Appendix

HAP Profiles
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OVERVIEW

This Appendix includes fact sheets (or profiles) for each of the 33 urban hazardous air

pollutants (HAP). As discussed in Chapter 3 of this Report, these were identified in the Strategy

as posing the greatest threat to public health in the largest number of urban areas. The fact sheets

for these HAP are arranged in alphabetical order, and each one provides the following

information:

C A brief hazard summary;

C Various physical properties (e.g., chemical formula, molecular weight, vapor pressure);

C Uses (e.g., in manufacturing processes, products, etc.);

C Sources and potential for exposure;

C How personal exposure can be assessed;

C Information on health hazards, including

C acute effects,

C chronic effects (noncancer), 

C reproductive/developmental effects, 

C cancer risks, and

C a summary of human health reference values and regulatory and advisory

numbers; and

C References.

The main sources of information for the fact sheets include EPA’s Integrated Risk

Information System (IRIS), Toxicological Profiles from the Agency for Toxic Substances and

Disease Registry (ATSDR), EPA’s Health Effects Assessment documents and International

Agency for Research on Cancer (IARC) monographs, as available. The actual sources for each

fact sheet are listed on the sheet. The summary of human health reference values and regulatory

and advisory numbers includes values developed by EPA and by ATSDR, the California EPA

(CalEPA), the American Conference of Governmental and Industrial Hygienists (ACGIH), the

American Industrial Hygiene Association (AIHA), the National Institute of Occupational Safety

and Health (NIOSH), and the Occupational Safety and Health Administration (OSHA).

Each fact sheet includes definitions of the acronyms used within the fact sheet, with the

exception of the abbreviations for units of measurement (and Hg) listed below.

EC: degrees Centigrade m

3

: meters cubed

EF: degrees Farenheit mL: milliliter

d: day mm: millimeter

dL: deciliter mg: milligram

g: gram ng: nanogram

h: hour ppb: parts per billion

Hg: mercury ppm: parts per million

kg: kilogram μg: microgram
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ACETALDEHYDE

75-07-0

Hazard Summary

Acetaldehyde is mainly used as an intermediate in the synthesis of other chemicals. It is

ubiquitous in the environment and may be formed in the body from the breakdown of

ethanol. Acute (short-term) exposure to acetaldehyde results in effects including irritation

of the eyes, skin, and respiratory tract. Symptoms of chronic (long-term) intoxication of

acetaldehyde resemble those of alcoholism. The U.S. Environmental Protection Agency

(EPA) considers acetaldehyde a probable human carcinogen (Group B2) based on

inadequate human cancer studies and animal studies that have shown nasal tumors in rats

and laryngeal tumors in hamsters.

Please Note: The main sources of information for this fact sheet are EPA's Health Assessment Document for

Acetaldehyde and the Integrated Risk Information System (IRIS), which contains information on inhalation chronic

toxicity of acetaldehyde and the reference concentration (RfC). Other secondary sources include the International

Agency for Research on Cancer (IARC) Monographs on Chemicals Carcinogenic to Humans.

Physical Properties

! The chemical formula for acetaldehyde is CH3CHO, and it has a molecular weight of

44.06 g/mol. (1)

! Acetaldehyde is a colorless mobile liquid that is flammable and miscible with water. (1,6)

! Acetaldehyde has a pungent suffocating odor, but at dilute concentrations, it has a fruity

and pleasant odor. The odor threshold of acetaldehyde is 0.05 ppm (0.09 mg/m3). (1,7)

! The vapor pressure for acetaldehyde is 740 mm Hg at 20 EC, and it has a log

octanol/water partition coefficient (log Kow) of 0.43. (1)

Uses

! The predominant use of acetaldehyde is as an intermediate in the synthesis of other

chemicals. (1)

! Acetaldehyde is used in the production of perfumes, polyester resins, and basic dyes.

Acetaldehyde is also used as a fruit and fish preservative, as a flavoring agent, and as a

denaturant for alcohol, in fuel compositions, for hardening gelatin, and as a solvent in the

rubber, tanning, and paper industries. (1,2)

Sources and Potential Exposure

! Acetaldehyde is ubiquitous in the ambient environment. It is an intermediate product of

higher plant respiration and is formed as a product of incomplete wood combustion in

fireplaces and wood stoves, coffee roasting, burning of tobacco, vehicle exhaust fumes,
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and coal refining and waste processing. Hence, many individuals are exposed to

acetaldehyde by breathing ambient air. It should be noted that residential fireplaces and

wood stoves are the two highest sources of emissions, followed by various industrial

emissions. (1)

! In Los Angeles, California, levels of acetaldehyde up to 32 ppb have been measured in

the ambient environment. (1)

! Exposure may also occur in individuals occupationally exposed to acetaldehyde during its

manufacture and use. (1,2)

! In addition, acetaldehyde is formed in the body from the breakdown of ethanol; this

would be a source of acetaldehyde among those who consume alcoholic beverages. (1)

Assessing Personal Exposure

! No information was located regarding the measurement of personal exposure to

acetaldehyde.

Health Hazard Information

Acute Effects:

! The primary acute effect of inhalation exposure to acetaldehyde is irritation of the eyes,

skin, and respiratory tract in humans. At higher exposure levels, erythema, coughing,

pulmonary edema, and necrosis may also occur and, at extremely high concentrations,

respiratory paralysis and death may occur. (1)

! Acute inhalation of acetaldehyde resulted in a depressed respiratory rate and elevated

blood pressure in experimental animals. (1)

! Tests involving acute exposure of animals, such as the LC50 and LD50 tests in rats, rabbits,

and hamsters, have demonstrated acetaldehyde to have low acute toxicity from inhalation

and moderate acute toxicity from oral or dermal exposure. (3)

Chronic Effects (Noncancer):

! In hamsters, chronic inhalation exposure to acetaldehyde has produced changes in the

nasal mucosa and trachea, growth retardation, slight anemia, and increased kidney weight.

(1,4)

! Symptoms of chronic intoxication of acetaldehyde in humans resemble those of

alcoholism. (5)

! The RfC for acetaldehyde is 0.009 mg/m3 based on degeneration of olfactory epithelium

in rats. The RfC is an estimate (with uncertainty spanning perhaps an order of magnitude)

of a continuous inhalation exposure to the human population (including sensitive

subgroups), that is likely to be without appreciable risk of deleterious noncancer effects

during a lifetime. It is not a direct estimator of risk, but rather a reference point to gauge

the potential effects. At exposures increasingly greater than the RfC, the potential for
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adverse health effects increases. Lifetime exposure above the RfC does not imply that an

adverse health effect would necessarily occur. (4)

! EPA has medium confidence in the principal studies because appropriate histopathology

was performed on an adequate number of animals and a no-observed-adverse-effect level

(NOAEL) and a lowest-observed-adverse-effect level (LOAEL) were identified, but the

exposure duration was short and only one species was tested; low confidence in the

database due to the lack of chronic data establishing NOAELs and due to the lack of

reproductive and developmental toxicity data; and, consequently, low confidence in the

RfC. (4)

! EPA has not established a reference dose (RfD) for acetaldehyde. (4)

Reproductive/Developmental Effects:

! No information is available on the reproductive or developmental effects of acetaldehyde

in humans.

! Acetaldehyde has been shown, in animals, to cross the placenta to the fetus. (1,4)

! Data from animal studies suggest that acetaldehyde may be a potential developmental

toxin. In one study, a high incidence of embryonic resorptions was observed in mice

injected with acetaldehyde. In rats exposed to acetaldehyde by injection, skeletal

malformations, reduced birth weight, and increased postnatal mortality have been

reported. (1,6)

Cancer Risk:

! Human data regarding the carcinogenic effects of acetaldehyde are inadequate. Only one

epidemiology study is available that has several limitations including short duration,

small number of subjects, and concurrent exposure to other chemicals and cigarettes.

(1,4,6)

! Increased incidences of nasal tumors in rats and laryngeal tumors in hamsters have been

observed following inhalation exposure to acetaldehyde. (1,4,6)

! EPA has classified acetaldehyde as a Group B2, probable human carcinogen. (1,4)

! EPA uses mathematical models, based on human and animal studies, to estimate the

probability of a person developing cancer from breathing air containing a specified

concentration of a chemical. EPA calculated an inhalation unit risk of 2.2 x 10-6 (μg/m3)

-1

.

EPA estimates that, if an individual were to continuously breathe air containing

acetaldehyde at an average of 0.5 μg/m3 (5 x 10-4 mg/m3) over his or her entire lifetime,

that person would theoretically have no more than a one-in-a-million increased chance of

developing cancer as a direct result of breathing air containing this chemical. Similarly,

EPA estimates that breathing air containing 5.0 μg/m3 (5 x 10-3 mg/m3) would result in

not greater than a one-in-a-hundred thousand increased chance of developing cancer, and

air containing 50.0 μg/m3 (5 x 10-2 mg/m3) would result in not greater than a one-in-ten

thousand increased chance of developing cancer. For a detailed discussion of confidence

in the potency estimates, please see IRIS. (4)
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0.0001

0.001

0.01

0.1

1

10

100

1000

10000

100000

LC50 (hamsters) (17,000 mg/m3)

Acetaldehyde

Health numbers

a

Ref.

3 Ref.

3

Ref.

4

Ref.

4

Ref.

4

Ref.

9

Ref.

4

OSHA PEL (360 mg/m3)

LC50 (rat s) (37,000 mg/m3)

LOAELc (respirat ory) (728 mg/m3)

NOAELc (respirat ory)

(273 mg/m3)

RfC (0.009 mg/m3)

ACGIH ceiling

(45 mg/m3)

Ref.

8

Cancer Risk

Level 1 in a

million risk

(5x10-4 mg/m3)

Ref.

10

Ref.

11

Ref.

11

AIHA ERPG-1

(18 mg/m3)

AIHA ERPG-2 (360 mg/m3)

NIOSH IDLH (3600 mg/m3)

Regulatory, advisory

numbers

b

Conversion Factors:

To convert from ppm to mg/m3: mg/m3 = (ppm) x (molecular weight of the compound)/(24.45).

For acetaldehyde: 1 ppm = 1.8 mg/m3.

To convert from μg/m3 to mg/m3: mg/m3 = (μg/m3) x (1 mg/1,000 μg).

Health Data from Inhalation Exposure

AIHA ERPG –American Industrial Hygiene Association's emergency response planning

guidelines. ERPG 1 is the maximum airborne concentration below which it is believed nearly all

individuals could be exposed up to one hour without experiencing other than mild transient

adverse health effects or perceiving a clearly defined objectionable odor; ERPG 2 is the

maximum airborne concentration below which it is believed nearly all individuals could be
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exposed up to one hour without experiencing or developing irreversible or other serious health

effects that could impair their abilities to take protective action.

ACGIH TLV ceiling – American Conference of Governmental and Industrial Hygienists’

threshold limit value ceiling; the concentration of a substance that should not be exceeded during

any part of the working exposure.

LC50 (Lethal Concentration50) – A calculated concentration of a chemical in air to which

exposure for a specific length of time is expected to cause death in 50% of a defined

experimental animal population.

NIOSH IDLH – National Institute of Occupational Safety and Health's immediately dangerous

to life or health limit; NIOSH recommended exposure limit to ensure that a worker can escape

from an exposure condition that is likely to cause death or immediate or delayed permanent

adverse health effects or prevent escape from the environment.

OSHA PEL – Occupational Safety and Health Administration's permissible exposure limit

expressed as a time-weighted average; the concentration of a substance to which most workers

can be exposed without adverse effect averaged over a normal 8-h workday or a 40-h workweek.

a

 Health Numbers are toxicological numbers from animal testing or risk assessment values

developed by EPA.

b

 Regulatory numbers are values that have been incorporated in Government regulations, while

advisory numbers are nonregulatory values provided by the Government or other groups as

advice.

c

 The LOAEL and NOAEL are from the critical study used as the basis for the EPA RfC.

References

1. U.S. Environmental Protection Agency (EPA). Health Assessment Document for

Acetaldehyde. EPA/600/8-86-015A. Environmental Criteria and Assessment Office,

Office of Health and Environmental Assessment, Office of Research and Development,

Research Triangle Park, NC. 1987.

2. M. Sittig. Handbook of Toxic and Hazardous Chemicals and Carcinogens. 2nd ed. Noyes

Publications, Park Ridge, NJ. 1985.

3. U.S. Department of Health and Human Services. Registry of Toxic Effects of Chemical

Substances (RTECS, online database). National Toxicology Information Program,

National Library of Medicine, Bethesda, MD. 1993.

4. U.S. Environmental Protection Agency (EPA). Integrated Risk Information System (IRIS)

on Acetaldehyde. National Center for Environmental Assessment, Office of Research and

Development, Washington, D.C. 1999.

5. The Merck Index. An Encyclopedia of Chemicals, Drugs, and Biologicals. 11th ed. Ed. S.

Budavari. Merck and Co. Inc., Rahway, NJ. 1989.
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6. International Agency for Research on Cancer (IARC). IARC Monographs on the

Evaluation of the Carcinogenic Risk of Chemicals to Humans: Allyl Compounds,

Aldehydes, Epoxides and Peroxides. Volume 36. World Health Organization, Lyon. 1985.

7. J.E. Amoore and E. Hautala. Odor as an aid to chemical safety: Odor thresholds

compared with threshold limit values and volatilities for 214 industrial chemicals in air

and water dilution. Journal of Applied Toxicology, 3(6):272-290. 1983.

8. American Conference of Governmental Industrial Hygienists (ACGIH). 1999 TLVs and

BEIs. Threshold Limit Values for Chemical Substances and Physical Agents, Biological

Exposure Indices. Cincinnati, OH. 1999.

9. Occupational Safety and Health Administration (OSHA). Occupational Safety and Health

Standards, Toxic and Hazardous Substances. Code of Federal Regulations. 29 CFR

1910.1000. 1998.

10. National Institute for Occupational Safety and Health (NIOSH). Pocket Guide to

Chemical Hazards. U.S. Department of Health and Human Services, Public Health

Service, Centers for Disease Control and Prevention. Cincinnati, OH. 1997.

11. American Industrial Hygiene Association (AIHA). The AIHA 1998 Emergency Response

Planning Guidelines and Workplace Environmental Exposure Level Guides Handbook.

1998.
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ACROLEIN

107-02-8

Hazard Summary

Acrolein is primarily used as an intermediate in the manufacture of acrylic acid. It can be

formed from the breakdown of certain pollutants in outdoor air or from burning tobacco

or gasoline. It is extremely toxic to humans from inhalation and dermal exposure. Acute

(short-term) inhalation exposure may result in upper respiratory tract irritation and

congestion. No information is available on its reproductive, developmental, or

carcinogenic effects in humans. The animal cancer data are limited, with one study

reporting an increased incidence of adrenocortical tumors in rats exposed to acrolein in

the drinking water. The U.S. Environmental Protection Agency (EPA) considers acrolein

a possible human carcinogen (Group C).

Please Note: The main sources of information for this fact sheet are EPA's Integrated Risk Information System

(IRIS), which contains information on inhalation chronic toxicity of acrolein and the reference concentration (RfC),

and the Agency for Toxic Substances and Disease Registry's (ATSDR's) Toxicological Profile for Acrolein.

Physical Properties

! Acrolein is a water-white or yellow liquid that burns easily and is easily volatilized. (1)

! Acrolein has a disagreeable odor and an odor threshold of 0.2 ppm. (1,8)

! The chemical formula for acrolein is C3H4O and the molecular weight is 56.06 g/mol. (1)

! The vapor pressure for acrolein is 220 mm Hg at 20 EC, and its log octanol/water

partition coefficient (log Kow) is -0.01. (1)

Uses

! The largest use for acrolein is as an intermediate in the manufacture of acrylic acid. (1)

Sources and Potential Exposure

! Acrolein can be formed from the breakdown of certain pollutants found in outdoor air,

from burning tobacco, or from burning gasoline. (1)

! Airborne exposure to acrolein may occur from breathing contaminated air, from smoking

tobacco or proximity to someone who is smoking, or from being near automobiles or oil

or coal power plants. In several large cities, acrolein has been measured at 9 ppb. (1)

! Occupational exposure to acrolein could occur in industries that use acrolein to make

other chemicals. (1)

! Small amounts of acrolein may be found in some foods, such as fried foods, cooking oils,

and roasted coffee. (1)
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! Acrolein has not been detected in drinking water and is not commonly found in surface

water. (1)

Assessing Personal Exposure

! There are currently no tests available to determine personal exposure to acrolein. (1)

Health Hazard Information

Acute Effects:

! Acute inhalation exposure to high levels (10 ppm) of acrolein in humans may result in

death. Effects on the lung, such as upper respiratory tract irritation and congestion, have

been noted at acrolein levels ranging from 0.17 ppm to 0.43 ppm. (1-3)

! Acrolein is considered to have high acute toxicity, based on short-term animal tests such

as the LC50 test in rats. (1,4)

Chronic Effects (Noncancer):

! The major effects from chronic (long-term) inhalation exposure to acrolein in humans

consist of general respiratory congestion and eye, nose, and throat irritation. (1,2,5)

! Acrolein is a strong dermal irritant, causing skin burns in humans. (1,2,5)

! Animal studies have reported that the respiratory system is the major target organ for

acrolein toxicity. (1,2,5)

! The RfC for acrolein is 0.00002 mg/m3 based on squamous metaplasia and neutrophilic

infiltration of nasal epithelium in rats. The RfC is an estimate (with uncertainty spanning

perhaps an order of magnitude) of a continuous inhalation exposure to the human

population (including sensitive subgroups) that is likely to be without appreciable risk of

deleterious noncancer effects during a lifetime. It is not a direct estimator of risk but

rather a reference point to gauge the potential effects. At exposures increasingly greater

than the RfC, the potential for adverse health effects increases. Lifetime exposure above

the RfC does not imply that an adverse health effect would necessarily occur. (3)

! EPA has high confidence in the studies on which the RfC was based because adequate

numbers of animals were used, careful attention was paid to experimental protocol, and

together they demonstrated a consistent profile of histopathological changes in the

respiratory system; low to medium confidence in the database due to the lack of chronic

data and adequately conducted reproductive or developmental studies; and, consequently,

medium confidence in the RfC.

! EPA has not established a reference dose (RfD) for acrolein. (3)

! EPA has calculated a provisional RfD of 0.02 mg/kg/d for acrolein. The provisional RfD

is a value that has had some form of Agency review, but it does not appear on IRIS. The

EPA announced recently (January 12, 2000, 65 FR 1863) its plan to conduct an IRIS

health assessment for acrolein to be completed by FY 2002. (6)
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Reproductive/Developmental Effects:

! No information is available on the reproductive or developmental effects of acrolein in

humans. (1)

! In the one available reproductive animal study, rats were exposed to acrolein by

inhalation, with no effects observed on the number of pregnancies or the number and

weights of the fetuses. (1)

! Acrolein has been reported to cause birth defects in rats when injected directly into the

embryonic tissue. (1)

Cancer Risk:

! No information is available on the carcinogenic effects of acrolein in humans. (1,3)

! Limited animal cancer data are available; one inhalation study in rats reported no

evidence of tumors in the respiratory tract or in other tissues and organs, while another

study reported an increased incidence of adrenocortical tumors in female rats exposed to

acrolein in drinking water. (1,3)

! EPA has classified acrolein as a Group C, possible human carcinogen, based on limited

evidence of carcinogenicity in animals, the structural similarity of acrolein to substances

possibly carcinogenic to humans, the carcinogenic potential of one of its metabolites, and

the lack of human data. (3)

Conversion Factors:

To convert from ppm to mg/m3: mg/m3 = (ppm) x (molecular weight of the compound)/(24.45).

For acrolein: 1 ppm = 2.29 mg/m3.

To convert from μg/m3 to mg/m3: mg/m3 = (μg/m3) x (1 mg/1,000 μg).
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Acrolein

0.00001

0.0001

0.001

0.01

0.1

1

10

100

1000

Health numbers

a Regulatory, advisory

numbers

b

Ref.

4

Ref.

3

Ref.

3

Ref.

10

Ref.

10

Ref.

8,9,

10,11

LC50 (rat s) (298 mg/m3)

LOAELc (respirat ory)

(0.917mg/ m3)

NIOSH IDLH (4.6 mg/m3)

RfC (0.00002 mg/ m3)

ACGIH ceiling,

OSHA PEL, NIOSH

REL, AIHA ERPG-1

(0.25 mg/m3)

NIOSH STEL (0.8 mg/m3)

Ref.

11

AIHA ERPG-2 (1.1 mg/m3)

Health Data from Inhalation Exposure

AIHA ERPG –American Industrial Hygiene Association's emergency response planning

guidelines. ERPG 1 is the maximum airborne concentration below which it is believed nearly all

individuals could be exposed up to one hour without experiencing other than mild transient

adverse health effects or perceiving a clearly defined objectionable odor; ERPG 2 is the

maximum airborne concentration below which it is believed nearly all individuals could be

exposed up to one hour without experiencing or developing irreversible or other serious health 

effects that could impair their abilities to take protective action 

ACGIH ceiling – American Conference of Governmental and Industrial Hygienists’ threshold

limit value ceiling; the concentration of a substance that should not be exceeded during any part

of the working exposure. 

LC50 (Lethal Concentration50) – A calculated concentration of a chemical in air to which
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exposure for a specific length of time is expected to cause death in 50% of a defined

experimental animal population. 

LOAEL – Lowest-observed-adverse-effect level. 

NIOSH IDLH – National Institute of Occupational Safety and Health's immediately dangerous

to life or health limit; NIOSH recommended exposure limit to ensure that a worker can escape

from an exposure condition that is likely to cause death or immediate or delayed permanent

adverse health effects or prevent escape from the environment. 

NIOSH REL – NIOSH's recommended exposure limit; NIOSH recommended exposure limit for

an 8- or 10-h time-weighted average exposure and/or ceiling. 

NIOSH STEL – NIOSH's short term exposure limit; NIOSH recommended exposure limit for a

15-minute period. 

OSHA PEL – Occupational Safety and Health Administration's permissible exposure limit

expressed as a time-weighted average; the concentration of a substance to which most workers

can be exposed without adverse effect averaged over a normal 8-h workday or a 40-h work week. 

a

 Health numbers are toxicological numbers from animal testing or risk assessment values

developed by EPA. 

b

 Regulatory numbers are values that have been incorporated in Government regulations, while

advisory numbers are nonregulatory values provided by the Government or other groups as

advice. 

c

 This LOAEL is from the critical study used as the basis for the EPA RfC.

References

1. Agency for Toxic Substances and Disease Registry (ATSDR). Toxicological Profile for

Acrolein. Public Health Service, U.S. Department of Health and Human Services,

Atlanta, GA. 1990.

2. U.S. Department of Health and Human Services. Hazardous Substances Data Bank

(HSDB, online database). National Toxicology Information Program, National 

Library of Medicine, Bethesda, MD. 1993.

3. U.S. Environmental Protection Agency (EPA). Integrated Risk Information System (IRIS)

on Acrolein. National Center for Environmental Assessment, Office of Research and

Development, Washington, D.C. 1999.

4. U.S. Department of Health and Human Services. Registry of Toxic Effects of Chemical

Substances (RTECS). National Toxicology Information Program, National Library of

Medicine, Bethesda, MD. 1993.

5. E.J. Calabrese and E.M. Kenyon. Air Toxics and Risk Assessment. Lewis Publishers,

Chelsea, MI. 1991.
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6. U.S. Environmental Protection Agency (EPA). Health Effects Assessment Summary

Tables. FY 1997 Update. Solid Waste and Emergency Response, Office of Emergency

and Remedial Response, Cincinnati, OH. EPA/540/R-97-036. 1997.

7. J.E. Amoore and E. Hautala. Odor as an aid to chemical safety: Odor thresholds

compared with threshold limit values and volatilities for 214 industrial chemicals in air

and water dilution. Journal of Applied Toxicology 3(6):272-290. 1983.

8. American Conference of Governmental Industrial Hygienists (ACGIH). 1999 TLVs and

BEIs. Threshold Limit Values for Chemical Substances and Physical Agents, Biological

Exposure Indices. Cincinnati, OH. 1999.

9. Occupational Safety and Health Administration (OSHA). Occupational Safety and Health

Standards, Toxic and Hazardous Substances. Code of Federal Regulations. 29 CFR

1910.1000. 1998.

10. National Institute for Occupational Safety and Health (NIOSH). Pocket Guide to

Chemical Hazards. U.S. Department of Health and Human Services, Public Health

Service, Centers for Disease Control and Prevention. Cincinnati, OH. 1997.

11. American Industrial Hygiene Association (AIHA). The AIHA 1998 Emergency Response

Planning Guidelines and Workplace Environmental Exposure Level Guides Handbook 

1998.
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ACRYLONITRILE

107-13-1

Hazard Summary

Exposure to acrylonitrile is primarily occupational: it is used in the manufacture of acrylic

acid and modacrylic fibers. Acute (short-term) exposure of workers to acrylonitrile has

been observed to cause mucous membrane irritation, headaches, dizziness, and nausea.

No information is available on the reproductive or developmental effects of acrylonitrile

in humans. Based on limited evidence in humans and evidence in rats, the U.S.

Environmental Protection Agency (EPA) has classified acrylonitrile as a probable human

carcinogen (Group B1).

Please Note: The main sources of information for this fact sheet are EPA's Integrated Risk Information System

(IRIS), which contains information on inhalation chronic toxicity of acrylonitrile and the reference concentration

(RfC) and the carcinogenic effects of acrylonitrile including the unit cancer risk for inhalation exposure, EPA's

Health Effects Assessment for Acrylonitrile, and the Agency for Toxic Substances and Disease Registry's

(ATSDR's) Toxicological Profile for Acrylonitrile.

Physical Properties

! The chemical formula for acrylonitrile is C3H3N, and its molecular weight is 53.06 g/mol.

(1,8)

! Acrylonitrile occurs as a colorless liquid that is soluble in water. (1,8)

! Acrylonitrile has a pungent, onion- or garlic-like odor, with an odor threshold of 47

mg/m3. (1)

! The vapor pressure for acrylonitrile is 100 mm Hg at 22.8 EC, and its log octanol/water

partition coefficient (log Kow) is -0.92. (1)

Uses

! Acrylonitrile is primarily used in the manufacture of acrylic and modacrylic fibers. It is

also used as a raw material in the manufacture of plastics (acrylonitrile-butadiene-styrene

and styrene-acrylonitrile resins), adiponitrile, acrylamide, and nitrile rubbers and barrier

resins. (1,6)

Sources and Potential Exposure

! Human exposure to acrylonitrile appears to be primarily occupational via inhalation. (1)

! Acrylonitrile may be released to the ambient air during its manufacture and use. (1)
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Assessing Personal Exposure

! Acrylonitrile can be detected in the blood to determine whether or not exposure has

occurred. Metabolites may be detected in the urine, but some breakdown products are not

specific to acrylonitrile. (1)

Health Hazard Information

Acute Effects:

! Workers exposed via inhalation to high levels of acrylonitrile for less than an hour

experienced mucous membrane irritation, headaches, nausea, feelings of apprehension

and nervous irritability; low grade anemia, leukocytosis, kidney irritation, and mild

jaundice were also observed in the workers, with these effects subsiding with the ending

of exposure. Symptoms associated with acrylonitrile poisoning include limb weakness,

labored and irregular breathing, dizziness and impaired judgment, cyanosis, nausea,

collapse, and convulsions. (1-4)

! A child died after being exposed to acrylonitrile by inhalation, suffering from respiratory

malfunction, lip cyanosis, and tachycardia before death. Several adults exposed to the

same concentration of acrylonitrile exhibited eye irritation, but no toxic effects. (1,4)

! Acute dermal exposure may cause severe burns to the skin. (3)

! Acute animal tests, such as the LC50 and LD50 tests in rats, mice, rabbits, and guinea pigs,

have demonstrated acrylonitrile to have high acute toxicity from inhalation and high to

extreme acute toxicity from oral or dermal exposure. (5)

Chronic Effects (Noncancer):

! In one study, headaches, fatigue, nausea, and weakness were frequently reported in

chronically (long-term) exposed workers. (6)

! In rats chronically exposed by inhalation, degenerative and inflammatory changes in the

respiratory epithelium of the nasal turbinates and effects on brain cells have been

observed. (1,4,6)

! The RfC for acrylonitrile is 0.002 mg/m3 based on degeneration and inflammation of

nasal respiratory epithelium in rats. The RfC is an estimate (with uncertainty spanning

perhaps an order of magnitude) of a continuous inhalation exposure to the human

population (including sensitive subgroups) that is likely to be without appreciable risk of

deleterious noncancer effects during a lifetime. It is not a direct estimator of risk but

rather a reference point to gauge the potential effects. At exposures increasingly greater

than the RfC, the potential for adverse health effects increases. Lifetime exposure above

the RfC does not imply that an adverse health effect would necessarily occur. (4)

! EPA has medium confidence in the study on which the RfC was based because, although

it was a well-conducted chronic study in an appropriate number of animals, it was

performed on only one species, did not identify a no-observed-adverse-effect level

(NOAEL), was confounded by the early sacrifice of rats with large mammary gland
National Air Toxics Program: The Integrated Urban Strategy

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A-17

tumors and the target organ (nasal turbinates) was examined only at the end of the study

in relatively few animals; medium to low confidence in the database because of the lack

of chronic or subchronic inhalation data in a second species, the lack of reproductive data

by the inhalation route and the existence of an oral study showing reproductive effects;

and, consequently, medium to low confidence in the RfC. (4)

! EPA has calculated a provisional reference dose (RfD) of 0.001 mg/kg/d for acrylonitrile

based on decreased sperm counts in mice. The provisional RfD is a value that has had

some form of Agency review, but it does not appear on IRIS. (7)

Reproductive/Developmental Effects:

! No information is available on the reproductive or developmental effects of acrylonitrile

in humans.

! Fetal malformations (including short tail, missing vertebrae, short trunk, omphalocele,

and hemivertebra) have been reported in rats exposed to acrylonitrile by inhalation. (1,4)

! In mice orally exposed to acrylonitrile, degenerative changes in testicular tubules and

decreased sperm count were observed. (1)

Cancer Risk:

! A statistically significant increase in the incidence of lung cancer has been reported in

several studies of chronically exposed workers. However, some of these studies contain

deficiencies such as lack of exposure information, short follow-up, and confounding

factors. (1,4,6,8)

! In several studies, an increased incidence of tumors has been observed in rats exposed by

inhalation, drinking water, and gavage. Astrocytomas in the brain and spinal cord and

tumors of the Zymbal gland (in the ear canal) have been most frequently reported, as well

as tumors of the stomach, tongue, small intestine, and mammary gland (in females).

(1-4,6,8)

! EPA has classified acrylonitrile as a Group B1, probable human carcinogen. (4)

! EPA uses mathematical models, based on human and animal studies, to estimate the

probability of a person developing cancer from breathing air containing a specified

concentration of a chemical. EPA calculated an inhalation unit risk estimate of 6.8 x 10-5

(μg/m3)

-1. EPA estimates that, if an individual were to continuously breathe air containing

acrylonitrile at an average of 0.01 μg/m3 (1 x 10-5 mg/m3), over his or her entire lifetime,

that person would theoretically have no more than a one-in-a-million increased chance of

developing cancer as a direct result of breathing air containing this chemical. Similarly,

EPA estimates that breathing air containing 0.1 μg/m3 (1 x 10-4 mg/m3) would result in

not greater than a one-in-a-hundred thousand increased chance of developing cancer, and

air containing 1.0 μg/m3 (1 x 10-3 mg/m3) would result in not greater than a one-in-ten

thousand increased chance of developing cancer. For a detailed discussion of confidence

in the potency estimates, please see IRIS. (4)

! EPA has calculated an oral cancer slope factor of 0.54 (mg/kg/d)-1. (4)
National Air Toxics Program: The Integrated Urban Strategy

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A-18

Acrylonitrile

0.00001

0.0001

0.001

0.01

0.1

1

10

100

1000

10000

Health numbers

a

Regulatory, advisory

numbersb

Ref.

5

Ref.

4

Ref.

4

Ref.

9,10 Ref.

11

LC50 (rats) (922 mg/m3)

LOAELc (respirat ory) (43 mg/m3)

RfC (0.002 mg/m3)

OSHA PEL, ACGIH TLV

(4.3 mg/m3)

NIOSH REL

(2 mg/m3)

Cancer Risk Level

1 in a million risk

(1 x 10-5 mg/m3)

NIOSH IDLH (180 mg/m3)

Ref.

11

AIHA ERPG-2 (76 mg/m3)

Ref.

12

AIHA ERPG-1 (22 mg/m3)

Ref.

12

Ref.

4

Conversion Factors:

To convert from ppm to mg/m3: mg/m3 = (ppm) x (molecular weight of the compound)/(24.45).

For acrylonitrile: 1 ppm = 2.17 mg/m3.

Health Data from Inhalation Exposure

ACGIH TLV – American Conference of Governmental and Industrial Hygienists' threshold

limit value expressed as a time-weighted average; the concentration of a substance to which most

workers can be exposed without adverse effect.

AIHA ERPG – American Industrial Hygiene Association's emergency response planning

guidelines. ERPG 1 is the maximum airborne concentration below which it is believed nearly all

individuals could be exposed up to one hour without experiencing other than mild transient

adverse health effects or perceiving a clearly defined objectionable odor; ERPG 2 is the

maximum airborne concentration below which it is believed nearly all individuals could be
National Air Toxics Program: The Integrated Urban Strategy

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A-19

exposed up to one hour without experiencing or developing irreversible or other serious health

effects that could impair their abilities to take protective action.

LC50 (Lethal Concentration50) – A calculated concentration of a chemical in air to which

exposure for a specific length of time is expected to cause death in 50% of a defined

experimental animal population.

LOAEL – Lowest-observed-adverse-effect level.

NIOSH IDLH – National Institute of Occupational Safety and Health's immediately dangerous

to life or health limit; NIOSH recommended exposure limit to ensure that a worker can escape

from an exposure condition that is likely to cause death or immediate or delayed permanent

adverse health effects or prevent escape from the environment.

NIOSH REL – NIOSH's recommended exposure limit; NIOSH-recommended exposure limit for

an 8- or 10-h time-weighted-average exposure and/or ceiling.

OSHA PEL – Occupational Safety and Health Administration's permissible exposure limit

expressed as a time-weighted average; the concentration of a substance to which most workers

can be exposed without adverse effect averaged over a normal 8-h workday or a 40-h workweek. 

a

 Health numbers are toxicological numbers from animal testing or risk assessment values

developed by EPA. 

b

 Regulatory numbers are values that have been incorporated in Government regulations, while

advisory numbers are nonregulatory values provided by the Government or other groups as

advice. 

c

 The LOAEL is from the critical study used as the basis for the EPA RfC. 

References

1. Agency for Toxic Substances and Disease Registry (ATSDR). Toxicological Profile for

Acrylonitrile. Public Health Service, U.S. Department of Health and Human Services,

Atlanta, GA. 1990.

2. International Agency for Research on Cancer (IARC). IARC Monographs on the

Evaluation of the Carcinogenic Risk of Chemicals to Humans: Some Monomers, Plastics

and Synthetic Elastomers, and Acrolein. Volume 19. World Health Organization, Lyon.

1979.

3. U.S. Environmental Protection Agency (EPA). Health Assessment Document for

Acrylonitrile (Revised Draft). EPA/600/8-82-007. Environmental Criteria and

Assessment Office, Office of Health and Environmental Assessment, Office of Research

and Development, Research Triangle Park, NC. 1982.

