorine gas at 0, 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 of toxicity 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 1 ppm, there were occasionaJ slight 

26 signs of upper respiratory irritation, and at 3 and 9 ppm, lacrimation and hyperemia of the 

27 conjunctiva occurred; nasal discharge and salivation were seen throughout the study. 

28 Gasping, lung rales, and mouth breathing were observed at 9 ppm. All groups of exposed 

29 rats had urinary staining of the 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 or 9 ppm when compared to controls. In both males 

August 1994 6-6 DRAFT-DO NOT QUOTE OR CITE 
1 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 of males and females exposed at 3 and 9 ppm. There was also an 

5 increase in serum glutamic oxaloacetic transaminase in females exposed at 9 ppm compared 

6 to controls. The specific gravity of urine tended to increase in all exposed groups. 

7 Histopathologic examination of the rats exposed to chlorine at 9 ppm indicated 

8 inflammation of the upper and lower respiratory tract (Barrow et al., 1979a). There was 

9 focal-to-multifocal mucopurulent inflammation of the nasal turbinates with increased secretory 

10 material and necrotic lesions. The tracheobronchial region showed epithelial hyperplasia and 

11 hypertrophy of the bronchiolar and alveolar duct epithelia, an increase of alveolar 

12 macrophages, and focal areas of necrosis. In rats exposed to 1 or 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 of both males and females exposed at 9 ppm 

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. The histologic 

18 changes in the liver correlated with increased actiyity of serum enzymes. There was also 

19 focal erosion of the gastric mucosa, but only in the animals exposed to 9 ppm. The authors 

20 believed that the results of this study may have been affected by the presence of chloramines 

21 produced by the reaction of chlorine with excreta. Barrow and Dodd (1979) detected 

22 ammonia and chloramines in inhalation chambers of rats exposed to chlorine, and they 

23 showed that chloramines are produced by the reaction of chlorine with excreta. Ammonia 

24 concentrations in a 99-L chamber with an airflow of 26 Umin and an animal_loading of 3.1% 

25 reached 1.6 ppm (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 of 26 L/min was 0.13 ppm for chloramines. 

28 Jiang et al. (1983) exposed groups of nine or ten 8-week-old male Fischer 344 rats and 

29 6-week-old male Swiss-Webster mice to chlorine gas at a concentration of 9.1 ppm 

30 (26.4 mg/m3

), 6 hlday for 1, 3, or 5 days. The exposure concentration was close to the 

31 RDso value (9.3 ppm [27 mg/m3]) (Barrow et al., 1977). After 1, 3, and 5 days, groups of 

August 1994 6-7 DRAFf-DO NOT QUOTE OR CITE 
1 animals were sacrificed for histologic examination of the respiratory tract. Five levels of the 

2 nasal passage and the nasopharynx, larynx, trachea, and lung~ were examined by light 

3 microscopy. Lesions were found in the nasal passages of exposed animals, with less severe 

4 changes noted in the nasopharynx, larynx, trachea, and lungs. Nasal lesions involved both 

5 olfactory an~ respiratory epithelia. In contrast to Day 1, after Days 3 and 5 of exposure, the 

6 lesions became more severe and were more posteriorly extended. There was epithelial 

7 degeneration, erosion, and ulceration after 1 to 3 days and neutrophil infiltration and 

8 squamous metaplasia at 5 days. The most severe lesions were found in the olfactory 

9 epithelium covering the middle third of the dorsal meatus in both mice and rats. There was 

10 some degeneration of the olfactory nerves in mice. Electron microscopy indicated complete 

11 loss of cilia in extensive areas and cellular exfoliation of the 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, or 5.0 ppm 

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 were prepared of the respiratory tract, heart, liver, kidneys, spleen, and testes. 

17 Pulmonary function tests were performed on 24 anesthetized rats from each exposure group. 

18 Animals in the 5-ppm exposure group had nasal discharge, excessive salivation, and 

19 lacrimation. Similar but less severe symptoms were noted in the rats exposed to 1.5 ppm 

20 chlorine. No outward signs of irritation were noted in the animals exposed to 0.5 ppm 

21 chlorine. None of the pulmonary function parameters examined demonstrated a statistically 

22 significant change in pulmonary function in exposed animals. However, the difference in 

23 expiratory flow rate at 25% of the vital capacity (VC), a measure of the degree of convexity 

24 or concavity of the effort-independent limb of the maximum expiratory flow yolume curve, 

25 was significantly reduced (p = 0.04, analysis of variance) in chlorine-exposed animals, 

26 indicating some degree of small airway involvement, but there was no exposure-related 

27 relationship observed among the exposed groups. Histopathological evaluation of the trachea 

28 of exposed animals showed a loss of epithelium and cilia. These changes were not severe 

29 · and were similar to those findings in the control animals, but the mean trachea pathology 

30 scores of the 0.5 and 5.0 ppm chlorine-exposed animals, using Kruskal-Wallis nonparametric 

31 test and the multiple comparisons techniques of Dunn and Miller, were significantly greater 

August 1994 6-8 DRAFr-DO NOT QUOTE OR CITE 
1 than those of the control group. Histopathological evaluation of other 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 5.0 ppm chlorine. The elastin content in the lungs of chlorine4 exposed animals was not significantly different from that of control animals. The authors 

5 also reported mean concentrations of 0.0395, 0.466, and 0.585 ppm chloramines, 

6 respectively, in the cages of chlorine-exposed animals. 

7 

8 6.1.1.3 Chronic Toxicity 

9 In a 12-mo chronic study, groups of four male and four female young adult rhesus 

10 monkeys were exposed to chlorine at concentrations of 0.1, 0.5, or 2.5 ppm (0.29, .1.45, or 

11 7.25 mg/m3) for 6 h/day, 5 days/week for 1 year (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 of chloramine 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 of nitrogen washout and pulmonary 

17 diffusing capacity. Electrocardiography evaluations, hematology (hematocrit, hemoglobin 

18 concentration, erythrocyte count, 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 occult blood, nitrites, bilirubin, ketones, and urobilinogen) were performed on all animals 

24 prior to initiation and monthly during the study; arterial blood gases were alsQ measured. 

25 At the end of 1 year, 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 or urinary 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 CITE 
1 The only exposure-related histopathologic change was a mild focal epithelial hyperplasia 

2 in the respiratory epithelium of the nose and trachea, which was associated with a loss of cilia 

3 and goblet cells. These lesions wtTe induced in both sexes exposed to 2. 3 ppm chlorine. 

4 Similar but less distinct changes were present only in the nasal passage of both 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 of acariasis were reported in 

7 tlle monkey population as the result of a 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, or 7.2 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 of the transitional epithelium of the lateral 

17 meatus. Most of these lesions, restricted to the nasal passages· of the 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 of eosinophilic proteinaceous material involving the respiratory, 

21 transitional, and olfactory epithelia, and, in some instances, the squamous epithelium of the 

22 nasal vestibule (Gross et al., 1993). 

23 

24 6.1.2 Hydrogen Chloride 

25 Most of the experimental animal studies for hydrogen chloride evaluate the effects of 

26 acute inhalation of the 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 of hydrogen chloride and formaldehyde. 

30 

31 

August 1994 6-10 DRAFT-DO NOT QUOTE OR CITE 
1 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 CFE rats (Table 6-2). Groups of 10 to 15 animals were exposed to various 

4 concentrations of hydrogen chloride gas or aerosol for 5 or 30 min. About 93% of the 

5 particle size of the aerosol droplets was in the range of 1 to 2 I'm. No mortalities occurred 

6 in mice exposed for 30 min to 410 ppm (615 mg/m3

) or in rats exposed forth~ same 

7 duration to 2,078 ppm (3, 117 mg/m3) hydrogen chloride gas. Death patterns observed were 

8 similar for both the gas and the aerosol. Most deaths occurred in 1 to 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 of the skin, such as the scrotum. Corneal 

11 erosion and clouding occurred in both species. According to the authors, the primary 

12 pathological lesions observed in the respiratory tract were alveolar emphysema, atelectasis, 

13 and edema of the lungs, as well as severe injury to the epithelium of the nose and trachea. 

14 

15 

TABLE 6-2. ACUTE TOXICITY VALUES FOR HYDROGEN CHLORIDE 

.IN MICE AND RATS . 

Minimal 

Exposure Lethal Number of 

Time LCso * Coneentration Deaths 

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 More recently, Hartzell et al. (1985) determined LC50 values for hydrogen chloride _for 

2 exposure times of 5, 10, 15, 22.5, 30, and 60 min. Groups of six to eight adult male 

3 Sprague-Dawley rats were.exposed to at least fiv~ concentrations of hydrogen chloride for 

4 each of the exposure times, followed by a 14-day observation period. Table 6-3 presents the 

5 LC50 values. A graph of LC50 versus time of exposure is shown in Figure 6-1. There is a 

6 discrepancy in the LC50 value reported by Hartzell et 31. (15,900 ppm [23,850 mg/m3]) and 

7 Danner et al. (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 concentration producing 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 time producing 50% mortality in exposed animals. 

VJ'he 95% confidence limits are in parentheses. 

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 of 7 to 10 should be applied in extrapolating the acute 

5 lethal effects of hydrogen chloride in mice to humans to compensate for the effective 

6 absorption of the gas in the nasal passages of mice. However, this theory is not consistent 

7 with observations of lower respiratory tract damage in animals only at very high 

8 concentrations of hydrogen chloride. 

August 1994 6-12 DRAFT-DO NOT QUOTE OR CITE 
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 adult male 

Sprague-Dawley rats versus time of exposure. 

Source: Hartzell et al. (1985). 

~f(__-1'{01....--

1 Higgins et al. (1972) investigated the effects of exposure to CO on the acute lethality of 

2 a 5-min exposure to hydrogen chloride in mice and rats. The concentration of CO 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 39,010 ppm [15,994 and 

7 58,515 mg/m3

] for mice and rats, respectively). In a later study, Hartzell et al. (1987) 

8 suggested that the acute lethal effects of hydrogen 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 the upper 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 of the nose, 1.5 to 2.0 mm apart, beginning at the 

3 external nares to the lateral canthi of the eyes, were examined histologically. At 17 ppm, - pul\-~<-

4 small superficial ulcerations occurred only in the respiratory epithelium at its 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 of the 

7 nasal cavity. At 723 ppm (1,084 mglm3

), more than the lower two-thirds of the upper 

8 respiratory tract was damaged, and the entire mucosa was destroyed at 1,973 ppm 

9 (2,954 mglm3). A concentration of 493 ppm (739 mg/m3) completely destroyed the 

10 squamous epithelium of the external nares. At 1,088 ppm (1,632 mg/m3), the underlying 

11 support structures were damaged; the cartilage of the nasal epithelium was necrotic, and the 

12 bone of the maxilloturbinate was eroded. At concentrations of 1,973 ppm or above, portions 

13 of the squamous, respiratory, and olfactory epithelium were all affected. At 7,279 ppm 

14 (10,918 mg/m3), total destruction of the mucosa and support structures, along with total 

15 destruction of the eyes, was observed in all animals. 

16 c'v~3 'r' Barrow et al. (1979b) compar~ the acute inhalation to~city of hydrogen chloride and 

17 the thermal decomposition products of polyvinyl chloride (PVC). Groups of four 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 20,000 ppm (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 et al. (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 of hydrogen chloride evolved from PVC, it was 

indicated by the authors that the acute toxicity of PVC was d~e primarily to the hydrogen 

chloride evolved in the thermal decomposition. -::)IJ.f!JA t 1/'4/i_ 

The acute inhalation toxicities of hydrogen 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 or 4,470 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 or 48 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 of the 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 soft tissues and cartilage, especially in the highest exposed group. 

7 By Day 14 postexposure, the authors reported that the mucosa lining of the respiratory tree 

8 had been restored; however, the ulcers had been replaced by scar tissue. 

9 Studies conducted in the 1930s with guinea pigs 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 or with 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 of three guinea pigs and three rabbits to hydrogen 

18 chloride gas concentrations of 33 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 or to 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 of 57 animals 6 days after exposure because of histological changes in the liver 

23 (parenchymal edema, congestion, necrosis, and hemorrhage) and lungs of animals exposed to 

24 high levels of hydrogen 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 of exposed animals, but it 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 of hydrogen chloride 

31 exposure in the absence ·of hematological and clinical analyses, or the result of respiratory 

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 or inadequacies are known to affect various organs and 

systems. 

Differences in hydrogen chloride-induced histopathological changes in the respiratory 

tract of mouth- and nose-breathing male Fischer 344 rats were reported by Stavert et al. CL-crry 

(1991). Seventy rats were divided into four groups (nose breathet: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 h following exposure. Nose-breathjng 

animals exposed to hydrogen chloride had severe, necrotizing rhinitis with full thiclmess 

necrosis of the turbinates, thrombosis of vessels of the nasal submucosa, and fibrinous 

pseudomembrane formation in the anterior portion of the nasal cavity. The trachea of some 

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 of these animals. 

The nasal cavities of rats fitted with mouthpieces were generally unaffected by the 

hydrogen chloride exposure, with the exception of an occasional find~g of blood and/or 

exudates in the nasal turbinates. Severe, diffuse, ulcerative tracheitis with necrosis of the 

mucosa and submucosa with fibrin membrane formation covering the ulcerated lumen of the 

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 of the larger bronchi was 

seen in some mouth-breathing, hydrogen chloride-exposed animals, but these lesions were not 

significantly greater than those reported in mouth-breathing, air-exposed animals. In some 

lungs, there were significantly elevated numbers of PMNs in alveoli surrounding some 

terminal bronchioles. However, whether the increase in PMNs was the result of a hydrogen 

chloride-induced inflammatory response by the alveoli o~ ~ge airway injury was not 

[t:i.tt-1 rJ.~fx I" (~flGA... "fj R ~~· /Cf 86 

determined. (Stavert et al., 1991). ,... CL-o«tl'tj' c L -o'(' 7 Kaplan et al. (1984) and Kaplan (1987) exposed nine juvenile male baboons 

(Papio cynocephalus) for 5 min to various levels of hydrogen 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 significant increase in escape time at any exposure 

4 level; it was 7.39 ± 4.26 s in exposed baboons, and the pretest average was 6.54 + 1.37 s. 

5 ,~ ppm hydrogen chloride, there were no reactions and no postexposure symptoms. 

6N°At~els of 810, 890, and 940 ppm (1,215, 1,335, and 1,410 mg/m~~~f\... 

7 agitation, salivation, and frothing at the mouth but no significant postexposure symptoms. 

8 At levels of 2,780 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 

significant postexposure 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 of the 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 of the epithelia of the trachea, and hepatocellular degeneration. 

These authors also studied escape impairment in male Sprague-Dawley ~ts. Exposure to . . -F levels of hydrogen chloride between 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 of the animal after about 4 min of exposure, with death approximately 

1 min later. However, there were severe to~f E_£ects at all levels, and mortality occurred at 

levels above 14,410 ppm (21,615 mg!m3}htdrogen chloride. . (' 

The incapacitating potential of hydrogen 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 a cylindrical 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 of the exposure) by statisti~y 

2 derived regression equations. The observed !i ranged from 5.5 min at 94,000 ppm 

3 (141,000 mg/m3

) to 185 min at 2,000 ppm. When the regression equations were fitted to 

4 each data set using 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 response time 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 3.0 in the equation suggest that the 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, guinea pigs 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 a 55-min exercise 

20 regime. The guinea pigs 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 of the 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 of chlorine and hydrogen chloride gas on ciliary 

27 activity in excised tracheal preparations of rabbits. The gases were passed over the tissue at a 

28 rate comparable to that of breathing 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 of ciliary 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 CITE 
220 

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. Incapacitation time as a function of hydrogen chloride concentration. 

Regression parameters: correlation coefficient = 0.96; standard error of 

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. Survival time as a function of hydrogen chloride concentration. Regression 

parameters: correlation coefficient = 0.92; standard error of 

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 of ciliary activity. Controls showed no effect on ciliary activity after 

exposure to circulated humid air for more than 15 min. 

(L-0{~0 

Flfects on Pubno1Ul1Y Function. Barrow et al. (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-effect level was 3 ppm (4 mg/m3). Chlorine, 

with an RD50 value of 9.3 ppm (27 mg/m3), was shown to be 33 times more potent than 

hydrogen chloride. C. l- 0 ~ 3 7 

Burleigh-Flayer et al. (1985) expoSed groups of four 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 of eight guinea pigs 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 a pause after each expiration. Sensory irritation occurred within a minute 

at 680, 1,040, or 1,380 ppm and after 6 min at 320 ppm. A concentration-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 of the 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 CITE 
1 regions. At 2 days, there was multifocal alveolitis and mild hemorrhaging in the alveolar 

2 regions, and squamous metaplasia, loss of cilia, 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 et al., 1985). 

5 Male Fischer 344 rats fitted with mouthpieces with attached ~ilastic endotracheal tubes 

6 and exposed to 1,300 ppm (1,937 mg/m3

) hydrogen chloride for 30 min have been reported 

7 to exhibit an 8% increase in minute volume over that of experimental animals fi~ with the 

8 mouthpiece but allowed to breath air. Nose-breathing animals exposed to hydrogen chloride 

9 under the same exposure regime demonstrated an overall decrease in minute volume (6%) 

10 over that of animals exposed to air. The decrease in minute volume in nose-exposed ~mals 

11 was likely the result of stimulation of the trigeminal nerve endings present in the nasal 

12 mucosa. The increase (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 of the anatomical sites of injury produced by hydrogen 

16c..v chloride exposure appears in Section 6.1.2.1. (..,{._ ... 0 "'1. b 7 

17 The effect of hydrogen chlo~monary function and blood gases was 

18 reported by Kaplan et al. (1988). Four ~~oups of three anaesthetized male baboons were t-ta~ .AE.L.. ~(.,. 

19 exposed to air or to 500, 5,000, or 10,000 ppm (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% of the 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, but the 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, but the 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 10,000 ppm. In animals exposed to 10,000 ppm hydrogen 

August 1994 6-22 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 

chloride, there was chronic nasal obstruction, mouth breathing, hypoxemia, changes in 

pulmonary function, and, in one animal, focal pulmonary fibrosis at 1 year after exposure 

(Anzueto et al., 1987). ~ 

~~ Intratracheal Exposures. The effects of intratracheal instillation of hydrochloric acid 

have been studied in dogs and goats. Greenfield et al. (1969) gave intratracheal instillation 

of 1, 2, or 3 mUkg of 0.1 N hydrochloric acid to mongrel dogs and sacrificed the animals at 

various time intervals up to 48 h. When instilled with 1 mUkg, dogs exhibited 

hyperventilation, increases in pH and Pa02, and a decrease in PaC02; no deaths occurred. 

Instillation of 2 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 

of dosage. 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 the presence of altered mechanical properties of the .. 

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 n cells. 

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 of compression 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 of Type I cells lining the alveoli. 

A morphometric study showed 69% of the parenchyma to be normal, 26% edematous, and 

5% hemorrhagic; 58% of the epithelium in the airways was damaged. 

In mongrel dogs, instillation of 2 ~ 0.1 N hydrochloric acid produced pulmonary 

edema that was caused, at least in part, by increased vascular permeability (Grimbert et al., 

1981). In goats, instillation of 2.5 mUkg 0.1 N hydrochloric acid reduced the total lung 

capacity (TLC) from 39 to 21 mUkg at 4 h (using a transpulmonary pressure of 35 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 et al., 1983). 

August 1994 6-23 DRAFT-DO NOT QUOTE OR CITE 
··-

1 Demial Toxicity. Vernot et al. (1977) tested the effects of hydrochloric acid on the skin 

2 of shaved rabbits. ·The test solution (0.5 mL) was applied to the back, and the area was 

3 covered with a patch 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 minor bums, a 2-min contact produced lesions that 

6 healed in 15 to 19 -days, and a 5- to 7-min contact produced more serious burns that required 

7 26 days to heal (GEO:MET Technologies, Inc., 1981). 

8 

9 Ocular Toxidty. Danner et al. (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 if those effects occurred at all the levels tested (2,000 to 30,000 ppm [3,000 to 

12 45,000 mg/m3]). 

13 Burleigh-Flayer et al. (1985) found corneal opacity in four of six guinea pigs exposed 

14 for 30 min to 1,040 ppm (1,560 mg/m3) hydrogen chloride and in five of five 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. ocular effects were noted: at 490 ppm (730 mg/m3

) moderate to marked PMN 

19 infiltration of the palpebral and global conjunctiva; at 1,074 ppm (1,600 mg/m3) necrosis of 

20 the exposed cornea and marked PMN infiltration of the eyelids; at 1,946 ppm (2,900 mg/m3) 

21 necrosis of the margins of the eyelids and extensive damage of the globes; and at 3, 188 ppm 

22 (4,750 mg/m3) rupture of the 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 1 min. The pH rapidly returned to normal by th~ natural 

25 buffering mechanism of the eye. Hydration of the corneal tissue increased unti1120 h, 

26 followed by a decrease and return to normal 168 h after onset of injury. Glycolysis and 

27 oxygen intake were markedly inhibited immediately after the injury. The inhibition of 

28 metabolism was due to the denaturation of glycolytic enzymes. 

29 

30 

August 1994 6-24 DRAFI'-DO NOT QUOTE OR CITE 
1 6.1.2.2 Subchronic Toxicity 

2 Very little information was found on the effects of hydrogen chloride gas in animals 

3 following repeated exposure. No mortalities occurred in three rabbits or three guinea pigs 

4 exposed to hydrogen chloride at 67 ppm (100 mg/m3), 6 hlday for 5 days nor in three 

5 rabbits, three guinea pigs, or one monkey exposed to 33.5 ppm (50 mg/m3), 6 hi day, 

6 5 days/week for 4 weeks (Machle et al., 1942). No evidence of toxic damage was noted 

7 when the animals were sacrificed several months later. The concentrations used were 

8 irritating to the eyes and mucous membranes. The World Health Organization (1982) 

9 reported eye and nasal irritation and slight respiratory difficulty in rabbits and guinea pigs 

10 exposed. to hydrogen chloride at 100 ppm (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 of 31 males and 21 females of each species/strain were exposed to hydrogen 

13 chloride at levels of 0, 10, 20, or 50 ppm (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 slight but 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, or urinalysis. Histologic examination showed minimum to 

18 mild rhinitis in both strains of rats. Lesions occurred in the anterior portion of the nasal 

19 cavity and were concentration- and time-related. In mice exposed to 50 ppm there was 

20 cheilitis and accumulation of macrophages in the perioral tissues after 90 days. Mice in all 

21 exposure groups developed eosinophilic globules in the epithelial lining of the nasal tissues 

22 (Toxigenics Incorporated, 1984). 