4. U.S. Environmental Protection Agency (EPA). Integrated Risk Information System (IRIS)

on Acrylonitrile, National Center for Environmental Assessment, Office of Research and

Development, Washington, D.C. 1999.
National Air Toxics Program: The Integrated Urban Strategy

Report to Congress

A-20

5. U.S. Department of Health and Human Services. Registry of Toxic Effects of Chemical

Substances (RTECS, online database). National Toxicology Information Program,

National Library of Medicine, Bethesda, MD. 1993.

6. U.S. Environmental Protection Agency (EPA). Health Effects Assessment for

Acrylonitrile. EPA/600/8-88/014. Environmental Criteria and Assessment Office, Office

of Health and Environmental Assessment, Office of Research and Development,

Cincinnati, OH. 1988.

7. U.S. Environmental Protection Agency (EPA). Health Effects Assessment Summary

Tables. FY 1997 Update. Solid Waste and Emergency Response, Office of Emergency

and Remedial Response, Cincinnati, OH. EPA/540/R-97-036. 1997.

8. U.S. Environmental Protection Agency (EPA). Health and Environmental Effects Profile

for Acrylonitrile. EPA/600/x-85/372. Environmental Criteria and Assessment Office,

Office of Health and Environmental Assessment, Office of Research and Development,

Cincinnati, OH. 1985.

9. Occupational Safety and Health Administration (OSHA). Occupational Safety and Health

Standards, Toxic and Hazardous Substances. Code of Federal Regulations. 29 CFR

1910.1045. 1998.

10. American Conference of Governmental Industrial Hygienists (ACGIH). 1999 TLVs and

BEIs. Threshold Limit Values for Chemical Substances and Physical Agents, Biological

Exposure Indices. Cincinnati, OH. 1999.

11. National Institute for Occupational Safety and Health (NIOSH). Pocket Guide to

Chemical Hazards. U.S. Department of Health and Human Services, Public Health

Service, Centers for Disease Control and Prevention. Cincinnati, OH. 1997.

12. American Industrial Hygiene Association (AIHA). The AIHA1998 Emergency Response

Planning Guidelines and Workplace Environmental Exposure Level Guides Handbook.

1998.
National Air Toxics Program: The Integrated Urban Strategy

Report to Congress

1

 This fact sheet addresses the toxicity of the inorganic arsenic compounds as well as the

toxicity of the gaseous arsenic trihydride: arsine.

A-21

ARSENIC COMPOUNDS1

107-02-8

Hazard Summary

Arsenic, a naturally occurring element, is found throughout the environment; for most

people, food is the major source of exposure. Acute (short-term) high-level inhalation

exposure to arsenic dust or fumes has resulted in gastrointestinal effects (nausea, diarrhea,

abdominal pain); central and peripheral nervous system disorders have occurred in

workers acutely exposed to inorganic arsenic. Chronic (long-term) inhalation exposure to

inorganic arsenic in humans is associated with irritation of the skin and mucous

membranes. Human data suggest a relationship between inhalation exposure of women

working at or living near metal smelters and an increased risk of reproductive effects,

such as spontaneous abortions. However, as these studies evaluated smelter pollutants in

general, arsenic's role is not clear. Chronic oral exposure has resulted in gastrointestinal

effects, anemia, peripheral neuropathy, skin lesions, hyperpigmentation, and liver or

kidney damage. Inorganic arsenic exposure in humans, by the inhalation route, has been

shown to be strongly associated with lung cancer, while ingestion of inorganic arsenic in

humans has been linked to a form of skin cancer and also to bladder, liver, and lung

cancer. The U.S. Environmental Protection Agency (EPA) has classified inorganic

arsenic as a Group A, human carcinogen.

Arsine is a gas consisting of arsenic and hydrogen. It is extremely toxic to humans, with

headaches, vomiting, and abdominal pains occurring within a few hours of exposure.

Death may occur from kidney failure and pulmonary edema. EPA has not classified arsine

for carcinogenicity.

Please Note: The main sources of information for this fact sheet are EPA's Integrated Risk Information System

(IRIS), which contains information on inhalation chronic toxicity and the reference concentration (RfC) for arsine,

oral chronic toxicity and the reference dose (RfD) for inorganic arsenic, and the carcinogenic effects of inorganic

arsenic including the unit cancer risk for inhalation exposure, and the Agency for Toxic Substances and Disease

Registry's (ATSDR's) Toxicological Profile for Arsenic.

Physical Properties

! Inorganic arsenic is a naturally occurring element in the earth's crust. (1)

! Pure inorganic arsenic is a gray-colored metal, but inorganic arsenic is usually found

combined with other elements such as oxygen, chlorine, and sulfur. (1)

! The chemical symbol for inorganic arsenic is As, and it has an atomic weight of 74.92

g/mol. (3)
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! The chemical formula for arsine is AsH3, and it has a molecular weight of 77.95 g/mol.

(8)

! Arsine is a colorless gas with a disagreeable garlic odor. (8)

! Arsenic combined with elements such as oxygen, chlorine, and sulfur forms inorganic

arsenic; inorganic arsenic compounds include arsenic pentoxide, arsenic trioxide, and

arsenic acid. Arsenic combined with carbon and hydrogen forms organic arsenic; organic

arsenic compounds include arsanilic acid, arsenobetaine, and dimethylarsinic acid. (1)

Uses

! The major use for inorganic arsenic is in wood preservation; arsine is used in the

microelectronics industry and in semiconductor manufacture. (2)

! Until the 1940s, inorganic arsenic solutions were widely used in the treatment of various

diseases, such as syphillis and psoriasis. Inorganic arsenic is still used as an antiparasitic

agent in veterinary medicine and in homeopathic and folk remedies in the U.S. and other

countries. (2)

Sources and Potential Exposure

! Inorganic arsenic is found throughout the environment; it is released into the air by

volcanoes, the weathering of arsenic-containing minerals and ores, and by commercial or

industrial processes. (1,2)

! For most people, food is the largest source of arsenic exposure (about 25 to 50 μg/d),

with lower amounts coming from drinking water and air. Among foods, some of the

highest levels are in fish and shellfish; however, this arsenic exists primarily as organic

compounds, which are essentially nontoxic. (1)

! Elevated levels of inorganic arsenic may be present in soil, either from natural mineral

deposits or contamination from human activities, which may lead to dermal or ingestion

exposure. (1)

! Workers in metal smelters and nearby residents may be exposed to above-average

inorganic arsenic levels from arsenic released into the air. (1)

! Other sources of inorganic arsenic exposure include burning plywood treated with an

arsenic wood preservative or dermal contact with wood treated with arsenic. (2)

! Most arsenic poisoning incidents in industry have involved the production of arsine, a

short-lived, extremely toxic gas. (3)

Assessing Personal Exposure

! Measurement of inorganic arsenic in the urine is the best way to determine recent

exposure (within the last 1 to 2 days), while measuring inorganic arsenic in hair or

fingernails may be used to detect high-level exposures that occurred over the past 6-12

months. (1)
National Air Toxics Program: The Integrated Urban Strategy

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A-23

Health Hazard Information

Acute Effects:

Inorganic Arsenic

! Acute inhalation exposure of workers to high levels of arsenic dusts or fumes has resulted

in gastrointestinal effects (nausea, diarrhea, abdominal pain), while acute exposure of

workers to inorganic arsenic has also resulted in central and peripheral nervous system

disorders. (1)

! Acute oral exposure to inorganic arsenic, at doses of approximately 600 μg/kg/d or higher

in humans, has resulted in death. Oral exposure to lower levels of inorganic arsenic has

resulted in effects on the gastrointestinal tract (nausea, vomiting), central nervous system

(CNS) (headaches, weakness, delirium), cardiovascular system (hypotension, shock),

liver, kidney, and blood (anemia, leukopenia). (1,2)

! Acute animal tests, such as the LD50 test in rats and mice, have shown inorganic arsenic

to have moderate to high acute toxicity. (5)

Arsine

! Acute inhalation exposure to arsine by humans has resulted in death; it has been reported

that a half-hour exposure to 25 to 50 ppm can be lethal. (4)

! The major effects from acute arsine exposure in humans include headaches, vomiting,

abdominal pains, hemolytic anemia, hemoglobinuria, and jaundice; these effects can lead

to kidney failure. (4,8)

! Arsine has been shown to have extreme acute toxicity from acute animal tests. (5)

Chronic Effects (Noncancer):

Inorganic arsenic

! Chronic inhalation exposure to inorganic arsenic in humans is associated with irritation of

the skin and mucous membranes (dermatitis, conjunctivitis, pharyngitis, and rhinitis).

(1,2)

! Chronic oral exposure to inorganic arsenic in humans has resulted in gastrointestinal

effects, anemia, peripheral neuropathy, skin lesions, hyperpigmentation, gangrene of the

extremities, vascular lesions, and liver or kidney damage. (1,2)

! No chronic inhalation exposure studies have been performed in animals for any inorganic

arsenic compound. (1)

! Some studies have suggested that inorganic arsenic is an essential dietary nutrient in

goats, chicks, and rats. However, no comparable data are available for humans. EPA has

concluded that essentiality, although not rigorously established, is plausible. (1,6)

! EPA has not established an RfC for inorganic arsenic. (6)
National Air Toxics Program: The Integrated Urban Strategy

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A-24

! The California Environmental Protection Agency (CalEPA) has established a chronic

inhalation reference level of 0.00003 mg/m3 based on developmental effects in mice. The

CalEPA reference exposure level is a concentration at or below which adverse health

effects are not likely to occur. It is not a direct estimator of risk, but rather a reference

point to gauge the potential effects. At lifetime exposures increasingly greater than the

reference exposure level, the potential for adverse health effects increases. (7)

! The RfD for inorganic arsenic is 0.0003 mg/kg/d based on hyperpigmentation, keratosis,

and possible vascular complications in humans. The RfD is an estimate (with uncertainty

spanning perhaps an order of magnitude) of a daily oral exposure to the human

population (including sensitive subgroups) that is likely to be without appreciable risk of

deleterious noncancer effects during a lifetime. (6)

! EPA has medium confidence in the study on which the RfD for inorganic arsenic was

based because, although an extremely large number of people were included in the

assessment (>40,000), the doses were not well characterized and other contaminants were

present. The supporting human toxicity database, while extensive, is somewhat flawed

and, consequently, EPA has assigned medium confidence to the RfD. (6)

Arsine

! The RfC for arsine is 0.00005 mg/m3 based on increased hemolysis, abnormal red blood

cell morphology, and increased spleen weight in rats, mice, and hamsters. (4)

! EPA has medium confidence in the RfC based on: high confidence in the studies on

which the RfC for arsine was based because the sample sizes were adequate, statistical

significance was reported, concentration dose-response relationships were documented,

three species were investigated, and both a no-observed-adverse-effect level (NOAEL)

and a lowest-observed-adverse-effect level (LOAEL) were identified; and medium

confidence in the database because there were three inhalation animal studies and a

developmental/reproductive study, but no data on human exposure. (4)

Reproductive/Developmental Effects:

Inorganic arsenic

! Several studies have suggested that women who work in, or live near, metal smelters may

have higher than normal spontaneous abortion rates, and their children may exhibit lower

than normal birth weights. However, these studies are limited because they were designed

to evaluate the effects of smelter pollutants in general and are not specific for inorganic

arsenic. (1)

! Ingested inorganic arsenic can cross the placenta in humans, exposing the fetus to the

chemical. (2)

! Oral animal studies have reported inorganic arsenic at very high doses to be fetotoxic and

to cause birth defects. (1)
National Air Toxics Program: The Integrated Urban Strategy

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A-25

Arsine

! Human studies have indicated higher than expected spontaneous abortion rates in women

in the microelectronics industry who were exposed to arsine. However, these studies have

several limitations, including small sample size and exposure to other chemicals in

addition to arsine. (4)

Cancer Risk:

Inorganic arsenic

! Human inhalation studies have reported inorganic arsenic exposure to be strongly

associated with lung cancer. (1,2,6)

! Ingestion of inorganic arsenic in humans has been associated with an increased risk of

nonmelanoma skin cancer and also to an increased risk of bladder, liver, and lung cancer.

(1,6)

! Animal studies have not associated inorganic arsenic exposure via the oral route with

cancer, and no cancer inhalation studies have been performed in animals for inorganic

arsenic. (1)

! EPA has classified inorganic arsenic as a Group A, human carcinogen. (6)

! EPA uses mathematical models, based on human and animal studies, to estimate the

probability of a person developing cancer from breathing air containing a specified

concentration of a chemical. EPA calculated an inhalation unit risk estimate of 4.3 x 10-3

(μg/m3)

-1. EPA estimates that, if an individual were to continuously breathe air containing

inorganic arsenic at an average of 0.0002 μg/m3 (2 x 10-7 mg/m3) over his or her entire

lifetime, that person would theoretically have no more than a one-in-a-million increased

chance of developing cancer as a direct result of breathing air containing this chemical.

Similarly, EPA estimates that continuously breathing air containing 0.002 μg/m3 (2 x 10-6

mg/m3) would result in not greater than a one-in-a-hundred thousand increased chance of

developing cancer, and air containing 0.02 μg/m3 (2 x 10-5 mg/m3) would result in not

greater than a one-in-ten thousand increased chance of developing cancer. For a detailed

discussion of confidence in the potency estimates, please see IRIS. (6)

! EPA has calculated an oral cancer slope factor of 1.5 (mg/kg/d)-1 for inorganic arsenic.

(6).

Arsine

! No cancer inhalation studies are available for arsine. (1)

! EPA has not classified arsine for carcinogenicity. (4)
National Air Toxics Program: The Integrated Urban Strategy

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A-26

Regulatory, advisory

numbersb

Arsenic

0.00000001

0.0000001

0.000001

0.00001

0.0001

0.001

0.01

0.1

1

10

Ref.

7

Ref.

7

Ref.

6

Ref.

11

ACGIH TLV, OSHA PEL (0.01 mg/ m3)

LOAELc (development al) (0.2 mg/ m3)

Cancer Risk

Level 1 in a

million risk

(2 x10-7 mg/ m3)

CaIEPA reference exposure level

(3 x 10-5 mg/ m3)

NIOSH ceiling

(0.002 mg/ m3)

NIOSH IDLH (5 mg/m3)

Ref.

9,10

Ref.

11

Health numbersa

Conversion Factors:

To convert from ppm to mg/m3: mg/m3 = (ppm) x (molecular weight of the compound)/(24.45).

For inorganic arsenic: 1 ppm = 3.06 mg/m3. For arsine: 1 ppm = 3.19 mg/m3.

To convert from μg/m3 to mg/m3: mg/m3 = (μg/m3) x (1 mg/1,000 μg).

Health Data from Inhalation Exposure (Inorganic Arsenic)

ACGIH TLV – American Conference of Governmental and Industrial Hygienists' threshold

limit value expressed as a time-weighted average; the concentration of a substance to which most

workers can be exposed without adverse effects.

LOAEL – Lowest-observed-adverse-effect level.

NIOSH IDLH – National Institute of Occupational Safety and Health's immediately dangerous
National Air Toxics Program: The Integrated Urban Strategy

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A-27

to life or health concentration; NIOSH recommended exposure limit to ensure that a worker can

escape from an exposure condition that is likely to cause death or immediate or delayed

permanent adverse health effects or prevent escape from the environment.

NIOSH REL ceiling – NIOSH's recommended exposure limit ceiling; the concentration that

should not be exceeded at any time.

OSHA PEL – Occupational Safety and Health Administration's permissible exposure limit

expressed as a time-weighted average; the concentration of a substance to which most workers

can be exposed without adverse effect averaged over a normal 8-h workday or a 40-h workweek.

a

 Health numbers are toxicological numbers from animal testing or risk assessment values

developed by EPA.

b

 Regulatory numbers are values that have been incorporated in Government regulations, while

advisory numbers are nonregulatory values provided by the Government or other groups as

advice.

c

 The LOAEL is from the critical study used as the basis for the CalEPA chronic reference

exposure level.

References

1. Agency for Toxic Substances and Disease Registry (ATSDR). Toxicological Profile for

Arsenic (Draft). U.S. Public Health Service, U.S. Department of Health and Human

Services, Atlanta, GA. 1998.

2. Agency for Toxic Substances and Disease Registry (ATSDR). Case Studies in

Environmental Medicine. Arsenic Toxicity. U.S. Public Health Service, U.S. Department

of Health and Human Services, Atlanta, GA. 1990.

3. U.S. Environmental Protection Agency (EPA). Health Assessment Document for

Inorganic Arsenic. EPA/540/1-86/020. Environmental Criteria and Assessment Office,

Office of Health and Environmental Assessment, Office of Research and Development,

Washington, DC. 1984.

4. U.S. Environmental Protection Agency (EPA). Integrated Risk Information System (IRIS)

on Arsine. National Center for Environmental Assessment, Office of Research and

Development, Washington, DC. 1999.

5. U.S. Department of Health and Human Services. Registry of Toxic Effects of Chemical

Substances (RTECS, online database). National Toxicology Information Program,

National Library of Medicine, Bethesda, MD. 1993.

6. U.S. Environmental Protection Agency (EPA). Integrated Risk Information System (IRIS)

on Arsenic. National Center for Environmental Assessment, Office of Research and

Development, Washington, DC. 1999
National Air Toxics Program: The Integrated Urban Strategy

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7. California Environmental Protection Agency (CalEPA). Technical Support Document for

the Determination of Noncancer Chronic Reference Exposure Levels. Draft for Public

Comment. Office of Environmental Health Hazard Assessment, Berkeley, CA. 1997.

8. M. Windolz. The Merck Index, An Encyclopedia of Chemicals, Drugs, and Biologicals.

10th ed. Merck and Co., Rahway, NJ. 1983.

9. American Conference of Governmental Industrial Hygienists (ACGIH). 1999 TLVs and

BEIs. Threshold Limit Values for Chemical Substances and Physical Agents. Biological

Exposure Indices. Cincinnati, OH. 1999.

10. Occupational Safety and Health Administration (OSHA). Occupational Safety and

Health Standards, Toxic and Hazardous Substances. Code of Federal Regulations. 29

CFR 1910.1000. 1998.

11. National Institute for Occupational Safety and Health (NIOSH). Pocket Guide to

Chemical Hazards. U.S. Department of Health and Human Services, Public Health

Service, Centers for Disease Control and Prevention. Cincinnati, OH. 1997.
National Air Toxics Program: The Integrated Urban Strategy

Report to Congress

A-29

BENZENE

71-43-2

Hazard Summary

Benzene is found in the air from emissions from burning coal and oil, gasoline service

stations, and motor vehicle exhaust. Acute (short-term) inhalation exposure of humans to

benzene may cause drowsiness, dizziness, headaches, as well as eye, skin, and respiratory

tract irritation, and, at high levels, unconsciousness. Chronic (long-term) inhalation

exposure has caused various disorders in the blood, including reduced numbers of red

blood cells and aplastic anemia, in occupational settings. Reproductive effects have been

reported for women exposed by inhalation to high levels, and adverse effects on the

developing fetus have been observed in animal tests. Increased incidence of leukemia

have been observed in humans occupationally exposed to benzene. The U.S.

Environmental Protection Agency (EPA) has classified benzene as a Group A, human

carcinogen.

Please Note: The main sources of information for this fact sheet are the Agency for Toxic Substances and Disease

Registry's (ATSDR's) Toxicological Profile for Benzene and EPA's Integrated Risk Information System (IRIS),

which contains information on the carcinogenic effects of benzene including the unit cancer risk for inhalation

exposure.

Physical Properties

! The chemical formula for benzene is C6H6, and it has a molecular weight of 78.11 g/mol.

(4)

! Benzene occurs as a volatile, colorless, highly flammable liquid that dissolves easily in

water. (1,7)

! Benzene has a sweet odor with an odor threshold of 1.5 ppm (5 mg/m3). (1)

! The vapor pressure for benzene is 95.2 mm Hg at 25 EC, and it has a log octanol/water

partition coefficient (log Kow) of 2.13. (1)

Uses

! Benzene is used as a constituent in motor fuels; as a solvent for fats, waxes, resins, oils,

inks, paints, plastics, and rubber; in the extraction of oils from seeds and nuts; and in

photogravure printing. It is also used as a chemical intermediate. Benzene is also used in

the manufacture of detergents, explosives, pharmaceuticals, and dyestuffs. (2,6)

Sources and Potential Exposure

! Individuals employed in industries that manufacture or use benzene may be exposed to

the highest levels of benzene. (1)
National Air Toxics Program: The Integrated Urban Strategy

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 Aplastic anemia is a risk factor for developing acute nonlymphocytic leukemia.

A-30

! Benzene is found in emissions from burning coal and oil, motor vehicle exhaust, and

evaporation from gasoline service stations and in industrial solvents. These sources

contribute to elevated levels of benzene in the ambient air, which may subsequently be

breathed by the public. (1)

! Tobacco smoke contains benzene and accounts for nearly half the national exposure to

benzene. (1)

! Individuals may also be exposed to benzene by consuming contaminated water. (1)

Assessing Personal Exposure

! Measurement of benzene in an individual's breath or blood or the measurement of

breakdown products in the urine (phenol) can provide information on recent personal

exposure. (1)

Health Hazard Information

Acute Effects:

! Coexposure to benzene with ethanol (e.g., alcoholic beverages) can increase benzene

toxicity. (1)

! Neurological symptoms of inhalation exposure to benzene include drowsiness, dizziness,

headaches, and unconsciousness in humans. Death may result from exposure to very high

levels of benzene. Ingestion of large amounts of benzene may result in vomiting,

dizziness, convulsions, and death in humans. (1)

! Exposure to liquid and vapor may irritate the skin, eyes, and upper respiratory tract.

Redness and blisters may result from dermal exposure to benzene. (1,2)

! Animal studies show neurologic, immunologic, and hematologic effects from inhalation

and oral exposure to benzene. (1)

! Tests involving acute exposure of animals, such as the LC50 and LD50 tests in rats, mice,

rabbits, and guinea pigs, have demonstrated benzene to have low acute toxicity from

inhalation, moderate acute toxicity from ingestion, and low or moderate acute toxicity

from dermal exposure. (3)

Chronic Effects (Noncancer):

! Chronic inhalation of certain levels of benzene causes disorders in the blood in humans.

Benzene specifically affects bone marrow (the tissues that produce blood cells). Aplastic

anemia1, excessive bleeding, and damage to the immune system (by changes in blood

levels of antibodies and loss of white blood cells) may develop. (1)

! In animals, chronic inhalation and oral exposure to benzene produces the same effects as

seen in humans. (1)

! Benzene causes both structural and numerical chromosomal aberrations in humans. (1)
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! EPA has not established a reference concentration (RfC) or a reference dose (RfD) for

benzene. (4)

! The California Environmental Protection Agency (CalEPA) has established a chronic

reference exposure level of 0.06 mg/m3 for benzene based on hematological effects in

humans. The CalEPA reference exposure level is a concentration at or below which

adverse health effects are not likely to occur. It is not a direct estimator of risk, but rather

a reference point to gauge the potential effects. At lifetime exposures increasingly greater

than the reference exposure level, the potential for adverse health effects increases. (5)

! ATSDR has established an acute inhalation minimal risk level (MRL) of 0.2 mg/m3 (0.05

ppm) based on immunological effects in mice and an intermediate MRL of 0.01 mg/m3

(0.004 ppm) based on neurological effects in mice. The MRL is an estimate of the daily

human exposure to a hazardous substance that is likely to be without appreciable risk of

adverse noncancer health effects over a specified duration of exposure. (1)

Reproductive/Developmental Effects:

! Several occupational studies suggest that benzene may impair fertility in women exposed

to high levels. However, these studies are limited due to lack of exposure history,

simultaneous exposure to other substances, and lack of follow-up. (1)

! Available human data on the developmental effects of benzene are inconclusive due to

concomitant exposure to other chemicals, inadequate sample size, and lack of quantitative

exposure data. (1)

! Adverse effects on the fetus, including low birth weight, delayed bone formation, and

bone marrow damage, have been observed where pregnant animals were exposed to

benzene by inhalation. (1)

Cancer Risk:

! Increased incidence of leukemia has been observed in humans occupationally exposed to

benzene. (1,4)

! EPA has classified benzene as a Group A, known human carcinogen. (4)

! EPA uses mathematical models, based on human and animal studies, to estimate the

probability of a person developing cancer from breathing air containing a specified

concentration of a chemical. EPA calculated a range of 2.2 x 10-6 to 7.8 x 10-6 as the

increase in the lifetime risk of an individual who is continuously exposed to 1 μg/m3 of

benzene in the air over their lifetime. EPA estimates that, if an individual were to

continuously breathe air containing benzene at an average of 0.13 to 0.45 μg/m3 (1.3 x

10-4 to 4.5 x 10-4 mg/m3) over his or her entire lifetime, that person would theoretically

have no more than a one-in-a-million increased chance of developing cancer as a direct

result of continuously breathing air containing this chemical. Similarly, EPA estimates

that continuously breathing air containing 1.3 to 4.5 μg/m3 (1.3 x 10-3 to 4.5 x 10-3 mg/m3)

would result in not greater than a one-in-a-hundred thousand increased chance of

developing cancer, and air containing 13 to 45 μg/m3 (1.3 x 10-2 to 4.5 x 10-2 mg/m3)

would result in not greater than a one-in-ten thousand increased chance of developing
National Air Toxics Program: The Integrated Urban Strategy

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A-32

Benzene

0.0001

0.001

0.01

0.1

1

10

100

1000

10000

100000

Health numbersa Regulatory, advisory

numbersb

Ref.

3

Ref.

7

Ref.

8,9

Ref.

7

Ref.

8

Ref.

5

Ref.

3

Ref.

9

CalEPA reference

exposure level

(0.06 mg/ m3)

 LC50 (rat s) (31,951 mg/ m3)

 LC50 (mice) (31,887 mg/ m3)

NOAELc (hemat ological)

(1.7 mg/ m3)

Cancer Risk

Level 1 in a

million risk

(1.3 t o 4.5 x

10-4 mg/ m3)

 OSHA STEL (16.3 mg/ m3)

 ACGIH STEL (8 mg/ m3)

 OSHA PEL, NIOSH STEL (3.2 mg/ m3)

 ACGIH TLV (1.6 mg/ m3)

NIOSH REL

(0.32 mg/ m3)

AIHA ERPG-2 (489 mg/ m3)

AIHA ERPG-1 (163 mg/ m3 Re )

f.

10

Ref.

10

Ref.

5

Ref.

4

cancer. For a detailed discussion of confidence in the potency estimates, please see IRIS.

(4)

! EPA has calculated an oral cancer slope factor of 2.9 x 10-2 (mg/kg/d)-1. (4)

Conversion Factors:

To convert from ppm to mg/m3: mg/m3 = (ppm) x (molecular weight of the compound)/(24.45).

For benzene: 1 ppm = 3.26 mg/m3.

To convert from μg/m3 to mg/m3: mg/m3 = (μg/m3) x (1 mg/1,000 μg).

Health Data from Inhalation Exposure

ACGIH STEL – American Conference of Governmental and Industrial Hygienists' short-term

exposure limit.

ACGIH TLV – American Conference of Governmental and Industrial Hygienists' threshold

limit value expressed as a time-weighted average; the concentration of a substance to which most
National Air Toxics Program: The Integrated Urban Strategy

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A-33

workers can be exposed without adverse effects.

AIHA ERPG – American Industrial Hygiene Association's emergency response planning

guidelines. ERPG 1 is the maximum airborne concentration below which it is believed nearly all

individuals could be exposed up to one hour without experiencing other than mild transient

adverse health effects or perceiving a clearly defined objectionable odor; ERPG 2 is the

maximum airborne concentration below which it is believed nearly all individuals could be

exposed up to one hour without experiencing or developing irreversible or other serious health

effects that could impair their abilities to take protective action.

LC50 (Lethal Concentration50) – A calculated concentration of a chemical in air to which

exposure for a specific length of time is expected to cause death in 50% of a defined

experimental animal population.

NIOSH REL – National Institute of Occupational Safety and Health's recommended exposure

limit; NIOSH-recommended exposure limit for an 8- or 10-h time-weighted-average exposure

and/or ceiling.

NIOSH STEL – NIOSH's short-term exposure limit; NIOSH recommended exposure limit for a

15-minute period.

NOAEL – No-observed-adverse-effect level.

OSHA PEL – Occupational Safety and Health Administration's permissible exposure limit

expressed as a time-weighted average; the concentration of a substance to which most workers

can be exposed without adverse effect averaged over a normal 8-h workday or a 40-h workweek.

OSHA STEL – Occupational Safety and Health Administration's short-term exposure limit.

a

 Health numbers are toxicological numbers from animal testing or risk assessment values

developed by EPA.

b

 Regulatory numbers are values that have been incorporated in Government regulations, while

advisory numbers are nonregulatory values provided by the Government or other groups as

advice.

c

 The NOAEL is from the critical study used as the basis for the CalEPA chronic reference

exposure level.

References

1. Agency for Toxic Substances and Disease Registry (ATSDR). Toxicological Profile for

Benzene (Update). Public Health Service, U.S. Department of Health and Human

Services, Atlanta, GA. 1997.

2. M. Sittig. Handbook of Toxic and Hazardous Chemicals and Carcinogens. 2nd ed. Noyes

Publications, Park Ridge, NJ. 1985.

3. U.S. Department of Health and Human Services. Registry of Toxic Effects of Chemical

Substances (RTECS, online database). National Toxicology Information Program,

National Library of Medicine, Bethesda, MD. 1993.
National Air Toxics Program: The Integrated Urban Strategy

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4. U.S. Environmental Protection Agency (EPA). Integrated Risk Information System (IRIS)

on Benzene. National Center for Environmental Assessment, Office of Research and

Development, Washington, DC. 1999.

5. California Environmental Protection Agency (CalEPA). Air Toxics Hot Spots Program

Risk Assessment Guidelines: Part III. Technical Support Document for the Determination

of Noncancer Chronic Reference Exposure Levels. SRP Draft. Office of Environmental

Health Hazard Assessment, Berkeley, CA. 1999.

6. The Merck Index. An Encyclopedia of Chemicals, Drugs, and Biologicals. 11th ed. Ed. S.

Budavari. Merck and Co. Inc., Rahway, NJ. 1989.

7. American Conference of Governmental Industrial Hygienists (ACGIH). 1999 TLVs and

BEIs. Threshold Limit Values for Chemical Substances and Physical Agents. Biological

Exposure Indices. Cincinnati, OH. 1999.

8. Occupational Safety and Health Administration (OSHA). Occupational Safety and

Health Standards, Toxic and Hazardous Substances. Code of Federal Regulations. 29

CFR 1910.1000. 1998.

9. National Institute for Occupational Safety and Health (NIOSH). Pocket Guide to

Chemical Hazards. U.S. Department of Health and Human Services, Public Health

Service, Centers for Disease Control and Prevention. Cincinnati, OH. 1997.

10. American Industrial Hygiene Association (AIHA). The AIHA1998 Emergency Response

Planning Guidelines and Workplace Environmental Exposure Level Guides Handbook.

1998.
National Air Toxics Program: The Integrated Urban Strategy

Report to Congress

1

 This fact sheet discusses beryllium and beryllium compounds. Most of the information

is on beryllium, except in those cases where there are differences in toxicity between beryllium

and beryllium compounds. In these cases, information on the beryllium compound is presented.

A-35

BERYLLIUM COMPOUNDS1

107-02-8

Hazard Summary

Inhalation exposure to beryllium primarily occurs in the workplaces where it is mined,

processed, or converted into alloys and chemicals, or from the burning of coal or fuel oil

and in tobacco smoke. Acute (short-term) inhalation exposure to high levels of beryllium

has been observed to cause inflammation of the lungs or acute pneumonitis (reddening

and swelling of the lungs) in humans; after exposure ends, these symptoms may be

reversible. Chronic (long-term) inhalation exposure of humans to beryllium has been

reported to cause chronic beryllium disease (berylliosis), in which granulomatous lesions

(noncancerous) develop in the lung. Inadequate information is available on the

reproductive or developmental effects of beryllium in humans or animals following

inhalation exposure. Inhalation exposure to beryllium has been demonstrated to cause

lung cancer in rats and monkeys. Human epidemiology studies are limited, but suggest a

causal relationship between beryllium exposure and an increased risk of lung cancer. The

U.S. Environmental Protection Agency (EPA) has classified beryllium as a Group B1,

probable human carcinogen.

Please Note: The main sources of information for this fact sheet are EPA's Integrated Risk Information System

(IRIS), which contains information on oral chronic toxicity and the reference dose (RfD) and inhalation chronic

toxicity and the reference concentration (RfC), and the carcinogenic effects of beryllium including the unit cancer

risk for inhalation exposure, EPA's Toxicological Review of Beryllium and Compounds, and the Agency for Toxic

Substances and Disease Registry's (ATSDR's) Toxicological Profile for Beryllium.

Physical Properties

! The chemical symbol for pure beryllium is Be, and its atomic weight is 9.012 g/mol. (1)

! Pure beryllium is a hard gray metal that does not occur naturally but does occur as a

chemical component of certain kinds of rocks, coal and oil, soil, and volcanic dust. (1)

! Beryllium is also present in a variety of compounds such as beryllium fluoride, beryllium

chloride, beryllium sulfate, beryllium oxide, and beryllium phosphate. (1)

! Pure beryllium is insoluble in water; however, some of its compounds are soluble in

water. (1)
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Uses

! Pure beryllium and its metal alloys have applications in electrical components, tools,

structural components for aircraft, missiles, and satellites, and other metal-fabricating

uses. (1)

! Beryllium is also used in consumer products, such as televisions, calculators, and

personal computers. (1)

Sources and Potential Exposure

! The greatest exposures to beryllium occur in the workplace (i.e., where it is mined,

processed, or converted into alloys and chemicals). (1)

! Individuals may also be exposed by inhalation of beryllium dust or fumes from the

burning of coal or fuel oil and in tobacco smoke, by the ingestion of many fruits and

vegetables and water, or through natural occurrence in soils. (1)

! The average concentration of beryllium measured in the air in the U.S. during the 1980s

was 0.03 ng/m3. Ambient concentrations measured in 50 cities between 1977 and 1981

were 0.1–0.4 ng/m3. (1)

Assessing Personal Exposure

! Beryllium levels can be measured in urine and blood, but the levels in urine are quite

variable, making it difficult to use these levels to assess total exposure. (1)

! Beryllium levels in tissues can be measured through biopsy procedures, however the

relationship to exposure is not well documented. (1)

! A medical test, termed the antigen-specific lymphocyte transformation test, can be used to

measure hypersensitivity in individuals previously exposed to beryllium and can also be

used to diagnose chronic beryllium disease. (1)

Health Hazard Information

Acute Effects:

! Acute inhalation exposure to high levels of beryllium has been observed to cause

inflammation of the lungs and acute pneumonitis (reddening and swelling of the lungs) in

humans; after exposure ends, these symptoms may be reversible. Acute pneumonitis may

cause death. (1-4)

! Acute animal tests, such as the LD50 test in rats and mice, have demonstrated beryllium

compounds to vary in acute toxicity, ranging from high to extreme acute toxicity from

oral exposure. (5)
National Air Toxics Program: The Integrated Urban Strategy

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A-37

Chronic Effects (Noncancer):

! Chronic occupational exposure of humans to beryllium by inhalation has been reported to

cause chronic beryllium disease (berylliosis), in which granulomatous lesions

(noncancerous) develop in the lung. The onset of these effects may be delayed by 3

months to more than 20 years. Symptoms of chronic beryllium disease include irritation

of the mucous membranes, reduced lung capacity, shortness of breath, fatigue, anorexia,

dyspnea, malaise, and weight loss. In some cases, chronic beryllium disease may cause

death. (1-4)

! Animal studies have also reported effects on the lung, such as chronic pneumonitis, from

chronic inhalation exposure. (1-3)

! Chronic inhalation exposure has also been observed to cause immunological effects in

humans and animals. (1-3)

! A skin allergy may result from dermal exposure to beryllium. Eye contact with beryllium

dust has been observed to cause acute conjunctivitis in humans. (1)

! The RfC for beryllium is 0.00002 mg/m3 based on respiratory effects in humans. The RfC

is an estimate (with uncertainty spanning perhaps an order of magnitude) of a continuous

inhalation exposure to the human population (including sensitive subgroups) that is likely

to be without appreciable risk of deleterious noncancer effects during a lifetime. It is not a

direct estimator of risk but rather a reference point to gauge the potential effects. At

exposures increasingly greater than the RfC, the potential for adverse health effects

increases. Lifetime exposure above the RfC does not imply that an adverse health effect

would necessarily occur. (3)

! EPA has medium confidence in the RfC due to: medium confidence in the study on

which the RfC is based because a no-observed-adverse-affect level (NOAEL) was not

identified in the study, but a NOAEL slightly below the lowest-observed-adverse-effect

level (LOAEL) was suggested in another study; and medium confidence in the database

due to lack of adequate exposure monitoring in the epidemiology studies and some

uncertainty regarding the mechanism associated with progression to chronic beryllium

disease in beryllium-sensitized individuals. (3)

! The RfD for beryllium is 0.002 mg/kg/d based on small intestinal lesions in dogs. (3)

! EPA has low to medium confidence in the RfD due to: medium confidence in the study

on which the RfD was based because it was administered by the oral route with multiple

doses for chronic duration, but there were small groups of animals, early mortality at the

high dose level, and no control for potential litter effects; and low to medium confidence

in the database because there is only one chronic study in dogs showing adverse effect

levels. (3)

Reproductive/Developmental Effects:

! The potential for beryllium to induce developmental or reproductive effects has not been

adequately assessed.