23 Kirsch and Drabke (1982) macroscopically examined the respiratory tract of guinea pigs 

24 exposed to hydrogen chloride at 0.1 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 guinea pigs (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 of exposure, 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 6 hlday.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 or moribund by the end of the third exposure. There was severe exfoliation, 

7 erosion, ulceration, and necrosis of the respiratory epithelium of the nasal cavity, but no 

8 squamous metaplasia. Ulceration and necrosis of the olfactory epithelium were less severe 

9 after exposure to hydrogen chloride than after exposure to chlorine, and there were no lesions 

10 in the trachea or lungs. 

11 Krishnan and Rao (1981) studied the effect of hydrogen chloride on the lung surfactant, 

12 a lipoprotein complex with high phospholipid content that 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 of the 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 of chronic exposure to hydrogen chloride 

24 (discussed in Section 8.2.1.2) evaluate the ability of hydrogen chloride to· e~ce the 

25 potential of formaldehyde to produce nasal tumors in rats. In these studies, hydrogen 

26 chloride was not found to enhance the carcinogenicity potential of formaldehyde. Additional 

27 studies are needed to adequately define the effects of chronic exposure to hydrogen chloride. 

28 

29 

30 

August 1994 6-26 DRAFf-DO NOT QUOTE OR CITE 
1 6.2 HUMAN TOXICITY 

2 6.2.1 Chlorine 

3 The toxicity of chlorine to humans as well as to other higher living organisms is 

4 primarily a function of its chemical form. For example, 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 or another nitrogen-containing compound may lead to the formation of 

8 chloramines. 

9 

10 6.2.1.1 Acute Exposure 

11 Controlled Human Studies. Experimental studies on chlorine in humans have been 

12 limited to the detection of the odor, the irritation threshold, and pulmonary function tests in 

13 volunteers exposed to low levels. The World Health Organization (1982) cited a 1969 

14 doctoral dissertation by Beck indicating 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 of odor perception after 1 to 24 min of exposure. 

17 Leonardos et al. (1969) reported an odor threshold of 0.3 ppm (0.8 mg/m3). Trained odor 

18 specialists capable of analyzing character and intensity of odor 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 of chemistry 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% of the trials. The World Health Organization (1982) cites a 

24 number of other studies with. wider ranges, but the chemical purity and laboratory conditions 

25 of these studies may have caused ·the wide scatter in the data. Table 6-4 lists some of the 

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 of literature values and standard toxicology sources cited 

29 ··irritation values of 3 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 CITE 
TABLE 6-4. THRESHOLD LEVELS FOR CHLORINE GAS 

Effect 

Odor perception 

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 1 ppm (2.9 mg/m3), and 0.5 ppm (1.5 mg/m3) was not irritating. 

3 The effects of exposure to low levels of chlorine on respiratory function in human 

4 volunteers have been studied by Rotman et al .. (1983). Eight ~onsmoking male subjects, 

5 19 to 33 years of age, with no history of respiratory disease, were exposed to 0.5 or 1.0 ppm 

6 (1.5 or 2.9 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 were performed prior to exposure and after 4 h of exposure; 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. The parameters measured included forced vital capacity 

12 (FVC), forced expiratory volume in 1 s (FEV 1), peak expiratory flow rate (PEFR}, forced 

13 expiratory flow rate at 50% and 25% (FEF50 and FEF25) of vital 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 of the throat at 1.0 ppm 

16 (2.9 mg/m3) but no subjective symptoms at 0.5 ppm (1.5 mg/m3). One subject who had a 

17 history of allergic rhinitis experienced severe distress during exposure, and shortness of 

18 breath and wheezing forced him to exit the chamber before the full 8 h of exposure to 

19 1.0 ppm 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 the preexposure 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 after chlorine 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, FEV 1, PEFR, FEF50, FEF25, and Raw after 8 h ·when 

8 compared to sham exposure using paired t tests. After the 4-h exposure to 1.0 ppm, there 

9 was a decrease in FEV1, PEFR, FEF50, FEF25, and TLC. The test results for the one 

10 subject with allergic rhinitis were markedly reduced after 4 h exposure at 1.0 ppm (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 FEV 1, 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 1.0 ppm chlorine caused decreases in PVC, FEV 1, PEFR, FEF50, and FEF25 • 

16 and increases in TLC and Raw· These changes were ~ore significant and longer lived. The 

17 authors concluded that exposure to even low levels of chlorine· can produce adverse effects on 

18 pulmonary function, and that the magnitude of the changes is related to the level of exposure. 

19. 

20 Case Repons. The acute toxic effects of chlorine 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% of the casualties 

23 from gassing (World Health Organization, 1982). Withers and Lees (1985a) reported that, in 

24 the battle of Ypres, there were 685 British casualties treated at a field station _after soldiers 

25 were exposed from a gas cloud attack with chlorine; 120 of the 685 examined were 

26 considered severe and of these, 33 died. Twenty-nine of the 33 died within 36 h of exposure 

27 and 4 during the following 3 days. Postmortem examination of 10 of the. 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 of the eyes, 

31 burning of the throat, and, in many, retching and vomiting; these symptoms were followed 

August 1994 6-29 DRAFf -DO NOT QUOTE OR CITE 
1 by pain behind the sternum and in the chest, weakness, and collapse. Delayed deaths we~e 

2 probably due to bronchial infection and pneumonia. 

3 Mortality has occurred from several accidental releases of chlorine from storage tanks, 

4 railroad cars, barges, pipelines, and cylinders. Simmons et al. (1974) have tabulated 

5 significant accidental chlorine releases that were recorded by the Chlorine Institute. between 

6 1926 and 1972. IIi five incidents (France, United States, Romania, Finland, and Germany) 

7 where storage tanks failed and released 15 to 30 tons of chlorine, approximately 117 deaths 

8 were reported. Bight railroad car accidents were recorded between 1934 and 1967 in the 

9 United States and Canada, involving releases of 9 to 55 tons;· several persons were gassed but 

10 only one death was reported. Four incidences occurring between 1920 and 1954 involving 

11 150-lb cylinders accounted for seven deaths. · 

12 One of the earliest accounts in which the clinical course of victims exposed to chlorine 

13 was well documented concerned an accident in Brooklyn, NY (Chasis et al., 1947). 

14 A cylinder containing approximately 100 lb of chlorine leaked through an orifice about 

15 1/8 inch in diameter for 17 min. The dense gas found its way into ventilation grates leading 

16 to the subway. No deaths occurred, but 418 persons were examined at eight hospitals, 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 of the published description. 

19 Few persons on the street at the time of the accident were affected; when the site of exposure 

20 was recorded on the medical charts, the location of 102 of 104 persons was in the subway. 

21 The immediate effects were burning of the eyes with lacrimation, burning of the 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 of consciousness was 

24 recorded for 8 of 115 persons. Most of the 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 present in 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 5 to 7 days. Cough increased in the admitted patients after about 3 days and became 

30 productive of thick 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 of abnormal changes was recognized (mottling, irregular densities, and differences 

3 in the degree of aeration of respiratory fields). However, when the patients were discharged 

4 from the hospital, the X rays were normal or returning to normal. These changes were 

5 interpreted as pneumonia 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 but progressively returned to normal in 2 to 3 days. Eleven of the patients were observ~ f~r 

8 16 mo after discharge. There was no evidence of pulmonary disease or any residual 

9 symptoms related to the chlorine exposure. 

10 Approximately 100 persons were treated for various degrees of exposure to chlorine 

11 when approximately 30 tons of liquid 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

) at the fringe of the area. Of the 75 people treated at a local hospital, 17 were 

15 hospitaHred, and an infant in a house near the wreck died. Ten of the hospitalized victims 

16 developed pulmonary edema. Most symptoms had cleared 12 days after the exposure. 

17 Weill et al. (1969) followed 12 of these subjects 3 and 7 years after the exposure and 

18 detected no appreciable effects on VC, TLC, RV, FEV 1, or DLco· This was based on 

19 observed values being within two standard deviations of the predicted value. However, it 

20 could not be determined if the standard values were corrected for age, sex, or weight factors. 

21 The authors concluded that permanent 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 off a cylinder that was being unloaded, were examined in local hosp~tals. Kowitz 

25 et al. (1967) followed 11 of 17 of the most serious cases serially for 2 years. In addition, 

26 59 _subjects, who had not been hospitalized, were examined 18 to 35 mo after the exposure. 

27 There were no fatalities. Functional residual capacity, VC, RV, FEV 1, PEFR, pulmonary 

28 compliance, blood gases, and DLco were measured. Seven of the 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 CITE 
1 VC) and DLco and increased airway resistance. At 6, 14, and 24 mo, there was some 

2 repair, but there were still residual abnormalities. In the 59 ~ubjects who were examined 

3 later, there were similar functional deficits that indicated slight, but permanent 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 no preexposure 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 of a malfunction in a water filtration plant. The incident also 

9 resulted in approximately 35 nonfatal exposures. Chlorine leaked 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 of exposure unknown. They were alert but were coughing, dyspneic, 

12 and cyanotic. Moist rales developed. The husband 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 were present in the pulmonary 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 similar to 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 of the kidneys. In the 35 survivors of this accident, transient minor 

24 reductions in DLco and moderate degrees of airway obstruction were observ~ and were 

25 reversed within a month of exposure. 

26 Chester et al. (1977) reported two siblings who had been accidentally exposed to 

27 chlorine in the same room. Both had reduced FEV 1 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 one patient. 

30 Beach et al. (1969) presented case reports of seven persons who had been accidentally 

31 exposed to chlorine gas for 3 to 10 min duration in separate accidents. Symptoms of cough, 

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 et al. (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 a public swimming pool. The level of exposure was not known, but the length of exposure 

10 was 2 to 5 min. The subjects were admitted to a hospital with symptoms of eye irritation, 

11 irritation of the upper respiratory tract, cough, tightness of the chest, and shortness of breath. 

12 All showed some degree of arterial hypoxemia. Chest X rays appeared normal. 

13 Pulmonary function tests were conducted 14 to 16 h after exposure as well as 1 mo 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 1 mo, 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 1 mo as compared to 

19 immediately after exposure. The results of these tests suggest some obstruction of the small 

20 airways, impaired gas transfer, mild pulmonary edema, and stiff lung. 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 1 day after exposure (lowered FEV 1, FEF25, 

27 and FEF50). Subjects were separated into groups based on chief complaint (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 of resolution of the obstructive abnormalities may have been associated with 

31 smoking habits, the number of subjects was too small to draw a conclusion. 

August 1994 6-33 DRAFT-DO NOT QUOTE OR CITE 
1 Charan et al. (1985) reported an industrial accident in which a large volume of chlorine 

2 gas was released, rose along the walls of a building, and settled on the roof where · 

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 of observation; they were examined physically, had 

5 chest X rays and arterial blood gas measurements, and received pulmonary function tests 

6 within 24 h. Pulmonary function tests were done at intervals up to 2 years on 11 of the 

7 ~ubjects. 

8 None of the subjects developed pulmonary edema. The ratio of FEV 1/VC was le8s than 

9 75% of the 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 of the 3 affected were 

11 heavy smokers. Residual volume was > 120% of the predicted value in 13 of 19 subjects; it 

12 progressively dropped and, by day 30, was less than 80% of the predicted value in 4 of the 

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 of chlorine, Schwartz et al. 

16 (1990) reevaluated 13 of the 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 of individuals with RV of < 80% of the predicted 

19 value increased over the 12-year period, suggesting that the chlorine-induced initial injury 

20 may have resulted in chronic stiffening of the airways. There was also a high prevalence of 

21 airflow obstruction throughout the observation period; however, the mean loss in FEV 1 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 of 23 people 

24 hospitalized, 21 of 25 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, FEV 1, 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 chlorine exposure. 

29 In the absence of valid estimates of exposure, mean annual lung function changes were 

30 evaluated based on smoking status, severity of injury, and distance from the site of chlorine 

August 1994 6-34 DRAFT-DO NOT QUOTE OR CITE 
·-

1 release. The severity of injury was based on the occurrence of wheeze, 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 tract injury were compared to exposed persons who appeared normal. 

6 Preexposure pulmonary function measurements were not taken; general populati~n values 

7 were used comparatively. Three weeks after the chlorine release, mean lung function indices 

8 did not show a consistent pattern of abnormality based on severity. of injury immediately 

9 following chlorine exposure or distance from the release, but there were some differences 

10 according to smoking category. Over the first year, lower respiratory tract symptoms 

11 (cough, wheeze, and dyspnea) declined from 90 to 64%, and even inconsistent relationships 

12 to severity of injury or distance from release were reported to disappear. Two years 

13 following exposure, the mean annual pulmonary function indices were reported to be 

14 decreased in exposed current smokers when compared to fonner smokers, never smokers, and 

15 the general population; FVC and FEV 1 were significantly (0.01 < p < 0.05) decreased. · 

16 There were no significant differences associated with severity o~ pulmonary injury or distance 

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 FEV 1 

20 and FEF25_

75); however, minimal effect was found relating distance or apparent severity of 

21 injury. The average annual change in FEV 1 over 6 years was -34 rnUyear in smokers and 

22 -18 mUyear in former and never smokers. There was no evidence of a persisting abnormal 

23 rate of decline in pulmonary function; however, evidence for a permanent loss of lung 

24 function, not reflected in rates of annual change, was not discerned from this.study. 

25 Preexposure measurements for the exposed cohort would be necessary to comparatively 

26 discern changes of this 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, or vapor, 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 of breath following 

August 1994 6-35 DRAFT-DO NOT QUOTE OR CITE 
1 exposure, and an examination revealed bilateral wheezes and a reduction in peak flow to ~0% 

2 of the predicted value. Twelve months following exposure, the subject reported experiencing 

3 breathlessness and wheeze .during exercise and at night. Pulmonary ventilatory studies 

4 showed a significant obstructive airflow defect with a major reversible component following 

5 the use of bronchodilators. Symptoms of nocturnal and exercise-induced wheeze persisted, 

6 despite regular use· of bronchodilators, over the next 5 years (Donnelly and FitzGerald, 

7 1990). 

8 Eighty-two patients were treated at a hospital after accidental exposure to chlorine gas 

9 from a leaking industrial unit (Abhyankar et al., 1989). All patients suffered from watering 

10 eyes, sneezing, cough, retrostemal burning, sputum, and dyspnea. Of 82 persons treated, 

11 62 underwent spirometry and 56 underwent flexible fiber-optic bronchoscopy on Days 

12 2 through 7 postexposure. In a follow-up study of 14 of the 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 (FEV 1/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 were not 

17 symptomatically worse, nor was it likely that they suffered additional lung damage because 

18 they had preexisting lung disease. It was estimated that the subjects were exposed to 30 ppm 

19 (87 mg/m3) chlorine. The length of the 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. The child 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. The patient'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 of reoccurring coughing and 

27 wheezing episodes. The authors 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 CITE 
1 FEV 1, FEV 1

/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 of pulmonary 

3 function measurements in normal children served as controls. There was a statistically 

4 significant (p > 0.005) decrease in VC, FVC, FEV 1, PEFR, and FEF75 in the chorine5 exposed children. The researchers reported another gas leak on the day of th~ study; 

6 however, details of that chlorine leak were not reported. 

7 Acute hypoxemic 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 subject became lethargic. Over the next 30 min, he became tachypneic and 

10 developed retractions and wheezing. The subject suddenly became comatose and cyanotic, 

11 requiring intubation and mechanical ventilation. Arterial blood gas results were pH 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 of accidental exposure to chlorine gas, 88 people, ages 21 to 60 years, 

15 were admitted to the hospital with dyspnea, .coughing, irritati_on of the throat and eyes, 

16 headaches, gi~diness, chest pain, and abdominal discomfort after being exposed to 

17 approximately 66 ppm (191.4 mg/m3

) chlorine for almost 1 h. Pulmonary function test 

18 48 h postexposure revealed respiratory incapacitation in 62 of the exposed individuals. 

19 Beginning on Day 5 postexposure, 56 of the exposed were subjected to bronchoscopy. 

20 Of the 56 individuals examined, 12 showed signs of chronic bronchitis, 28 had scattered 

21 hemorrhagic spots under the bronchial mucosa, and 7 showed signs of bronchial erosion 

22 (Shroff et al., 1988). 

23 Cytopathologic features from bronchial brushing were determined on 28 patients, 5 days 

24 postexposure (Shroff et al., 1988). According to the authors, the most signi~cant finding 

25 was that termed "irritation forms" of bronchial epithelial cells. These cells had a rounding of 

26 the cytoplasmic borders with a hint of terminal end plates bearing cilia, the nuclei had 

27 evidence of chromatolysis, dense nuclear membranes, and pseudonucleoli. In 15 smears, 

28 there were 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 the background were noted. Proliferating fibroblasts 

August 1994 6-37 DRAFT-DO NOT QUOTE OR CITE 
1 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. There were abundant PMNs, erythrocytes, and 

5 pigmented ~d nonpigmented AMs against a necrotic background. There were also fragments 

6 of proliferating fibrob~ and hyperplastic basal cells and few columnar epithelial and goblet 

7 cells. Bronchial brushings obtained from these same patients 25 days postexposure showed 

8 occasional fibrotic fragments, mononuclear cells, pigmented and nonpigmented AMs, and 

9 ciliated columnar and goblet epithelial cells. The authors hYPothesized that these patients are 

10 at risk of developing obliterative bronchiolitis at a later date as a result of the chlorine 

11 exposure (Shroff et al., 1988). 

12 Of the patients exposed, 16 were followed for 1 year following the chlorine exposure. 

13 Persistent cough was noted in four of the patients for 4 to 6 weeks following exposure. 

14 A repeat bronchoscopy indicated that the mucosal erosion, originally noted in 2 of the 

15 16 patients following chlorine exposure, showed healing. There were no residual symptoms 

16 in any of these patients 1 year after the chlorine exposure and the chest X rays and 

17 pulmonary function tests were normal (Moulick et al., 1992). 

18 Cases of accidental exposure to chlorine have been reported due to mixing of bleach and 

19 toilet bowl cleaner (Jones, 1972; Bernardini et al., 1990; Mrvos et al., 1993) or bleach and 

20 phosphoric acid cleaners (Anonymous, 1991; Mrvos et al., 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 of the self-abuse, heart size returned to normal, but pulmonary hypertension 

26 persisted (Rafferty, 1980). 

27 Chlorine will probably be perceived at all levels that are injurious, but it is generally 

28 considered that levels of chlorine that 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 of tolerable levels of chlorine for a· short 

31 period of time 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 glass jar. 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 report by Dixon and Drew (1968) suggests that there is 

5 a possibility that occasional exposure to low concentrations of chlo~e may result in 

6 development of a 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. cannister respirators were available and were 

9 used by all but one of the six men. He was exposed to the chlorine cloud for about 30 min 

10 without using the respirator and reported to the plant "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 of chemical injury to the respiratory tract of 

15 fire fighters due to acute massive inhalation of a commercial solvent. In a review of effects 

16 of irritating gases, Summer and Haponik (1981) stated that acute massive inhalation exposure 

17 to chlorine, as well ~ to phosgene, ammonia, sulfur dioxide, and oxides of nitrogen, results 

18 in similar pathophysiological 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 of the 

21 small and medium bronchi, and atelectasis are common findings during Phase ll (6 h to 

22 8 days). 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 persist throughout 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 of exposure to cause adverse effects in humans are ill-defined. 

28 Standard reference sources give variable values of exposure that cause irritation, that are 

29 dangerous to humans, or that are intolerable or lethal (Withers and Lees 1985b). It is 

30 considered that inhalation of 4 ppm (11.6 mg/m3

) chlorine causes irritation, inhalati~n of 

31 14 to 21 ppm (40.6 to 60.9 mg/m3) or 40 to 60 ppm (116 to 174 mg/m3) for a 0.1 to 

August 1994 6-39 DRAFT-DO NOT QUOTE OR CITE 
1 1.0 his dangerous, 100 ppm (290 mg/m3) is intolerable and incapacitating, and even a short 

2 exposure to 1,000 ppm (2,900 mg/m3

) is lethal. However, there are many factors th~t may 

3 determine the degree of response and whether there is complete recovery or residual effects 

4 (i.e., the respiratory health of the victim, predisposition to asthma, age, smoking habits, 

5 degree of respiratory damage, and specific care and therapy). 

6 

7 6.2.1.2 Chronic Exposure 

8 Faure et al. (1983) and Barret and Faure (1984) have recorded their experience over 

9 a span of 20 years with 186 subjects occupationally exposed to chlorine. Pulmonary edema 

10 developed in about 4% of the cases. Forty-three of 129 of the workers that underweQt 

11 spirometric measurements had abnormal tests: an obstructive pattern in 27 cases, a restrictive 

12 pattern in 13 cases, and mixed syndrome in 3 cases. In 21 of 79 ~ studied, DLco was 

13 abnormal; most of the subjects (11 of 13) with restrictive ·syndrome had abnormal DLco· 

14 The 56 subjects who had at least three acute episodes of exposure in the previous 5 years 

15 were compared to 197 controls; there were no long-term effects on FEV 1, 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 not have been 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 of the 

26 two groups being 31.2 + 11.0 years. The average number of chlorine exposure years was 

27 10.9 + 2.8 years. Time-weighted average exposures to chlorine ranged from 0.006 to 

28 1.42 ppm (0.02 to 4.12 mg/m3) with a mean of 0.15 ± 0.29 ppm (0.43 + 0.84 mg/m3). 

29 Practically all exposures were less than the American Conference .of Governmental Industrial 

30 Hygienists threshold limit value of 1 ppm (2.9 mg/m3) (only 2% were greater than 1 ppm). 

31 Exposure data were obtained from only 332 of 600 workers; hence, the useful population was 

August 1994 6-40 DRAFT-DO NOT QUOTE OR CITE 
1 332 workers. The parameters 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 of a positive 

4 correlation between exposure and increased tooth decay (p = 0. 025) and between exposure 

5 and leukocytosis (p = 0.05), no other parameters were affected. Pulmonary function tests 

6 revealed normal values in the vast majority of workers, including controls and those exposed 

7 to chlorine. 

8 A cross-sectional study of 139 workers at risk in 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. Significant exposure was defined as severe enough to 

11 have been treated with oxygen; 55 of the 139 workers had been so exposed at least once 

12 during their employment. All others were considered to be exposed to less than 1 ppm. 