! Limited information is available on the reproductive or developmental effects of

beryllium in humans following inhalation exposure. A case control study found no

association between paternal occupational exposure and the risk of stillbirth, pre-term
National Air Toxics Program: The Integrated Urban Strategy

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A-38

delivery, or small-for-gestational-age infants, although this study has limited sensitivity.

(2,3)

! No data are available on reproductive or developmental effects in animals following

inhalation. (2,3)

Cancer Risk:

! Several human epidemiological studies have investigated the relationship between

beryllium exposure in workers and lung cancer deaths. Although there are shortcomings

in all the studies, the results are suggestive of a causal relationship between beryllium

exposure and an increased risk of lung cancer. (2,3)

! Beryllium compounds have been shown to cause lung cancer from inhalation exposure in

rats and monkeys. (1–3)

! EPA has classified beryllium as a Group B1, probable human carcinogen. (3)

! EPA uses mathematical models, based on human and animal studies, to estimate the

probability of a person developing cancer from breathing air containing a specified

concentration of a chemical. EPA calculated an inhalation unit risk estimate of 2.4 x 10-3

(μg/m3)

-1. EPA estimates that, if an individual were to continuously breathe air containing

beryllium at an average of 0.0004 μg/m3 (4 x 10-7 mg/m3) over his or her entire lifetime,

that person would theoretically have no more than a one-in-a-million increased chance of

developing cancer as a direct result of breathing air containing this chemical. Similarly,

EPA estimates that continuously breathing air containing 0.004 μg/m3 (4 x 10-6 mg/m3)

would result in not greater than a one-in-a-hundred thousand increased chance of

developing cancer, and air containing 0.04 μg/m3 (4 x 10-5 mg/m3) would result in not

greater than a one-in-ten thousand increased chance of developing cancer. For a detailed

discussion of confidence in the potency estimates, please see IRIS. (3)

Conversion Factors:

To convert from ppm to mg/m3: mg/m3 = (ppm) x (molecular weight of the compound)/(24.45).

Beryllium and its compounds do not exist in the atmosphere in the vapor phase; therefore, an air

conversion factor is not applicable. (1)
National Air Toxics Program: The Integrated Urban Strategy

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A-39

Beryllium

0.0000001

0.000001

0.00001

0.0001

0.001

0.01

0.1

1

10

Health numbersa Regulatory, advisory

numbersb

Ref.

3

Ref.

3

Ref.

3

Ref.

7,8 Ref.

6

NOAELc (respirat ory) (0.0001 mg/m3)

RfC (2 x 10-5 mg/ m3)

Cancer Risk Level

1 in a million risk

(4 x10-7 mg/ m3)

OSHA PEL, ACGIH TLV

(0.002 mg/m3)

NIOSH REL

(0.0005 mg/ m3)

Ref.

9

AIHA ERPG-2 (0.025 mg/m3)

NIOSH IDLH (4 mg/m3)

Ref.

6

Health Data from Inhalation Exposure

ACGIH TLV – American Conference of Governmental and Industrial Hygienists' threshold

limit value expressed as a time-weighted average; the concentration of a substance to which most

workers can be exposed without adverse effects.

AIHA ERPG – American Industrial Hygiene Association's emergency response planning

guidelines. ERPG 1 is the maximum airborne concentration below which it is believed nearly all

individuals could be exposed up to one hour without experiencing other than mild transient

adverse health effects or perceiving a clearly defined objectionable odor; ERPG 2 is the

maximum airborne concentration below which it is believed nearly all individuals could be

exposed up to one hour without experiencing or developing irreversible or other serious health

effects that could impair their abilities to take protective action.

NIOSH IDLH – National Institute of Occupational Safety and Health's immediately dangerous
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A-40

to life or health concentration; NIOSH recommended exposure limit to ensure that a worker can

escape from an exposure condition that is likely to cause death or immediate or delayed

permanent adverse health effects or prevent escape from the environment.

NIOSH REL – NIOSH's recommended exposure limit; NIOSH-recommended exposure limit for

an 8- or 10-h time-weighted-average exposure and/or ceiling.

OSHA PEL – Occupational Safety and Health Administration's permissible exposure limit

expressed as a time-weighted average; the concentration of a substance to which most workers

can be exposed without adverse effect averaged over a normal 8-h workday or a 40-h workweek.

a

 Health numbers are toxicological numbers from animal testing or risk assessment values

developed by EPA.

b

 Regulatory numbers are values that have been incorporated in Government regulations, while

advisory numbers are nonregulatory values provided by the Government or other groups as

advice.

c

 This NOAEL is from the critical study used as the basis of the EPA RfC.

References

1. Agency for Toxic Substances and Disease Registry (ATSDR). Toxicological Profile for

Beryllium (Draft). Public Health Service, U.S. Department of Health and Human

Services, Altanta, GA. 1992.

2. U.S. Environmental Protection Agency (EPA). Toxicological Review of Beryllium and

Compounds. In support of summary information on IRIS. National Center for

Environmental Assessment, Washington, DC. 1998.

3. U.S. Environmental Protection Agency (EPA). Integrated Risk Information System (IRIS)

on Beryllium. National Center for Environmental Assessment, Office of Research and

Development, Washington, DC. 1999.

4. U.S. Department of Health and Human Services. Hazardous Substances Data Bank

(HSDB, online database). National Toxicology Information Program, National Library of

Medicine, Bethesda, MD. 1993.

5. U.S. Department of Health and Human Services. Registry of Toxic Effects of Chemical

Substances (RTECS, online database). National Toxicology Information Program,

National Library of Medicine, Bethesda, MD. 1993.

6. National Institute for Occupational Safety and Health (NIOSH). Pocket Guide to

Chemical Hazards. U.S. Department of Health and Human Services, Public Health

Service, Centers for Disease Control and Prevention. Cincinnati, OH. 1997.

7. Occupational Safety and Health Administration (OSHA). Occupational Safety and

Health Standards, Toxic and Hazardous Substances. Code of Federal Regulations. 29

CFR 1910.1000. 1998.
National Air Toxics Program: The Integrated Urban Strategy

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8. American Conference of Governmental Industrial Hygienists (ACGIH). 1999 TLVs and

BEIs. Threshold Limit Values for Chemical Substances and Physical Agents. Biological

Exposure Indices. Cincinnati, OH. 1999.

9. American Industrial Hygiene Association (AIHA). The AIHA 1998 Emergency Response

Planning Guidelines and Workplace Environmental Exposure Level Guides Handbook.

1998.
National Air Toxics Program: The Integrated Urban Strategy

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1,3-BUTADIENE

106-99-0

Hazard Summary

1,3-Butadiene is found in ambient air primarily as a compound of motor vehicle exhaust.

Acute (short-term) exposure to 1,3-butadiene by inhalation in humans results in irritation

of the eyes, nasal passages, throat, and lungs, and causes neurological effects such as

blurred vision, fatigue, headache, and vertigo. Epidemiological studies have reported a

possible association between 1,3-butadiene exposure and cardiovascular diseases. No

information is available on the reproductive or developmental effects of 1,3-butadiene in

humans, while animal studies have reported these type of effects. Epidemiological studies

of workers in rubber plants have shown an association between 1,3-butadiene exposure

and increased incidence of leukemia. Animal studies have reported tumors at various sites

from 1,3-butadiene exposure. The U.S. Environmental Protection Agency (EPA) has

classified 1,3-butadiene as a Group B2, probable human carcinogen.

Please Note: The main sources of information for this fact sheet are EPA's Integrated Risk Information System

(IRIS), which contains information on the carcinogenic effects of 1,3-butadiene including the unit cancer risk for

inhalation exposure, and the Agency for Toxic Substances and Disease Registry's (ATSDR's) Toxicological Profile

for 1,3-Butadiene.

Physical Properties

! 1,3-Butadiene is a colorless gas with a mild gasoline-like odor. (1)

! The odor threshold for 1,3-butadiene is 1.6 ppm. (7)

! The chemical formula for 1,3-butadiene is C4H6, and the molecular weight is 54.09 

g/mol. (1)

! The vapor pressure for 1,3-butadiene is 2100 mm Hg at 25 EC, and it has an

octanol/water partition coefficient (log Kow) of 1.99. (1)

Uses

! 1,3-Butadiene is used in the production of rubber and plastics. It is also used in

copolymers including acrylics. (1)

Sources and Potential Exposure

! Sources of 1,3-butadiene released into the air include manufacturing and processing

facilities, motor vehicle exhaust, forest fires or other combustion, and cigarette smoke. (1)

! 1,3-Butadiene was detected in ambient air of cities and suburban areas from 1970 to 1982

at an average level of 0.3 ppb. (1)

! Higher levels of 1,3-butadiene may be found in highly industrialized cities or near oil

refineries, chemical manufacturing plants, and plastic and rubber factories. (1)
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! 1,3-Butadiene has been found in drinking water and in plastic or rubber food containers,

but not in food samples. (1)

! Occupational exposure to 1,3-butadiene may occur in the rubber, plastics, and resins

industries. (1)

Assessing Personal Exposure

! There is no reliable medical test available at this time to assess personal exposure to

1,3-butadiene. (1)

Health Hazard Information

Acute Effects:

! Acute exposure to 1,3-butadiene by inhalation in humans results in irritation of the eyes,

nasal passages, throat, and lungs. Neurological effects, such as blurred vision, fatigue,

headache, and vertigo, have also been reported at very high exposure levels. (1,3)

! Dermal exposure to 1,3-butadiene causes a sensation of cold, followed by a burning

sensation, which may lead to frostbite. (1)

! Tests involving acute exposure of animals, such as the LC50 test in rats and mice, have

shown 1,3-butadiene to have low acute toxicity. (1,4)

Chronic Effects (Noncancer):

! One epidemiological study reported that chronic (long-term) exposure to 1,3-butadiene

via inhalation resulted in an increase in cardiovascular diseases, such as rheumatic and

arteriosclerotic heart diseases, while other human studies have reported effects on the

blood. (1)

! Animal studies have reported effects on the respiratory and cardiovascular systems,

blood, and liver from chronic, inhalation exposure to 1,3-butadiene. (1)

! EPA has not established a reference concentration (RfC) or a reference dose (RfD) for

1,3-butadiene. (5)

! The California Environmental Protection Agency (CalEPA) has established a chronic

reference level of 0.008 mg/m3 for 1,3-butadiene based on reproductive effects in mice.

The CalEPA reference exposure level is a concentration at or below which adverse health

effects are not likely to occur. It is not a direct estimator of risk, but rather a reference

point to gauge the potential effects. At lifetime exposures increasingly greater than the

reference exposure level, the potential for adverse health effects increases. (6)

Reproductive/Developmental Effects:

! No information is available on reproductive or developmental effects of 1,3-butadiene in

humans. (1)

! Animal studies using mice have reported developmental effects, such as skeletal

abnormalities and decreased fetal weights, and reproductive effects, including an
National Air Toxics Program: The Integrated Urban Strategy

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A-45

increased incidence of ovarian atrophy, testicular atrophy, and sperm abnormalities from

inhalation exposure to 1,3-butadiene. (1)

Cancer Risk:

! A large epidemiological study of synthetic rubber industry workers demonstrated a

consistent association between 1,3-butadiene exposure and occurrence of leukemia (10,

11).

! Several epidemiological studies of workers in styrene-butadiene rubber factories have

shown an increased incidence of respiratory, bladder, stomach, and

lymphato-hematopoietic cancers. However, these studies are not sufficient to determine a

causal association between 1,3-butadiene exposure and cancer due to possible exposure to

other chemicals and other confounding factors. (1,5,6)

! Animal studies have reported tumors at a variety of sites from inhalation exposure to

1,3-butadiene. (1,5,6)

! EPA has classified 1,3-butadiene as a Group B2, probable human carcinogen. However,

based on recently available human data, EPA is evaluating a classification of known

human carcinogen. (5)

! EPA uses mathematical models, based on human and animal studies, to estimate the

probability of a person developing cancer from continuously breathing air containing a

specified concentration of a chemical. EPA is currently reevaluating their inhalation unit

risk estimate of 2.8 x 10-4 (μg/m3)

-1 that was derived in 1991. A revised unit risk estimate

of 2.1 x 10-6 (μg/m3)

-1 was presented to EPA’s Science Advisory Board (SAB) for review

in 1998. As a result of SAB comments, the estimate will be revised and is likely to be

lower than the 1991 value. (12)

Conversion Factors:

To convert from ppm to mg/m3: mg/m3 = (ppm) x (molecular weight of the compound)/(24.45).

For 1,3-butadiene: 1 ppm = 2.21 mg/m3.

To convert from μg/m3

 to mg/m3: mg/m3 = (μg/m3) x (1 mg/1,000 μg).
National Air Toxics Program: The Integrated Urban Strategy

Report to Congress

A-46

1,3-Butadiene

0.000001

0.00001

0.0001

0.001

0.01

0.1

1

10

100

1000

10000

100000

1000000

Health numbersa Regulatory, advisory

numbersb

Ref.

1

Ref.

4

Ref.

6

Ref.

6

Ref.

8 Ref.

9

Ref.

8

LC50 (rat s) (269,896 mg/ m3)

LC50 (mice) (285,382 mg/ m3)

LOAELc (reproduct ive)

(13.9 mg/ m3)

CalEPA reference

exposure

level (0.008 mg/ m3)

Cancer Risk

Level 1 in a

million risk

(4 x 10-6

mg/ m3)

OSHA STEL (11 mg/ m3)

ACGIH TLV (4.4 mg/ m3)

OSHA PEL

(2.2 mg/ m3)

AIHA ERPG-1 (22.1 mg/ m3)

AIHA ERPG-2 (442 mg/ m3)

Ref.

10

Ref.

10

Ref.

5

NIOSH IDLH (4420mg/ m3)

Ref.

13

Health Data from Inhalation Exposure

ACGIH TLV – American Conference of Governmental and Industrial Hygienists' threshold

limit value expressed as a time-weighted average; the concentration of a substance to which most

workers can be exposed without adverse effects.

AIHA ERPG – American Industrial Hygiene Association's emergency response planning

guidelines. ERPG 1 is the maximum airborne concentration below which it is believed nearly all

individuals could be exposed up to one hour without experiencing other than mild transient

adverse health effects or perceiving a clearly defined objectionable odor; ERPG 2 is the

maximum airborne concentration below which it is believed nearly all individuals could be

exposed up to one hour without experiencing or developing irreversible or other serious health

effects that could impair their abilities to take protective action.

LC50 (Lethal Concentration50) – A calculated concentration of a chemical in air to which

exposure for a specific length of time is expected to cause death in 50% of a defined

experimental animal population.

LOAEL – Lowest-observed-adverse-affect level.
National Air Toxics Program: The Integrated Urban Strategy

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A-47

NIOSH IDLH – National Institute of Occupational Safety and Health's immediately dangerous

to life or health concentration; NIOSH recommended exposure limit to ensure that a worker can

escape from an exposure condition that is likely to cause death or immediate or delayed

permanent adverse health effects or prevent escape from the environment.

OSHA PEL – Occupational Safety and Health Administration's permissible exposure limit

expressed as a time-weighted average; the concentration of a substance to which most workers

can be exposed without adverse effect averaged over a normal 8-h workday or a 40-h workweek.

OSHA STEL – OSHA's short-term exposure limit.

a

 Health numbers are toxicological numbers from animal testing or risk assessment values

developed by EPA.

b

 Regulatory numbers are values that have been incorporated in Government regulations, while

advisory numbers are nonregulatory values provided by the Government or other groups as

advice.

c

 The LOAEL is from the critical study used as the basis for the CalEPA chronic reference

exposure level.

References

1. Agency for Toxic Substances and Disease Registry (ATSDR). Toxicological Profile for

1,3-Butadiene. Public Health Service, U.S. Department of Health and Human Services,

Atlanta, GA. 1992.

2. E.J. Calabrese and E.M. Kenyon. Air Toxics and Risk Assessment. Lewis Publishers.

1991.

3. U.S. Department of Health and Human Services. Hazardous Substances Data Bank

(HSDB, online database). National Toxicology Information Program, National Library of

Medicine, Bethesda, MD. 1993.

4. U.S. Department of Health and Human Services. Registry of Toxic Effects of Chemical

Substances (RTECS, online database). National Toxicology Information Program,

National Library of Medicine, Bethesda, MD. 1993.

5. U.S. Environmental Protection Agency (EPA). Integrated Risk Information System (IRIS)

on 1,3-Butadiene. National Center for Environmental Assessment, Office of Research

and Development, Washington, DC. 1999.

6. California Environmental Protection Agency (CalEPA). Technical Support Document for

the Determination of Noncancer Chronic Reference Exposure Levels. Draft for Public

Comment. Office of Environmental Health Hazard Assessment, Berkeley, CA. 1997.

7. J.E. Amoore and E. Hautala. Odor as an aid to chemical safety: Odor thresholds

compared with threshold limit values and volatilities for 214 industrial chemicals in air

and water dilution. Journal of Applied Toxicology, 3(6):272-290. 1983.
National Air Toxics Program: The Integrated Urban Strategy

Report to Congress

A-48

8. Occupational Safety and Health Administration (OSHA). Occupational Safety and

Health Standards, Toxic and Hazardous Substances. Code of Federal Regulations. 29

CFR 1910.1000. 1998.

9. American Conference of Governmental Industrial Hygienists (ACGIH). 1999 TLVs and

BEIs. Threshold Limit Values for Chemical Substances and Physical Agents. Biological

Exposure Indices. Cincinnati, OH. 1999.

10. Delzell E, Sathiakumar N, Hovinga M, et al. A follow-up study of synthetic rubber

workers. Toxicology 113:182-9. 1996.

11. Macaluso M, Larson R, Delzell E, et al. Leukemia and cumulative exposure to butadiene,

styrene and benzene among workers in the synthetic rubber industry. Toxicology

113:190-202. 1996.

12. U.S. Environmental Protection Agency (EPA). An SAB Report: Review of the Health Risk

Assessment of 1,3-Butadiene. Science Advisory Board, Washington, DC. 

EPA-SAB-EHC-99-003. 1998.

13. National Institute for Occupational Safety and Health (NIOSH). Pocket Guide to

Chemical Hazards. U.S. Department of Health and Human Services, Public Health

Service, Centers for Disease Control and Prevention. Cincinnati, OH. 1997.

14. American Industrial Hygiene Association (AIHA). The AIHA 1998 Emergency Response

Planning Guidelines and Workplace Environmental Exposure Level Guides Handbook.

1998.
National Air Toxics Program: The Integrated Urban Strategy

Report to Congress

1

 This fact sheet discusses cadmium and cadmium compounds. Most of the information is

on cadmium, except in those cases where there are differences in toxicity between cadmium and

cadmium compounds. In these cases, information on the cadmium compound is presented.

A-49

CADMIUM COMPOUNDS1

Hazard Summary

The main sources of cadmium in the air are the burning of fossil fuels such as coal

or oil and the incineration of municipal waste. The acute (short-term) effects of

cadmium in humans through inhalation exposure consist mainly of effects on the

lung, such as pulmonary irritation. Chronic (long-term) inhalation or oral

exposure to cadmium leads to a build-up of cadmium in the kidneys that can cause

kidney disease. Cadmium has been shown to be a developmental toxicant in

animals, resulting in fetal malformations and other effects, but no conclusive

evidence exists in humans. An association between cadmium exposure and an

increased risk of lung cancer has been reported from human studies, but these

studies are inconclusive due to confounding factors. Animal studies have

demonstrated an increase in lung cancer from long-term inhalation exposure to

cadmium. The U.S. Environmental Protection Agency (EPA) has classified

cadmium as a Group B1, probable human carcinogen.

Please Note: The main sources of information for this fact sheet are EPA's Integrated Risk Information System

(IRIS), which contains information on oral chronic toxicity and the reference dose (RfD), and the carcinogenic

effects of cadmium including the unit cancer risk for inhalation exposure, and the Agency for Toxic Substances and

Disease Registry's (ATSDR's) Toxicological Profile for Cadmium.

Physical Properties

! Cadmium is a soft silver-white metal that is usually found in combination with other

elements. (1)

! Cadmium compounds range in solubility in water from quite soluble to practically

insoluble. (1)

! The chemical symbol for cadmium is Cd and the atomic weight is 112.41 g/mol. (1)

Uses

! Most cadmium used in the U.S. today is obtained as a byproduct from the smelting of

zinc, lead, or copper ores. (1)

! Cadmium is used to manufacture pigments and batteries and in the metal-plating and

plastics industries. (1)
National Air Toxics Program: The Integrated Urban Strategy

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Sources and Potential Exposure

! The largest sources of airborne cadmium in the environment are the burning of fossil

fuels such as coal or oil, and incineration of municipal waste materials. Cadmium may

also be emitted into the air from zinc, lead, or copper smelters. (1)

! For nonsmokers, food is generally the largest source of cadmium exposure. Cadmium

levels in some foods can be increased by the application of phosphate fertilizers or

sewage sludge to farm fields. (1)

! Smoking is another important source of cadmium exposure. Smokers have about twice as

much cadmium in their bodies as do nonsmokers. (1)

Assessing Personal Exposure

! The amount of cadmium present in blood or urine can be measured by atomic absorption

spectrophotometry and used as an indication of cadmium exposure. (1)

! A more precise method, called neutron activation analysis, can be used to measure

cadmium concentrations in the liver or kidney. (1)

Health Hazard Information

Acute Effects:

! Acute inhalation exposure to high levels of cadmium in humans may result in effects on

the lung, such as bronchial and pulmonary irritation. A single acute exposure to high

levels of cadmium can result in long-lasting impairment of lung function. (1,3,4)

! Cadmium is considered to have high acute toxicity, based on short-term animal tests such

as the LC50 test in rats. (5)

Chronic Effects (Noncancer):

! Chronic inhalation and oral exposure of humans to cadmium results in a build-up of

cadmium in the kidneys that can cause kidney disease, including proteinuria, a decrease in

glomerular filtration rate, and an increased frequency of kidney stone formation. (1,3,4)

! Other effects noted in humans from chronic exposure to cadmium in air are effects on the

lung, including bronchiolitis and emphysema. (1,3,4)

! Chronic inhalation or oral exposure of animals to cadmium results in effects on the

kidney, liver, lung, bone, immune system, blood, and nervous system. (1,3)

! The RfD for cadmium in drinking water is 0.0005 mg/kg/d, and the RfD for dietary

exposure to cadmium is 0.001 mg/kg/d; both are based on significant proteinuria in

humans. The RfD is an estimate (with uncertainty spanning perhaps an order of

magnitude) of a daily oral exposure to the human population (including sensitive

subgroups) that is likely to be without appreciable risk of deleterious noncancer effects

during a lifetime. It is not a direct estimator of risk, but rather a reference point to gauge

the potential effects. At exposures increasingly greater than the RfD, the potential for
National Air Toxics Program: The Integrated Urban Strategy

Report to Congress

A-51

adverse health effects increases. Lifetime exposure above the RfD does not imply that an

adverse health effect would necessarily occur. (6)

! EPA has high confidence in both RfD values based primarily on a strong database for

cadmium toxicity in humans and animals that also permits calculation of pharmacokinetic

parameters of cadmium absorption, distribution, metabolism, and elimination. (6)

! EPA has not established a reference concentration (RfC) for cadmium. (6)

! The California Environmental Protection Agency (CalEPA) has established a chronic

reference exposure level of 0.00001 mg/m3 for cadmium based on kidney and respiratory

effects in humans. The CalEPA reference exposure level is a concentration at or below

which adverse health effects are not likely to occur. (7)

Reproductive/Developmental Effects:

! Limited evidence exists for an association between inhalation exposure and a reduction in

sperm number and viability in humans. (1)

! Human developmental studies on cadmium are limited, although there is some evidence

to suggest that maternal cadmium exposure may result in decreased birth weights. (1)

! Animal studies provide evidence that cadmium has developmental effects, such as low

fetal weight, skeletal malformations, interference with fetal metabolism, and impaired

neurological development, via inhalation and oral exposure. (1,3,4)

! Limited animal data are available, although some reproductive effects, such as decreased

reproduction and testicular damage, have been noted following oral exposures. (1)

Cancer Risk:

! Several occupational studies have reported an excess risk of lung cancer in humans from

exposure to inhaled cadmium. However, the evidence is limited rather than conclusive

due to confounding factors. (1,3,6)

! Animal studies have reported cancer resulting from inhalation exposure to several forms

of cadmium, while animal ingestion studies have not demonstrated cancer resulting from

exposure to cadmium compounds. (1,3,6)

! EPA considers cadmium to be a probable human carcinogen and has classified it as a

Group B1 carcinogen. (6)

! EPA uses mathematical models, based on human and animal studies, to estimate the

probability of a person developing cancer from breathing air containing a specified

concentration of a chemical. EPA calculated an inhalation unit risk estimate of 1.8 x 10-3

(μg/m3)

-1. EPA estimates that, if an individual were to continuously breathe air containing

cadmium at an average of 0.0006 μg/m3 (6 x 10-7 mg/m3) over his or her entire lifetime,

that person would theoretically have no more than a one-in-a-million increased chance of

developing cancer as a direct result of breathing air containing this chemical. Similarly,

EPA estimates that continuously breathing air containing 0.006 μg/m3 (6 x 10-6 mg/m3)

would result in not greater than a one-in-a-hundred thousand increased chance of

developing cancer, and air containing 0.06 μg/m3 (6 x 10-5 mg/m3) would result in not

greater than a one-in-ten thousand increased chance of developing cancer. For a detailed

discussion of confidence in the potency estimates, please see IRIS. (6)
National Air Toxics Program: The Integrated Urban Strategy

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A-52

Cadmium

0.0000001

0.000001

0.00001

0.0001

0.001

0.01

0.1

1

10

100

1000

10000

Health numbersa Regulatory, advisory

numbersb

Ref.

5

Ref.

7

Ref.

8

Ref.

10 Ref.

10

Ref.

7

Ref.

6

Ref.

9

Ref.

9

LC50 (rat s) (500 mg/ m3)

LOAELc (kidney and respirat ory)

(0.02 mg/ m3)

ACGIH TLV (dust s) (0.01 mg/ m3)

OSHA PEL (fumes) (0.1 mg/ m3)

NIOSH IDLH (dust or fumes) (9 mg/ m3)

OSHA PEL (dust s) (0.2 mg/ m3)

Cancer Risk

Level 1 in a

million risk

(6 x 10 -7 mg/ m3)

CalEPA reference exposure

level (0.0001 mg/ m3)

Conversion Factors:

To convert from ppm to mg/m3: mg/m3 = (ppm) x (molecular weight of the compound)/(24.45).

For cadmium: 1 ppm = 4.6 mg/m3.

To convert from μg/m3 to mg/m3: mg/m3 = (μg/m3) x (1 mg/1000 μg).

Health Data from Inhalation Exposure

ACGIH TLV – American Conference of Governmental and Industrial Hygienists' threshold

limit value expressed as a time-weighted average; the concentration of a substance to which most

workers can be exposed without adverse effects.

LC50 (Lethal Concentration50) – A calculated concentration of a chemical in air to which
National Air Toxics Program: The Integrated Urban Strategy

Report to Congress

A-53

exposure for a specific length of time is expected to cause death in 50% of a defined

experimental animal population.

LOAEL – Lowest-observed-adverse-affect level.

NIOSH IDLH – National Institute of Occupational Safety and Health's immediately dangerous

to life and health; NIOSH concentration representing the maximum level of a pollutant from

which an individual could escape within 30 minutes without escape-impairing symptoms or

irreversible health effects.

OSHA PEL – Occupational Safety and Health Administration's permissible exposure limit

expressed as a time-weighted average; the concentration of a substance to which most workers

can be exposed without adverse effect averaged over a normal 8-h workday or a 40-h workweek.

a

 Health numbers are toxicological numbers from animal testing or risk assessment values

developed by EPA.

b

 Regulatory numbers are values that have been incorporated in Government regulations, while

advisory numbers are nonregulatory values provided by the Government or other groups as

advice.

c

 The LOAEL is from the critical study used as the basis for the CalEPA chronic reference

exposure level.

References

1. Agency for Toxic Substances and Disease Registry (ATSDR). Toxicological Profile for

Cadmium. Draft for Public Comment. Public Health Service, U.S. Department of Health

and Human Services, Atlanta, GA. 1997.

2. U.S. Environmental Protection Agency (EPA). Deposition of Air Pollutants to the Great

Waters. First Report to Congress. EPA-453/R-93-055. Office of Air Quality Planning

and Standards, Research Triangle Park, NC. 1994.

3. E.J. Calabrese and E.M. Kenyon. Air Toxics and Risk Assessment. Lewis Publishers,

Chelsea, MI. 1991.

4. U.S. Department of Health and Human Services. Hazardous Substances Data Bank

(HSDB, online database). National Toxicology Information Program, National Library of

Medicine, Bethesda, MD. 1993.

5. U.S. Department of Health and Human Services. Registry of Toxic Effects of Chemical

Substances (RTECS, online database). National Toxicology Information Program,

National Library of Medicine, Bethesda, MD. 1993.

6. U.S. Environmental Protection Agency (EPA). Integrated Risk Information System (IRIS)

on Cadmium. National Center for Environmental Assessment, Office of Research and

Development, Washington, DC. 1999.
National Air Toxics Program: The Integrated Urban Strategy

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A-54

7. California Environmental Protection Agency (CalEPA). Technical Support Document for

the Determination of Noncancer Chronic Reference Exposure Levels. Draft for Public

Comment. Office of Environmental Health Hazard Assessment, Berkeley, CA. 1997.

8. National Institute for Occupational Safety and Health (NIOSH). Pocket Guide to

Chemical Hazards. U.S. Department of Health and Human Services, Public Health

Service, Centers for Disease Control and Prevention. Cincinnati, OH. 1997.

9. American Conference of Governmental Industrial Hygienists (ACGIH). 1999 TLVs and

BEIs. Threshold Limit Values for Chemical Substances and Physical Agents. Biological

Exposure Indices. Cincinnati, OH. 1999.

10. Occupational Safety and Health Administration (OSHA). Occupational Safety and

Health Standards, Toxic and Hazardous Substances. Code of Federal Regulations. 29

CFR 1910.1000. 1998.
National Air Toxics Program: The Integrated Urban Strategy

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A-55

CARBON TETRACHLORIDE

56-23-5

Hazard Summary

Carbon tetrachloride may be found in both ambient outdoor and indoor air. Human

symptoms of acute (short-term) inhalation and oral exposures to carbon tetrachloride

include headache, weakness, lethargy, nausea, and vomiting. Depression of the central

nervous system (CNS) has also been reported. More severe acute exposures result in

kidney and liver damage and extreme exposures have resulted in delayed pulmonary

edema (resulting from kidney damage). Chronic (long-term) inhalation or oral exposure

to carbon tetrachloride also produces liver and kidney damage in humans. Little

information is available on the reproductive or developmental effects of carbon

tetrachloride in humans. Reproductive effects have been observed in animals exposed to

carbon tetrachloride orally and by inhalation. Human data on the carcinogenic effects of

carbon tetrachloride are limited. Studies in animals have shown that ingestion of carbon

tetrachloride increases the risk of liver cancer. The U.S. Environmental Protection

Agency (EPA) has classified carbon tetrachloride as a Group B2, probable human

carcinogen.

Please Note: The main sources of information for this fact sheet are EPA's Integrated Risk Information System

(IRIS), which contains information on oral chronic toxicity of carbon tetrachloride and the reference dose (RfD),

and the carcinogenic effects of carbon tetrachloride including the unit cancer risk for inhalation exposure, and the

Agency for Toxic Substances and Disease Registry's (ATSDR's) Toxicological Profile for Carbon Tetrachloride.

Physical Properties

! The chemical formula for carbon tetrachloride is CCl4, and its molecular weight is 153.8

g/mol. (1,2)

! Carbon tetrachloride is a clear, nonflammable liquid which is almost insoluble in water.

(1)

! Carbon tetrachloride has a sweet characteristic odor, with an odor threshold above 10

ppm. (1)

! The vapor pressure for carbon tetrachloride is 91.3 mm Hg at 20 EC, and its log

octanol/water partition coefficient (log Kow) is 2.64. (1)

Uses

! Carbon tetrachloride was produced in large quantities to make refrigerants and

propellants for aerosol cans, as a solvent for oils, fats, lacquers, varnishes, rubber waxes,

and resins, and as a grain fumigant and a dry cleaning agent. Consumer and fumigant uses

have been discontinued and only industrial uses remain. (1)
National Air Toxics Program: The Integrated Urban Strategy

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Sources and Potential Exposure

! Individuals may be exposed to carbon tetrachloride in the air from accidental releases

from production and uses, and from its disposal in landfills. (1)

! Carbon tetrachloride is also a common contaminant of indoor air; the sources of exposure

appear to be building materials or products, such as cleaning agents, used in the home. (1)

! Workers involved in the manufacture or use of carbon tetrachloride are most likely to

have significant exposures to carbon tetrachloride. (1)

! Individuals may also be exposed to carbon tetrachloride by drinking contaminated water.