13 (2.9 mg/m3

) chlorine gas; in continuous 8-h air sampling, 99% of the samples had less than 

14 1 ppm chlorine. Duration of worker exposure was not presented. Postanterior lung X-ray 

15 films were normal in 82 subjects and abnormal in 56 (data for one subject were lost). Only 

16 one of the 56 workers with abnormal findings on X ray had abnormal respiratory function. 

17 Regardless of chlorine exposure, 75% of the workers denied cough or sputum production. 

18 Differences in FEV0.

5, among other function tests, did not correlate with cough and sputum 

19 production or abnormal chest films. The study showed a decreased FEV 1 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 of workers and uncontrolled potentially 

23 confounding variables. 

24 Ferris et al. (1979) reported on the follow-up of a 1963 mortality and ~orbidity study 

25 with pulp and paper workers who were potentially exposed to chlorine, sulfur dioxide, 

26 chlorine dioxide, and/or hydrogen sulfide in Berlin, NH. This was a prospective cohort 

27 study of 200 subjects (271 in 1963), which indicated that the number.of observed 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 of U.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 of 71 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 of death. There were 

2 no differences in respiratory symptoms or prevalence of chronic nonspecific respiratory 

3 diseases in the pulp or paper mill when data were not adjusted for smoking. When data were 

4 standardized for smoking and values compared for the general population of Berlin, NH, 

5 there was not much difference in relative risk for developing chronic respiratory disease in 

6 pulp workers; however, current cigarette smokers and pipe smokers (combined) had an 

7 increased relative risk. The chronic nonspecific respiratory effects of chlorine exposure could 

8 not be separated from the results presented. There was no chlorine-related effect on 

9 pulmonary function in 27 actively employed chlorine-exposed workers. Two deficiencies of 

10 this study are the use ·of the general population as controls, which may have underestimated 

11 relative risk, and the self-selection of workers· 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 of mortality or morbidity. 

15 Enarson et al. (1984) evaluated the respiratory health of 392 workers at a pulpmill and, 

16 for the purpose of comparison, studied a cohort of 310 workers in a railroad 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 of chlorine were low, below the current permissible 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 but the 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. The number of workers 

August 1994 6-42 DRAFT-DO NOT QUOTE OR CITE 
.. ·" 

1 in the bleach area of the plant was only 15, and 4 were nonsmokers; .the small numbers in 

2 this group weaken the conclusions of the authors. 

3 Salisbury et al. (1991) evaluated changes in lung function in male pulpmill workers 

4 exposed to chlorine/chlorine dioxide between 1981 and 1988. Exposed subjects were divided 

5 into two groups; lifetime nonsmokers (13) and continuous smokers (24). The workers were 

6 individually matched for age, years of employment, and pack-years of smoking to men who 

7 did not report chlorine exposure over the same time period. A statistically significant 

8 reduction in MMEF and FEV 1/FVC ratio was noted in the chlorine/chlorine dioxide-exposed 

9 subjects over the nonexposed subjects for the 8-year period for both smokers and 

10 nonsmokers. 

11 Savad (1982) reported a 1980 outbreak of tooth enamel erosion in users of a public 

12 swimming pool that was chlorinated by gassing with chlorine. Prindle et al. (1983) reported 

13 a cross-sectional study of enamel erosion in competitive swimmers. Using a questionnaire 

14 mailed to swim club members (747 respondents), they quantified exposure by number of laps 

15 swum per day. Of the 452 frequent swimmers, 69 (15%) reported enamel erosion (or 

16 symptoms), whereas only 9 of the 295 infrequent or nonswimmers reported symptoms (3%). 

17 In addition, of the 59 members on the swim team, 23 (39%) reported signs of tooth erosion, 

18 compared to 15% of all frequent swimmers (p < 0.001). Confirmation of randomly selected 

19 cases and controls was conducted by an oral pathologist. However, the author suggested that 

20 dental erosion may have been an effect of the acidity of the water rather than chlorine per se. 

21 

22 6.2.2 Hydrogen Chloride 

23 Only limited information was found in the primary literature on the inhalation toxicity 

24 of hydrogen chloride gas or aerosol in humans, and this information has been. largely 

25 restricted to the detection of odor and irritation thresholds. It is known, however, that 

26 hydrogen chloride is a strong irritant, and because of its high water solubility the major 

27 effects of acute inhalation exposure are thought to be limited to the upper respiratory tract 

28 (National Research Council, 1976). 

29 

30 

August 1994 6-43 DRAFT-DO NOT QUOTE OR CITE 
1 6.2.2.1 Acute Exposure 

2 Threshold levels for hydrogen chloride odor perception ~ave been repo~ to be as low 

3 as 0.07 ppm (0.1 mg/m3) and as high as 306 ppm (459 mg/m3

). Under laboratory 

4 conditions, however, the threshold level is likely to be about 0.2 ppm (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 of analyzing character and intensity of odor 

7 were used for the studies, and the threshold was defined as the level perceived by all four 

8 panelists. Inhalation of irritating levels of hydrogen chloride has resulted in coughing, pain, 

9 inflammation, and edema of the nasal passages and larynx (National Research Council, 1976; 

10 World Health Organization, 1982). 

11 GEOMET Technologies, Inc. (1981) reported that sustained inhalation of high 

12 concentrations of hydrogen chloride causes edema, emphysema, and damage to pulmonary 

13 blood vessels. Male volunteers 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 on brief exposures; 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). nie World Health Organization (1982) reported that inhalation of approximately 

18 35 ppm (52 mg/m3) can induce sneezing, laryngitis, chest pain, hoarseness, and a feeling of 

19 suffocation. 

20 Ingestion of hydrochloric acid results in severe corrosion of the mouth, throat, and 

21 stomach followed by vomiting with loss of blood; kidney damage may also occur during 

22 acute intoxication. Ingestion of a corrosive dose will cause pain 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 in human epidermal cells. In one study, application of 

27 1.4 N hydrochloric acid (3%) to human skin in patch tests produced inflammatory responses 

28 but did not alter the rate of cell mitosis, and another study showed that topical application of 

29 0.001 N hydrochloric acid (0.0036%) did not produce pain 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 of mild asthma, 

2 experienced a rapid and severe bronchospasm after being exposed to a pool-cleaning product 

3 containing hydrochloric acid. The patient was treated with bronchodilators and steroids. One 

4 year later, while still on bronchodilators and steroids, he still was experiencing marked 

5 symptoms of asthma triggered by exposure to mild irritants or minimal exercise. He also 

6 experienced frequent episodes of nocturnal asthma. Airway obstruction was completely 

7 reversed by albuterol; however, a progressive decline of more than 20% in FEV 1 was 

8 observed 4 h after inhalation. No effect on DLco was noted (Boulet, 1988). 

9 Soni et al. (1985) reported the death of a 44-year-old man 5 days after intentional 

10 ingestion of 200 mL of muriatic acid (27% hydrochloric acid). On arriving at the hospital, 

11 he had 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 of the 

15 esophagus, along with total gastric and duodenal necrosis and large areas of necrosis through 

16 the small and large bowels. Extensive areas of burnt tissue on the liver surface and 

17 mesentery were found; suggesting extensive leakage of the 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 of workers to hydrogen 

22 chloride may cause an increase in dental erosion. In a cross-sectional inv~tigation, with 

23 a prospective phase, ten Bruggen Cate (1968) studied the incidence of industrial dental 

24 erosion in a total of 555 acid. workers in 48 plants over ~ period of 2 years. .The workers 

25 were exposed to a number of acids including hydrochloric acid. The selection of the 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. The incidence and 

28 severity of dental erosion in the teeth of exposed workers increased over the period of the 

29 study. Only the anterior teeth were affected; cuspids and molars, which are protected by the 

30 cheeks, were not. Grading of erosion severity was as follows: Grade 1, loss of enamel only; 

31 

August 1994 6-45 DRAFf-DO NOT QUOTE OR CITE 
1 Grade 2, loss of enamel with involvement of dentine; and Grade 3, loss of enamel and 

2 dentine with exposure of secondary dentine. 

3 Exposure measurements were qualitative and varied for many of the 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 of the labial surfaces of the 

6 incisors. However, the incidence of mild erosion increased in the control population as 

7 a function of years of service; after 15 years of service, the incidence in controls and 

8 lower-exposed group was similar (approximately 35% of workers). The results of the 

9 prospective phase of the study (several examinations of the same workers over a 2-year 

10 period) support the conclusions of the cross-sectional phase that continued exposure 

11 exacerbates the lesions. Interestingly, the exposed workers had no perceived or reported 

12 pain. Periodontal disease appeared to be more prevalent in the exposed workers, but the 

13 incidence was not statistically significant. 

14 Remijn et al. (1982) examined a cohort of approximately 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 of exposure 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 of ten 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-half of the surfaces of the incisor 

21 teeth," and that 90% of the workers had at least a Grade 1 erosion; no cases of 

22 Grade 3 erosion were diagnosed. The monitoring study leads to the conclusion that the 

23 piclders worked approximately 27% of the time with concentrations of hydrochloric acid 

24 greater than the maximum allowable concentration-ceiling (MAC-C) value of .5 ppm 

25 (7 mg/m3). The probability of zinc levels exceeding the MAC-C was 1%. Upon 

26 examination, the picklers showed the greatest incidence and severity of dental erosion. 

27 Because of the small number of workers, multivariate analysis of the data as a function of 

28 age, exposure time, and exposure level was not possible. A control cohort was not included 

29 in the study. 

August 1994 6-46 DRAFf-DO NOT QUOTE OR CITE 
I 

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31 Givan, D. C.; Eigen, H.; Tepper, R. S. (1989) Longitudinal evaluation of pulmonary function in an infant 

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52 

53 Hasan, F. M.; Gehshan, A.; Fuleihan, F. J.D. (1983) Resolution of pulmonary dysfunction following acute 

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3 

4 Higgins, E. A.; Fiorca, V.; Thomas, A. A.; Davis, H. V. (1972) Acute toxicity of brief exposures to HF, HCl, 

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6 

7 Jiang, X. Z.; Buckley, L. A.; Morgan, K. T. (1983) Pathology of toxic responses to the RDSO concentration of 

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9 

10 Jones, F. L., Jr. (1972) Chlorine poisoning from mixing household cleaners. JAMA J. Am. Med. Assoc. 

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12 

13 Jones, R. N.; Hughes, J. M.; Glindmeyer, H.; Weill, H. (1986) Lung function after acute chlorine exposure. 

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18 

19 Kaplan, H. L. (1987) Effects of irritant gases on avoidance/escape performance and respiratory response of the 

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21 

22 Kaplan, H. L.; Grand, A. F.; Rogers, W. R.; Switzer, W. G.; Hartzell, G. E. (1984) A research study of the 

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27 Kaplan, H. L.; Anzueto, A.; Switzer, W. G.; Hinderer, R. K. (1988) Effects of hydrogen chloride on respiratory 