(1,2)

! In the past, ingestion of bread or other products made with carbon tetrachloride-fumigated

grain may have contributed to dietary exposure, but this route of exposure is no longer of

significance. (1)

Assessing Personal Exposure

! Measurement of carbon tetrachloride in exhaled breath has been the most convenient

method for determining exposure; measurements in blood, fat, or other tissues have also

been used as indicators of exposure. However, these tests are not routinely available and

cannot be used to predict whether any health effects will result. (1)

Health Hazard Information

Acute Effects:

! Acute inhalation and oral exposures to high levels of carbon tetrachloride have been

observed primarily to damage the liver and kidneys of humans. Depression of the CNS

has also been reported. Symptoms of acute exposure in humans include headache,

weakness, lethargy, nausea, and vomiting. (1-6)

! Delayed pulmonary edema has been observed in humans exposed to high levels of carbon

tetrachloride by inhalation and ingestion, but this is believed to be due to injury to the

kidney rather than direct action of carbon tetrachloride on the lung. (1)

! Acute animal exposure tests, such as the LC50 and LD50 tests in rats, mice, rabbits, and

guinea pigs, have demonstrated carbon tetrachloride to have low toxicity from inhalation

exposure, low-to-moderate toxicity from ingestion, and moderate toxicity from dermal

exposure. (7)

Chronic Effects (Noncancer):

! Chronic inhalation or oral exposure to carbon tetrachloride produces liver and kidney

damage in humans and animals. (1,3,6,8)

! EPA has not established a reference concentration (RfC) for carbon tetrachloride. (9)

! The California Environmental Protection Agency (CalEPA) has established a chronic

reference exposure level of 0.04 mg/m3 for carbon tetrachloride based on liver effects in

guinea pigs. The CalEPA reference exposure level is a concentration at or below which
National Air Toxics Program: The Integrated Urban Strategy

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A-57

adverse health effects are not likely to occur. It is not a direct estimator of risk, but rather

a reference point to gauge the potential effects. At lifetime exposures increasingly greater

than the reference exposure level, the potential for adverse health effects increases. (10)

! ATSDR has established an acute inhalation minimal risk level (MRL) of 1.3 mg/m3 (0.2

ppm) based on liver effects in rats, and an intermediate MRL of 0.3 mg/m3 (0.05 ppm)

also based on liver effects in rats. The MRL is an estimate of the daily human exposure to

a hazardous substance that is likely to be without appreciable risk of adverse noncancer

health effects over a specified duration of exposure. (1)

! The RfD for carbon tetrachloride is 0.0007 mg/kg/d based on the occurrence of liver

lesions in rats. The RfD is an estimate (with uncertainty spanning perhaps an order of

magnitude) of a daily oral exposure to the human population (including sensitive

subgroups) that is likely to be without appreciable risk of deleterious noncancer effects

during a lifetime. (9)

! EPA has medium confidence in the RfD based on: high confidence in the principal study

on which the RfD was based because the study was well conducted and good

dose-response was observed in the liver, which is the target organ for carbon tetrachloride

toxicity; and medium confidence in the database because four additional subchronic

studies support the RfD, but reproductive and teratology endpoints are not well

investigated; and, consequently, medium confidence in the RfD. (9)

Reproductive/Developmental Effects:

! No information is available on the reproductive effects of carbon tetrachloride in humans.

Limited epidemiological data have indicated a possible association between certain birth

outcomes (e.g., birth weight, cleft palate) and drinking water exposure. However, as the

water contained multiple chemicals, the role of carbon tetrachloride is unclear. (1)

! Decreased fertility and degenerative changes in the testes have been observed in animals

exposed to carbon tetrachloride by inhalation. (1,6)

! Birth defects have not been observed in animals exposed to carbon tetrachloride by

inhalation or ingestion. (1,2,8)

Cancer Risk:

! Occasional reports have noted the occurrence of liver cancer in workers who had been

exposed to carbon tetrachloride by inhalation exposure; however, the data are not

sufficient to establish a cause-and-effect relationship. (1,6,8,9,11,12)

! Liver tumors have developed in rats and mice exposed to carbon tetrachloride by gavage.

(1-4,6,8,9,11,12)

! EPA has classified carbon tetrachloride as a Group B2, probable human carcinogen. (8,9)

! EPA uses mathematical models, based on human and animal studies, to estimate the

probability of a person developing cancer from continuously breathing air containing a

specified concentration of a chemical. EPA calculated an inhalation unit risk of 1.5 x 10-5

(μg/m3)

-1. EPA estimates that, if an individual were to continuously breathe air containing

carbon tetrachloride at an average of 0.07 μg/m3 (7 x 10-5 mg/m3) over his or her entire
National Air Toxics Program: The Integrated Urban Strategy

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A-58

Carbon Tetrachloride

0.00001

0.0001

0.001

0.01

0.1

1

10

100

1000

10000

100000

1000000

Health numbersa Regulatory, advisory

numbersb

Ref.

10

Ref.

10

Ref.

9

Ref.

14 Ref.

15 Ref.

16

LC50 (mice) (59,938 mg/ m3)

LOAELd (liver) (31.5 mg/ m3)

CalEPA

reference

exposure level

(0.04 mg/ m3)

OSHA PEL (63 mg/ m3)

NIOSH REL

(12.6 mg/m 3)

LC50 (rat s) (50,336 mg/ m3)

Cancer Risk

Levelc 1 in a

million risk

(7 x 10 -5

mg/ m3)

Ref.

1

ATSDR int ermediat e MRL

(0.3 mg/ m3)

NIOSH IDLH (1260 mg/ m3)

AIHA ERPG-2 (630 mg/ m3)

AIHA ERPG-1 (126 mg/ m3)

Ref.

16 Ref.

17

Ref.

17

Ref.

7

Ref.

7

ACGIH TLV (31 mg/ m3)

lifetime, that person would theoretically have no more than a one-in-a-million increased

chance of developing cancer as a direct result of breathing air containing this chemical.

! Similarly, EPA estimates that continuously breathing air containing 0.7 μg/m3 (7 x 10-4

mg/m3) would result in not greater than a one-in-a-hundred thousand increased chance of

developing cancer, and air containing 7.0 μg/m3 (7 x 10-3 mg/m3) would result in not

greater than a one-in-a-ten thousand increased chance of developing cancer. (9)

! EPA has calculated an oral cancer slope factor of 1.3 x 10-1 (mg/kg/d)-1. For a detailed

discussion of confidence in the potency estimates, please see IRIS. (9)

Conversion Factors:

To convert from ppm to mg/m3: mg/m3 = (ppm) x (molecular weight of the compound)/(24.45).

For carbon tetrachloride: 1 ppm = 6.3 mg/m3

.

Health Data from Inhalation Exposure
National Air Toxics Program: The Integrated Urban Strategy

Report to Congress

A-59

AIHA ERPG – American Industrial Hygiene Association's emergency response planning

guidelines. ERPG 1 is the maximum airborne concentration below which it is believed nearly all

individuals could be exposed up to one hour without experiencing other than mild transient

adverse health effects or perceiving a clearly defined objectionable odor; ERPG 2 is the

maximum airborne concentration below which it is believed nearly all individuals could be

exposed up to one hour without experiencing or developing irreversible or other serious health

effects that could impair their abilities to take protective action.

ACGIH TLV – American Conference of Governmental and Industrial Hygienists' threshold

limit value expressed as a time-weighted average; the concentration of a substance to which most

workers can be exposed without adverse effects.

LC50 (Lethal Concentration50) – A calculated concentration of a chemical in air to which

exposure for a specific length of time is expected to cause death in 50% of a defined

experimental animal population.

LOAEL – Lowest-observed-adverse-affect level.

NIOSH IDLH – National Institute of Occupational Safety and Health's immediately dangerous

to life or health concentration; NIOSH recommended exposure limit to ensure that a worker can

escape from an exposure condition that is likely to cause death or immediate or delayed

permanent adverse health effects or prevent escape from the environment.

NIOSH REL – NIOSH's recommended exposure limit; NIOSH-recommended exposure limit for

an 8- or 10-h time-weighted-average exposure and/or ceiling.

OSHA PEL – Occupational Safety and Health Administration's permissible exposure limit

expressed as a time-weighted average; the concentration of a substance to which most workers

can be exposed without adverse effect averaged over a normal 8-h workday or a 40-h workweek.

a

 Health numbers are toxicological numbers from animal testing or risk assessment values

developed by EPA.

b

 Regulatory numbers are values that have been incorporated in Government regulations, while

advisory numbers are nonregulatory values provided by the Government or other groups as

advice.

c

 These cancer risk estimates were derived from oral data and converted to provide the estimated

inhalation risk.

d

 The LOAEL is from the critical study used as the basis for the CalEPA chronic reference

exposure level.

References

1. Agency for Toxic Substances and Disease Registry (ATSDR). Toxicological Profile for

Carbon Tetrachloride (Update). Public Health Service, U.S. Department of Health and

Human Services, Atlanta, GA. 1994.

2. U.S. Environmental Protection Agency (EPA). Carbon Tetrachloride Health Advisory.

Office of Drinking Water, Washington, DC. 1987.
National Air Toxics Program: The Integrated Urban Strategy

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3. U.S. Department of Health and Human Services. Hazardous Substances Databank

(HSDB, online database). National Toxicology Information Program, National Library of

Medicine, Bethesda, MD. 1993.

4. International Agency for Research on Cancer (IARC). IARC Monographs on the

Evaluation of the Carcinogenic Risk of Chemicals to Humans: Some Halogenated

Hydrocarbons. Volume 20. World Health Organization, Lyon. 1979.

5. M. Sittig. Handbook of Toxic and Hazardous Chemicals and Carcinogens. 2nd ed. Noyes

Publications, Park Ridge, NJ. 1985.

6. U.S. Environmental Protection Agency (EPA). Health Affects Document for Carbon

Tetrachloride. EPA/600/8-82-001F. Environmental Criteria and Assessment Office,

Office of Health and Environmental Assessment, Office of Research and Development,

Cincinnati, OH. 1984.

7. U.S. Department of Health and Human Services. Registry of Toxic Effects of Chemical

Substances (RTECS, online database). National Toxicology Information Program,

National Library of Medicine, Bethesda, MD. 1993.

8. U.S. Environmental Protection Agency (EPA). Updated Health Effects Assessment for

Carbon Tetrachloride. EPA/600/8-89/088. Environmental Criteria and Assessment

Office, Office of Health and Environmental Assessment, Office of Research and

Development, Cincinnati, OH. 1989.

9. U.S. Environmental Protection Agency (EPA). Integrated Risk Information System (IRIS)

on Carbon Tetrachloride. National Center for Environmental Assessment, Office of

Research and Development, Washington, DC. 1999.

10. California Environmental Protection Agency (CalEPA). Technical Support Document for

the Determination of Noncancer Chronic Reference Exposure Levels. Draft for Public

Comment. Office of Environmental Health Hazard Assessment, Berkeley, CA. 1997.

11. International Agency for Research on Cancer (IARC). IARC Monographs on the

Evaluation of the Carcinogenic Risk of Chemicals to Humans: Chemicals, Industrial

Processes and Industries Associated with Cancer in Humans. Supplement 4. World

Health Organization, Lyon. 1982.

12. International Agency for Research on Cancer (IARC). IARC Monographs on the

Evaluation of the Carcinogenic Risk of Chemicals to Man. Volume 1. World Health

Organization, Lyon. 1972.

13. The Merck Index. An Encyclopedia of Chemicals, Drugs, and Biologicals. 11th ed. Ed. S.

Budavari. Merck and Co. Inc., Rahway, NJ. 1989.
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14. Occupational Safety and Health Administration (OSHA). Occupational Safety and

Health Standards, Toxic and Hazardous Substances. Code of Federal Regulations. 29

CFR 1910.1000. 1998.

15. American Conference of Governmental Industrial Hygienists (ACGIH). 1999 TLVs and

BEIs. Threshold Limit Values for Chemical Substances and Physical Agents. Biological

Exposure Indices. Cincinnati, OH. 1999.

16. National Institute for Occupational Safety and Health (NIOSH). Pocket Guide to

Chemical Hazards. U.S. Department of Health and Human Services, Public Health

Service, Centers for Disease Control and Prevention. Cincinnati, OH. 1997.

17. American Industrial Hygiene Association (AIHA). The AIHA 1998 Emergency Response

Planning Guidelines and Workplace Environmental Exposure Level Guides Handbook.

1998.
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CHLOROFORM

67-66-3

Hazard Summary

Chloroform may be released to the air as a result of its formation in the chlorination of

drinking water, wastewater and swimming pools. Other sources include pulp and paper

mills, hazardous waste sites, and sanitary landfills. The major effect from acute

(short-term) inhalation exposure to chloroform is central nervous system (CNS)

depression. Chronic (long-term) exposure to chloroform by inhalation in humans has

resulted in effects on the liver, including hepatitis and jaundice, and CNS effects, such as

depression and irritability. Little information is available on the reproductive or

developmental effects of chloroform in humans, while animal studies have reported

developmental effects, such as decreased fetal body weight and fetal resorptions, and

reproductive effects, such as decreased conception rates, in animals exposed to

chloroform by inhalation. No studies are available on the carcinogenic effects of

chloroform in humans or animals after inhalation exposure. Chloroform has been shown

to be carcinogenic in animals after oral exposure, resulting in an increase in kidney and

liver tumors. The U.S. Environmental Protection Agency (EPA) has classified chloroform

as a Group B2, probable human carcinogen.

Please Note: The main sources of information for this fact sheet are EPA's Integrated Risk Information System

(IRIS), which contains information on oral chronic toxicity and the reference dose (RfD), and the carcinogenic

effects of chloroform including the unit cancer risk for inhalation exposure, and the Agency for Toxic Substances

and Disease Registry's (ATSDR's) Toxicological Profile for Chloroform.

Physical Properties

! Chloroform is a colorless liquid that is not very soluble in water and is very volatile. (1,6)

! Chloroform has a pleasant, nonirritating odor; the odor threshold is 85 ppm. (1)

! The chemical formula for chloroform is CHCl3, and it has a molecular weight of 119.38

g/mol. (1)

! The vapor pressure for chloroform is 159 mm Hg at 20 EC, and it has a log octanol/water

partition coefficient (log Kow) of 1.97. (1)

Uses

! The vast majority of the chloroform produced in the U.S. is used to make HCFC-22. The

rest is produced for export and for miscellaneous uses. (1)

! Chloroform was used in the past as an extraction solvent for fats, oils, greases, and other

products; as a dry cleaning spot remover; in fire extinguishers; as a fumigant; and as an

anesthetic. However, chloroform is no longer used in these products. (1)
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Sources and Potential Exposure

! Chloroform may be released to the air from a large number of sources related to its

manufacture and use, as well as its formation in the chlorination of drinking water,

wastewater, and swimming pools. Pulp and paper mills, hazardous waste sites, and

sanitary landfills are also sources of air emissions. The background level of chloroform in

ambient air in the early 1990's was estimated at 0.00004 ppm. (1)

! Human exposure to chloroform may occur through drinking water, where chloroform is

formed as a result of the chlorination of naturally occurring organic materials found in

raw water supplies. Measurements of chloroform in drinking water during the 1970's and

1980's ranged from 0.022 to 0.068 ppm. (1)

! Chloroform may also be found in some foods and beverages, largely from the use of tap

water during production processes. (1)

Assessing Personal Exposure

! Chloroform can be detected in blood, urine, and body tissues. However, these methods

are not very reliable because chloroform is rapidly eliminated from the body, and the tests

are not specific for chloroform. (1)

Health Hazard Information

Acute Effects:

! The major effect from acute inhalation exposure to chloroform in humans is CNS

depression. At very high levels (40,000 ppm), chloroform exposure may result in death,

with concentrations in the range of 1,500 to 30,000 ppm producing anesthesia, and lower

concentrations (<1,500 ppm) resulting in dizziness, headache, tiredness, and other effects.

(1,2)

! Effects noted in humans exposed to chloroform via anesthesia include changes in

respiratory rate, cardiac effects, gastrointestinal effects, such as nausea and vomiting, and

effects on the liver and kidney. Chloroform is not currently used as a surgical anesthetic.

(1,2)

! In humans, a fatal oral dose of chloroform may be as low as 10 mL (14.8 g), with death

due to respiratory or cardiac arrest. (1,2)

! Tests involving acute exposure of animals, such as the LC50 and LD50 tests in rats, have

shown chloroform to have low acute toxicity from inhalation exposure and moderate

acute toxicity from oral exposure. (3)

Chronic Effects (Noncancer):

! Chronic exposure to chloroform by inhalation in humans is associated with effects on the

liver, including hepatitis and jaundice, and CNS effects, such as depression and

irritability. Inhalation exposures of animals have also resulted in effects on the kidney.

(1,2)
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! Chronic oral exposure to chloroform in humans has resulted in effects on the blood, liver,

and kidney. (1,2)

! EPA has not established a reference concentration (RfC) for chloroform. (4)

! The California Environmental Protection Agency (CalEPA) has established a chronic

reference exposure level of 0.3 mg/m3 for chloroform based on exposures resulting in

kidney and liver effects in rats. The CalEPA reference exposure level is a concentration at

or below which adverse health effects are not likely to occur. It is not a direct estimator

of risk, but rather a reference point to gauge the potential effects. At lifetime exposures

increasingly greater than the reference exposure level, the potential for adverse health

effects increases. (5)

! ATSDR has established an acute inhalation minimal risk level (MRL) of 0.5 mg/m3 (0.1

ppm) based on exposures resulting in liver effects in mice, an intermediate inhalation

MRL of 0.2 mg/m3 (0.05 ppm) based on worker exposures resulting in liver effects in

humans, and a chronic inhalation MRL of 0.1 mg/m3

 (0.02 ppm) also based on liver

effects in humans. The MRL is an estimate of the daily human exposure to a hazardous

substance that is likely to be without appreciable risk of adverse noncancer health effects

over a specified duration of exposure. (1)

! The RfD for chloroform is 0.01 mg/kg/d based on exposures resulting in fatty cyst

formation in the livers of dogs. The RfD is an estimate (with uncertainty spanning

perhaps an order of magnitude) of a daily oral exposure to the human population

(including sensitive subgroups) that is likely to be without appreciable risk of deleterious

noncancer effects during a lifetime. (4)

! EPA has medium to low confidence in the RfD due to: medium confidence in the critical

study on which the RfD was based because it was of chronic duration, used a fairly large

number of dogs, measured multiple endpoints using only two treatment doses, and a

no-observed-effect level (NOEL) was not determined; and medium to low confidence in

the database because several studies support the choice of a lowest-observed-adverseeffect level (LOAEL), but a NOEL was not found. (4)

Reproductive/Developmental Effects:

! Little information is available on the reproductive or developmental effects of chloroform

in humans, via any route of exposure. A possible association between certain birth

outcomes (e.g., low birth weight, cleft palate) and consumption of contaminated drinking

water was reported. However, because multiple contaminants were present, the role of

chloroform is unclear. (1)

! Animal studies have demonstrated developmental effects, such as decreased fetal body

weight, fetal resorptions, and malformations in the offspring of animals exposed to

chloroform via inhalation. (1)

! Reproductive effects, such as decreased conception rates, decreased ability to maintain

pregnancy, and an increase in the percentage of abnormal sperm were observed in

animals exposed to chloroform through inhalation. (1)

! Animal studies have noted decreased fetal weight, increased fetal resorptions, but no

evidence of birth defects, in animals orally exposed to chloroform. (1)
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Cancer Risk:

! No information is available regarding cancer in humans or animals after inhalation

exposure to chloroform. (1)

! Epidemiologic studies suggest an association between cancer of the large intestine,

rectum, and/or bladder and the constituents of chlorinated drinking water, including

chloroform. However, there are no epidemiologic studies of water containing only

chloroform. (1)

! Chloroform has been shown to be carcinogenic in animals after oral exposure, resulting in

an increase in kidney and liver tumors. (1)

! EPA has classified chloroform as a Group B2, probable human carcinogen. (4)

! EPA uses mathematical models, based on human and animal studies, to estimate the

probability of a person developing cancer from breathing air containing a specified

concentration of a chemical. EPA calculated an inhalation unit risk estimate of 2.3 x 10-5

(μg/m3)

-1. EPA estimates that, if an individual were to continuously breathe air containing

chloroform at an average of 0.04 μg/m3 (4 x 10-5 mg/m3) over his or her entire lifetime,

that person would theoretically have no more than a one-in-a-million increased chance of

developing cancer as a direct result of breathing air containing this chemical. Similarly,

EPA estimates that continuously breathing air containing 0.4 μg/m3 (4 x 10-4 mg/m3)

would result in not greater than a one-in-a-hundred thousand increased chance of

developing cancer, and air containing 4.0 μg/m3 (4 x 10-3 mg/m3) would result in not

greater than a one-in-ten thousand increased chance of developing cancer. For a detailed

discussion of confidence in the potency estimates, please see IRIS. (4)

! EPA has calculated an oral cancer slope factor of 6.1 x 10-3 (mg/kg/d)-1. (4)

Conversion Factors:

To convert from ppm to mg/m3: mg/m3 = (ppm) x (molecular weight of the compound)/(24.45).

For chloroform: 1 ppm = 4.88 mg/m3.

To convert from μg/m3 to mg/m3: mg/m3 = (μg/m3) x (1 mg/1,000 μg).
National Air Toxics Program: The Integrated Urban Strategy

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Chloroform

0.00001

0.0001

0.001

0.01

0.1

1

10

100

1000

10000

100000

1000000

Health numbers

a

Regulatory, advisory

numbersb

Ref.

3

Ref.

5

Ref.

5

Ref.

4

Ref.

7

Ref.

8

Ref.

9

LC50 (rats) (47,702 mg/ m3)

LOAELc (kidney and liver) (122 mg/m3)

CalEPA reference exposure

level (0.3 mg/m3)

OSHA PEL (240 mg/m3)

Cancer Risk Level

1 in a million risk

(4 x 10-5 mg/m3)

c

ACGIH TLV (49 mg/ m3)

NIOSH STEL

(9.8 mg/ m3)

Ref.

9

NIOSH IDLH (2,440 mg/ m3)

Health Data from Inhalation Exposure

ACGIH TLV – American Conference of Governmental and Industrial Hygienists' threshold

limit value expressed as a time-weighted average; the concentration of a substance to which most

workers can be exposed without adverse effects.

LC50 (Lethal Concentration50) – A calculated concentration of a chemical in air to which

exposure for a specific length of time is expected to cause death in 50% of a defined

experimental animal population.

LOAEL – Lowest-observed-adverse-effect level.

NIOSH REL – National Institute of Occupational Safety and Health's recommended exposure

limit; NIOSH-recommended exposure limit for an 8- or 10-h time-weighted-average exposure

and/or ceiling.

OSHA PEL – Occupational Safety and Health Administration's permissible exposure limit

expressed as a time-weighted average; the concentration of a substance to which most workers

can be exposed without adverse effect averaged over a normal 8-h workday or a 40-h workweek.
National Air Toxics Program: The Integrated Urban Strategy

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a

 Health numbers are toxicological numbers from animal testing or risk assessment values

developed by EPA.

b

 Regulatory numbers are values that have been incorporated in Government regulations, while

advisory numbers are nonregulatory values provided by the Government or other groups as

advice.

c

 These cancer risk estimates were derived from oral data and converted to provide the estimated

inhalation risk.

d

 The LOAEL is from the critical study used as the basis for the CalEPA chronic reference

exposure level.

References

1. Agency for Toxic Substances and Disease Registry (ATSDR). Toxicological Profile for

Chloroform. Public Health Service, U.S. Department of Health and Human Services,

Atlanta, GA. 1997.

2. U.S. Department of Health and Human Services. Hazardous Substances Data Bank

(HSDB, online database). National Toxicology Information Program, National Library of

Medicine, Bethesda, MD. 1993.

3. U.S. Department of Health and Human Services. Registry of Toxic Effects of Chemical

Substances (RTECS, online database). National Toxicology Information Program,

National Library of Medicine, Bethesda, MD. 1993.

4. U.S. Environmental Protection Agency (EPA). Integrated Risk Information System (IRIS)

on Chloroform. National Center for Environmental Assessment, Office of Research and

Development, Washington, DC. 1999.

5. California Environmental Protection Agency (CalEPA). Technical Support Document for

the Determination of Noncancer Chronic Reference Exposure Levels. Draft for Public

Comment. Office of Environmental Health Hazard Assessment, Berkeley, CA. 1997.

6. The Merck Index. An Encyclopedia of Chemicals, Drugs, and Biologicals. 11th ed. Ed. S.

Budavari. Merck and Co. Inc., Rahway, NJ. 1989.

7. Occupational Safety and Health Administration (OSHA). Occupational Safety and

Health Standards, Toxic and Hazardous Substances. Code of Federal Regulations. 29

CFR 1910.1000. 1998.

8. American Conference of Governmental Industrial Hygienists (ACGIH). 1999 TLVs and

BEIs. Threshold Limit Values for Chemical Substances and Physical Agents. Biological

Exposure Indices. Cincinnati, OH. 1999.
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9. National Institute for Occupational Safety and Health (NIOSH). Pocket Guide to

Chemical Hazards. U.S. Department of Health and Human Services, Public Health

Service, Centers for Disease Control and Prevention. Cincinnati, OH. 1997.
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CHROMIUM COMPOUNDS

Hazard Summary

Chromium occurs in the environment primarily in two valence states, trivalent chromium

(Cr III) and hexavalent chromium (Cr VI). Exposure may occur from natural or industrial

sources of chromium.

The respiratory tract is the major target organ for chromium (VI) toxicity, for acute

(short-term) and chronic (long-term) inhalation exposures. Shortness of breath, coughing,

and wheezing were reported from a case of acute exposure to chromium (VI), while

perforations and ulcerations of the septum, bronchitis, decreased pulmonary function,

pneumonia, and other respiratory effects have been noted from chronic exposure. Limited

human studies suggest that chromium (VI) inhalation exposure may be associated with

complications during pregnancy and childbirth, while animal studies have not reported

reproductive effects from inhalation exposure to chromium (VI). The U.S.

Environmental Protection Agency (EPA) has classified chromium (VI) as a Group A,

known human carcinogen. Human studies have clearly established that inhaled

chromium (VI) is a human carcinogen, resulting in an increased risk of lung cancer.

Animal studies have shown chromium (VI) to cause lung tumors via inhalation exposure.

Chromium III is much less toxic than chromium (VI). The respiratory tract is also the

major target organ for chromium (III) toxicity, similar to chromium (VI). Chromium (III)

is an essential element in humans, with a daily intake of 50 to 200 μg/d recommended for

an adult. The body can detoxify some amount of chromium (VI) to chromium (III).

Please Note: The main sources of information for this fact sheet are EPA's Integrated Risk Information System

(IRIS), which contains information on inhalation chronic toxicity and the reference concentration (RfC) and oral

chronic toxicity and the reference dose (RfD), and the carcinogenic effects of chromium including the unit cancer

risk for inhalation exposure, EPA's Toxicological Review of Trivalent Chromium and Toxicological Review of

Hexavalent Chromium, and the Agency for Toxic Substances and Disease Registry's (ATSDR's) Toxicological

Profile for Chromium.

Physical Properties

! The metal, chromium (Cr), is a steel-gray solid with a high melting point and an atomic

weight of 51.996 g/mol. Chromium has oxidation states ranging from chromium (-II) to

chromium (+VI). (1)

! Chromium forms a large number of compounds, in both the chromium (III) and the

chromium (VI) forms. Chromium compounds are stable in the trivalent state, with the

hexavalent form being the second most stable state. (1)

! The chromium (III) compounds are sparingly soluble in water and may be found in water

bodies as soluble chromium (III) complexes, while the chromium (VI) compounds are

readily soluble in water. (1)
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Uses

! The metal chromium is used mainly for making steel and other alloys. (1)

! Chromium compounds, in either the chromium (III) or chromium (VI) forms, are used for

chrome plating, the manufacture of dyes and pigments, leather and wood preservation,

and treatment of cooling tower water. Smaller amounts are used in drilling muds, textiles,

and toner for copying machines. (1)

Sources and Potential Exposure

! Chromium is a naturally occurring element in rocks, animals, plants, soil, and volcanic

dust and gases. (1)

! Chromium occurs in the environment predominantly in one of two valence states:

trivalent chromium (Cr III), which occurs naturally and is an essential nutrient, and

hexavalent chromium (Cr VI), which, along with the less common metallic chromium (Cr

0), is most commonly produced by industrial processes. (1)

! Chromium (III) is essential to normal glucose, protein, and fat metabolism and is thus an

essential dietary element. The body has several systems for reducing chromium (VI) to

chromium (III). This chromium (VI) detoxification leads to increased levels of chromium

(III). (1)

! Air emissions of chromium are predominantly of trivalent chromium, and in the form of

small particles or aerosols. (1, 2)

! The most important industrial sources of chromium in the atmosphere are those related to

ferrochrome production. Ore refining, chemical and refractory processing,

cement-producing plants, automobile brake lining and catalytic converters for

automobiles, leather tanneries, and chrome pigments also contribute to the atmospheric

burden of chromium. (3)

! The general population is exposed to chromium (generally chromium [III]) by eating

food, drinking water, and inhaling air that contains the chemical. The average daily intake

from air, water, and food is estimated to be approximately less than 0.2 to 0.4 μg, 2.0 μg,

and 60 μg, respectively. (1)

! Dermal exposure to chromium may occur during the use of consumer products that

contain chromium, such as wood treated with copper dichromate or leather tanned with

chromic sulfate. (1)

! Occupational exposure to chromium occurs from chromate production, stainless-steel

production, chrome plating, and working in tanning industries; occupational exposure can

be two orders of magnitude higher than exposure to the general population. (1)

! People who live in the vicinity of chromium waste disposal sites or chromium

manufacturing and processing plants have a greater probability of elevated chromium

exposure than the general population. These exposures are generally to mixed chromium

(VI) and chromium (III). (1)
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Assessing Personal Exposure

! Laboratory tests can detect chromium in the blood, urine, and hair of exposed individuals.

(1, 5)

! Laboratory tests find it difficult to separate chromium VI from chromium III; in many

cases analysis is done for total chromium. (1)

Health Hazard Information

Acute Effects:

Chromium VI

! Chromium (VI) is much more toxic than chromium (III), for both acute and chronic

exposures. (1,3,4)

! The respiratory tract is the major target organ for chromium (VI) following inhalation

exposure in humans. Shortness of breath, coughing, and wheezing were reported in cases

where an individual inhaled very high concentrations of chromium trioxide. (1,4)

! Other effects noted from acute inhalation exposure to very high concentrations of

chromium (VI) include gastrointestinal and neurological effects, while dermal exposure

causes skin burns. (1,4,5)

! Ingestion of high amounts of chromium (VI) causes gastrointestinal effects in humans and

animals, including abdominal pain, vomiting, and hemorrhage. (1)

! Acute animal tests, such as the LC50 and LD50 tests in rats, have shown chromium (VI) to

have extreme toxicity from inhalation (LC50 = 30-140 mg/m3) and oral (LD50 <100

mg/kg) exposure. (1,6)

Chromium III

! Chromium (III) is an essential element in humans, with a daily intake of 50 to 200 μg/d

recommended for adults. (1)

! Acute animal tests have shown chromium (III) to have moderate toxicity from oral

exposure, with LD50 values of 200-2000 mg/kg and much lower toxicity from acute

dietary exposures. (1,6)

Chronic Effects (Noncancer):

Chromium VI

! Chronic inhalation exposure to chromium (VI) in humans results in effects on the

respiratory tract, with perforations and ulcerations of the septum, bronchitis, decreased

pulmonary function, pneumonia, asthma, and nasal itching and soreness reported. (1,4,5)

! Chronic human exposure to high levels of chromium (VI) by inhalation or oral exposure

may produce effects on the liver, kidney, gastrointestinal and immune systems, and

possibly the blood. (1,4,5)
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! Rat studies have shown that, following inhalation exposure, the lung and kidney have the

highest tissue levels of chromium. (1,4,5)

! Dermal exposure to chromium (VI) may cause contact dermatitis, sensitivity, and

ulceration of the skin. (1,4,5)

! The RfC for chromium (VI) (particulates) is 0.0001 mg/m3 based on respiratory effects in

rats. The RfC is an estimate (with uncertainty spanning perhaps an order of magnitude) of

a continuous inhalation exposure to the human population (including sensitive subgroups)

that is likely to be without appreciable risk of deleterious noncancer effects during a

lifetime. It is not a direct estimator of risk but rather a reference point to gauge the

potential effects. At exposures increasingly greater than the RfC, the potential for adverse

health effects increases. Lifetime exposure above the RfC does not imply that an adverse

health effect would necessarily occur. (7)

! EPA has medium confidence in the RfC for chromium VI (particulates) based on medium

confidence in the study on which it was based because of uncertainties regarding upper

respiratory tract, reproductive, and renal effects resulting from the exposures. (7)

! The RfC for chromium (VI) (chromic acid mists and dissolved Cr (VI) aerosols) is

0.000008 mg/m3 based on respiratory effects in humans. (7)

! EPA has low confidence in the RfC based on low confidence in the study on which the

RfC for chromium (VI) (chromic acid mists and dissolved Cr (VI) aerosols) is based

because of uncertainties regarding the exposure characterization and the role of direct

contact for the critical effect; and low confidence in the database because the supporting

studies are equally uncertain regarding the exposure characterization. (7)

! The RfD for chromium (VI) is 0.003 mg/kg/d based on the exposure at which no effects

were noted in rats exposed to chromium in the drinking water. (7)

! EPA has low confidence in the RfD based on: low confidence in the study on which the

RfD for chromium (VI) was based because a small number of animals were tested, a

small number of parameters were measured, and no toxic effects were noted at the highest

dose tested; and low confidence in the database because the supporting studies are of

equally low quality and developmental endpoints are not well studied. (7)

Chromium III

! Although data from animal studies have identified the respiratory tract as the major target

organ for chronic chromium exposure, these data do not demonstrate that the effects

observed following inhalation of chromium (VI) particulates are relevant to inhalation of

chromium (III). (8)

! EPA has not established an RfC for chromium (III). (8)

! The RfD for chromium (III) is 1.5 mg/kg/d based on the exposure level at which no

effects were observed in rats exposed to chromium (III) in the diet. (8)

! EPA has low confidence in the RfD based on: low confidence in the study on which the

RfD for chromium (III) was based due to the lack of explicit detail on study protocol and

results; and low confidence in the database due to the lack of high-dose supporting data.

(8)
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Reproductive/Developmental Effects:

Chromium VI

! Limited information on the reproductive effects of chromium (VI) in humans exposed by

inhalation suggest that exposure to chromium (VI) may result in complications during

pregnancy and childbirth. (1)

! Animal studies have not reported reproductive or developmental effects from inhalation

exposure to chromium (VI). Oral studies have reported severe developmental effects in

mice such as gross abnormalities and reproductive effects including decreased litter size,

reduced sperm count, and degeneration of the outer cellular layer of the seminiferous

tubules. (1,4)

Chromium III

! No information is available on the reproductive or developmental effects of chromium

(III) in humans. (3)

! A study of mice fed high levels of chromium (III) in their drinking water has suggested a

potential for reproductive effects, although various study characteristics preclude a

definitive finding. (3)

! No developmental effects were reported in the offspring of rats fed chromium (III) during

their developmental period. (1,3)

Cancer Risk:

Chromium VI

! Epidemiological studies of workers have clearly established that inhaled chromium is a

human carcinogen, resulting in an increased risk of lung cancer. Although chromiumexposed workers were exposed to both chromium (III) and chromium (VI) compounds,

only chromium (VI) has been found to be carcinogenic in animal studies, so EPA has

concluded that only chromium (VI) should be classified as a human carcinogen. (1,7)

! Animal studies have shown chromium (VI) to cause lung tumors via inhalation exposure.

(1,5)

! EPA has classified chromium (VI) as a Group A, known human carcinogen by the

inhalation route of exposure. Carcinogenicity by the oral route of exposure cannot be

determined and has been classified by EPA as a Group D. (7)

! EPA uses mathematical models, based on human and animal studies, to estimate the

probability of a person developing cancer from breathing air containing a specified

concentration of a chemical. EPA calculated an inhalation unit risk estimate of 1.2 x 10-2

(μg/m3)

-1. EPA estimates that, if an individual were to continuously breathe air containing

chromium at an average of 0.00008 μg/m3 (8 x 10-8 mg/m3) over his or her entire lifetime,

that person would theoretically have no more than a one-in-a-million increased chance of

developing cancer as a direct result of breathing air containing this chemical. Similarly,

EPA estimates that continuously breathing air containing 0.0008 μg/m3 (8 x 10-7 mg/m3)
National Air Toxics Program: The Integrated Urban Strategy

Report to Congress

A-76

would result in not greater than a one-in-a-hundred thousand increased chance of

developing cancer during their lifetime, and air containing 0.008 μg/m3 (8 x 10-6 mg/m3)

would result in not greater than a one-in-ten-thousand increased chance of developing

cancer during their lifetime. For a detailed discussion of confidence in the potency

estimates, please see IRIS. (7)

Chromium III

! No data are available on the carcinogenic potential of chromium (III) compounds alone.

(1,8)

! EPA has classified chromium (III) as a Group D carcinogen, not classifiable as to

carcinogenicity in humans. (8)

! EPA has stated that "the classification of chromium (VI) as a known human carcinogen

raises a concern for the carcinogenic potential of chromium (III)." (8)

Conversion Factors:

To convert from ppm to mg/m3: mg/m3 = (ppm) x (molecular weight of the compound)/(24.45).

For chromium: 1 ppm = 2.12 mg/m3.

To convert from μg/m3 to mg/m3: mg/m3 = (μg/m3) x (1 mg/1,000 μg).
National Air Toxics Program: The Integrated Urban Strategy

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0.00000001

0.0000001

0.000001

0.00001

0.0001

0.001

0.01

0.1

1

10

100

1000

Chromium

Health numbers

a Regulatory, advisory

numbersb

LC50 (rat s) (45 mg/ m3) (Cr VI)

Benchmark dosec (respirat ory)

(0.016 mg/ m3)

LOAELd (respirat ory)

(0.002 mg/ m3)

RfC (0.0001 mg/m3)

(Cr VI part iculat es)

RfC (8 x 10-6 mg/ m3)

(chromic acid mist s)

Cancer Risk

Level 1 in a

million risk

(8 x 10-8

mg/m3)

OSHA PEL (1 mg/ m3)

(Cr met al and insoluble)

OSHA PEL ACGIH TLV

(& metal), NIOSH REL

(Cr III cmpds) (0.5 mg/m3)

ACGIH TLV, NIOSH REL

(chromic acid cmpds)

 (0.05 mg/m3)

ACGIH TLV (0.01

mg/m3)(insoluble

Cr VI)

NIOSH IDLH (25 mg/ m3) (Cr III)

NIOSH IDLH (15 mg/ m3) (Cr VI)

Ref.

1

Ref.

7

Ref.

7

Ref.

7

Ref.

7

Ref.

9

Ref.

9,10

11,

Ref.

10,

11 Ref.

10

Ref.

7

Ref.

11

Ref.

11

Health Data from Inhalation Exposure

ACGIH TLV – American Conference of Governmental and Industrial Hygienists' threshold

limit value expressed as a time-weighted average; the concentration of a substance to which most

workers can be exposed without adverse effects.

LC50 (Lethal Concentration50) – A calculated concentration of a chemical in air to which

exposure for a specific length of time is expected to cause death in 50% of a defined

experimental animal population.

LOAEL – Lowest-observed-adverse-affect level.

NIOSH IDLH – National Institute of Occupational Safety and Health's immediately dangerous

to life or health concentration; NIOSH recommended exposure limit to ensure that a worker can

escape from an exposure condition that is likely to cause death or immediate or delayed

permanent adverse health effects or prevent escape from the environment.

NIOSH REL – NIOSH's recommended exposure limit; NIOSH-recommended exposure limit for

an 8- or 10-h time-weighted-average exposure and/or ceiling.

OSHA PEL – Occupational Safety and Health Administration's permissible exposure limit
National Air Toxics Program: The Integrated Urban Strategy

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A-78

expressed as a time-weighted average; the concentration of a substance to which most workers

can be exposed without adverse effect averaged over a normal 8-h workday or a 40-h workweek.

a

 Health numbers are toxicological numbers from animal testing or risk assessment values

developed by EPA.

b

 Regulatory numbers are values that have been incorporated in Government regulations, while

advisory numbers are nonregulatory values provided by the Government or other groups as

advice.

c

 The benchmark dose is from the critical study used as the basis for the EPA's RfC for Cr(VI)

particulates.

d

 The LOAEL is from the critical study used as the basis for the EPA's RfC for chromic acid

mists and dissolved Cr (VI) aerosols.

References

1. Agency for Toxic Substances and Disease Registry (ATSDR). Toxicological Profile for

Chromium. Public Health Service, U.S. Department of Health and Human Services, Atlanta, GA.

1998.

2. SAIC. PM/Toxics Integration: Addressing Co-Control Benefits. Submitted to U.S.

Environmental Protection Agency, Office of Air Quality Planning and Standards, Research

Triangle Park, NC. 1998.

3. U.S. Environmental Protection Agency (EPA). Toxicological Review of Trivalent

Chromium. National Center for Environmental Assessment, Office of Research and

Development, Washington, DC. 1998.

4. U.S. Environmental Protection Agency (EPA). Toxicological Review of Hexavalent

Chromium. National Center for Environmental Assessment, Office of Research and

Development, Washington, DC. 1998.

5. World Health Organization (WHO). Chromium. Environmental Health Criteria 61. Geneva,

Switzerland. 1988.

6. U.S. Department of Health and Human Services. Registry of Toxic Effects of Chemical

Substances (RTECS, online database). National Toxicology Information Program, National

Library of Medicine, Bethesda, MD. 1993.

7. U.S. Environmental Protection Agency (EPA). Integrated Risk Information System (IRIS)

on Chromium VI. National Center for Environmental Assessment, Office of Research and

Development, Washington, DC. 1993.

8. U.S. Environmental Protection Agency (EPA). Integrated Risk Information System (IRIS)

on Chromium III. National Center for Environmental Assessment, Office of Research and

Development, Washington, DC. 1993.
National Air Toxics Program: The Integrated Urban Strategy

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A-79

9. Occupational Safety and Health Administration (OSHA). Occupational Safety and Health

Standards, Toxic and Hazardous Substances. Code of Federal Regulations. 29 CFR 1910.1000. 

1998.

10. American Conference of Governmental Industrial Hygienists (ACGIH). 1999 TLVs and

BEIs. Threshold Limit Values for Chemical Substances and Physical Agents, Biological

Exposure Indices. Cincinnati, OH. 1999.

11. National Institute for Occupational Safety and Health (NIOSH). Pocket Guide to Chemical

Hazards. U.S. Department of Health and Human Services, Public Health Service, Centers for

Disease Control and Prevention. Cincinnati, OH. 1997.
National Air Toxics Program: The Integrated Urban Strategy

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1

 Coke oven emissions include coal tar, creosote, and coal tar pitch.

A-81

COKE OVEN EMISSIONS1

Hazard Summary

Exposure to coke oven emissions may occur for workers in the aluminum, steel, graphite,

electrical, and construction industries. No information is available on the effects of coke

oven emissions in humans from acute (short-term) exposure. Animal studies have

reported weakness, depression, shortness of breath, general edema, and effects on the

liver from acute oral exposure to coke oven emissions. Chronic (long-term) exposure to

coke oven emissions in humans results in conjunctivitis, severe dermatitis, and lesions of

the respiratory system and digestive system. No information is available on the

reproductive or developmental effects of coke oven emissions in humans or animals.

Cancer is the major concern from exposure to coke oven emissions. Epidemiologic

studies of coke oven workers have reported an increase in cancer of the lung, trachea,

bronchus, kidney, prostate, and other sites. Animal studies have reported tumors of the

lung and skin from inhalation exposure to coal tar. The U.S. Environmental Protection

Agency (EPA) has classified coke oven emissions as a Group A, known human

carcinogen.

Please Note: The main source of information for this fact sheet is EPA's Integrated Risk Information System (IRIS),

which contains information on the carcinogenic effects of coke oven emissions including the unit cancer risk for

inhalation exposure. Other secondary sources include the Hazardous Substances Data Bank (HSDB), a database of

summaries of peer-reviewed literature, and The Handbook of Toxic and Hazardous Chemicals and Carcinogens, a

reference book that summarizes the key effects from exposure to hazardous chemicals.

Physical Properties

! Coke oven emissions are a mixture of coal tar, coal tar pitch, and creosote and contain

chemicals such as benzo(a)pyrene, benzanthracene, chrysene, and phenanthrene. (1)

! Condensed coke oven emissions are a brownish, thick liquid or semisolid with a

naphthalene-like odor, while uncondensed coke oven emissions are vapors that escape

when the ovens are changed and emptied. (2)

! The odor threshold for coke oven emissions is not available. The actual chemical content

of the emissions depends on the process variables.

Uses

! Chemicals recovered from coke oven emissions are used as a raw material for plastics,

solvents, dyes, drugs, waterproofing, paints, pipecoating, roads, roofing, insulation, and

as pesticides and sealants. (2)
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Sources and Potential Exposure

! Occupational exposure to coke oven emissions may occur for those workers in the

aluminum, steel, graphite, electrical, and construction industries. (1)

Assessing Personal Exposure

! No information is available on the assessment of personal exposure to coke oven

emissions.

Health Hazard Information

Acute Effects:

! No information is available on the effects of coke oven emissions from acute exposure in

humans.

! Animal studies have reported weakness, depression, shortness of breath, general edema,

and effects on the liver from acute oral exposure to coke oven emissions. (2)

Chronic Effects (Noncancer):

! Chronic exposure to coke oven emissions in humans results in conjunctivitis, severe

dermatitis, and lesions of the respiratory and digestive systems. (2)

! Animal studies have reported effects on the liver from chronic oral exposure to coke oven

emissions. (2)

! EPA has not established a reference concentration (RfC) or a reference dose (RfD) for

coke oven emissions. (3)

Reproductive/Developmental Effects:

! No information is available on the reproductive or developmental effects of coke oven

emissions in humans or animals.

Cancer Risk:

! Epidemiologic studies of coke oven workers have reported an increase in cancer of the

lung, trachea, bronchus, kidney, prostate, and other sites. (3)

! Animal studies have reported tumors of the lung and skin from inhalation exposure to

coal tar. (3)

! EPA has classified coke oven emissions as a Group A, known human carcinogen. (3)

! EPA uses mathematical models, based on human and animal studies, to estimate the

probability of a person developing cancer from breathing air containing a specified

concentration of a chemical. EPA calculated an inhalation unit risk estimate of 6.2 x 10-4

(μg/m3)

-1. EPA estimates that, if an individual were to continuously breathe air containing

coke oven emissions at an average of 0.002 μg/m3 (2 x 10-6 mg/m3) over his or her entire
National Air Toxics Program: The Integrated Urban Strategy

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A-83

0.000001

0.00001

0.0001

0.001

0.01

0.1

1

Coke Oven Emissions

Health numbers

a Regulatory, advisory

numbers

b

Ref.

3

Ref.

5

Ref.

6,7 Ref.

6 Ref.

5

Cancer Risk Level

1 in a million risk

(2 x 10-6 mg/m3)

NIOSH REL (coke oven emissions) (0.5 - 0.7 mg/m3)

OSHA PEL, ACGIH TLV (coal t ar pit ch volatiles)

(0.2 mg/m3) OSHA PEL (coke oven emissions)

 (0.15 mg/ m3)

NIOSH REL

(coal tar pit ch

volatiles)

(0.1 mg/m3)

lifetime, that person would theoretically have no more than a one-in-a-million increased

chance of developing cancer as a direct result of continuously breathing air containing

this chemical. Similarly, EPA estimates that breathing air containing 0.02 μg/m3 (2 x 10-5

mg/m3) would result in not greater than a one-in-a-hundred-thousand increased chance of

developing cancer during a lifetime, and air containing 0.2 μg/m3 (2 x 10-4 mg/m3) would

result in not greater than a one-in-ten-thousand increased chance of developing cancer

during a lifetime. For a detailed discussion of confidence in the potency estimates, please

see IRIS. (3)

Health Data from Inhalation Exposure

ACGIH TLV – American Conference of Governmental and Industrial Hygienists' threshold

limit value expressed as a time-weighted average; the concentration of a substance to which most

workers can be exposed without adverse effects.

NIOSH REL – National Institute of Occupational Safety and Health's recommended exposure
National Air Toxics Program: The Integrated Urban Strategy

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A-84

limit; NIOSH-recommended exposure limit for an 8- or 10-h time-weighted-average exposure

and/or ceiling.

OSHA PEL – Occupational Safety and Health Administration's permissible exposure limit

expressed as a time-weighted average; the concentration of a substance to which most workers

can be exposed without adverse effects averaged over a normal 8-h workday or a 40-h

workweek.

a

 Health numbers are toxicological numbers from animal testing or risk assessment values

developed by EPA.

b

 Regulatory numbers are values that have been incorporated in Government regulations, while

advisory numbers are nonregulatory values provided by the Government or other groups as

advice.

References

1. M. Sittig. Handbook of Toxic and Hazardous Chemicals and Carcinogens. 2nd ed. Noyes

Publications, Park Ridge, NJ. 1985.

2. U.S. Department of Health and Human Services. Hazardous Substances Data Bank

(HSDB, online database). National Toxicology Information Program, National Library of

Medicine, Bethesda, MD. 1993.

3. U.S. Environmental Protection Agency (EPA). Integrated Risk Information System (IRIS)

on Coke Oven Emissions. National Center for Environmental Assessment, Office of

Research and Development, Washington, DC. 1999.

4. U.S. Department of Health and Human Services. Registry of Toxic Effects of Chemical

Substances (RTECS, online database). National Toxicology Information Program,

National Library of Medicine, Bethesda, MD. 1993.

5. National Institute for Occupational Safety and Health (NIOSH). Pocket Guide to

Chemical Hazards. U.S. Department of Health and Human Services, Public Health

Service, Centers for Disease Control and Prevention. Cincinnati, OH. 1997.

6. Occupational Safety and Health Administration (OSHA). Occupational Safety and

Health Standards, Toxic and Hazardous Substances. Code of Federal Regulations. 29

CFR 1910.1000. 1998.

7. American Conference of Governmental Industrial Hygienists (ACGIH). 1999 TLVs and

BEIs. Threshold Limit Values for Chemical Substances and Physical Agents, Biological

Exposure Indices. Cincinnati, OH. 1999.
National Air Toxics Program: The Integrated Urban Strategy

Report to Congress

A-85

1,2-DICHLOROETHANE (ETHYLENE DICHLORIDE)

107-06-2

Hazard Summary

Exposure to low levels of 1,2-dichloroethane can occur from breathing ambient or

workplace air. Inhalation of concentrated 1,2-dichloroethane vapor can induce effects on

the human nervous system, liver, and kidneys, as well as respiratory distress, cardiac

arrhythmia, nausea, and vomiting. Similar effects have been reported in animals exposed

by inhalation. Clouding of the cornea and eye irritation have been observed in animals.

Chronic (long-term) inhalation exposure to 1,2-dichloroethane produced effects on the

liver and kidneys in animals. No information is available on the reproductive or

developmental effects of 1,2-dichloroethane in humans. Decreased fertility and increased

embryo mortality have been observed in inhalation studies of rats. The U.S.

Environmental Protection Agency (EPA) has classified 1,2-dichloroethane as a Group B2,

probable human carcinogen. Epidemiological studies are not conclusive regarding the

carcinogenic effects of 1,2-dichloroethane, due to concomitant exposure to other

chemicals. Following treatment by gavage, several tumor types were induced in rats and

mice.

Please Note: The main sources of information for this fact sheet are EPA's Integrated Risk Information System

(IRIS), which contains information on the carcinogenic effects of 1,2-dichloroethane including the unit cancer risk

for inhalation exposure, and the Agency for Toxic Substances and Disease Registry's (ATSDR's) Toxicological

Profile for 1,2-Dichloroethane.

Physical Properties

! The chemical formula for 1,2-dichloroethane is C2H4Cl2, and its molecular weight is

98.96 g/mol. (1)

! 1,2-Dichloroethane occurs as a colorless, oily, heavy liquid that is slightly soluble in

water. (1)

! 1,2-Dichloroethane has a pleasant chloroform-like odor, with an odor threshold of 6-10

ppm. (1)

! The vapor pressure for 1,2-dichloroethane is 64 mm Hg at 20 EC, and its log

octanol/water partition coefficient (log Kow) is 1.48. (1)

Uses

! 1,2-Dichloroethane is primarily used in the production of vinyl chloride as well as other

chemicals. It is used in solvents in closed systems for various extraction and cleaning

purposes in organic synthesis. It is also added to leaded gasoline as a lead scavenger. (1)

! It is also used as a dispersant in rubber and plastics, as a wetting and penetrating agent.

(1)
National Air Toxics Program: The Integrated Urban Strategy

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! It was formerly used in ore flotation, as a grain fumigant, as a metal degreaser, and in

textile and PVC cleaning. (1)

Sources and Potential Exposure

! Inhalation of 1,2-dichloroethane in the ambient or workplace air is generally the main

route of human exposure. The compound may be released during its production, storage,

use, transport, and disposal. (1)

! Exposure may also occur through the consumption of contaminated water. But usually

1,2-dichloroethane will evaporate quickly into the air from the water or soil. (1)

! The average levels of 1,2-dichloroethane in the air of seven urban locations in 1980-1981

ranged from 0.1 to 1.5 ppb. (1)

Assessing Personal Exposure

! Breath samples may be used to determine whether or not someone has been recently

exposed to 1,2-dichloroethane. (1)

Health Hazard Information

Acute Effects:

! Inhaling concentrated 1,2-dichloroethane can be lethal to humans. An occupationally

exposed man died from cardiac arrhythmia after acute (short-term) inhalation exposure to

concentrated vapors of 1,2-dichloroethane; congestion of the lungs, degenerative changes

in the myocardium, and damage to the liver, kidneys, and nerve cells in the brain were

also observed. (1)

! Acute inhalation exposure to 1,2-dichloroethane can affect the nervous system, with

effects including narcosis, nausea, and vomiting. (1)

! Effects reported in animals exposed by inhalation are similar to those for humans. (1)

! Clouding of the cornea and eye irritation have been observed in animals and are thought

to be the result of vapor contact with the eyes. (1)

! Cardiac arrhythmia, pulmonary edema, bronchitis, hemorrhagic gastritis and colitis,

depression, and changes in the brain tissue have been reported in humans that ingested

large amounts of 1,2-dichloroethane. (1)

! Acute animal tests, such as the LC50 and LD50 tests in rats, mice, and rabbits, have

demonstrated 1,2-dichloroethane to have moderate acute toxicity from inhalation or

dermal exposure and moderate to high acute toxicity from oral exposure. (2)

Chronic Effects (Noncancer):

! Chronic inhalation exposure to 1,2-dichloroethane produced effects on the liver and

kidneys in animals. (1)
National Air Toxics Program: The Integrated Urban Strategy

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! Some studies have reported changes in the liver and kidneys and effects on the immune

system and central nervous system (CNS) in animals chronically exposed by ingestion.

(1)

! EPA has not established a reference dose (RfD) or a reference concentration (RfC) for

1,2-dichloroethane. (3)

! ATSDR has established an intermediate oral minimal risk level (MRL) of 0.2 mg/kg/d

based on kidney effects in animals. The MRL is an estimate of the daily human exposure

to a hazardous substance that is likely to be without appreciable risk of adverse noncancer

health effects over a specified duration of exposure. Exposure to a level above the MRL

does not mean that adverse health effects will occur. The MRL is intended to serve as a

screening tool. (1)

! ATSDR has established a chronic inhalation MRL of 0.8 mg/m3 (0.2 ppm) based on liver

effects in animals and an acute inhalation MRL of 0.8 mg/m3 (0.2 ppm) based on

immunological effects in animals. (1)

! The California Environmental Protection Agency (CalEPA) has established a chronic

reference exposure level of 0.4 mg/m3 for 1,2-dichloroethane based on liver effects in

rats. The CalEPA reference exposure level is a concentration at or below which adverse

health effects are not likely to occur. (5)

Reproductive/Developmental Effects:

! No information is available on the reproductive or developmental effects of

1,2-dichloroethane in humans.

! Decreased fertility and increased embryo mortality have been observed in inhalation

studies of rats. (1)

Cancer Risk:

! Epidemiological occupational studies could not link exposure to 1,2-dichloroethane

specifically with excess cancer incidence. (1)

! An increased incidence of colon and rectal cancer in men over 55 years of age exposed to

1,2-dichloroethane in the drinking water has been reported. However, the study

population was concomitantly exposed to other chemicals. (1)

! Following treatment by gavage, several tumor types (including increased incidences of

forestomach squamous-cell carcinomas, circulatory system hemangiosarcomas, mammary

adenocarcinoma, alveolar/bronchiolar adenomas, endometrial stromal polyps and

sarcomas, and hepatocellular carcinomas) were induced in rats and mice. (1,3,4)

! An increased incidence of lung papillomas has been reported in mice after topical

application. (1,3)

! EPA has classified 1,2-dichloroethane as a Group B2, probable human carcinogen. (3)

! EPA uses mathematical models, based on human and animal studies, to estimate the

probability of a person developing cancer from breathing air containing a specified

concentration of a chemical. EPA calculated an inhalation unit cancer risk estimate of 2.6

x 10-5 (μg/m3)

-1. EPA estimates that, if an individual were to continuously breathe air

containing 1,2-dichloroethane at an average of 0.04 μg/m3 (4 x 10-5 mg/m3) over his or
National Air Toxics Program: The Integrated Urban Strategy

Report to Congress

A-88

her entire lifetime, that person would theoretically have no more than a one-in-a-million

increased chance of developing cancer as a direct result of breathing air containing this

chemical. Similarly, EPA estimates that breathing air containing 0.4 μg/m3 (4 x 10-4

mg/m3) would result in not greater than a one-in-a-hundred thousand increased chance of

developing cancer, and air containing 4.0 μg/m3 (4 x 10-3 mg/m3) would result in not

greater than a one-in-ten thousand increased chance of developing cancer. For a detailed

discussion of confidence in the potency estimates, please see IRIS. (3)

Conversion Factors:

To convert from ppm to mg/m3: mg/m3 = (ppm) x (molecular weight of the compound)/(24.45).

For 1,2-dichloroethane: 1 ppm = 4.05 mg/m3. To convert from μg/m3 to mg/m3: mg/m3 = (μg/m3)

x (1 mg/1,000 μg).
National Air Toxics Program: The Integrated Urban Strategy

Report to Congress

A-89

1,2-Dichloroethane

0.00001

0.0001

0.001

0.01

0.1

1

10

100

1000

10000

100000

Health numbers

a Regulatory, advisory

numbersb

Ref.

2

Ref.

5

Ref.

5

Ref.

3

Ref.

6 Ref.

6

Ref.

7

Ref.

8

LC50 (rat s) (4,047 mg/m3)

LOAELc (liver) (8.5 mg/m3)

CalEPA reference

exposure level (0.4 mg/m3)

Cancer Risk Level

1 in a million risk

(4 x 10-5 mg/m3)

OSHA ceiling (405 mg/m3)

OSHA PEL (202 mg/m3)

ACGIH TLV (40 mg/m3)

NIOSH REL

(4 mg/m3)

Health Data from Inhalation Exposure

ACGIH TLV – American Conference of Governmental and Industrial Hygienists' threshold

limit value expressed as a time-weighted average; the concentration of a substance to which most

workers can be exposed without adverse effects.

LC50 (Lethal Concentration50) – A calculated concentration of a chemical in air to which

exposure for a specific length of time is expected to cause death in 50% of a defined

experimental animal population.

LOAEL – Lowest-observed-adverse-affect level.

NIOSH REL – National Institute of Occupational Safety and Health recommended exposure

limit; NIOSH-recommended exposure limit for an 8- or 10-h time-weighted-average exposure

and/or ceiling.

OSHA PEL – Occupational Safety and Health Administration's permissible exposure limit
National Air Toxics Program: The Integrated Urban Strategy

Report to Congress

A-90

expressed as a time-weighted average; the concentration of a substance to which most workers

can be exposed without adverse effect averaged over a normal 8-h workday or a 40-h workweek.

OSHA PEL ceiling – OSHA's permissible exposure limit ceiling value; the concentration of a

substance that should not be exceeded at any time.

a

 Health numbers are toxicological numbers from animal testing or risk assessment values

developed by EPA.

b

 Regulatory numbers are values that have been incorporated in Government regulations, while

advisory numbers are nonregulatory values provided by the Government or other groups as

advice.

c

 The LOAEL is from the critical study used as the basis for the CalEPA chronic reference

exposure level.

d

 These cancer risk estimates were derived from oral data and converted to provide the estimated

inhalation risk.

References

1. Agency for Toxic Substances and Disease Registry (ATSDR). Toxicological Profile for

1,2-Dichloroethane. Public Health Service, U.S. Department of Health and Human

Services, Atlanta, GA. 1992.

2. U.S. Department of Health and Human Services. Registry of Toxic Effects of Chemical

Substances (RTECS, online database). National Toxicology Information Program,

National Library of Medicine, Bethesda, MD. 1993.

3. U.S. Environmental Protection Agency (EPA). Integrated Risk Information System (IRIS)

on 1,2-Dichloroethane. National Center for Environmental Assessment, Office of

Research and Development, Washington, DC. 1999.

4. U.S. Environmental Protection Agency (EPA). Health Effects Assessment for

1,2-Dichloroethane. EPA/540/1-86/002. Environmental Criteria and Assessment Office,

Office of Health and Environmental Assessment, Office of Research and Development,

Cincinnati, OH. 1986.

5. California Environmental Protection Agency (CalEPA). Technical Support Document for

the Determination of Noncancer Chronic Reference Exposure Levels. Draft for Public

Comment. Office of Environmental Health Hazard Assessment, Berkeley, CA. 1997.

6. Occupational Safety and Health Administration (OSHA). Occupational Safety and

Health Standards, Toxic and Hazardous Substances. Code of Federal Regulations. 29

CFR 1910.1000. 1998.

7. American Conference of Governmental Industrial Hygienists (ACGIH). 1999 TLVs and

BEIs. Threshold Limit Values for Chemical Substances and Physical Agents. Biological

Exposure Indices. Cincinnati, OH. 1999.
National Air Toxics Program: The Integrated Urban Strategy

Report to Congress

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8. National Institute for Occupational Safety and Health (NIOSH). Pocket Guide to

Chemical Hazards. U.S. Department of Health and Human Services, Public Health

Service, Centers for Disease Control and Prevention. Cincinnati, OH. 1997.
National Air Toxics Program: The Integrated Urban Strategy

Report to Congress

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1,2-DICHLOROPROPANE (PROPYLENE DICHLORIDE)

78-87-5

Hazard Summary

1,2-Dichloropropane is used as a chemical intermediate in several industries. Acute

(short-term) inhalation exposure to high levels of 1,2-dichloropropane by humans results

in effects on the lungs, gastrointestinal system, blood, liver, kidneys, central nervous

system (CNS), and eyes. No information is available on the chronic (long-term) effects of

1,2-dichloropropane in humans, and animal studies have reported effects on the

respiratory system and blood from chronic inhalation exposure. Limited information is

available on the reproductive or developmental effects of 1,2-dichloropropane in humans.

Animal studies have reported reproductive and developmental effects from

1,2-dichloropropane exposure by gavage. No information is available regarding the

carcinogenic effects of 1,2-dichloropropane in humans from inhalation or oral exposure.

Animal studies have reported an increased incidence of mammary gland tumors in female

rats and liver tumors in male and female mice given 1,2-dichloropropane by gavage. The

U.S. Environmental Protection Agency (EPA) has provisionally classified

1,2-dichloropropane as a Group B2, probable human carcinogen.

Please Note: The main sources of information for this fact sheet are the Agency for Toxic Substances and Disease

Registry's (ATSDR's) Toxicological Profile for 1,2-Dichloropropane and EPA's Integrated Risk Information

System (IRIS), which contains information on inhalation chronic toxicity of 1,2-dichloropropane and the reference

concentration (RfC).

Physical Properties

! The chemical formula for 1,2-dichloropropane is C3H6Cl2, and the molecular weight is

112.99 g/mol. (1)

! 1,2-Dichloropropane is a colorless liquid which evaporates quickly at room temperature.

(1)

! 1,2-Dichloropropane has a chloroform-like odor and an odor threshold of 0.25 ppm. (1)

! The vapor pressure for 1,2-dichloropropane is 49.67 mm Hg at 25 EC, and it has a log

octanol/water partition coefficient (log Kow) of 1.99. (1)

! 1,2-Dichloropropane has a half-life in air ranging from 16 to greater than 23 days. (1)

Uses

! 1,2-Dichloropropane is used as a chemical intermediate in the production of chlorinated

organic chemicals, as an industrial solvent, in ion exchange manufacture, in toluene

diisocyanate production, in photographic film manufacture, for paper coating, and for

petroleum catalyst regeneration. (1)
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! 1,2-Dichloropropane was used in the past as a soil fumigant for a variety of crops. This

use has been discontinued, and pesticide formulations containing 1,2-dichloropropane are

no longer available in the U.S.. (1)

Sources and Potential Exposure

! 1,2-Dichloropropane has been detected at low levels in ambient air, with an average level

in air of about 0.022 ppb. (1)

! An early 1980s nationwide survey of water supplies derived from groundwater found that

13 of 945 water supplies contained 1,2-dichloropropane at levels around 1 ppb. (1)

! Occupational exposure to 1,2-dichloropropane may occur during its production, during its

use in chemical reactions or as an industrial solvent, or from evaporation from wastewater

that contains the chemical. (1)

Assessing Personal Exposure

! Medical tests can detect 1,2-dichloropropane in urine and blood. 1,2-Dichloropropane

leaves the body quickly, and thus the tests should be done soon after the exposure. (1)

Health Hazard Information

Acute Effects:

! Acute exposure of humans to very high levels of 1,2-dichloropropane from inhalation and

oral exposure results in effects on the gastrointestinal system, blood, liver, kidneys, and

CNS. Additional effects noted in humans, from inhalation exposure only, are effects on

the lung (chest discomfort, shortness of breath, and cough) and the eyes (conjunctival

hemorrhages). (1)

! Animal studies have reported effects on the respiratory system, liver, kidneys, eyes, and

CNS from acute inhalation exposure to 1,2-dichloropropane. (1)

! Tests involving acute exposure of animals, such as the LC50 and LD50 tests in rats, have

shown 1,2-dichloropropane to have moderate acute toxicity from inhalation and oral

exposure. (1,2)

Chronic Effects (Noncancer):

! No information is available on the effects from chronic exposure to 1,2-dichloropropane

in humans from inhalation or oral exposure. (1)

! Chronic animal studies, via inhalation exposure, have reported effects on the respiratory

system and blood, while oral animal studies have noted effects on the blood, liver, and

CNS. (1,3)

! The RfC for 1,2-dichloropropane is 0.004 mg/m3 based on hyperplasia of the nasal

mucosa in rats. The RfC is an estimate (with uncertainty spanning perhaps an order of

magnitude) of a continuous inhalation exposure to the human population (including

sensitive subgroups) that is likely to be without appreciable risk of deleterious noncancer
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A-95

effects during a lifetime. It is not a direct estimator of risk but rather a reference point to

gauge the potential effects. At exposures increasingly greater than the RfC, the potential

for adverse health effects increases. Lifetime exposure above the RfC does not imply that

an adverse health effect would necessarily occur. (4)

! EPA has high confidence in the RfC based on: high confidence in the study on which the

RfC was based because it used an adequate number of animals, exposure concentrations,

and controls, examined three species, focused on known target organs, and the incidence

and severity of the nasal lesions were exposure-related, and medium confidence in the

database because there are no chronic inhalation studies. (4)

! EPA has not established a reference dose (RfD) for 1,2-dichloropropane. (4)

! ATSDR has established an acute oral minimal risk level (MRL) of 0.1 mg/kg/d based on

neurological effects in rats; an intermediate oral MRL of 0.07 mg/kg/d based on

hematological effects in rats; and a chronic oral MRL of 0.09 mg/kg/d based on liver

effects in mice. The MRL is an estimate of the daily human exposure to a hazardous

substance that is likely to be without appreciable risk of adverse noncancer health effects

over a specified duration of exposure. (1)

Reproductive/Developmental Effects:

! A case was reported of a woman who was hospitalized with metrorrhagia (bleeding from

the uterus between menstrual periods) after acute inhalation exposure to

1,2-dichloropropane. No other information is available on the reproductive or

developmental effects of 1,2-dichloropropane in humans. (1)

! No reproductive effects were noted in several animal inhalation studies. (1)

! Developmental effects, such as an increased incidence of delayed ossification of the

bones of the skull, and reproductive effects such as testicular degeneration and increased

incidences of infection of the ovary, uterus, or other organs, have been observed in

animals exposed to 1,2-dichloropropane by gavage. It is not known if the infections

observed were related to 1,2-dichloropropane treatment since controls were also infected.

(1)

Cancer Risk:

! No studies are available regarding carcinogenic effects in humans from inhalation or oral

exposure to 1,2-dichloropropane. (1)

! An increased incidence of mammary gland tumors in female rats and liver tumors in male

and female mice were reported in studies in which 1,2-dichloropropane was given by

gavage. (1)

! EPA has provisionally classified 1,2-dichloropropane as a Group B2, probable human

carcinogen, with an oral cancer slope factor of 6.8 x 10-2 (mg/kg/d)-1. (5)
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0.001

0.01

0.1

1

10

100

1000

10000

100000

1,2-Dichloropropane

Health numbersa Regulatory, advisory

numbers

b

Ref.

1

Ref.

4

Ref.

4

Ref.

6

Ref.

7,6

LC50 (rats) (9,242 mg/m3)

LOAELc (respirat ory)

(69.3 mg/ m3)

RfC (0.004 mg/m3)

OSHA PEL, ACGIH

TLV (350 mg/ m3)

ACGIH STEL (508 mg/m3)

NIOSH IDLH (1,800 mg/m3)

Ref.

8

Conversion Factors:

To convert from ppm to mg/m3: mg/m3 = (ppm) x (molecular weight of the compound)/(24.45).

For dichloropropane: 1 ppm = 4.62 mg/m3.

Health Data from Inhalation Exposure

ACGIH STEL – American Conference of Governmental and Industrial Hygienists' short-term

exposure limit; 15-min time-weighted-average exposure that should not be exceeded at any time

during a workday even if the 8-h time-weighted-average is within the threshold limit value.
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ACGIH TLV – American Conference of Governmental and Industrial Hygienists' threshold

limit value expressed as a time-weighted average; the concentration of a substance to which most

workers can be exposed without adverse effects.

LC50 (Lethal Concentration50) – A calculated concentration of a chemical in air to which

exposure for a specific length of time is expected to cause death in 50% of a defined

experimental animal population.

LOAEL – Lowest-observed-adverse-effect level.