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29 

30 Kirsch, V. H.; Drabke, P. {1982) Zur Beurteilung biologischer Wirkungen von Chlorwasserstoff [Assessing the 

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39 

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42 

43 Kowitz, T. A.; Reba, R. C.; Parker, R. T.; Spicer, W. S., Jr. (1967) Effects of chlorine gas upon respiratory 

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45 

46 Krishnan, B.; Rao, A. S. {1981) Surface activity & phospholipid content of saline extract from control 

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48 

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52 

53 Leonardos, G.; Kendall, D.; Barnard, N. {1969) Odor threshold determinations of 53 odorant chemicals. J. Air 

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4 

5 Lucia, H. L.; Barrow, C. S.; Stock, M. F.; Alarie, Y. (1977) A semi-quantitative method for assessing anatomic 

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8 

9 Machle, W.; Kitzmiller, K. V.; Scott, E. W.; Treon, J. F. (1942) The effect of the inhalation of hydrogen 

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11 

12 Malek, D. E.; Alarie, Y. (1989) Ergometer within a whole-body plethysmograph to evaluate performance of 

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14 

15 Moulick, N. D.; Banavali, S.; Abhyankar, A. D.; Borkar, S.; Aiyengar, J.; Kapadia, N. M.; Khokhani, R. C. 

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18 

19 Mrvos, R.; Dean, B. S.; Krenzelok, E. P. (1993) Home exposures to chlorine/chloramine gas: review of 

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21 

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29 

30 Oddoy, A.; Drabke, P.; Feigner, U.; Kirsch, H.; Lachmann, B.; Merker, G.; Robertson, B.; Vogel, J. (1982) 

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35 Patil, L. R. S.; Smith, R. G.; Vorwald, A. J.; Mooney, T. F., Jr. (1970) The health of diaphragm cell workers 

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37 

38 Pherwani, A. V.; Khanna, S. A.; Patel, R. B. (1989) Effect of chlorine gas leak on the pulmonary functions of 

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40 

41 Ploysongsang, Y.; Beach, B. C.; DiLisio, R. E. (1982) Pulmonary function changes after acute inhalation of 

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43 

44 Prindle, R. A.; Elzay, R. P.; Armstrong, C. W.; Funkhouser, L. S.; Miller, G. B., Jr. (1983) Erosion of dental 

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47 Rafferty, P. (1980) Voluntary chlorine inhalation: a new form of self-abuse? Br. Med. J. 281: 1178-1179. 

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49 Remijn, B.; Koster, P.; Houtbuijs, D.; Boleij, J.; Willems, H.; Brunekreef, B.; Biersteker, K.; van Loveren, C. 

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1 Rotman, H. H.; Fliegelman, M. J.; Moore, T.; Smith, R.. G.; Anglen, D. M.; Kowalski, C. J.; Weg, J. G. 

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4 

5 Rupp, H.; Henschler, D. (1967) Wirkungen geringer Chlor- und Bromkonzentrationen auf den Menschen [Effects 

6 of low chlorine and bromine concentrations on man]. Int. Arch. Gewerbepathol. Gewerbehyg. 23: 79-90. 

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8 Salisbury, D. A.; Enarson, D. A.; Chan-Yeung, M.; Kermedy, S. M. (1991) First-aid reports of acute chlorine 

9 gassing among pulpmill workers as predictors of bmg health consequences. Am. J. Ind. Med. 20: 71-81. 

10 

11 Savad, E. N. (1982) Enamel erosion ••• multiple cases with a common cause(?) J. N.J. Dent. Assoc. 

12 53: 32, 35-37, 60. 

13 

14 Schlagbauer, M.; Renschler, D. (1967) Toxicitaet von Chlor und Brom bei einmaliger und wiederholter 

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16 Gewerbepathol. Gewerbehyg. 23: 91-98. 

17 

18 Schwartz, D. A.; Smith, D. D.; J.aksbminarayan, S. (1990) The pulmonary sequelae associated with acCidental 

19 inhalation of chlorine 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 in 28 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 

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28 Silver, S. D.; McGrath, F. P.; Ferguson, R. L. (1942) Chlorine. Median lethal concentration for mice. 

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32 

33 Simmons, J. A.; Erdmann, R. C.; Naft, B. N. (1974) The risk of catastrophic spills of toxic chemicals. Los 

34 Angeles, CA: University of California School of Engineering and Applied Science; report no. 

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36 

37 Soni, N.; O'Rourke, I.; Pearson, I. (1985) Ingestion of hydrochloric 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 of hydrogen 

40 fluoride, hydrogen chloride, and hydrogen bromide 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 

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45 

46 Summer, W.; Haponik, E. (1981) Inhalation of irritant 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 of hydrogen chloride gas in B6C,F1 mice, 

51 Sprague-Dawley rats and Fischer-344 rats. Research Triangle Park, NC: Chemical Industry Institute of 

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53 

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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 of ammonia, chlorine, hydrogen cyanide, hydrogen 

11 sulphide, and sulphur dioxide gases. V. Animals. Contrib. Boyce Thompson lnst. 11: 365-385. 

12 

13 Weill, H.; George, R.; Schwarz, M.; Ziskind, M. (1969) Late evaluation of pulmonary function after acute 

14 exposure to chlorine 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) The assessment of major hazards: the lethal toxicity of chlorine; 

20 part 1, review of information on toxicity. J. Hazard. Mater. 12: 231-282. 

21 

22 Withers, R. M. J.; Lees, F. P. (1985b) The assessment of major hazards: the lethal toxicity of chlorine; 

23 part 2, model of toxicity 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 of studies have addressed the teratological and reproductive effects of 

8 ingested chlorine and the by-products of water chlorination (hypochlorous acid and 

9 hypochlorite). For the most part, chlorine and the by-products of water chlorination were not 

10 found to affect reproduction in mice (Les, 19~8; Chernoff et al., 1979; Staples et al., 1979) 

11 or rats (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/L hypochlorous acid 

15 for 2.5 mo prior to mating and throughout gestation, but the results of this experiment were 

16 limited by the small numbers of animals tested and the fmding of a higher rate of soft 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 of chlorine 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, or 5.0 ppm (0, 1.4, 4.3, or 

22 14.5 mg/m3) chlorine gas for 6 h/day, 5 days/week for 62 days. Six days after termination 

23 of exposure, 8 male and 10 female rats from each exposure group were mated with 

24 unexposed animals~ Female rats were then sacrificed on Day 19 of gestation. Analysis of 

25 the number of viable embryos, late and early reabsorptions, and corpea lutea did not show a 

26 chlorine-related effect on the reproductive potential of either male or female animals. 

27 The only other study on the teratological or reproductive effects of chlorine 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), 5 h/day, every other day for 1 to 

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 of two exposed rabbits. 

2 The rabbits were reported to have exhibited nasal irritation, sneezing, and labored breathing. 

3 Histopathological examination of the respiratory tract showed catarrhal inflammation of the· 

4 upper respiratory tract, metaplasia of the bronchi, suppurative bronchitis and pneumonia, 

5 pleuritis, emphysema, and atelectasis. There were also granulomas in the brain and other 

6 organs and necrosis of the liver. The authors believe that all of the changes noted in the 

7 exposed rabbits were the direct result of the toxic action of chlorine; however, the Worl~ 

8 Health Organization (1982) reported that lesions of the nature noted in the exposed rabbits are 

9 typical of several 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 of inhaled hydrogen chloride. In the first of these studies, Pavlova 

14 (1976) exposed two groups of 8 to 15 female Wistar rats to 302 ppm (450 mg/m3) hydrogen 

15 chloride gas for 1 h; one group was exposed 12 days prior to mating and the other group on 

16 Day 9 of gestation. In both groups, signs of severe dyspnea and cyanosis were noted, and 

17 mortality occurred in one-third of the 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 of 2 to 3 mo, functionai abnormalities in the organs of the 

23 progeny were similar to those found in the mothers. Progeny of dams exposed before 

24 pregnancy were affected more severely than were progeny of those 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 of these abnormalities in progeny of mothers exposed to hydrogen chloride prior to 

29 conception is thought to be the result of conception taking place in spite of the maternal organ 

30 damage. 

August 1994 7-2 DRAFT-DO NOT QUOTE OR CITE 
1 In the other study, female Wistar rats and mixed-strain rats were exposed to 302 ppm 

2 (450 mg/m3) hydrogen chloride for 1 h prior to mating. Exposure killed 30% of Wistar and 

3 20% of the mixed-strain rats. In rats 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 increase in relative lung 

7 weights of the 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 of either 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 of chlorine between 0.9 to 1.8 ppm (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 of pregnancies ~d the lack of a control group preclude any conclusions 

17 based on this study. 

18 

19 

20 

August 1994 7-3 DRAFf-DO NOT QUOTE OR CITE 
1 REFERENCES 

2 Abdel-Rahman, M. S.; Berardi, M. R.; Bull, R. J. (1982) Effect of chlorine 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) The fetotoxic potential of municipal 

9 drinking water in the mouse. Teratology 19: 165-169. 

10 

11 Dnlckrey, H. (1968) Chloriertes Trinkwasser, Toxmtaets-Pruefungen an Ratten ueber sieben Generationen 

12 [Chlorinated drinking water, toxicity studies in seven generations of rats]. Food Cosmet. Toxicol. 

13 6: 147-154. 

14 

15 GEOMET Technologies, Inc. (1981) Hydrogen .chloride: report 4, occupational ha7Md assessment. Cincinnati, 

16 OH: U.S. Department of Health 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 of Fischer-344 rats subchronically exposed to 0, 0.5, 1.5, or 5.0 ppm chlorine 

20 [informal report]. Upton, NY: Brookhaven National Laboratory; Interagency agreement no. 

21 222-Y01-ES-9-0043. 

22 

23 Les, E. P. (1968) Effect of acidified-chlorinated water on reproduction 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 of chemicals ~ed for drinking water 

27 disinfection for production of chromosomal damage and sperm-head abnormalities in mice. Environ. 

28 Mutagen. 7: 201-21.1. 

29 

30 Pavlova, T. E. (1976) Disturbance of development of the progeny of rats exposed to hydrogen chloride. Bull. 

31 Exp. Bioi. Med. 82: 1078-1081. 

32 

33 Skljanskaja, R. M.; Rappoport, J. L. (1935) Experimentelle Studien ueber chronische Vergiftung von Kaninchen 

34 mit geringen Chlorkonzentrationen und die Entwicklung der Nachkommenscbaft der chlorvergifteten 

35 Kaninchen [Experimental studies on chronic 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 die Einwirkung des Chlors auf den 

39 weiblichen Organismus [On the effect of chlorine on the female organism]. Arch. Hyg. Bakteriol. 

40 114: 103-114. 

41 

42 Staples, R. E.; Worthy, W. C.; Marks, T.. A. (1979) Influence of drinking water-tap versus purified-on 

43 embryo and fetal development in mice. Teratology 19: 237-243. 

44 

45 World Health Organization. (1982) Chlorine and hydrogen chloride. Geneva, Switzerland: World Health 

46 Organization. (Environmental health criteria 21). 

47 

August 1994 7-4 DRAFf-DO NOT QUOTE OR CITE 
1 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 of the 

7 direct mutagenic potential of chlorine is a difficult undertaking. For instance, a number of 

8 the chlorine reaction products, chlorinated organic and inorganic compounds formed during 

9 the treatment of drinking water and waste water, have been shown to possess mutagenic 

10 potential in various test systems (Meier et al., 1983; Dolara et al., 1981; Mickey and 

11 Holden, 1971; Cumming, 1978; Shih and Lederberg, 1976; Zoeteman et al., 1982; Stover 

12 et al., 1983; Rannug et al., 1981; Douglas et al., 1982; Lee et al., 1981). It has 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 et al., 

15 1956). However, there is no indication that chlorine per se is mutagenic in humans or other 

16 mammals (National Research Council, 1976). In fact, analysis of metaphase cells of bone . 