NIOSH IDLH – National Institute of Occupational Safety and Health's immediately dangerous

to life or health concentration; NIOSH recommended exposure limit to ensure that a worker can

escape from an exposure condition that is likely to cause death or immediate or delayed

permanent adverse health effects or prevent escape from the environment.

OSHA PEL – Occupational Safety and Health Administration's permissible exposure limit

expressed as a time-weighted average; the concentration of a substance to which most workers

can be exposed without adverse effect averaged over a normal 8-h workday or a 40-h workweek.

a

 Health numbers are toxicological numbers from animal testing or risk assessment values

developed by EPA.

b

 Regulatory numbers are values that have been incorporated in Government regulations, while

advisory numbers are nonregulatory values provided by the Government or other groups as

advice.

c

 This LOAEL is from the critical study used as the basis for the EPA RfC.

References

1. Agency for Toxic Substances and Disease Registry (ATSDR). Toxicological Profile for

1,2-Dichloropropane (Draft). Public Health Service, U.S. Department of Health and

Human Services. 1989.

2. U.S. Department of Health and Human Services. Registry of Toxic Effects of Chemical

Substances (RTECS, online database). National Toxicology Information Program,

National Library of Medicine, Bethesda, MD. 1993.

3. U.S. Department of Health and Human Services. Hazardous Substances Data Bank

(HSDB, online database). National Toxicology Information Program, National Library of

Medicine, Bethesda, MD. 1993.

4. U.S. Environmental Protection Agency(EPA). Integrated Risk Information System (IRIS)

on 1,2-Dichloropropane. National Center for Environmental Assessment, Office of

Research and Development, Washington, DC. 1999.

5. U.S. Environmental Protection Agency (EPA). Health Effects Assessment Summary

Tables. FY-1997 Update. National Center for Environmental Assessment, Office of

Research and Development, Office of Emergency Response and Remedial Response,

Washington, DC. 1997.
National Air Toxics Program: The Integrated Urban Strategy

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6. American Conference of Governmental Industrial Hygienists (ACGIH). 1999 TLVs and

BEIs. Threshold Limit Values for Chemical Substances and Physical Agents, Biological

Exposure Indices. Cincinnati, OH. 1999.

7. Occupational Safety and Health Administration (OSHA). Occupational Safety and

Health Standards, Toxic and Hazardous Substances. Code of Federal Regulations. 29

CFR 1910.1000. 1998.

8. National Institute for Occupational Safety and Health (NIOSH). Pocket Guide to

Chemical Hazards. U.S. Department of Health and Human Services, Public Health

Service, Centers for Disease Control and Prevention. Cincinnati, OH. 1997.
National Air Toxics Program: The Integrated Urban Strategy

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1,3-DICHLOROPROPENE

542-75-6

Hazard Summary

1,3-Dichloropropene is used as a component in formulations for soil fumigants. Acute

(short-term) inhalation exposure of humans following a spill caused mucous membrane

irritation, chest pain, and breathing difficulties. Effects on the lung have been observed in

rats acutely exposed to 1,3-dichloropropene by inhalation. Chronic (long-term) dermal

exposure may result in skin sensitization in humans. Damage to the nasal mucosa and

urinary bladder are the primary health effects of rodents chronically exposed to

1,3-dichloropropene by inhalation. A study of male workers engaged in the manufacture

of 1,3-dichloropropene indicated no significant effect on fertility at exposure levels

occurring in the work environment. The only developmental effect seen in animal studies

was fewer fetuses per litter in rats exposed to high levels by inhalation, and no

reproductive effects have been noted. Information on the carcinogenic effects of

1,3-dichloropropene in humans is limited; two cases of histiocytic lymphomas and one

case of leukemia have been reported in humans accidentally exposed by inhalation to

concentrated vapors during cleanup of a tank truck spill. An increased incidence of

bronchioalveolar adenomas has been reported in male mice exposed by inhalation but not

in rats or female mice. The U.S. Environmental Protection Agency (EPA) has classified

1,3-dichloropropene as a Group B2, probable human carcinogen. 

Please Note: The main sources of information for this fact sheet are EPA's Integrated Risk Information System

(IRIS), which contains information on inhalation chronic toxicity of 1,3-dichloropropene and the reference

concentration (RfC), oral chronic toxicity and the reference dose (RfD), and the carcinogenic effects of

1,3-dichloropropene, and the Agency for Toxic Substances and Disease Registry's (ATSDR's) Toxicological Profile

for 1,3-Dichloropropene.

Physical Properties

! The chemical formula for 1,3-dichloropropene is C3H4Cl2, and its molecular weight is

110.98 g/mol. (1)

! 1,3-Dichloropropene occurs as a colorless liquid that dissolves in water. (1)

! 1,3-Dichloropropene has a sweet chloroform-like odor, with an odor threshold of 1 ppm.

(1)

! The vapor pressure for 1,3-dichloropropene is 34 to 43 mm Hg at 25 EC, and its log

octanol/water partition coefficient (log Kow) is 1.60. (1)

! The half-life of 1,3-dichloropropene in ambient air may range from 7 to 50 hours. (1)

Uses

! 1,3-Dichloropropene is the predominant component of several formulations used in

agriculture as soil fumigants for parasitic nematodes. (1,4)
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Sources and Potential Exposure

! Workers may be occupationally exposed to 1,3-dichloropropene, dermally or by

inhalation, during its manufacture, formulation, or application as a soil fumigant. (1, 2)

! The general public may be exposed via inhalation near source areas or from the

consumption of contaminated drinking water from wells near some hazardous waste sites.

(1,2)

Assessing Personal Exposure

! 1,3-Dichloropropene or its breakdown products can be detected in blood and urine to

determine whether or not exposure has occurred. However, metabolites measured in

blood and urine are not specific to 1,3-dichloropropene. (1)

Health Hazard Information

Acute Effects:

! Acute inhalation exposure of humans after a tank truck spill resulted in mucous

membrane irritation, cough, chest pain, and breathing difficulties. (1)

! Effects on the lung, including emphysema and edema, have been observed in rats acutely

exposed to 1,3-dichloropropene by inhalation. (1)

! Lung congestion and hemorrhage, ulcerations of the glandular stomach, hemorrhage of

the small intestine, dark and patchy liver, and hemorrhage of the liver have been observed

in rats acutely exposed to 1,3-dichloropropene in their diet or via gavage. Neurotoxic

effects, including hunched posture, lethargy, ptosis, ataxia, and decreased respiratory rate,

have also been observed in orally exposed rats. (1)

! Acute animal tests, such as the LC50 and LD50 tests in rats, mice, and rabbits, have

demonstrated 1,3-dichloropropene to have moderate acute toxicity from inhalation,

moderate to high acute toxicity from oral exposure, and high acute toxicity from dermal

exposure. (3)

Chronic Effects (Noncancer):

! Chronic dermal exposure may result in skin sensitization in humans. (1)

! Damage to the nasal mucosa and urinary bladder are the primary health effects of rodents

chronically exposed to 1,3-dichloropropene by inhalation. Hyperplastic lesions of the

upper respiratory tract and degeneration of the olfactory epithelium in the nasal turbinates

have been observed in chronically exposed rats and mice. Chronic inhalation exposure of

mice has resulted in changes in the urinary bladder. (1,4,5)

! In one study, reversible cloudy swelling of the renal tubular epithelium was reported in

rats chronically exposed by inhalation. (1,4,5)

! In rats and mice chronically exposed by inhalation, hyperplasia and hyperkeratosis of the

forestomach have been observed, while hyperplasia of the forestomach and of the urinary

bladder have resulted from chronic oral exposure. (1,4)
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! The RfC for 1,3-dichloropropene is 0.02 mg/m3 based on hypertrophy/hyperplasia of the

nasal respiratory epithelium in mice. The RfC is an estimate (with uncertainty spanning

perhaps an order of magnitude) of a continuous inhalation exposure to the human

population (including sensitive subgroups) that is likely to be without appreciable risk of

deleterious noncancer effects during a lifetime. It is not a direct estimator of risk but

rather a reference point to gauge the potential effects. At exposures increasingly greater

than the RfC, the potential for adverse health effects increases. Lifetime exposure above

the RfC does not imply that an adverse health effect would necessarily occur. (5)

! EPA has high confidence in the RfC based on: high confidence in the study on which the

RfC was based because it is a well-designed study using two species of animals (both

sexes) and including detailed histopathological examinations of numerous tissues with

extensive analysis of the respiratory system and corroborative studies performed in both

rats and mice have also shown this to be a sensitive endpoint; and high confidence in the

database because several studies reported similar effects on the respiratory system at

comparable exposure levels, and acute effects observed in humans were similar to the

animal effects. (5)

! The RfD for 1,3-dichloropropene is 0.0003 mg/kg/d based on increased organ weights in

rats. (5)

! EPA has low confidence in the RfD based on: low confidence in the study on which the

RfD was based because it is of low quality and of short duration (90 days), and low

confidence in the database because of the remaining studies, only two teratology studies

were considered acceptable. (5)

Reproductive/Developmental Effects:

! A study of male workers engaged in the manufacture of 1,3-dichloropropene indicated no

significant effect on fertility at exposure levels occurring in the work environment. (4)

! No evidence of developmental toxicity was observed in rats or rabbits exposed to

1,3-dichloropropene by inhalation, but significant maternal toxicity was seen in both

species. (4)

! In one study of rats exposed by inhalation, fewer fetuses per litter were reported at the

highest exposure concentration. (1)

! In other studies, no adverse reproductive effects were observed in rats and mice exposed

by inhalation. (1,5)

Cancer Risk:

! Information on the carcinogenic effects of 1,3-dichloropropene in humans is limited. Two

cases of histiocytic lymphomas and one case of leukemia have been reported in

emergency response personnel exposed to concentrated 1,3-dichloropropene vapors

during cleanup of a tank truck spill. (1,4,5)

! An increased incidence of bronchioalveolar adenomas has been reported in male mice

exposed by inhalation but not in rats or female mice. (1,4)
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! Forestomach, adrenal and thyroid tumors, and liver nodules in rats and forestomach,

urinary bladder, and lung tumors in mice have been observed in rodents exposed to

1,3-dichloropropene via gavage. (1,4,5)

! EPA has classified 1,3-dichloropropene as a Group B2, probable human carcinogen. (5)

! EPA uses mathematical models, based on human and animal studies, to estimate the

probability of a person developing cancer from breathing air containing a specified

concentration of a chemical. EPA has calculated a provisional inhalation unit risk

estimate of 3.7. x 10-5 (μg/m3)

-1. (6)

! EPA has calculated a provisional oral cancer slope factor of 0.18 (mg/kg/d)-1. (6)

Conversion Factors:

To convert from ppm to mg/m3: mg/m3 = (ppm) x (molecular weight of the compound)/(24.45).

For 1,3-dichloropropene: 1 ppm = 4.54 mg/m3.
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1,3-Dichloropropene

0.01

0.1

1

10

100

1000

10000

Health numbersa

advisory

Regulatory,

numbersb

Ref.

3

Ref.

3

Ref.

5

Ref.

5

Ref.

7,8

LC50 (mice) (4,650 mg/ m3)

LC50 (rats) (2,270 mg/ m3)

LOAELc (respiratory) (83.5 mg/ m3)

RfC (0.02 mg/ m3)

ACGIH TLV, NIOSH

REL (5 mg/ m3)

NOAELc (respiratory) (20.9 mg/ m3)

Ref.

5

Health Data from Inhalation Exposure

ACGIH TLV – American Conference of Governmental and Industrial Hygienists' threshold

limit value expressed as a time-weighted average; the concentration of a substance to which most

workers can be exposed without adverse effects.

LC50 (Lethal Concentration50) – A calculated concentration of a chemical in air to which

exposure for a specific length of time is expected to cause death in 50% of a defined

experimental animal population.

LOAEL – Lowest-observed-adverse-effect level.

NIOSH REL – National Institute of Occupational Safety and Health's recommended exposure

limit; NIOSH-recommended exposure limit for an 8- or 10-h time-weighted-average exposure

and/or ceiling.
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NOAEL – No-observed-adverse-effect level.

OSHA PEL – Occupational Safety and Health Administration's permissible exposure limit

expressed as a time-weighted average; the concentration of a substance to which most workers

can be exposed without adverse effect averaged over a normal 8-h workday or a 40-h workweek.

a

 Health numbers are toxicological numbers from animal testing or risk assessment values

developed by EPA.

b

 Regulatory numbers are values that have been incorporated in Government regulations, while

advisory numbers are nonregulatory values provided by the Government or other groups as

advice.

c

 The LOAEL and NOAEL are from the critical study used as the basis for the EPA RfC.

References

1. Agency for Toxic Substances and Disease Registry (ATSDR). Toxicological Profile for

1,3-Dichloropropene. Public Health Service, U.S. Department of Health and Human

Services. 1992.

2. U.S. Department of Health and Human Services. Hazardous Substances Data Bank

(HSDB, online database). National Toxicology Information Program, National Library of

Medicine, Bethesda, MD. 1993.

3. U.S. Department of Health and Human Services. Registry of Toxic Effects of Chemical

Substances (RTECS, online database). National Toxicology Information Program,

National Library of Medicine, Bethesda, MD. 1993.

4. U.S. Environmental Protection Agency (EPA). Health and Environmental Effects Profile

for 1,3-Dichloropropene. ECAO-CIN-G074. Environmental Criteria and Assessment

Office, Office of Health and Environmental Assessment, Office of Research and

Development, Cincinnati, OH. 1989.

5. U.S. Environmental Protection Agency (EPA). Integrated Risk Information System (IRIS)

on 1,3-Dichloropropene. National Center for Environmental Assessment, Office of

Research and Development, Washington, DC. 1999.

6. U.S. Environmental Protection Agency (EPA). Health Effects Assessment Summary

Tables. FY-1997 Update. National Center for Environmental Assessment, Office of

Research and Development, Office of Emergency and Remedial Response, Washington,

DC. 1997.

7. American Conference of Governmental Industrial Hygienists (ACGIH). 1999 TLVs and

BEIs. Threshold Limit Values for Chemical Substances and Physical Agents, Biological

Exposure Indices. Cincinnati, OH. 1999.
National Air Toxics Program: The Integrated Urban Strategy

Report to Congress

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8. National Institute for Occupational Safety and Health (NIOSH). Pocket Guide to

Chemical Hazards. U.S. Department of Health and Human Services, Public Health

Service, Centers for Disease Control and Prevention. Cincinnati, OH. 1997.
National Air Toxics Program: The Integrated Urban Strategy

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ETHYLENE DIBROMIDE (1,2-DIBROMOETHANE)

106-93-4

Hazard Summary

Exposure to ethylene dibromide primarily occurs from its past use as an additive to

leaded gasoline and as a fumigant. Ethylene dibromide is extremely toxic to humans.

Changes in the liver and kidney have been noted in humans who died from ingestion of

ethylene dibromide. The chronic (long-term) effects of exposure to ethylene dibromide

have not been well documented in humans. Animal studies indicate that chronic exposure

to ethylene dibromide may result in toxic effects to the liver, kidney, and the testis,

irrespective of the route of exposure. Limited data on men occupationally exposed to

ethylene dibromide indicate that long-term exposure to ethylene dibromide can impair

reproduction by damaging sperm cells in the testicles. Animal studies have demonstrated

reproductive and developmental effects from ethylene dibromide exposure. Human data

are considered inadequate in providing evidence of cancer by exposure to ethylene

dibromide. Several animal studies indicate that long-term exposure to ethylene dibromide

increases the incidences of a variety of tumors in rats and mice in both sexes by all routes

of exposure. The U.S. Environmental Protection Agency (EPA) has classified ethylene

dibromide as a Group B2, probable human carcinogen. 

Please Note: The main sources of information for this fact sheet EPA's Integrated Risk Information System (IRIS),

which contains information on the carcinogenic effects of ethylene dibromide including the unit cancer risk for

inhalation exposure, and the Agency for Toxic Substances and Disease Registry's (ATSDR's) Toxicological Profile

for 1,2-Dibromoethane.

Physical Properties

! Ethylene dibromide is a colorless liquid with a mild sweet odor, like chloroform. (1,7)

! Ethylene dibromide is slightly soluble in water. (1,7)

! The chemical formula for ethylene dibromide is C2H4Br2, and it has a molecular weight of

187.88 g/mol. (1,7)

! The vapor pressure for ethylene dibromide is 11.0 mm Hg at 25 EC, and it has a log

octanol/water partition coefficient (log Kow) of 86. (1).

! Ethylene dibromide reacts with hydroxyl radicals in the atmosphere, with a half-life for

this reaction of approximately 40 days. In water, its half-life ranges from 2.5 to 13.2

years, and in soil it was detected 19 years after it had been applied. (1)

Uses

! Ethylene dibromide was used in the past as an additive to leaded gasoline; however, since

leaded gasoline is now banned, it is no longer used for this purpose. (1)
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! Ethylene dibromide was used as a fumigant to protect against insects, pests, and

nematodes in citrus, vegetable, and grain crops, and as a fumigant for turf, particularly on

golf courses. In 1984, EPA banned its use as a soil and grain fumigant. (1)

! Ethylene dibromide is currently used in the treatment of felled logs for bark beetles and

termites, and control of wax moths in beehives. (1)

! Ethylene dibromide is also used as an intermediate for dyes, resins, waxes, and gums. (1)

Sources and Potential Exposure

! Possible sources of ethylene dibromide emissions to the ambient air are production and

processing facilities. (1)

! Exposure could occur from inhalation of ambient air near industries that use ethylene

dibromide or through the ingestion of contaminated drinking water. (1)

Assessing Personal Exposure

! There is no known reliable medical test to determine whether someone has been exposed

to ethylene dibromide. (1)

Health Hazard Information

Acute Effects:

! Clinical signs in humans and animals related to acute inhalation exposure to ethylene

dibromide are depression and collapse. Ethylene dibromide is a severe skin irritant that

can cause blistering. (1,2)

! Exposure to high concentrations of ethylene dibromide through inhalation, ingestion, or

skin contact can result in death. Changes in the liver and kidney are reported in humans

who died from ingestion of ethylene dibromide. (1,2)

! Tests involving acute exposure of animals, such as the LD50 test in rats, have shown

ethylene dibromide to have high acute toxicity from oral exposure, while the LC50 test in

rats has demonstrated moderate acute toxicity from inhalation exposure. (3)

Chronic Effects (Noncancer):

! The chronic effects of exposure to ethylene dibromide have not been extensively

documented in humans. In one case in which a worker breathed ethylene dibromide for

several years, he developed bronchitis, headache, and depression. His health improved

after he stopped breathing air contaminated with ethylene dibromide. (1,2)

! Animal studies indicate that prolonged exposure to ethylene dibromide may result in

toxic effects to the liver, kidney, and the testis whether by inhalation, ingestion, or skin

contact. (1,2)

! EPA has not established a reference dose (RfD) or a reference concentration (RfC) for

ethylene dibromide. (4)
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! EPA has calculated a provisional RfC of 0.0002 mg/m3 for ethylene dibromide based on

reproductive effects in humans. The RfC is an estimate (with uncertainty spanning

perhaps an order of magnitude) of a continuous inhalation exposure to the human

population (including sensitive subgroups) that is likely to be without appreciable risk of

deleterious noncancer effects during a lifetime. It is not a direct estimator of risk but

rather a reference point to gauge the potential effects. At exposures increasingly greater

than the RfC, the potential for adverse health effects increases. Lifetime exposure above

the RfC does not imply that an adverse health effect would necessarily occur. The

provisional RfC is a value that has had some form of Agency review, but it does not

appear on IRIS. (5)

Reproductive Effects/Developmental:

! Developmental effects have not been documented in humans. Limited data on men

occupationally exposed to ethylene dibromide indicate that long-term exposure to

ethylene dibromide can impair reproduction by damaging sperm cells in the testicles.

(1,2)

! Animals that breathed or ate food containing ethylene dibromide for short or long periods

were less fertile than control animals or had abnormal sperm. Pregnant animals that were

sick from exposure to ethylene dibromide have had pups with birth defects. (1,2)

Cancer Risk:

! Two cancer studies on workers exposed to ethylene dibromide have been carried out.

Neither study reported a statistically significant increase in cancer mortality; however

these studies are considered inadequate due to confounding factors. (4)

! Several animal studies indicate that long-term exposure to ethylene dibromide increases

the incidences of a variety of tumors in rats and mice in both sexes by inhalation, by

gavage, or by administration to the skin. (4)

! EPA has classified ethylene dibromide as a Group B2, probable human carcinogen. (4)

! EPA uses mathematical models, based on animal studies, to estimate the probability of a

person developing cancer from breathing air containing a specified concentration of a

chemical. EPA has calculated an inhalation unit risk estimate of 2.2 x 10-4 (μg/m3)

-1. EPA

estimates that, if an individual were to continuously breathe air containing ethylene

dibromide at an average of 0.005 μg/m3 (5 x 10-6 mg/m3) over his or her entire lifetime,

that person would theoretically have no more than a one-in-a-million increased chance of

developing cancer as a direct result of breathing air containing this chemical. Similarly,

EPA estimates that continuously breathing air containing 0.05 μg/m3 (5 x 10-5 mg/m3)

would result in not greater than a one-in-hundred thousand increased chance of

developing cancer, and air containing 0.5 μg/m3 (5 x 10-4 mg/m3) would result in not

greater than a one-in-ten thousand increased chance of developing cancer in their lifetime.

For a detailed discussion of confidence in the potency estimates, please see IRIS. (4)

! EPA has calculated an oral cancer slope factor of 85 (mg/kg/d)-1. (4)
National Air Toxics Program: The Integrated Urban Strategy

Report to Congress

A-110

1,2-Dibromoethane

0.000001

0.00001

0.0001

0.001

0.01

0.1

1

10

100

1000

10000

100000

1000000

Health numbersa Regulatory, advisory

numbersb

Ref.

4

LC50 (rat s) (14,300 mg/ m3)

LOAELc (reproduct ive)

(0.7 mg/ m3)

Provisional RfC

0.0002 mg/ m3)

Cancer Risk

Level 1 in a

million risk

(5 x 10-6

mg/ m3)

OSHA 5 min. max (385 mg/ m3)

OSHA ceiling (231 mg/m3)

OSHA PEL (154 mg/ m3)

NIOSH REL

(0.4 mg/ m3)

NIOSH ceiling (1.0 mg/m3)

Ref.

3

Ref.

5

Ref.

7

Ref.

7

Ref.

7

Ref.

8

Ref.

5

Ref.

8

Conversion Factors:

To convert from ppm to mg/m3: mg/m3 = (ppm) x (molecular weight of the compound)/(24.45).

For ethylene dibromide: 1 ppm = 7.7 mg/m3.

To convert from μg/m3 to mg/m3: mg/m3 = (μg/m3) x (1 mg/1,000 μg).

Health Data from Inhalation Exposure

LC50 (Lethal Concentration50) – A calculated concentration of a chemical in air to which

exposure for a specific length of time is expected to cause death in 50% of a defined

experimental animal population.

LOAEL – Lowest-observed-adverse-affect level.

NIOSH ceiling – National Institute of Occupational Safety and Health's ceiling limit;

NIOSH--recommended 15-min exposure limit, which should not be exceeded.
National Air Toxics Program: The Integrated Urban Strategy

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NIOSH REL – NIOSH's recommended exposure limit; NIOSH-recommended exposure limit for

an 8- or 10-h time-weighted-average exposure and/or ceiling.

OSHA PEL – Occupational Safety and Health Administration's permissible exposure limit

expressed as a time-weighted average; the concentration of a substance to which most workers

can be exposed without adverse effect averaged over a normal 8-h workday or a 40-h workweek.

a

 Health numbers are toxicological numbers from animal testing or risk assessment values

developed by EPA.

b

 Regulatory numbers are values that have been incorporated in Government regulations, while

advisory numbers are nonregulatory values provided by the Government or other groups as

advice.

c

 The LOAEL is from the critical study used as the basis for the EPA Provisional RfC.

References

1. Agency for Toxic Substances and Disease Registry (ATSDR). Toxicological Profile for

1,2-Dibromoethane. Public Health Service, U.S. Department of Health and Human

Services, Atlanta, GA. 1992.

2. U.S. Department of Health and Human Services. Hazardous Substances Data Bank

(HSDB, online database). National Toxicology Information Program, National Library of

Medicine, Bethesda, MD. 1993.

3. U.S. Department of Health and Human Services. Registry of Toxic Effects of Chemical

Substances (RTECS, online database). National Toxicology Information Program,

National Library of Medicine, Bethesda, MD. 1993.

4. U.S. Environmental Protection Agency (EPA). Integrated Risk Information System (IRIS)

on 1,2-Dibromoethane. National Center for Environmental Assessment, Office of

Research and Development, Washington, DC. 1999.

5. U.S. Environmental Protection Agency (EPA). Health Effects Assessment Summary

Tables. FY-1997 Update. National Center for Environmental Assessment, Office of

Research and Development, Office of Emergency and Remedial Response, Washington,

DC. 1997.

6. The Merck Index. An Encyclopedia of Chemicals, Drugs, and Biologicals. 11th ed. Ed. S.

Budavari. Merck and Co. Inc., Rahway, NJ. 1989.

7. Occupational Safety and Health Administration (OSHA). Occupational Safety and

Health Standards, Toxic and Hazardous Substances. Code of Federal Regulations. 29

CFR 1910.1000. 1998.
National Air Toxics Program: The Integrated Urban Strategy

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A-112

8. National Institute for Occupational Safety and Health (NIOSH). Pocket Guide to

Chemical Hazards. U.S. Department of Health and Human Services, Public Health

Service, Centers for Disease Control and Prevention. Cincinnati, OH. 1997.
National Air Toxics Program: The Integrated Urban Strategy

Report to Congress

A-113

ETHYLENE OXIDE

75-21-8

Hazard Summary

The major use for ethylene oxide is as a chemical intermediate in industry. The acute

(short-term) effects of ethylene oxide in humans consist mainly of central nervous system

(CNS) depression and irritation of the eyes and mucous membranes. High concentrations

of ethylene oxide produce weakness, nausea, bronchitis, pulmonary edema, emphysema,

and death. Chronic (long-term) exposure to ethylene oxide in humans can cause irritation

of the eyes, skin, and mucous membranes; and problems in the functioning of the brain

and nerves. Limited evidence in both animal and human studies indicate that inhalation

exposure to ethylene oxide may result in adverse reproductive effects such as an increased

rate of miscarriages. These effects could be seen from acute as well as chronic exposures.

Some human cancer data show an increase in the incidence of leukemia, stomach cancer,

cancer of the pancreas, and Hodgkin's disease in workers exposed to ethylene oxide.

However these data are considered to be limited and inconclusive due to uncertainties in

the studies. Ethylene oxide has been shown to cause lung, gland, and uterine tumors in

laboratory animals. The U.S. Environmental Protection Agency (EPA) has classified

ethylene oxide as a Group B1, probable human carcinogen.

Please Note: The main source of information for this fact sheet is the Agency for Toxic Substances and Disease

Registry's (ATSDR's) Toxicological Profile for Ethylene Oxide. Other secondary sources include the Hazardous

Substances Data Bank (HSDB), a database of summaries of peer-reviewed literature, and the Registry of Toxic

Effects of Chemical Substances (RTECS), a database of toxic effects that are not peer reviewed.

Physical Properties

! Ethylene oxide is a colorless gas with a sweet odor. (1,6)

! The chemical formula for ethylene oxide is C2H4O and the molecular weight is 44.1

g/mol. (6)

! The vapor pressure for ethylene oxide is 1,095 mm Hg at 20 EC, and it has an

octanol/water partition coefficient (log Kow) of -0.30. (6)

! Ethylene oxide is very soluble in water and is flammable. (1)

! Ethylene oxide has an odor threshold of 430 ppm. (7)

! Ethylene oxide has an estimated half-life in air ranging from 69 to 149 days, while its

half-life in water is about 50 years. (1).

Uses

! Ethylene oxide is used mainly as a chemical intermediate in the manufacture of textiles,

detergents, polyurethane foam, antifreeze, solvents, medicinals, adhesives, and other

products. (1)
National Air Toxics Program: The Integrated Urban Strategy

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A-114

! Relatively small amounts of ethylene oxide are used as a fumigant, a sterilant for food

(spices) and cosmetics, and in hospital sterilization of surgical equipment and plastic

devices that cannot be sterilized by steam. (1)

Sources and Potential Exposure

! Sources of ethylene oxide emissions into the air include uncontrolled emissions or

venting with other gases in industrial settings. (1)

! Other sources of ethylene oxide air emissions include automobile exhaust and its release

from commodity-fumigated materials, as well as its use as a sterilizer of medical

equipment. (1)

! The general population may be exposed to ethylene oxide through breathing

contaminated air or from smoking tobacco or being in the proximity to someone who is

smoking. Certain occupational groups (e.g., workers in ethylene oxide manufacture or

processing plants, sterilization technicians, and workers involved in fumigation) may be

exposed in the workplace. (1)

Assessing Personal Exposure

! There are tests currently available to determine personal exposure to ethylene oxide, such

as the determination of ethylene oxide in the blood or the amount breathed out of the

lungs. (1)

Health Hazard Information

Acute Effects:

! Acute inhalation exposure of workers to high levels of ethylene oxide has resulted in

nausea, vomiting, neurological disorders, bronchitis, pulmonary edema, emphysema, and

even death at very high concentrations. (1,2)

! Dermal or ocular contact with solutions of ethylene oxide has caused irritation of the eyes

and skin in humans. (1,2)

! Tests involving acute exposure of animals, such as the LD50 test in rats, has shown

ethylene oxide to have high acute toxicity from oral exposure. LC50 tests in rats, mice,

dogs, and guinea pigs have also shown high acute toxicity from ethylene oxide exposure.

(3)

Chronic Effects (Noncancer):

! Major effects observed in workers exposed to ethylene oxide at low levels for several

years are irritation of the eyes, skin, and mucous membranes and problems in the

functioning of the brain and nerves. (1,2)

! There is evidence suggesting that long-term exposure to high levels of ethylene oxide, at

a level of 700 ppm, can result in cataracts in humans. (2)
National Air Toxics Program: The Integrated Urban Strategy

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A-115

! EPA has not established a reference dose (RfD) or a reference concentration (RfC) for

ethylene oxide.

! The California Environmental Protection Agency (CalEPA) has established a chronic

reference exposure level of 0.005 mg/m3 for ethylene oxide based on hematological

effects in humans. The CalEPA reference exposure level is a concentration at or below

which adverse health effects are not likely to occur. It is not a direct estimator of risk, but

rather a reference point to gauge the potential effects. At lifetime exposures increasingly

greater than the reference exposure level, the potential for adverse health effects

increases. (4)

! ATSDR has an established an intermediate inhalation minimal risk level (MRL) of 0.2

mg/m3 (0.09 ppm) based on respiratory effects in humans. The MRL is an estimate of the

daily human exposure to a hazardous substance that is likely to be without appreciable

risk of adverse noncancer health effects over a specified duration of exposure. (1)

Reproductive/Developmental Effects:

! Some evidence exists indicating that inhalation exposure to ethylene oxide can cause an

increased rate of miscarriages in female workers. These effects could be seen from acute,

as well as chronic, exposure. (1,2)

! Various adverse reproductive effects have been noted in inhalation exposure studies of

animals including decreased number of implantation sites, decreased testicular weights

and sperm concentration, and testicular degeneration. (1,2)

Cancer Risk:

! Human occupational studies have shown elevated cases of leukemia, stomach and

pancreatic cancer, and Hodgkin's disease in workers exposed to ethylene oxide by

inhalation. However, the data are considered to be limited and inconclusive due to the

small number of individuals studied and uncertainties about the exposure levels. (1,2)

! Animal studies have shown lung, gland, and uterine tumors caused by inhalation

exposure to ethylene oxide. (1,2)

! EPA has classified ethylene oxide as a Group B1, probable human carcinogen. (5)

! EPA uses mathematical models, based on human and animal studies, to estimate the

probability of a person developing cancer from breathing air containing a specified

concentration of a chemical. EPA has calculated a provisional inhalation unit cancer risk

estimate of 1.0 x 10-4 (μg/m3)

-1 . A provisional value is one that has not received

Agencywide review. (5)

! EPA has calculated a provisional oral cancer slope factor of 1.0 (mg/kg/d)-1. (5)

Conversion Factors:

To convert from ppm to mg/m3: mg/m3 = (ppm) x (molecular weight of the compound)/(24.45).

For ethylene oxide: 1 ppm = 1.8 mg/m3.
National Air Toxics Program: The Integrated Urban Strategy

Report to Congress

A-116

Ethylene Oxide

0.001

0.01

0.1

1

10

100

1000

10000

Health numbersa

advisory

Regulatory,

numbersb

Ref.

3

Ref.

3

Ref.

3

Ref.

3

Ref.

4

Ref.

4

Ref.

8,9

Ref.

10

LC50 (dogs) (1,730 mg/m3)

LC50 (mice) (1,507 mg/m3)

LC50 (rats)

(1,442 mg/ m3)

LC50 (guinea pigs) (1,500 mg/ m3)

LOAELc

(hemat ological)

(0.3 mg/ m3)

CalEPA

reference

exposure

level (0.005

mg/ m3)

NIOSH REL

(0.2 mg/ m3)

ACGIH TLV, OSHA

PEL (1.8 mg/ m3)

NIOSH IDLH

(1440 mg/ m3)

Ref.

11

Ref.

10

AIHA ERPG-2

(90 mg/ m3)

Health Data from Inhalation Exposure

ACGIH TLV – American Conference of Governmental and Industrial Hygienists' threshold

limit value expressed as a time-weighted average; the concentration of a substance to which most

workers can be exposed without adverse effects.

AIHA ERPG – American Industrial Hygiene Association's emergency response planning

guidelines. ERPG 1 is the maximum airborne concentration below which it is believed nearly all

individuals could be exposed up to one hour without experiencing other than mild transient

adverse health effects or perceiving a clearly defined objectionable odor; ERPG 2 is the

maximum airborne concentration below which it is believed nearly all individuals could be

exposed up to one hour without experiencing or developing irreversible or other serious health

effects that could impair their abilities to take protective action.
National Air Toxics Program: The Integrated Urban Strategy

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A-117

LC50 (Lethal Concentration50) – A calculated concentration of a chemical in air to which

exposure for a specific length of time is expected to cause death in 50% of a defined

experimental animal population.

LOAEL – Lowest-observed-no-adverse-affect level.

NIOSH IDLH – National Institute of Occupational Safety and Health's immediately dangerous

to life or health concentration; NIOSH recommended exposure limit to ensure that a worker can

escape from an exposure condition that is likely to cause death or immediate or delayed

permanent adverse health effects or prevent escape from the environment.

NIOSH REL – NIOSH's recommended exposure limit; NIOSH-recommended exposure limit for

an 8- or 10-h time-weighted-average exposure and/or ceiling.

OSHA PEL – Occupational Safety and Health Administration's permissible exposure limit

expressed as a time-weighted average; the concentration of a substance to which most workers

can be exposed without adverse effect averaged over a normal 8-h workday or a 40-h workweek.

a

 Health numbers are toxicological numbers from animal testing or risk assessment values

developed by EPA.

b

 Regulatory numbers are values that have been incorporated in Government regulations, while

advisory numbers are nonregulatory values provided by the Government or other groups as

advice.

c

 The LOAEL is from the critical study used as the basis for the CalEPA chronic reference

exposure level.

References

1. Agency for Toxic Substances and Disease Registry (ATSDR). Toxicological Profile for

Ethylene Oxide. U.S. Public Health Service, U.S. Department of Health and Human

Services. 1990.

2. U.S. Department of Health and Human Services. Hazardous Substances Data Bank

(HSDB, online database). National Toxicology Information Program, National Library of

Medicine, Bethesda, MD. 1993.

3. U.S. Department of Health and Human Services. Registry of Toxic Effects of Chemical

Substances (RTECS, online database). National Toxicology Information Program,

National Library of Medicine, Bethesda, MD. 1993.

4. California Environmental Protection Agency (CalEPA). Technical Support Document for

the Determination of Noncancer Chronic Reference Exposure Levels. Draft for Public

Comment. Office of Environmental Health Hazard Assessment, Berkeley, CA. 1997.

5. U.S. Environmental Protection Agency (EPA). Health Effects Assessment Summary

Tables. FY 1997 Update. National Center for Environmental Assessment, Office of

Research and Development, Washington, DC. 1997.
National Air Toxics Program: The Integrated Urban Strategy

Report to Congress

A-118

6. The Merck Index. An Encyclopedia of Chemicals, Drugs, and Biologicals. 11th ed. Ed. S.

Budavari. Merck and Co. Inc., Rahway, NJ. 1989.

7. J.E. Amoore and E. Hautala. Odor as an aid to chemical safety: Odor thresholds

compared with threshold limit values and volatilities for 214 industrial chemicals in air

and water dilution. Journal of Applied Toxicology, 3(6):272-290. 1983

8. American Conference of Governmental Industrial Hygienists (ACGIH). 1999 TLVs and

BEIs. Threshold Limit Values for Chemical Substances and Physical Agents, Biological

Exposure Indices. Cincinnati, OH. 1999.

9. Occupational Safety and Health Administration (OSHA). Occupational Safety and

Health Standards, Toxic and Hazardous Substances. Code of Federal Regulations. 29

CFR 1910.1000. 1998.

10. National Institute for Occupational Safety and Health (NIOSH). Pocket Guide to

Chemical Hazards. U.S. Department of Health and Human Services, Public Health

Service, Centers for Disease Control and Prevention. Cincinnati, OH. 1997.

11. American Industrial Hygiene Association (AIHA). The AIHA 1998 Emergency Response

Planning Guidelines and Workplace Exposure Level Guides Handbook. 1998.
National Air Toxics Program: The Integrated Urban Strategy

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A-119

FORMALDEHYDE

50-00-0

Hazard Summary

Formaldehyde is used mainly to produce resins used in particle board products and as an

intermediate in the synthesis of other chemicals. Exposure to formaldehyde may occur by

breathing contaminated indoor air, tobacco smoke, or ambient urban air. Acute

(short-term) and chronic (long-term) inhalation exposure to formaldehyde in humans can

result in respiratory symptoms, and eye, nose, and throat irritation. Reproductive effects,

such as menstrual disorders and pregnancy problems, have been reported in female

workers exposed to formaldehyde. Limited human studies have reported an association

between formaldehyde exposure and lung and nasopharyngeal cancer. Animal inhalation

studies have reported an increased incidence of nasal squamous cell cancer. The U.S.

Environmental Protection Agency (EPA) has classified formaldehyde as a Group B2,

probable human carcinogen.

Please Note: The main sources of information for this fact sheet are EPA's Health and Environmental Effects

Profile for Formaldehyde and the Integrated Risk Information System (IRIS), which contains information on oral

chronic toxicity and the reference dose (RfD), and the carcinogenic effects of formaldehyde including the unit

cancer risk for inhalation exposure. 

Physical Properties

! The chemical formula for formaldehyde is CH2O, and the molecular weight is 30.03

g/mol. (1)

! The vapor pressure for formaldehyde is 10 mm Hg at -88 EC, and its log octanol/water

partition coefficient (log Kow) is -0.65. (1)

! Formaldehyde is a colorless gas with a pungent, suffocating odor at room temperature;

the odor threshold for formaldehyde is 0.83 ppm. (1,8)

! Formaldehyde is readily soluble in water at room temperature. (1)

! Commercial formaldehyde is produced and sold as an aqueous solution containing 37 to

50 percent formaldehyde by weight. (1)

Uses

! Formaldehyde is used predominantly as a chemical intermediate. It also has minor uses in

agriculture, as an analytical reagent, in concrete and plaster additives, cosmetics,

disinfectants, fumigants, photography, and wood preservation. (1,2)

! One of the most common uses of formaldehyde in the U.S. is manufacturing

urea-formaldehyde resins, used in particle board products. (7)

! Formaldehyde (as urea formaldehyde foam) was extensively used as an insulating

material until 1982 when it was banned by the U.S. Consumer Product Safety

Commission. (1,2)
National Air Toxics Program: The Integrated Urban Strategy

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Sources and Potential Exposure

! The highest levels of airborne formaldehyde have been detected in indoor air, where it is

released from various consumer products such as building materials and home

furnishings. One survey reported formaldehyde levels ranging from 0.10 to 3.68 ppm in

homes. Higher levels have been found in new manufactured or mobile homes than in

older conventional homes. (1)

! Formaldehyde has also been detected in ambient air; the average concentrations reported

in U.S. urban areas were in the range of 11 to 20 ppb. The major sources appear to be

power plants, manufacturing facilities, incinerators, and automobile exhaust emissions.

(7)

! Smoking is another important source of formaldehyde. (1)

! Formaldehyde may also be present in food, either naturally or as a result of

contamination. (1)

Assessing Personal Exposure

! Blood levels of formaldehyde can be measured. However, these measurements are only

useful when exposure by inhalation to relatively large amounts of formaldehyde has

occurred. (2)

Health Hazard Information

Acute Effects:

! The major toxic effects caused by acute formaldehyde exposure via inhalation are eye,

nose, and throat irritation and effects on the nasal cavity. (1,2)

! Other effects seen from exposure to high levels of formaldehyde in humans are coughing,

wheezing, chest pains, and bronchitis. (1,2)

! Ingestion exposure to formaldehyde in humans has resulted in corrosion of the

gastrointestinal tract and inflammation and ulceration of the mouth, esophagus, and

stomach. (1,2)

! Acute animal tests, such as the LC50 and LD50 tests in rats and rabbits have shown

formaldehyde to have high acute toxicity from inhalation, oral, and dermal exposure. (3)

Chronic Effects (Noncancer):

! Chronic exposure to formaldehyde by inhalation in humans has been associated with

respiratory symptoms and eye, nose, and throat irritation. (1,2,4,5)

! Repeated contact with liquid solutions of formaldehyde has resulted in skin irritation and

allergic contact dermatitis. (5)

! Animal studies have reported effects on the nasal respiratory epithelium and lesions in the

respiratory system from chronic inhalation exposure to formaldehyde. (1,2,4,5)
National Air Toxics Program: The Integrated Urban Strategy

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A-121

! The RfD for formaldehyde is 0.2 mg/kg/d based on a decrease in body weight gain and

effects on the stomach in rats. The RfD is an estimate (with uncertainty spanning perhaps

an order of magnitude) of a daily oral exposure to the human population (including

sensitive subgroups) that is likely to be without appreciable risk of deleterious noncancer

effects during a lifetime. It is not a direct estimator of risk but rather a reference point to

gauge the potential effects. At exposures increasingly greater than the RfD, the potential

for adverse health effects increases. Lifetime exposure above the RfD does not imply that

an adverse health effect would necessarily occur. (6)

! EPA has high confidence in the study on which the RfD was based since it consisted of

an adequate number of animals of both sexes, as well as a thorough examination of

toxicological and histological parameters; medium confidence in the database as several

additional chronic bioassays and reproductive and developmental studies support the

critical effect and study; and, consequently, medium confidence in the RfD. (6)

! EPA has not established a reference concentration (RfC) for formaldehyde. (6)

! The Agency for Toxic Substances and Disease Registry (ATSDR) has established a

chronic inhalation minimal risk level (MRL) of 0.003 ppm (0.004 mg/m3) based on

respiratory effects in humans. The MRL is an estimate of the daily human exposure to a

hazardous substance that is likely to be without appreciable risk of adverse noncancer

health effects over a specified duration of exposure. (7)

Reproductive/Developmental Effects:

! An increased incidence of menstrual disorders were observed in female workers using

urea-formaldehyde resins. However, possible confounding factors were not evaluated in

this study. (1,2)

! A study of hospital workers who sterilize equipment did not report an association

between formaldehyde exposure and increased spontaneous abortions. (1,2)

! Developmental effects, such as birth defects, have not been observed in animal studies

with formaldehyde. (1,2)

Cancer Risk:

! Occupational studies have noted statistically significant associations between exposure to

formaldehyde and increased incidence of lung and nasopharyngeal cancer. This evidence

is considered to be "limited," rather than "sufficient," due to possible exposure to other

agents that may have contributed to the excess cancers. (1,6)

! Animal studies have reported an increased incidence of nasal squamous cell carcinomas

by inhalation exposure. (1,6)

! EPA has classified formaldehyde as a Group B1, probable human carcinogen. (6)

! EPA uses mathematical models, based on human and animal studies, to estimate the

probability of a person developing cancer from breathing air containing a specified

concentration of a chemical. EPA calculated an inhalation unit risk estimate of 1.3 x 10-5

(μg/m3)

-1. EPA estimates that, if an individual were to continuously breathe air containing

formaldehyde at an average of 0.08 μg/m3 (8.0 x 10-5 mg/m3) over his or her entire

lifetime, that person would theoretically have no more than a one-in-a-million increased
National Air Toxics Program: The Integrated Urban Strategy

Report to Congress

A-122

chance of developing cancer as a direct result of breathing air containing this chemical.

Similarly, EPA estimates that breathing air containing 0.8 μg/m3 (8.0 x 10-4 mg/m3)

would result in not greater than a one-in-a-hundred thousand increased chance of

developing cancer, and air containing 8.0 μg/m3 (8.0 x 10-3 mg/m3) would result in not

greater than a one-in-ten-thousand increased chance of developing cancer. For a detailed

discussion of confidence in the potency estimates, please see IRIS. (6)

Conversion Factors:

To convert from ppm to mg/m3: mg/m3 = (ppm) x (molecular weight of the compound)/(24.45).

For formaldehyde: 1 ppm = 1.23 mg/m3. 
National Air Toxics Program: The Integrated Urban Strategy

Report to Congress

A-123

Formaldehyde

0.00001

0.0001

0.001

0.01

0.1

1

10

100

1000

Health numbers

a Regulatory, advisory

numbers

b

Ref.

3 Ref.

3

Ref.

7

Ref.

6

Ref.

11 Ref.

9

Ref.

10

LC50 (mice) (400 mg/ m3)

LC50 (rat s) (203 mg/ m3)

ATSDR chronic MRL

(0.004 mg/ m3)

Cancer Risk Level

1 in a million risk

(8 x 10-5 mg/ m3)

OSHA PEL (0.9 mg/m3)

ACGIH STEL (0.4 mg/ m3)

NIOSH REL

(0.02 mg/m3)

NIOSH IDLH (25 mg/ m3)

Ref.

10

AIHA ERPG-2 (12 mg/m3)

Ref.

12 AIHA ERPG-1 (1.2 mg/m3

)

Ref.

12

Health Data from Inhalation Exposure

AIHA ERPG – American Industrial Hygiene Association's emergency response planning

guidelines. ERPG 1 is the maximum airborne concentration below which it is believed nearly all

individuals could be exposed up to one hour without experiencing other than mild transient

adverse health effects or perceiving a clearly defined objectionable odor; ERPG 2 is the

maximum airborne concentration below which it is believed nearly all individuals could be

exposed up to one hour without experiencing or developing irreversible or other serious health

effects that could impair their abilities to take protective action. 

ACGIH STEL – American Conference of Governmental and Industrial Hygienists' short-term

exposure limit expressed as a time-weighted average exposure; the concentration of a substance

which should not be exceeded at any time during a workday.

LC50 (Lethal Concentration50) – A calculated concentration of a chemical in air to which

exposure for a specific length of time is expected to cause death in 50% of a defined
National Air Toxics Program: The Integrated Urban Strategy

Report to Congress

A-124

experimental animal population.

NIOSH IDLH – National Institute of Occupational Safety and Health's immediately dangerous

to life or health limit; NIOSH recommended exposure limit to ensure that a worker can escape

from an exposure condition that is likely to cause death or immediate or delayed permanent

adverse health effects or prevent escape from the environment.

NIOSH REL – NIOSH's recommended exposure limit; NIOSH recommended exposure limit for

an 8- or 10-h time-weighted average exposure and/or ceiling.

OSHA PEL – Occupational Safety and Health Administration's permissible exposure limit

expressed as a time-weighted average; the concentration of a substance to which most workers

can be exposed without adverse effect averaged over a normal 8-h workday or a 40-h workweek. 

a

 Health numbers are toxicological numbers from animal testing or risk assessment values

developed by EPA. 

b

 Regulatory numbers are values that have been incorporated in Government regulations, while

advisory numbers are nonregulatory values provided by the Government or other groups as

advice. 

References

1. U.S. Environmental Protection Agency (EPA). Health and Environmental Effects Profile

for Formaldehyde. EPA/600/x-85/362. Environmental Criteria and Assessment Office,

Office of Health and Environmental Assessment, Office of Research and Development,

Cincinnati, OH. 1988.

2. World Health Organization (WHO). Environmental Health Criteria for Formaldehyde.

Volume 89. World Health Organization, Geneva, Switzerland. 1989.

3. U.S. Department of Health and Human Services. Registry of Toxic Effects of Chemical

Substances (RTECS, online database). National Toxicology Information Program,

National Library of Medicine, Bethesda, MD. 1993.

4. E.J. Calabrese and E.M. Kenyon. Air Toxics and Risk Assessment. Lewis Publishers,

Chelsea, MI. 1991.

5. U.S. Department of Health and Human Services. Hazardous Substances Databank

(HSDB, online database). National Toxicology Information Program, National Library 

of Medicine, Bethesda, MD. 1993.

6. U.S. Environmental Protection Agency (EPA). Integrated Risk Information System (IRIS)

on Formaldehyde. National Center for Environmental Assessment, Office of Research

and Development, Washington, DC. 1999.

7. Agency for Toxic Substances and Disease Registry (ATSDR). Toxicological Profile for

Formaldehyde (Draft). Public Health Service, U.S. Department of Health and Human

Services, Atlanta, GA. 1997.
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8. J.E. Amoore and E. Hautala. Odor as an aid to chemical safety: Odor thresholds

compared with threshold limit values and volatilities for 214 industrial chemicals in air

and water dilution. Journal of Applied Toxicology, 3(6):272-290. 1983.

9. American Conference of Governmental Industrial Hygienists (ACGIH). 1999 TLVs and

BEIs. Threshold Limit Values for Chemical Substances and Physical Agents, Biological

Exposure Indices. Cincinnati, OH. 1999.

10. National Institute for Occupational Safety and Health (NIOSH). Pocket Guide to

Chemical Hazards. U.S. Department of Health and Human Services, Public Health

Service, Centers for Disease Control and Prevention. Cincinnati, OH. 1997.

11. Occupational Safety and Health Administration (OSHA). Occupational Safety and

Health Standards, Toxic and Hazardous Substances. Code of Federal Regulations 29

CFR 1910.1048. 1998.

12. American Industrial Hygiene Association (AIHA). The AIHA 1998 Emergency Response

Planning Guidelines and Workplace Environmental Exposure Level Guides Handbook. 

1998.
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HEXACHLOROBENZENE

118-74-1

Hazard Summary

Hexachlorobenzene is formed as a byproduct during the manufacture of other chemicals. 

It was widely used as a pesticide until 1965. Chronic (long-term) oral exposure to

hexachlorobenzene in humans results in a liver disease with associated skin lesions. 

Animal studies have reported effects on the liver, skin, kidneys, immune system, and

blood from chronic oral exposure to hexachlorobenzene. Hexachlorobenzene may cause

developmental effects in humans and has been found to decrease the survival rates of

newborn animals. Epidemiologic studies of persons orally exposed to hexachlorobenzene

have not shown an increased cancer incidence. However, based on animal studies that

have reported cancer of the liver, thyroid, and kidney from oral exposure to

hexachlorobenzene, the U.S. Environmental Protection Agency (EPA) has classified

hexachlorobenzene as a Group B2, probable human carcinogen. Very little inhalation

data are available.

Please Note: The main sources of information for this fact sheet are EPA's Integrated Risk Information System

(IRIS), which contains information on oral chronic toxicity and the reference dose (RfD), and the carcinogenic

effects of hexachlorobenzene including the unit cancer risk for inhalation exposure, and the Agency for Toxic

Substances and Disease Registry's (ATSDR's) Toxicological Profile for Hexachlorobenzene. 

Physical Properties

! Hexachlorobenzene is a white crystalline solid that is not very soluble in water. (1)

! The odor threshold for hexachlorobenzene is not available.

! The chemical formula for hexachlorobenzene is C6Cl6, and the molecular weight is 284.8

g/mol. (1)

! The vapor pressure for hexachlorobenzene is 1.09 x 10-5 mm Hg at 20 EC, and it has a log

octanol/water partition coefficient (log Kow) of 6.18. (1)

Uses

! There are currently no commercial uses of hexachlorobenzene in the U.S.. (1)

! Hexachlorobenzene was used as a pesticide until 1965 and was also used in the

production of rubber, aluminum, and dyes and in wood preservation. (1)

! Hexachlorobenzene is currently formed as a byproduct during the manufacture of other

chemicals (mainly solvents) and pesticides. (1)

Sources and Potential Exposure

! Inhalation exposure to hexachlorobenzene may occur through proximity to industrial sites

where it is formed as a byproduct or to waste facilities where it is disposed. (1)
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! Occupational exposure, via inhalation and dermally, can occur at industries where

hexachlorobenzene is produced as a byproduct. (1)

! Exposure to hexachlorobenzene can also occur through consuming foods tainted with

hexachlorobenzene. (1)

! Hexachlorobenzene has been listed as a pollutant of concern in EPA's Great Waters

Program due to its persistence in the environment, potential to bioaccumulate, and

toxicity to humans and the environment (2).

Assessing Personal Exposure

! Medical tests can measure levels of hexachlorobenzene in the fat or blood. (1)

Health Hazard Information

Acute Effects:

! No information is available on the acute (short-term) effects of hexachlorobenzene in

humans. (1,3)

! Acute animal tests, such as the LD50 tests in rats and mice, have shown

hexachlorobenzene to have low-to-moderate acute toxicity from oral exposure. (4)

Chronic Effects (Noncancer):

! Humans who ingested hexachlorobenzene in heavily contaminated bread during a 4-year

poisoning incident were sickened with a liver disease with associated skin lesions

(porphyria cutanea tarda). (1)

! Animal studies have reported effects on the liver, skin, immune system, kidneys, and

blood from chronic oral exposure to hexachlorobenzene. (1,3)

! Very little data are available on the health effects of hexachlorobenzene in humans or

animals following inhalation exposure.

! EPA has determined that there are inadequate data to establish a reference concentration

(RfC) for hexachlorobenzene. (5)

! The California Environmental Protection Agency (CalEPA) has established a chronic

inhalation reference exposure level of 0.003 mg/m3 for hexachlorobenzene. The CalEPA

reference exposure level is a concentration at or below which adverse health effects are

not likely to occur. It is not a direct estimator of risk but rather a reference point to gauge

the potential effects. At lifetime exposures increasingly greater than the reference

exposure level, the potential for adverse health effects increases. (6)

! The RfD for hexachlorobenzene is 0.0008 mg/kg/d based on liver effects in rats. The RfD

is an estimate (with uncertainty spanning perhaps an order of magnitude) of a daily oral

exposure to the human population (including sensitive subgroups) that is likely to be

without appreciable risk of deleterious noncancer effects during a lifetime. (5)

! EPA has medium confidence in the study used as the basis for the RfD because it had an

unusual dosing scheme making it difficult to determine the true doses received by each
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experimental group; high confidence in the database due to the extensive number of

quality research studies available; and consequently medium confidence in the RfD. (5)

Reproductive/Developmental Effects:

! One human study reported abnormal physical development in young children who

ingested contaminated bread during a 4-year poisoning incident. (1)

! Hexachlorobenzene has been found to decrease the survival rates of newborn animals and

to cross the placenta and accumulate in fetal tissue in several animal species. (3)

! Neurological, teratogenic, liver, and immune system effects have been reported in the

offspring of animals orally exposed to hexachlorobenzene while they were pregnant. (1)

Cancer Risk:

! Human data regarding the carcinogenic effects of hexachlorobenzene are inadequate. (5)

! Hexachlorobenzene, when administered orally, has been shown to induce tumors of the

liver, thyroid, and kidney in several animal species. (1,3,5)

! EPA has classified hexachlorobenzene as a Group B2, probable human carcinogen. (5)

! EPA uses mathematical models, based on human and animal studies to estimate the

probability of a person developing cancer from breathing air containing a specified

concentration of a chemical. EPA calculated an inhalation unit risk estimate of 4.6 x 10-4

(μg/m3)

-1. EPA estimates that, if an individual were to continuously breathe air containing

hexachlorobenzene at an average of 0.002 μg/m3 (2.0 x 10-6 mg/m3) over his or her entire

lifetime, that person would theoretically have no more than a one-in-a-million increased

chance of developing cancer as a direct result of breathing air containing this chemical.

Similarly, EPA estimates that breathing air containing 0.02 μg/m3 (2.0 x 10-5 mg/m3)

would result in not greater than a one-in-a-hundred thousand increased chance of

developing cancer, and air containing 0.2 μg/m3 (2.0 x 10-4 mg/m3) would result in not

greater than a one-in-ten thousand increased chance of developing cancer. For a detailed

discussion of confidence in the potency estimates, please see IRIS. (5)

! EPA has calculated an oral cancer slope factor of 1.6 (mg/kg/d)-1. (5)

Conversion Factors:

To convert from ppm to mg/m3: mg/m3 = (ppm) x (molecular weight of the compound)/(24.45).

For hexachlorobenzene: 1 ppm = 11.6 mg/m3.
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Hexachlorobenzene

0.000001

0.00001

0.0001

0.001

0.01

0.1

1

10

100

1000

10000

100000

Health numbersa Regulatory, advisory

numbersb

Ref.

4

Ref.

6

Ref.

7

LC50 (rat s) (3,600 mg/ m3)

CalEPA reference exposure

level (0.003 mg/m3)

Cancer Risk Level

1 in a million risk

(2 x 10-6 mg/ m3)

ACGIH TLV (0.002 mg/ m3)

Ref.

5

Health Data from Inhalation Exposure

ACGIH TLV – American Conference of Governmental and Industrial Hygienists' threshold

limit value expressed as a time-weighted average; the concentration of a substance to which most

workers can be exposed without adverse effects.

LC50 (Lethal Concentration50) – A calculated concentration of a chemical in air to which

exposure for a specific length of time is expected to cause death in 50% of a defined

experimental animal population. 

a

 Health numbers are toxicological numbers from animal testing or risk assessment values

developed by EPA. 

b

 Regulatory numbers are values that have been incorporated in Government regulations, while

advisory numbers are nonregulatory values provided by the Government or other groups as

advice. 
National Air Toxics Program: The Integrated Urban Strategy

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c

 These cancer risk estimates were derived from oral data and converted to provide the estimated

inhalation risk. 

References

1. Agency for Toxic Substances and Disease Registry (ATSDR). Toxicological Profile for

Hexachlorobenzene (Update). Public Health Service, U.S. Department of Health and

Human Services, Atlanta, GA. 1996.

2. U.S. Environmental Protection Agency (EPA). Deposition of Air Pollutants to the Great

Waters. First Report to Congress. EPA-453/R-93-055. Office of Air Quality Planning and

Standards, Research Triangle Park, NC. 1994.

3. U.S. Department of Health and Human Services. Hazardous Substances Data Bank

(HSDB, online database). National Toxicology Information Program, National Library of

Medicine, Bethesda, MD. 1993.

4. U.S. Department of Health and Human Services. Registry of Toxic Effects of Chemical

Substances (RTECS, online database). National Toxicology Information Program,

National Library of Medicine, Bethesda, MD. 1993.

5. U.S. Environmental Protection Agency (EPA). Integrated Risk Information System (IRIS)

on Hexachlorobenzene. National Center for Environmental Assessment, Office of

Research and Development, Washington, DC. 1999.

6. California Environmental Protection Agency (CalEPA). Technical Support Document for

the Determination of Noncancer Chronic Reference Exposure Levels. Draft for Public

Comment. Office of Environmental Health Hazard Assessment, Berkeley, CA. 1997.

7. American Conference of Governmental Industrial Hygienists (ACGIH). 1999 TLVs and

BEIs. Threshold Limit Values for Chemical Substances and Physical Agents, Biological

Exposure Indices. Cincinnati, OH. 1999.
National Air Toxics Program: The Integrated Urban Strategy

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HYDRAZINE

302-01-2

Hazard Summary

Individuals may be exposed to hydrazine in the workplace or to small amounts in tobacco

smoke. Symptoms of acute (short-term) exposure to high levels of hydrazine may include

irritation of the eyes, nose, and throat, dizziness, headache, nausea, pulmonary edema,

seizures, and coma in humans. Acute exposure can also damage the liver, kidneys, and

central nervous system (CNS) in humans. The liquid is corrosive and may produce

dermatitis from skin contact. Effects to the lungs, liver, spleen, and thyroid have been

reported in animals chronically (long-term) exposed to hydrazine via inhalation. 

Exposure of rodents to hydrazine has resulted in fetotoxicity and damage to reproductive

organs. Increased incidences of lung and liver tumors have been observed in mice

exposed to hydrazine. Tumors in the nasal cavity were observed in rats and hamsters

exposed by inhalation. The U.S. Environmental Protection Agency (EPA) has classified

hydrazine as a Group B2, probable human carcinogen.

Please Note: The main sources of information for this fact sheet are EPA's Integrated Risk Information System

(IRIS), which contains information on the carcinogenic effects of hydrazine including the unit cancer risk for

inhalation exposure, EPA's Health and Environmental Effects Profile for Hydrazine, and the Agency for Toxic

Substances and Disease Registry's (ATSDR's) Toxicological Profile for Hydrazines.

Physical Properties

! The chemical formula for hydrazine is H4N2, and its molecular weight is 32.05 g/mol. (6)

! Hydrazine occurs as a colorless, oily, flammable liquid that is miscible with water. (6,8)

! Hydrazine has a penetrating odor, resembling that of ammonia, with an odor threshold of

3.7 ppm. (8,9)

! The vapor pressure for hydrazine is 14.4 mm Hg at 25 EC, and its log octanol/water

partition coefficient (log Kow) is 0.08. (6)

Uses

! Hydrazine is used in agricultural chemicals (pesticides), chemical blowing agents,

pharmaceutical intermediates, photography chemicals, boiler water treatment for

corrosion protection, textile dyes, and as fuel for rockets and spacecraft. (4,6,8,10)

Sources and Potential Exposure

! Individuals may be occupationally exposed to hydrazine in the workplace. (1,2,10)

! Accidental discharge into water, air, and soil may occur during storage, handling,

transport, and improper waste disposal. However, hydrazine rapidly degrades in the

environment and is rarely encountered. (2,3)
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! Small amounts of hydrazine have been detected in tobacco smoke. (2,10)

Assessing Personal Exposure

! Hydrazine may be detected in the blood of exposed individuals. (1,2)

Health Hazard Information

Acute Effects:

! Symptoms of acute exposure to high levels of hydrazine include irritation of the eyes,

nose, and throat, temporary blindness, dizziness, headache, nausea, pulmonary edema,

seizures, and coma in humans. Acute exposure can also damage the liver, kidneys, and

the CNS in humans. (2-4)

! The liquid is corrosive and may produce chemical burns and severe dermatitis from skin

contact. (1,4)

! Acute animal tests, such as the LC50 and LD50 tests in rats, mice, rabbits, and guinea pigs,

have demonstrated hydrazine to have high acute toxicity from inhalation and ingestion

and extreme acute toxicity from dermal exposure. (5)

Chronic Effects (Noncancer):

! Information is not available on the chronic effects of hydrazine in humans.

! In animals chronically exposed to hydrazine by inhalation, effects on the respiratory

system, liver, spleen, and thyroid have been observed. (10)

! EPA has not established a reference concentration (RfC) or a reference dose (RfD) for

hydrazine. (4)

! The California Environmental Protection Agency (CalEPA) has calculated a chronic

inhalation reference exposure level of 0.0002 mg/m3 based on liver and thyroid effects in

hamsters. The CalEPA reference exposure level is a concentration at or below which

adverse health effects are not likely to occur. It is not a direct estimator of risk but rather

a reference point to gauge the potential effects. At lifetime exposures increasingly greater

than the reference exposure level, the potential for adverse health effects increases. (11)

! ATSDR has calculated an intermediate inhalation minimal risk level (MRL) of 0.005

mg/m3 (0.004 ppm) based on liver effects in mice. The MRL is an estimate of the daily

human exposure to a hazardous substance that is likely to be without appreciable risk of

adverse noncancer health effects over a specified duration of exposure. (10)

Reproductive/Developmental Effects:

! Information is not available on the reproductive or developmental effects of hydrazine in

humans.

! Data regarding developmental effects in animals are limited to a study in which hydrazine

injected into pregnant rats resulted in fetotoxicity including increased fetal and neonatal 

mortality. (6,10)
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! Inhalation of hydrazine for a year resulted in effects to the ovaries, endometrium, and

uterus in female rats and to the testes in male hamsters. (10)

Cancer Risk:

! Adequate information is not available on the carcinogenic effects of hydrazine in humans.

(4)

! Increased incidences of lung and liver tumors have been observed in mice exposed to

hydrazine by inhalation, in their drinking water, via gavage and injection. Tumors in the

nasal cavity were observed in rats and hamsters exposed by inhalation. (4,6,7)

! EPA has classified hydrazine as a Group B2, probable human carcinogen. (4)

! EPA uses mathematical models, based on human and animal studies, to estimate the

probability of a person developing cancer from breathing air containing a specified

concentration of a chemical. EPA calculated an inhalation unit risk estimate of 4.9 x 10-3

(μg/m3)

-1. EPA estimates that, if an individual were to continuously breathe air containing

hydrazine at an average of 0.0002 μg/m3 (2.0 x 10-7 mg/m3) over his or her entire lifetime,

that person would theoretically have no more than a one-in-a-million increased chance of

developing cancer as a direct result of breathing air containing this chemical. Similarly,

EPA estimates that breathing air containing 0.002 μg/m3 (2.0 x 10-6 mg/m3) would result

in not greater than a one-in-a-hundred thousand increased chance of developing cancer,

and air containing 0.02 μg/m3 (2.0 x 10-5 mg/m3) would result in not greater than a

one-in-ten thousand increased chance of developing cancer. For a detailed discussion of

confidence in the potency estimates, please see IRIS. (4)

! EPA has calculated an oral cancer slope factor of 3.0 (mg/kg/d)-1. (4)

Conversion Factors:

To convert from ppm to mg/m3: mg/m3 = (ppm) x (molecular weight of the compound)/(24.45).

For hydrazine: 1 ppm = 1.31 mg/m3.
National Air Toxics Program: The Integrated Urban Strategy

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0.0000001

0.000001

0.00001

0.0001

0.001

0.01

0.1

1

10

100

1000

10000

Cancer Risk Level

1 in a million risk

(2 x 10-7 mg/m3)

Hydrazine

Health numbersa

Regulatory, advisory

numbersb

Ref.

5 Ref.

5

Ref.

11

Ref.

11

Ref.

4

Ref.

12

Ref.

13

LC50 (rat s) (747 mg/m3)

LC50 (mice) (330 mg/m3)

LOAELc (liver and t hyroid)

(0.3 mg/m3)

CalEPA reference exposure

level (0.0002 mg/ m3)

OSHA PEL (1.3 mg/ m3)

ACGIH TLV

(0.013 mg/m3)

Ref.

14

NIOSH IDLH (66 mg/m3)

Health Data from Inhalation Exposure

ACGIH TLV – American Conference of Governmental and Industrial Hygienists' threshold

limit value expressed as a time-weighted average; the concentration of a substance to which most

workers can be exposed without adverse effects.

LC50 (Lethal Concentration50) – A calculated concentration of a chemical in air to which

exposure for a specific length of time is expected to cause death in 50% of a defined

experimental animal population.

LOAEL – Lowest-observed-adverse-effect level

NIOSH IDLH – National Institute of Occupational Safety and Health's immediately dangerous

to life or health limit; NIOSH recommended exposure limit to ensure that a worker can escape

from an exposure condition that is likely to cause death or immediate or delayed permanent

adverse health effects or prevent escape from the environment.
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OSHA PEL – Occupational Safety and Health Administration's permissible exposure limit

expressed as a time-weighted average; the concentration of a substance to which most workers

can be exposed without adverse effect averaged over a normal 8-h workday or a 40-h workweek. 

a

 Health numbers are toxicological numbers from animal testing or risk assessment values

developed by EPA. 

b

 Regulatory numbers are values that have been incorporated in Government regulations, while

advisory numbers are nonregulatory values provided by the Government or other groups as

advice. 

c

 The LOAEL is from the critical study used as the basis for the CalEPA chronic reference

exposure level. 

References

1. M. Sittig. Handbook of Toxic and Hazardous Chemicals and Carcinogens. 2nd ed. Noyes

Publications, Park Ridge, NJ. 1985.

2. World Health Organization (WHO). Environmental Health Criteria 68: Hydrazine.

Geneva, Switzerland. 1987.

3. U.S. Department of Health and Human Services. Hazardous Substances Data Bank

(HSDB, online database). National Toxicology Information Program, National Library of

Medicine, Bethesda, MD. 1993.

4. U.S. Environmental Protection Agency (EPA). Integrated Risk Information System (IRIS)

on Hydrazine/Hydrazine Sulfate. National Center for Environmental Assessment, Office

of Research and Development, Washington, DC. 1999.

5. U.S. Department of Health and Human Services. Registry of Toxic Effects of Chemical

Substances (RTECS, online database). National Toxicology Information Program,

National Library of Medicine, Bethesda, MD. 1993.

6. U.S. Environmental Protection Agency (EPA). Health and Environmental Effects Profile

for Hydrazine and Hydrazine Sulfate. EPA/600/x-84/332. Environmental Criteria and

Assessment Office, Office of Health and Environmental Assessment, Office of Research

and Development, Cincinnati, OH. 1984.

7. International Agency for Research on Cancer (IARC). IARC Monographs on the

Evaluation of the Carcinogenic Risk of Chemicals to Man: Some Aromatic Amines,

Hydrazine and Related Substances, N-Nitroso Compounds and Miscellaneous Alkylating

Agents. Volume 4. World Health Organization, Lyon. 1974.

8. The Merck Index. An Encyclopedia of Chemicals, Drugs, and Biologicals. 11th ed. Ed. S.

Budavari. Merck and Co. Inc., Rahway, NJ. 1989.
National Air Toxics Program: The Integrated Urban Strategy

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9. J.E. Amoore and E. Hautala. Odor as an aid to chemical safety: Odor thresholds

compared with threshold limit values and volatilities for 214 industrial chemicals in air

and water dilution. Journal of Applied Toxicology, 3(6):272-290. 1983.

10. Agency for Toxic Substances and Disease Registry (ATSDR). Toxicological Profile for

Hydrazines. Public Health Service, U.S. Department of Health and Human Services,

Atlanta, GA. 1997.