17 marrow and peripheral blood lymphocytes for sister chromatid exchange in rats 

18 subchronically exposed to up to 5 ppm (14.5 mg/m3) chlorine showed no significant effects. 

19 There were also no effects reported on cellular proliferation of bone marrow cells, the 

20 frequency of chromosomal 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 CITE 
1 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 of chlorine. 

5 Male Fischer 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, or 7.2 mg/m3) chlorine gas 6 h/day, 5 days/week for a period of 

7 2 years. Female Fischer 344 rats were exposed to the same chlorine gas concentrations but 

8 for 3 alternate days per week for the 2-year period. Complete histopathology was performed 

9 on all control animals and animals in the highest exposure group, and target organs were 

10 ex-ed in animals in the two lowest exposed groups. No exposure related neoplasms were 

11 found in any of the animals examined (Grosset al., 1993). Also, no increased inciden~ of 

12 malignant tumors was reported in 236 BD II rats given highly chlorinated water (containing 

13 100 mg/L free chlorine) over seven generations (Druckrey, 1968) or in rats fed a cake diet 

14 containing 1,250 or 2,500 ppm chlorine for 104 weeks (Fisher et al., 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 of male 

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 be carcinogenic in mice, rats, and humans, may be formed by the gas-phase reaction of 

22 hydrogen chloride and formaldehyde. Exposure to hydrogen chloride at 10.2 ppm 

23 (14.3 mg/m3), 6 hlday, 5 days/week for 382 exposures over 588 days did not induce any 

24 nasal tumors. The addition of hydrogen chloride gas (10 ppm [14 mg/m3]) to formaldehyde 

25 (14 ppm) did not enhance the carcinogenic response of formaldehyde. When hydrogen 

26 chloride and formaldehyde were premixed at high concentrations to m~mize the formation 

27 of bis(chloromethyl)ether and then diluted 75-fold to give chamber concentrations of 10 ppm 

28 hydrogen chloride and 14 ppm formaldehyde, there was no clear increase in the carcinogenic 

29 response. The authors concluded that under the conditions of the study, hydrogen chloride 

30 was not carcinogenic, and that formaldehyde accounted for most if not all of the carcinogenic 

31 activity of the mixture. 

August 1994 8-2 DRAFT-DO NOT QUOTE OR CITE 
1 In siriillar studies, Sellakumar et al. (1985) concluded that hydrogen chloride did not 

2 appreciably influence the nasal carcinogenicity of formaldehyde. 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 in the nasal epithelium, nor were there any preneoplastic or neoplastic 

7 lesions. Lesions found in the nasal mucosa of rats exposed to hydrogen chloride included 

8 rhinitis (81 of 99 exposed compared to 72 of 99 controls), epithelial or squamous hyperplasia 

9 (62 of 99 exposed compared to 51 of 99 controls), and· squamous metaplasia (9 of 99 exposed 

10 compared to 5 of 99 controls). There was also hyperplasia of the larynx (22 of 99 exposed 

11 compared to 2 of 99 controls) and trachea (26 of 99 exposed compared to 2 of 99 controls). 

12 

13 8.2.2 Epidemiological Studies 

14 It must be kept in mind that, when chlorine is used as a disinfectant in drinking water, 

15 it has the potential to form chloroform from the reaction of organic compounds that persist 

16 through the purification process. Chloroform has been shown to be a carcinogenic substance 

17 and reported as such by the U.S. Environmental Protection Agency (EPA) (1985). The 

18 overall weight of evidence 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 but inadequate 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 or hydrogen chloride. 

24 A cohort mortality study (Reeve et al., 1983) was performed on some 1~666 white male 

25 employees of a Texas-based chemical company. These employees constituted a 5% 

26 systematic sample of an alphabetized list of the production and nonproduction work force 

27 from 1940 to 1977. The chief cause of death of interest to the researchers was malignant 

28 neoplasms of the brain, because previous studies seem to indicate that employees of the 

29 petroleum refining and chemical industry are subject to a higher risk of brain cancer. Other 

30 causes of death were not considered. A further restriction imposed by the researchers 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 of a four-county area surrounding the Texas plant). 

2 This led the researchers to generate three sets of expected rates from which to calculate 

3 expected deaths. The first (method A) involved the assumptions that none of the cohort 

4 members had moved from the four-county area and that each was at risk of death from a 

5 brain tumor from the time of first exposure through the end of the exposure period or his 

6 death, whichever came first (person-years). Two other estimates considered that the subjects 

7 had migrated outside of the four-county area. In the first of these estimates (method B), . . 

8 person-years were assumed to cease accumulating on the last day of employment. In the 

9 second case (method C), expected deaths, calculated in four distinct lengths of employment 

10 categories, were obtained by multiplying the expected deaths, determined by method A, by 

11 the fraction of the number of those persons with malignant neoplasms residing only in the 

12 four-county study area to the total number of malignant 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 of the 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 risk of brain tumors with increasing employment for 

22 the segment of the cohort that began work prior to 1945. No statistical analyses were done 

23 because of the authors' uncertainty regarding the handling of a 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 20 years 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 of employment prior to 1945, the authors concluded that those 

29 hired before 1945 were probably subject to an incr~ed risk of brain 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 CITE 
1 Apparently, the authors' main purpose was to demonstrate the efficacy of a variation in 

2 a rather well-established methodological design, and made no .effort to identify any likely 

3 occupational exposure as the cause of the slight suggested excesses of brain cancer. The 

4 authors' only reference to any possible exposure is a general statement that populations 

5 employed in .the petroleum refining and chemical industries may be at increased risk of 

6 developing brain tumors, without identifying any possible etiologic agents. 

7 The authors could have avoided the whole problem of small numbers in the study 

8 results if they had been more judicious in their selection of methodologies. Reducing the size 

9 of a cohort to manageable proportions is laudable; however, rather well-established methods 

10 of reducing the cohort size have been developed by the National Institute for Occupational 

11 Safety and Health (NIOSH). Taking a systematic random sample of all employees who ever 

12 worked at the plant implies that the researcher intends to make inferences about the 

13 population as a whole concerning certain health conditions that might exist in the plant. But, 

14 if the purpose is to identify certain agents or plant departments, it might be better to look for 

15 commonalities in the individual cases and then define a cohort consisting of only those who 

16 have greatest potential for exposure to those commonalities. The approach utilized by these 

17 authors is inappropriate to identify single agents responsible for an excess in the risk of a 

18 disease. As a result, this paper falls short in its ability to identify any department or agent 

19 responsible for the suggested excess of brain lesions. 

20 A second study (Bond et al., 1983) was undertaken as a sequel to the study that 

21 identified an excess number of brain tumors in the chemical plant in.Texas (Reeve et al., 

22 1983). Bond and associates examined the brain tumors identified in the study by Reeve and 

23 co-workers, refined the case definition, conducted a more vigorous case ascertainment, and 

24 increased the total number of net cases of "primary intercranial neoplasms" fr~m 25 to 28. 

25 They then conducted a case-control study of brain tumors utilizing two matched comp~son 

26 groups; the purpose of which was to identify a likely etiologic agent, but nothing specific. 

27 Control group A (four controls per each case) was selected from all white male noncancer 

28 deaths known to the company. They were matched on the ba8is of age at death and year of 

29 death. The second control group (group B) was selected from white male members of the 

30 5% sample for all eligible cohort employees that formed the basis of the original cohort · 

August 1994 8-5 DRAFT-DO NOT QUOTE OR CITE 
1 mortality study (Reeve et al., 1983). Cases were matched with controls on the basis of age 

2 and duration of employment at the plant. 

3 The authors found that the agents to which both cases and controls had the greatest 

4 potential for exposure were chlorine, hydrogen chloride, and sulfur dioxide. Although the 

5 risk of brain tumors from exposure to all three of these 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 of an elevated risk appeared. One 

8 explanation for the nonsignificant elevated risk seen in control group A is the lack of test 

9 sensitivity because it was based upon small numbers. If all cases of brain cancer had been 

10 enumerated from the plant sample, company records, deaths recorded in the four-county area 

11 surrounding the plant, and unsolicited reports to the NIOSH, it may have been possible to 

12 increase the power of the study enough to detect a risk. On the other hand, as was pointed 

13 out by the authors, duration of employment 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 of employment in control group A (employees from the 5% 

16 sample), they found that the mean length of employment was an average·of 41 man-months 

17 · longer than that of the cases. They attribute this to a bias introduced from inclusion of 

18 greater numbers of skilled laborers in control group A, who just happened 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 In addition to controlling for length of employment, a minimum latent period also 

23 should have been specified in the evaluation of brain cancer deaths. Of note is the large 

24 number of cases (17) listed whose minimum lapse of time since initial emploY.ment was over 

25 20 years. Exposure variable comparisons of cases with matched controls should have been 

26 done for those with 20 or more years of latency. In fact, 24 of the 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 of those· who worked there. As a possibly b~tter 

30 approach to keep the cohort size manageable, a minimum length of employment 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 of the deficiencies outlined above, and, also fails to evaluate ·mortality 

3 for other site-specific cancers from exposure to chlorine or hydrogen chloride. 

4 In a later case-control study, Bond et al. (1985b) identified 26 cases of renal cancer in 

5 former employees of the same Texas petrochemical plant previou~ly studied by Bond et al. 

6 (1983) and Reeve et al. (1983). Only five of the renal cancer deaths occurring in this group 

7 were found as part of the 5% sample discussed in the earlier studies. The re~g 21 cases 

8 were found as the result of an intensive effort on the part of the company by matching· the 

9 mortality files of the Texas Bureau of Vital Statistics and the M. D. Anderson Hospital and 

10 Tumor Institute in 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 of the earlier study of brain cancer with 

13 certain differences as follow. In control group A, referents were selected from all white male 

14 decedents who were part of the same random sample that was chosen earlier minus those who 

15 died from cancer. Four controls were matched on the basis of date of birth and duration of 

16 employment. A total of 92 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 the basis of date of birth, date of 

19 hire, and date of termination. A total of 98 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 employment in 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 1 year or longer in the chlorine work area, the risk of renal 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 of six separate chlorine production and chlorine cell maintenance areas. 

29 The elevated risks were for employment in the cell maintenance area of chlorine production 

30 (i.e, caustic solution and asbestos, but not chlorine). The authors indicated that this is an 

31 entry-level job that does not involve actual exposure to chlorine. It involves the preparation 

August 1994 8-7 DRAFT-DO NOT QUOTE OR CITE 
1 of an asbestos slurry in a caustic or water 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, it would be impossible to determine which of the agents above 

5 was the one that caused the excess in renal cancer. 

6 This study has several problems, one of which is the likelihood that not all cases of 

7 renal cancer in this plant population are enumerated in the 24 cases studied by the author due 

8 to the unusual manner in which renal cancer cases were identified. More of them may 

9 remain unidentified simply because unconventional methods for determining vital status were 

· 10 followed. Furthermore, a simple cohort mortality study might have been the more 

11 appropriate choice of a methodology to be utilized, rather than the case-control method. That 

12 this is probably the better procedure has been recognized by Bond and co-researchers. 

13 In summary, it appears that the excess of renal cancer in the employees who worked in 

14 the cell maintenance area of chlorine production of this company cannot be attributed to 

15 exposure to chlorine because of the likelihood of multiple chemical exposures occurring in · 

16 workers in that area. As a result, this study does not provide convincing evidence of a causal 

17 relationship between exposure to chlorine and an excess risk of renal cancer. 

18 Another cohort mortality study (Bond et al., 1985a) was completed on the 5% 

19 systematic random sample of all present and past white male employees of the petrochemical 

20 plant in Texas that was suspected of being associated with a high risk of brain cancer. The 

21 initial purpose of the sample was to provide an estimate of the extent of brain cancer to be 

22 found in this plant, but later this sample also was used for determining directions for 

23 additional research on cause-specific mortality. Ultimately, this baseline data source provided 

24 the material from which several case control studies (Reeve et al., 1983; Bon~ et al., 1983; 

25 Bond et al., 1985b) were derived. 

26 Cause-specific mortality was analyzed by duration of employment and date of hire. 

" 

27 These data provided the basis for developing a surrogate for exposure. Significant excess 

28 risks of mortality were found due to total cancer (71 observed, 55.5 expected), ill-defined 

29 conditions (8 observed, 3.3 expected), and all external causes of death (57 observed, 

30 40.7 expected). In addition, excess cancer mortality was primarily due to significant excess 

31 cancer risks of kidney 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 of pancreatic 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 cancer remained statistically significant (26 observed, 14.8 expected). 

4 With the added requirement that a minimum of 15 years service must be achieved, cancer of 

5 the kidney and lung cancer remained statistically significant as follows: 2 persons died with 

6 kidney cancer but only 0.3 were expected, and 6 former employees with lung cancer died, 

7 whereas only 2.3 were expected. 

8 The authors mentioned that many chemical agents were present in this plant during 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 some 40,000 persons.had been employed in this plant from 1940 to 

12 1977. 

13 A major problem with this study is the fact that it is a random sample of the 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% of the sample consisted of employees with a duration of employment 

17 less than 1 year. The authors concluded that it was beyond the sco~ of the study to look for 

18 cause-specific agents responsible for the excesses that were seen. They do speculate, 

19 however, that certain confounders (i.e, smoking and/or region of residence) may have had an 

20 influence. "Region of residence" comprises regional differences in health care delivery, 

21 death certification practices, lifestyle factors, or other environmental exposures. 

22 In conclusion, there ap~s to be a suggestion of an association of certain cause23 specific mortality with employment at this plant, but that it is not possible to determine from 

24 this study whether it is due to confounders or to some agent in the workplace= This study is 

25 inadequate to conclude that either chlorine or hydrogen chloride is responsible. 

26 Bond et al. (1991) reported on a case-control study of trachea, bronchus, and lung 

27 cancer occurring from 1940 through 1980 in a cohort of 19,608 male employees exposed to a 

28 variety of chemicals at the Dow Chemical Company's Freeport, TX, facility. The case group 

29 consisted of 308 cancer decedents. Two control groups of 308 males each, individually 

August 1994 8-9 DRAFT-DO NOT QUOTE OR CITE 
1 matched to cases by race, year of birth (within 5 years), and year of hire, were chosen; one 

2 was a decedent series and the other living. Of the cohort, 41.9% of the subjects in the case 

3 groups and 41.6% of the controls were judged to have been exposed to hydrogen chloride. · 

4 Smoking histories were obtained for 70.8% of the exposed and 75.5% of the controls. 

5 A pack-years index was calculated for each subject to.permit control for potential 

6 confounding by the smoking. Latency was evaluated by excluding all exposures within 

7 15 years of death. 

8 Exposure to hydrogen chloride occurred in areas where hydrogen chloride was a 

9 by-product of an electrochemical reaction or in areas where hydrogen chloride was used as a 

10 raw material in a reaction. Based on available monitoring· data and the amount of time 

11 required to be spent in the respective job, 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, or clerical 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 the highest exposure group. 

17 The duration of hydrogen chloride exposure was calculated by adding the time spent on 

18 the jobs with TWAs above zero. A cumulative exposure score was derived for each subject 

19 by multiplying the time spent on each job by the midpoint of the TWA range for that job 

20 (0, 0.25, 1.5, and 3.75) and summing across all jobs. Based on an examination of the 

21 distribution of all subjects, four categories of cumulative 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 of too 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 of lung 

26 cancer was associated with exposure to hydrogen chloride under the conditions of this study. 

27 There was no relationship between lung cancer and the duration of exposure, nor was there a 

28 relationship between the highest average hydrogen chloride exposure and lung cancer. 

29 Allowing for the 15-year latency period betw~n exposure to hydrogen chloride and death 

30 slightly lowered the risk estimate (Bond et al., 1991). 

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J 

1 Because there are no adequate epidemiological studies or animal carcinogenicity studies 

2 for chlorine and hydrogen chloride in the present 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 and hydrogen chloride induction of nasal cancer in the rat. JNCI J. 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 of brain 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 of chemical 

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 of renal cancer mortality at a Texas chemical 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 and hydrogen chloride exposure: 

16 results from a nested case-amtrol study of chemical workers. J. Occup. Mecl. 33: 958-961. 

17 

18 Cumming, R. B. (1978) The potential for increased mutagenic risk to the human population due to the products 

19 of water chlorination. In: Jolley, R. L., ed. Water chlorination: environmental impact and health effects, 

20 volume 1, proceedings of the conference; October 1975; Oak Ridge, TN. Ann Arbor, MI: Ann Arbor 

21 Science Publishers, Inc.; pp. 229-241. 

22 

23 Dolara, P.; Ricci, V.; Burrini, D.; Griftini, 0. (1981) Effect of ozonation and chlorination on the mutagenic 

24 potential of drinking 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 of chlorination-stage pulp 

27 and paper mill effluents in a battery of mammalian 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 of rats]. Food Cosmet. Toxicol. 

31 6: 147-154. 

32 

33 Ehrenberg, L.; Gustafsson, A.; Lundqvist, U. (1956) Chemically induced mutation and sterility in barley. Acta 

34 Chem. Scand. 10: 492-494. 

35 

36 Fisher, N.; Hutchinson, J. B.; Berry, R.; Hardy, J.; Ginocchio, A. V. (1983) Long-term toxicity and 

37 carcinogenicity studies of cake JD&4e from chlorinated flour: 1. studies in rats. 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 of chlorine in B6C3Fl mice and F344 rats [abstract]. Toxicologist 13: 150. 

42 

43 Kutzman, R. S. (1983) A study of Fischer-344 rats subchronically exposed to 0, 0.5, 1.5, or 5.0 ppm chlorine 

44 [informal report]. Upton, NY: Brookhaven National Laboratory; Interagency agreement no. 

45 222-Y01-ES-9-0043. 

46 

47 Lee, E. G-H.; Mueller, J. C.; Walden, C. C.; Stich, H. (1981) Mutagenic properties of pulp mill effluents. Pulp 

48 Pap. Can:· 82: T149-T154. 

49 

50 Meier, J. R.; Lingg, R. D.; Bull, R. J. (1983) Formation of mutagens following chlorination of humic 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 CITE 
1 Mickey, G. H.; Holden, H., Jr. (1971) Chromosomal effects of chlorine on mammalian cells 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 of Environmental Pollutants; EPA report no. EP A/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 of effiuents from 

9 chlorine bleaching of pulp. J. Toxicol. Environ. Health 7: 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 of brain tumors among chemical plant employees 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 of formaldehyde and 

16 hydrogen chloride in rats. Toxi9(>1. Appl. Pharmacol. 81: 401-406. 

17 

18 Shih, K. L.; Lederberg, J. (1976) Effects of chloramine on Bacillus 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. Water chlorination: environmental impact 

24 and health effects, volume 4, book 2, environment, health, and risk, proceedings of the 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 of Health 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 of drinking 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 CITE 
1 

2 

9. REGULATIONS AND STANDARDS 

3 

4 9.1 CHLORINE 

5 The National Institute for OcCupational Safety and Health (1976) recommended a 

6 15-min ceiling concentration of 0.5 ppm (1.5 mg/m3) for chlorine in workplace air. The 

7 Occupational Safety and Health Administration (OSHA) established a ceiling permissible 

8 exposure limit of 1 ppm (3 mg/m3) for the gas. The American Conference of Governmental 

9 Industrial Hygienists (ACGIH) recommended a tentative 8-h time-weighted average \fW A) 

10 threshold limit value (TLV) of 0.5 ppm (1.5 mg/m3) and a 15-min short-term exposure TLV 

11 of 1 ppm (3 mg/m3) for chlorine (American Conference of Governmental Industrial 

12 Hygienists, 1987). These recommendations were based on chronic effects noted in the lung 

13 and digestive system (American Conference of Governmental Industrial Hygienists, 1986). 

14 The TWA 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 1 ppm (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 set public emergency limits (PELs) of 3 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 of mucous membranes (National Research Council, 1973). 

22 

23 

24 9.2 HYDROGEN CHLORIDE 

25 The OSHA established a ceiling permissible exposure limit for hydrogen chloride of 

26 5 ppm (7 mg/m3). The ACGIH also recommended a TL V of 5 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 of Governmental Industrial Hygienists, 1987). 

29 The NRC Subcommittee on Hydrogen Chloride recommended STPLs of 4 ppm (6 mg/m3) 

30 for 10 min and 2 ppm (3 mg/m3

) for 30 or 60 min. Similarly, PELs of 7 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 of 7E-3 mg/m3• The RfC is an estimate (with 

5 uncertainty spanning perhaps an order of magnitude) of continuous exposure concentration to 

6 the human population (including sensitive subgroups) that is likely to be without appreciable 

7 risk of deleterious noncancer effects over a lifetime exposure (U.S. Environmental Protection 

8 Agency, 1993). See Chapter 6 for a discussion of the effects of chronic hydrogen chloride 

9 exposure on experimental animals. 

10 

11 

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30 

REFERENCES 

American Conference of Governmental Industrial Hygienists. (1986) Documentation of the threshold limit values 

and biological exposure indices. Sth ed. Cincinnati, OH: American Conference of Governmental 

Industrial Hygienists, Inc.; pp. 117, 313. 

American Conference of Governmental Industrial Hygienists. (1987) TLVs: threshold limit values and biological 

exposure indices for 1987-1988. Cincinnati, OH: American.Conference of Governmental Industrial 

Hygienists; pp. 23, 40. 

GEOMET Technologies, Inc. (1981) Hydrogen chloride: report 4, occupational hazard assessment. Cincinnati, 

OH: U.S. Department of Health and Human Services, National Institute for Occupational Safety and 

Health; NIOSH contract no. 210-79-0001. Available from: NTIS, Springfield, VA; PB83-10S296. 

International Labour Office. (1980) Occupational exposure limits 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 of reference dose for inhalation; acute 

toxicity; and ambient water quality criteria for aquatic organisms for hydrogen chloride as of March 11]. 

Cincinnati, OH: U.S. Environmental Protection Agency, Office of Health and Environmental 

Assessment, Environmental Criteria and assessment Office. Available from: TOXNET, National Library 

of Medicine, Rockville, MD. 

National Institute for Occupational Safety and Health. (1976) Criteria for a recommended standard ... occupational 

exposure to chlorine. Cincinnati, OH: U.S. Department of Health, Education, and Welfare, NIOSH 

publication no. 76-170. Available from: NTIS, ~pringfield, VA; PB~266367/2. 

National Research Gouncil. (1973) Guides for short-term exposures of the public to air pollutants. VID. Guide 

for chlorine. Washington, DC: U.S. Environmental Protection Agency; report no. NAS/ACTIP-628.9. 

Available from: NTIS, Springfield, VA; PB-244339. 

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