11. California Environmental Protection Agency (CalEPA). Technical Support Document for

the Determination of Noncancer Chronic Reference Exposure Levels. Draft for Public

Comment. Office of Environmental Health Hazard Assessment, Berkeley, CA. 1997.

12. Occupational Safety and Health Administration (OSHA). Occupational Safety and

Health Standards, Toxic and Hazardous Substances. Code of Federal Regulations. 29

CFR 1910.1000. 1998.

13. American Conference of Governmental Industrial Hygienists (ACGIH). 1999 TLVs and

BEIs. Threshold Limit Values for Chemical Substances and Physical Agents, Biological

Exposure Indices. Cincinnati, OH. 1999.

14. National Institute for Occupational Safety and Health (NIOSH). Pocket Guide to

Chemical Hazards. U.S. Department of Health and Human Services, Public Health

Service, Centers for Disease Control and Prevention. Cincinnati, OH. 1997.
National Air Toxics Program: The Integrated Urban Strategy

Report to Congress

1 Human exposure to lead occurs through a combination of inhalation and oral exposure, with

inhalation generally contributing a greater proportion of the dose for occupationally exposed groups, and

the oral route generally contributing a greater proportion of the dose for the general population. The

effects of lead are the same regardless of the route of exposure (inhalation or oral) and are correlated

with internal exposure as blood lead levels. For this reason, this fact sheet will not discuss the exposure

in terms of route but will present it in terms of blood lead levels.

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LEAD COMPOUNDS1

Hazard Summary

Lead is used in the manufacture of batteries, metal products, paints, and ceramic glazes. 

Exposure to lead can occur from breathing contaminated workplace air or dust or eating

lead-based paint chips or contaminated dirt. Lead is a very toxic element, causing a

variety of effects at low dose levels. Brain damage, kidney damage, and gastrointestinal

distress are seen from acute (short-term) exposure to high levels of lead in humans. 

Chronic (long-term) exposure to lead in humans results in effects on the blood, central

nervous system (CNS), blood pressure, kidneys, and Vitamin D metabolism. Children

are particularly sensitive to the chronic effects of lead, with slowed cognitive

development, reduced growth and other effects reported. Reproductive effects, such as

decreased sperm count in men and spontaneous abortions in women, have been

associated with lead exposure. The developing fetus is at particular risk from maternal

lead exposure, with low birth weight and slowed postnatal neurobehavioral development

noted. Human studies are inconclusive regarding lead exposure and cancer, while animal

studies have reported an increase in kidney cancer from lead exposure by the oral route. 

The U.S. Environmental Protection Agency (EPA) considers lead to be a Group B2,

probable human carcinogen.

Please Note: The main sources of information for this fact sheet are EPA's Integrated Risk Information System

(IRIS), which contains information on the carcinogenic effects of lead, and the Agency for Toxic Substances and

Disease Registry's (ATSDR's) Toxicological Profile for Lead.

Physical Properties

! Lead is a naturally occurring, bluish-gray metal that is found in small quantities in the

earth's crust. (1,2)

! Lead is present in a variety of compounds such as lead acetate, lead chloride, lead

chromate, lead nitrate, and lead oxide. (1,2)

! Pure lead is insoluble in water; however, the lead compounds vary in solubility from

insoluble to water soluble. (1,2)

! The chemical symbol for lead is Pb, and the atomic weight is 207.2 g/mol. (1)

! The vapor pressure for lead is 1.0 mm Hg at 980 EC. (1)
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Uses

! The primary use of lead is in the manufacture of batteries. (1)

! Lead is also used in the production of metal products, such as sheet lead, solder (but no

longer in food cans), and pipes, and in ceramic glazes, paint, ammunition, cable covering,

and other products. (1)

! Tetraethyl lead was used in gasoline to increase the octane rating until lead additives were

phased out and eventually banned from use in gasoline by the EPA beginning in 1973. (1)

Sources and Potential Exposure

! The largest source of lead in the atmosphere has been from leaded gasoline combustion,

but with the phase down of lead in gasoline, air lead levels have decreased considerably.

Other airborne sources include combustion of solid waste, coal, and oils, emissions from

iron and steel production and lead smelters, and tobacco smoke. (1,2)

! Exposure to lead can also occur from food and soil. Children are at particular risk to lead

exposure since they commonly put hands, toys, and other items in their mouths, which

may come in contact with lead-containing dust and dirt. (1,2)

! Lead-based paints were commonly used for many years and flaking paint, paint chips, and

weathered paint powder may be a major source of lead exposure, particularly for children.

(1,2)

! Lead in drinking water is due primarily to the presence of lead in certain pipes, solder,

and fixtures. (1,2)

! Exposure to lead may also occur in the workplace, such as lead smelting and refining

industries, steel and iron factories, gasoline stations, and battery manufacturing plants.

(1,2)

! Lead has been listed as a pollutant of concern to EPA's Great Waters Program due to its

persistence in the environment, potential to bioaccumulate, and toxicity to humans and

the environment. (3)

Assessing Personal Exposure

! The amount of lead in the blood can be measured to determine if exposure to lead has

occurred. (1,2)

! The level of lead in the blood is measured in μg/dL.

! The Centers for Disease Control concluded in 1993 that blood lead concentrations at or

around 10 μg/dL present a public health risk to sensitive populations. 

! Exposure to lead can also be evaluated by measuring erythrocyte protoporphyrin (EP), a

component of red blood cells known to increase when the amount of lead in the blood is

high. This method was commonly used to screen children for potential lead poisoning.

(1,2)

! Methods to measure lead in teeth or bones by X-ray fluorescence techniques are not

widely available. (1)
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Health Hazard Information

Acute Effects:

! Death from lead poisoning may occur in children who have blood lead levels greater than

125 μg/dL, and brain and kidney damage have been reported at blood lead levels of

approximately 100 μg/dL in adults and 80 μg/dL in children. (1,2)

! Gastrointestinal symptoms, such as colic, have also been noted in acute exposures at

blood lead levels of approximately 60 μg/dL in adults and children. (1,2)

! Short-term (acute) animal tests, such as the LC50 test in rats, have shown lead to have

moderate to high acute toxicity. (4)

Chronic Effects (Noncancer):

! Chronic exposure to lead in humans can affect the blood. Anemia has been reported in

adults at blood lead levels of 50 to 80 μg/dL, and in children at blood lead levels of 40 to

70 μg/dL. (1,2)

! Lead also affects the nervous system. Neurological symptoms have been reported in

workers with blood lead levels of 40 to 60 μg/dL, and slowed nerve conduction in

peripheral nerves in adults occurs at blood lead levels of 30 to 40 μg/dL. (1,2)

! Children are particularly sensitive to the neurotoxic effects of lead. A greatly expanded

body of research has shown that even low levels of lead exposure can result in

neurobehavioral changes, such as lowered IQ, in developing children. There is evidence

that blood lead levels of 10 to 30 μg/dL, or lower, may affect the hearing threshold and

growth in children. (1,2)

! Other effects from chronic lead exposure in humans include effects on blood pressure and

kidney function, and interference with vitamin D metabolism. (1,2,5)

! Animal studies have reported effects similar to those found in humans, with effects on the

blood, kidneys, and nervous, immune, and cardiovascular systems noted. (1,2,5)

! EPA has not established a reference concentration (RfC) or a reference dose (RfD) for

elemental lead or inorganic lead compounds. (6)

! EPA has established an RfD for tetraethyl lead (an organometallic form of lead) of 1 x

10-7 mg/kg/d based on effects in the liver and thymus of rats. The RfD is an estimate

(with uncertainty spanning perhaps an order of magnitude) of a daily oral exposure to the

human population (including sensitive subgroups) that is likely to be without appreciable

risk of deleterious noncancer effects during a lifetime. It is not a direct estimator of risk,

but rather a reference point to gauge the potential effects. At exposures increasingly

greater than the RfD, the potential for adverse health effects increases. Lifetime exposure

above the RfD does not imply that an adverse health effect would necessarily occur. (7)

! EPA has medium to low confidence in the RfD due to: medium to low confidence in the

study on which the RfD for tetraethyl lead was based because, although only a few

animals per sex per dose level were tested, a good histopathologic exam was conducted

and a dose-severity was observed; and medium to low confidence in the database because

some supporting information was available. (7)
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! The EPA has set a national ambient air quality standard (NAAQS) for lead at 1.5 μg/m3

as a quarterly average concentration. The NAAQS was set on the basis of evidence that

numerous health effects were associated with lead exposure, including impairment of

heme synthesis, and in recognition that young children (age 1-5 years) were a particularly

sensitive group to lead effects. (11,12)

Reproductive/Developmental Effects:

! Studies on male lead workers have reported severe depression of sperm count and

decreased function of the prostate and/or seminal vesicles at blood lead levels of 40 to 50

μg/dL. These effects may be seen from acute as well as chronic exposures. (1,5)

! Occupational exposure to high levels of lead has been associated with a high likelihood of

spontaneous abortion in pregnant women. However, the lowest blood lead levels at

which this occurs has not been established. These effects may be seen from acute as well

as chronic exposures. (1,5)

! Exposure to lead during pregnancy produces toxic effects on the human fetus, including

increased risk of preterm delivery, low birth weight, and impaired mental development. 

These effects have been noted at maternal blood lead levels of 10 to 15 μg/dL, and

possibly lower. Decreased IQ scores have been noted in children at blood lead levels of

approximately 10 to 50 μg/dL. (1,2)

! Human studies are inconclusive regarding the association between lead exposure and

other birth defects, while animal studies have shown a relationship between high lead

exposure and birth defects. (1,5)

Cancer Risk:

! Human studies are inconclusive regarding lead exposure and an increased cancer risk.

Four major human studies of workers exposed to lead have been carried out; two studies

did not find an association between lead exposure and cancer, one study found an

increased incidence of respiratory tract and kidney cancers, and the fourth study found

excesses for lung and stomach cancers. However, all of these studies are limited in

usefulness because the route(s) of exposure and levels of lead to which the workers were

exposed were not reported. In addition, exposure to other chemicals probably occurred.

(1,2,6)

! Animal studies have reported kidney tumors in rats and mice exposed to lead via the oral

route. (1,2,5,6)

! EPA considers lead to be a Group B2, probable human carcinogen. (6)

Conversion Factors:

To convert from ppm to mg/m3: mg/m3 = (ppm) x (molecular weight of the compound)/(24.45).

For lead: 1 ppm = 8.5 mg/m3.
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Lead

0.001

0.01

0.1

1

10

100

1000

10000

100000

Health numbersa Regulatory, advisory

numbersb

Ref.

4

Ref.

4

Ref.

8 Ref.

9,10

Ref.

5

LC50 (t etramet hyl lead)

(8,870 mg/m3)

NIOSH REL (0.10 mg/m3)

OSHA PEL & ACGIH TLV

(0.05 mg/m3)

LC50 (t etraet hyl lead)

(850 mg/m3)

NAAQS

(0.0015 mg/m3)

Ref.

8

NIOSH IDLH (100 mg/m3)

Health Data from Inhalation Exposure

ACGIH TLV – American Conference of Governmental and Industrial Hygienists' threshold

limit value expressed as a time-weighted average; the concentration of a substance to which most

workers can be exposed without adverse effects.

LC50 (Lethal Concentration50) – A calculated concentration of a chemical in air to which

exposure for a specific length of time is expected to cause death in 50% of a defined

experimental animal population.

NIOSH REL – National Institute of Occupational Safety and Health's recommended exposure

limit; NIOSH-recommended exposure limit for an 8- or 10-h time-weighted-average exposure

and/or ceiling.

NIOSH IDLH – NIOSH's immediately dangerous to life or health concentration; NIOSH
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recommended exposure limit to ensure that a worker can escape from an exposure condition that

is likely to cause death or immediate or delayed permanent adverse health effects or prevent

escape from the environment.

NAAQS – National Ambient Air Quality Standard. NAAQS set by EPA for pollutants that are

considered to be harmful to public health and the environment; the NAAQS for lead is 1.5 μg/m3,

maximum arithmetic mean averaged over a calendar quarter.

OSHA PEL – Occupational Safety and Health Administration's permissible exposure limit

expressed as a time-weighted average; the concentration of a substance to which most workers

can be exposed without adverse effect averaged over a normal 8-h workday or a 40-h workweek.

a

 Health numbers are toxicological numbers from animal testing or risk assessment values

developed by EPA.

b

 Regulatory numbers are values that have been incorporated in Government regulations, while

advisory numbers are nonregulatory values provided by the Government or other groups as

advice.

References

1. Agency for Toxic Substances and Disease Registry (ATSDR). Toxicological Profile for

Lead (Update). Draft for Public Comment. Public Health Service, U.S. Department of

Health and Human Services, Atlanta, GA. 1997.

2. Agency for Toxic Substances and Disease Registry (ATSDR). Case Studies in

Environmental Medicine, Lead Toxicity. Public Health Service, U.S. Department of

Health and Human Services, Atlanta, GA. 1992.

3. U.S. Environmental Protection Agency (EPA). Deposition of Air Pollutants to the Great

Waters. First Report to Congress. EPA-453/R-93-055. Office of Air Quality Planning

and Standards, Research Triangle Park, NC. 1994.

4. U.S. Department of Health and Human Services. Registry of Toxic Effects of Chemical

Substances (RTECS, online database). National Toxicology Information Program,

National Library of Medicine, Bethesda, MD. 1993.

5. U.S. Department of Health and Human Services. Hazardous Substances Data Bank

(HSDB, online database). National Toxicology Information Program, National Library of

Medicine, Bethesda, MD. 1993.

6. U.S. Environmental Protection Agency (EPA). Integrated Risk Information System (IRIS)

on Lead and Compounds (Inorganic). National Center for Environmental Assessment,

Office of Research and Development, Washington, DC. 1999.

7. U.S. Environmental Protection Agency (EPA). Integrated Risk Information System (IRIS)

on Tetraethyl Lead. National Center for Environmental Assessment, Office of Research

and Development, Washington, DC. 1999.
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8. National Institute for Occupational Safety and Health (NIOSH). Pocket Guide to

Chemical Hazards. U.S. Department of Health and Human Services, Public Health

Service, Centers for Disease Control and Prevention. Cincinnati, OH. 1997.

9. Occupational Safety and Health Administration (OSHA). Occupational Safety and

Health Standards, Toxic and Hazardous Substances. Code of Federal Regulations 29

CFR 1910.1025. 1998.

10. American Conference of Governmental Industrial Hygienists (ACGIH). 1999 TLVs and

BEIs. Threshold Limit Values for Chemical Substances and Physical Agents, Biological

Exposure Indices. Cincinnati, OH. 1999.

11. U.S. Environmental Protection Agency (EPA). National Ambient Air Quality Standard

for Lead. 43 FR 46246, October 5, 1978.

12. U.S. Environmental Protection Agency (EPA). Review of the National Ambient Air

Quality Standards for Lead: Assessment of Scientific and Technical Information. Office

of Air Quality Planning and Standards, Research Triangle Park, NC 27711. EPA-450/2-

89-022. December 1990.
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MANGANESE COMPOUNDS

Hazard Summary

Manganese is naturally ubiquitous in the environment. Manganese is essential for normal

physiologic functioning in humans and animals. Health effects in humans have been

associated with both deficiencies and excess intakes of manganese. Chronic (long-term)

exposure to low levels of manganese in the diet is considered to be nutritionally essential

in humans, with a recommended daily allowance of 2 to 5 mg/d. Chronic exposure to

high levels of manganese by inhalation in humans results primarily in central nervous

system (CNS) effects. Visual reaction time, hand steadiness, and eye-hand coordination

were affected in chronically-exposed workers. A syndrome named manganism may result

from chronic exposure to higher levels; manganism is characterized by feelings of

weakness and lethargy, tremors, a mask-like face, and psychological disturbances.

Respiratory effects have also been noted in workers chronically exposed by inhalation. 

Impotence and loss of libido have been noted in male workers afflicted with manganism

attributed to high-level inhalation exposures to manganese. No studies are available

regarding the carcinogenic effects of manganese in humans, and animal studies are

inadequate. The U.S. Environmental Protection Agency (EPA) has classified manganese

as a Group D, not classifiable as to carcinogenicity in humans.

Please Note: The main sources of information for this fact sheet are EPA's Integrated Risk Information System

(IRIS), which contains information on inhalation chronic toxicity of manganese and the reference concentration

(RfC), oral chronic toxicity and the reference dose (RfD), and the Agency for Toxic Substances and Disease

Registry's (ATSDR's) Toxicological Profile for Manganese.

Physical Properties

! Manganese is a silver-colored metal that forms compounds in the environment with

chemicals such as oxygen, sulfur, and chlorine. (1)

! Manganese compounds are solids that do not evaporate; however, small dust particles can

become suspended in air. (1)

! Manganese can dissolve in water. (1)

! The chemical symbol for manganese is Mn, and elemental manganese has an atomic

weight of 54.94 g/mol. (1)

! Some manganese compounds are: manganese dioxide (MnO2), manganese tetraoxide

(Mn3O4), manganese salts (chloride, sulfate, carbonate, and nitrate), manganese silicate,

and potassium permanganate (KMnO4).

Uses

! Metallic manganese is used primarily in steel production to improve hardness, stiffness,

and strength. It is also used in carbon steel, stainless steel, and high-temperature steel,

along with cast iron and superalloys. (1)
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! Manganese compounds have a variety of uses. Manganese dioxide is used in the

production of dry-cell batteries, matches, fireworks, and the production of other

manganese compounds. (1)

! Manganese chloride is used as a catalyst in the chlorination of organic compounds, in

animal feed, and in dry-cell batteries, while manganese sulfate is used as a fertilizer,

livestock nutritional supplement, in glazes and varnishes, and in ceramics. (1)

! Potassium permanganate is used for water purification purposes in water and

waste-treatment plants. (1)

Sources and Potential Exposure

! Manganese is a naturally occurring substance found in many types of rock and soil; it is

ubiquitous in the environment and found in low levels in water air, soil, and food. (1)

! Manganese can also be released into the air by iron and steel production plants, power

plants, and coke ovens. (1)

! The average manganese levels in various media are as follows: levels in drinking water

are approximately 0.004 ppm; average air levels are approximately 0.02 μg/m3; levels in

soil range from 40 to 900 ppm; the average daily intake from food ranges from 1 to 5

mg/d. (1)

! People who work in factories where manganese metal is produced from manganese ore or

where manganese compounds are used to make steel or other products are most likely to

be exposed through inhalation to higher than normal levels of manganese. (1)

Assessing Personal Exposure

! Several tests are available for measuring manganese in blood, urine, hair, or feces. As

manganese is naturally present in the body, some manganese is always found in these

materials. In addition, excess manganese is usually removed from the body within a few

days, making it difficult to measure past exposure to manganese. (1)

Health Hazard Information

Acute Effects:

! No reports of effects in humans following acute (short-term) effects of exposure to

manganese are available.

! Effects to the lung have been reported following acute exposure of rats to manganese via

inhalation. (1)

! Manganese is considered to have moderate acute toxicity based on short-term tests, such

as the LD50 test given by gavage in rats. However, other animal tests in which manganese

has been given orally have indicated that manganese has low acute oral toxicity. (1)
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Chronic Effects (Noncancer):

! Chronic exposure to manganese at low levels is nutritionally essential in humans. The

recommended daily intake of manganese is 2 to 5 mg/d for adults and adolescents. (1)

! No cases of manganese deficiency have been observed in the general population. 

However, manganese deficiency in animals has been associated with impaired growth,

skeletal abnormalities, impaired reproductive function in females, and testicular

degeneration in males. (1)

! Chronic inhalation exposure of humans to manganese results primarily in effects on the

nervous system. Slower visual reaction time, poorer hand steadiness, and impaired

eye-hand coordination were reported in several studies of workers occupationally exposed

to manganese dust in air. (1,3)

! Chronic inhalation exposure of humans to high levels may result in a syndrome called

manganism and typically begins with feelings of weakness and lethargy and progresses to

other symptoms such as gait disturbances, clumsiness, tremors, speech disturbances, a

mask-like facial expression, and psychological disturbances. (1,3)

! Other chronic effects reported in humans from inhalation exposure to manganese are

respiratory effects such as an increased incidence of cough, bronchitis, dyspnea during

exercise, and an increased susceptibility to infectious lung disease. (1,3)

! The RfC for manganese is 0.00005 mg/m3 based on impairment of neurobehavioral

function in humans. The RfC is an estimate (with uncertainty spanning perhaps an order

of magnitude) of a continuous inhalation exposure to the human population (including

sensitive subgroups) that is likely to be without appreciable risk of deleterious noncancer

effects during a lifetime. It is not a direct estimator of risk but rather a reference point to

gauge the potential effects. At exposures increasingly greater than the RfC, the potential

for adverse health effects increases. Lifetime exposure above the RfC does not imply that

an adverse health effect would necessarily occur. (3)

! EPA has medium confidence in the RfC due to medium confidence in the principal

studies on which the RfC was based and medium confidence in the database. Neither of

the principal studies identified a no-observed-adverse-effect level (NOAEL) for

neurobehavioral effects, nor did either study directly measure particle size or provide

information on the particle size distribution. These limitations of the studies are mitigated

by the fact that the principal studies found similar indications of neurobehavioral

dysfunction, and these findings were consistent with the results of other human studies.

EPA has medium confidence in the database because the duration of exposure was

relatively limited in the principal and supporting studies, the majority of studies did not

specify the species of manganese, and the reproductive and developmental effects have

not been adequately studied. (3)

! EPA has established a RfD for manganese of 0.14 mg/kg/d based on CNS effects in

humans. The RfD is estimated to be an intake for the general population that is not

associated with adverse health effects; this is not meant to imply that intakes above the

RfD are necessarily associated with toxicity. Some individuals may, in fact, consume a

diet that contributes more than 10 mg Mn/day without any cause for concern. When

assessing risk from manganese in drinking water or soil, a modified RfD of 0.05 mg/kg/d

is recommended. (3)
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! EPA has medium confidence in the RfD due to medium confidence in the studies on

which the RfD for manganese was based; and medium confidence in the database. (3)

Reproductive/Developmental Effects:

! Reproductive effects, such as impotence and loss of libido, have been noted in male

workers afflicted with manganism attributed to occupational exposure to high levels of

manganese by inhalation. No information is available on developmental effects of

manganese in humans. (1,3)

! Animal studies have reported degenerative changes in the seminiferous tubules leading to

sterility from intratracheal instillation of high doses of manganese (experimentally

delivering the manganese directly to the trachea). In young animals exposed to

manganese orally, decreased testosterone production and retarded growth of the testes

were reported. (1)

! Decreased activity levels and a decrease in average pup weight have been noted in the

offspring of mice exposed to manganese by inhalation. (1)

Cancer Risk:

! No studies are available regarding carcinogenic effects in humans or animals from

inhalation exposure to manganese. (1,3)

! No studies are available regarding cancer in humans from oral exposure to manganese.

Oral animal studies on manganese sulfate are inadequate, with several studies reporting

negative results, one study reporting an increased incidence of thyroid gland follicular cell

adenomas and hyperplasia, and one study noting an increased incidence of pancreatic

tumors. (1,3)

! EPA has classified manganese as a Group D, not classifiable as to carcinogenicity in

humans. (3)

Conversion Factors:

To convert from ppm to mg/m3: mg/m3 = (ppm) x (molecular weight of the compound)/(24.45).

For manganese: 1 ppm = 2.25 mg/m3.

To convert from μg/m3 to mg/m3: mg/m3 = (μg/m3) x (1 mg/1,000 μg).
National Air Toxics Program: The Integrated Urban Strategy

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Manganese

0.00001

0.0001

0.001

0.01

0.1

1

10

100

1000

Health numbersa Regulatory, advisory

numbersb

Ref.

3

Ref.

4

Ref.

6

Ref.

7

LOAELc for

neurological

effect s (0.05 mg/m3)

OSHA ceiling (5 mg/m3)

NIOSH PEL (1 mg/m3)

ACGIH TLV

(0.2 mg/m3)

NIOSH IDLH (500 mg/m3)

Ref.

6

Ref.

3

RfC (5x10-5 mg/m3)

Health Data from Inhalation Exposure

ACGIH TLV – American Conference of Governmental and Industrial Hygienists' threshold

limit value expressed as a time-weighted average; the concentration of a substance to which most

workers can be exposed without adverse effects.

LOAEL – Lowest-observed-adverse-effect level.

NIOSH REL – National Institute of Occupational Safety and Health's recommended exposure

limit; NIOSH-recommended exposure limit for an 8- or 10-h time-weighted-average exposure

and/or ceiling.

NIOSH IDLH – NIOSH's immediately dangerous to life or health concentration; NIOSH

recommended exposure limit to ensure that a worker can escape from an exposure condition that

is likely to cause death or immediate or delayed permanent adverse health effects or prevent

escape from the environment.
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OSHA PEL – Occupational Safety and Health Administration's permissible exposure limit

expressed as a time-weighted average; the concentration of a substance to which most workers

can be exposed without adverse effect averaged over a normal 8-h workday or a 40-h workweek.

OSHA ceiling – OSHA's short-term exposure limit ceiling; an exposure that should not be

exceeded at any time during a workday even if the 8-h time-weighted-average is within the

threshold limit value.

a

 Health numbers are toxicological numbers from animal testing or risk assessment values

developed by EPA.

b

 Regulatory numbers are values that have been incorporated in Government regulations, while

advisory numbers are nonregulatory values provided by the Government or other groups as

advice.

c

 This LOAEL is from the critical study used as the basis for the EPA RfC.

References

1. Agency for Toxic Substances and Disease Registry (ATSDR). Toxicological Profile for

Manganese (Update). Draft for Public Comment. U.S. Public Health Service, U.S.

Department of Health and Human Services, Altanta, GA. 1997.

2. National Academy of Sciences (NAS). Drinking Water and Health. Volume 3. National

Academy Press, Washington, DC. 1989.

3. U.S. Environmental Protection Agency (EPA). Integrated Risk Information System (IRIS)

on Manganese. National Center for Environmental Assessment, Office of Research and

Development, Washington, DC. 1999.

4. Occupational Safety and Health Administration (OSHA). Occupational Safety and

Health Standards, Toxic and Hazardous Substances. Code of Federal Regulations 29

CFR 1910.1000. 1998.

5. E.J. Calabrese and E.M. Kenyon. Air Toxics and Risk Assessment. Lewis Publishers,

Chelsea, MI. 1991.

6. National Institute for Occupational Safety and Health (NIOSH). Pocket Guide to

Chemical Hazards. U.S. Department of Health and Human Services, Public Health

Service, Centers for Disease Control and Prevention. Cincinnati, OH. 1997.

7. American Conference of Governmental Industrial Hygienists (ACGIH). 1999 TLVs and

BEIs. Threshold Limit Values for Chemical Substances and Physical Agents, Biological

Exposure Indices. Cincinnati, OH. 1999.
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MERCURY COMPOUNDS

Hazard Summary

Mercury exists in three forms: elemental mercury, inorganic mercury compounds

(primarily mercuric chloride), and organic mercury compounds (primarily methyl

mercury). All forms of mercury are quite toxic, and each form exhibits different health

effects.

Acute (short-term) exposure to high levels of elemental mercury in humans results in

central nervous system (CNS) effects such as tremors, mood changes, and slowed sensory

and motor nerve function. High inhalation exposures can also cause kidney damage.

Effects on the gastrointestinal tract and respiratory system have also been noted in

humans from acute inhalation exposure. Chronic (long-term) exposure to elemental

mercury in humans also affects the CNS, with effects such as erethism (increased

excitability), irritability, excessive shyness, and tremors. Human studies are inconclusive

regarding elemental mercury and cancer. The U.S. Environmental Protection Agency

(EPA) has classified elemental mercury as a Group D, not classifiable as to human

carcinogenicity.

Acute exposure to inorganic mercury by the oral route may result in effects such as

nausea, vomiting, and severe abdominal pain. The major effect from chronic exposure to

inorganic mercury is kidney damage. Animal studies have reported effects such as

alterations in testicular tissue, increased resorption rates, and abnormalities of

development. Mercuric chloride (an inorganic mercury compound) exposure has been

shown to result in forestomach, thyroid, and renal tumors in experimental animals. EPA

has classified inorganic mercury as Group C, possible human carcinogen.

Acute exposure of humans to very high levels of methyl mercury results in CNS effects

such as blindness, deafness, and impaired level of consciousness. Chronic exposure to

methyl mercury in humans also affects the CNS with symptoms such as paresthesia (a

sensation of pricking on the skin), blurred vision, malaise, speech difficulties, and

constriction of the visual field. Methyl mercury exposure, via the oral route, has led to

significant developmental effects. Infants born to women who ingested high levels of

methyl mercury exhibited mental retardation, ataxia, constriction of the visual field,

blindness, and cerebral palsy. No human studies are available on the carcinogenic effects

of methyl mercury, and one animal study reported renal tumors in mice. EPA has

classified methyl mercury as Group C, possible human carcinogen.

Please Note: The main sources of information for this fact sheet are EPA's Integrated Risk Information System

(IRIS), which contains information on inhalation chronic toxicity and the reference concentration (RfC) for

elemental mercury, oral chronic toxicity and the reference dose (RfD) for inorganic and methyl mercury, EPA's

Mercury Study Report to Congress, and the Agency for Toxic Substances and Disease Registry's (ATSDR's)
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Toxicological Profile for Mercury. Other secondary sources include the World Health Organization's Environmental

Health Criteria Documents on Methyl Mercury and Inorganic Mercury.

Physical Properties

! Elemental mercury is a silver-white metal with an atomic weight of 200.59 g/mol. (1)

! Mercury is a liquid at room temperature and has a vapor pressure of 0.002 mm Hg at 25

EC. (1)

! Mercury can exist in three oxidation states — elemental, mercurous, and mercuric — and

it can be part of both inorganic and organic compounds. (1)

! Inorganic mercury compounds include mercuric chloride, mercuric sulfide, mercurous

chloride. Organic mercury compounds include mercuric acetate, methylmercuric

chloride, dimethyl mercury, and phenylmercuric acetate. (1)

Uses

Elemental Mercury

! Elemental mercury is used in thermometers, barometers, and pressure-sensing devices. It

is also used in batteries, lamps, industrial processes, refining, lubrication oils, and dental

amalgams. (1)

Inorganic Mercury

! Inorganic mercury was used in the past in laxatives, skin-lightening creams and soaps,

and in latex paint. In 1990, EPA canceled registration for all interior paints that contained

mercury. Mercury use in exterior paint was discontinued after 1991. (1)

Methyl Mercury

! Methyl mercury has no industrial uses; it is formed in the environment from the

methylation of the inorganic mercurial ion. (1)

Sources and Potential Exposure

Elemental Mercury

! A major source of exposure for elemental mercury is through inhalation in occupational

settings. (1,3,4)

! Another source of exposure to low levels of elemental mercury in the general population

is elemental mercury released in the mouth from dental amalgam fillings. (3-5)
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Inorganic Mercury

! The general population is usually not exposed to inorganic mercury compounds to any

significant extent today, as most products containing these compounds have now been

banned. Limited exposure could occur through the use of old cans of latex paint, which

until 1990, could contain mercury compounds to prevent bacterial and fungal growth.

(1,4)

Methyl Mercury

! The most important organic mercury compound, in terms of human exposure, is methyl

mercury. Methyl mercury exposure occurs primarily through the diet, with fish and fish

products as the dominant source. Sources of past exposure to methyl mercury include

fungicide-treated grains and meat from animals fed such grain. However, fungicides

containing mercury are banned in the U.S. today, and this source of exposure is now

negligible. (1)

! Mercury has been listed as a pollutant of concern to EPA's Great Waters Program due to

its persistence in the environment, potential to bioaccumulate, and toxicity to humans and

the environment. (6)

Assessing Personal Exposure

! Laboratory tests can detect mercury in blood, urine, and hair samples. (1)

Health Hazard Information

Acute Effects:

Elemental Mercury

! The major systems impacted by human inhalation of elemental mercury are the kidneys

and CNS. Acute exposure to high levels of elemental mercury in humans results in CNS

effects, such as tremors, irritability, insomnia, memory loss, neuromuscular changes,

headaches, slowed sensory and motor nerve function, and reduction in cognitive function.

(1,2)

! Acute inhalation exposure of humans to high concentrations has resulted in kidney effects

ranging from mild transient proteinuria to acute renal failure. (1,2)

! Gastrointestinal effects and respiratory effects, such as chest pains, dyspnea, cough,

pulmonary function impairment, and interstitial pneumonitis have also been noted from

human inhalation exposure to elemental mercury. (1,2)

Inorganic Mercury

! Symptoms noted after acute oral exposure to inorganic mercury compounds include a

metallic taste in the mouth, nausea, vomiting, and severe abdominal pain. (1,2,7)
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! The acute lethal dose for most inorganic mercury compounds for an adult is 1 to 4 g or 14

to 57 mg/kg for a 70-kg person. (1,7)

Methyl Mercury

! Acute inhalation exposure to high levels of methyl mercury, which is extremely rare, has

resulted in severe CNS effects, including blindness, deafness, impaired level of

consciousness, and death. (8)

! It has been estimated that the minimum lethal dose of methyl mercury for a 70-kg person

ranges from 20 to 60 mg/kg. (8)

Chronic Effects (Noncancer):

Elemental Mercury

! The CNS is the major target organ for elemental mercury toxicity in humans. Effects

noted include erethism (increased excitability), irritability, excessive shyness, insomnia,

severe salivation, gingivitis, and tremors. (1,2,9)

! Chronic exposure to elemental mercury also affects the kidney in humans, with the

development of proteinuria. (1,2,9)

! Acrodynia is a rare syndrome found in children exposed to elemental mercury

compounds. It is characterized by severe leg cramps, irritability, paresthesia (a sensation

of prickling on the skin), and painful pink fingers and peeling hands, feet, and nose. (1,2)

! EPA has not established an RfD for elemental mercury. (11)

! The RfC for elemental mercury is 0.0003 mg/m3 based on CNS effects in humans. The

RfC is an estimate (with uncertainty spanning perhaps an order of magnitude) of a

continuous inhalation exposure to the human population (including sensitive subgroups)

that is likely to be without appreciable risk of deleterious noncancer effects during a

lifetime. It is not a direct estimator of risk but rather a reference point to gauge the

potential effects. At exposures increasingly greater than the RfC, the potential for adverse

health effects increases. Lifetime exposure above the RfC does not imply that an adverse

health effect would necessarily occur. (11)

! EPA has medium confidence in the RfC due to: medium confidence in the studies on

which the RfC was based because there were sufficient number of human subjects,

inclusion of appropriate control groups, and exposure levels in a number of the studies

had to be extrapolated from blood mercury levels; and medium confidence in the database

due to a lack of human or multispecies reproductive/developmental studies. (11)

Inorganic Mercury

! The primary effect from chronic exposure to inorganic mercury is kidney damage,

primarily due to mercury-induced autoimmune glomerulonephritis (induction of an

immune response to the body's kidney tissue). (1,2,9,10)

! Acrodynia may also occur from exposure to inorganic mercury compounds. (1,2,9,10)
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! The RfD for inorganic mercury (mercuric chloride) is 0.0003 mg/kg/d based on

autoimmune effects in rats. (12)

! EPA has high confidence in the RfD based on the weight of evidence from the studies

using Brown-Norway rats and the entirety of the mercuric chloride database. (12)

! EPA has not established an RfC for inorganic mercury. (12)

Methyl Mercury

! The primary effect from chronic exposure to methyl mercury in humans is damage to the

CNS. The earliest effects are symptoms such as paresthesia, blurred vision, and malaise.

Effects at higher doses include deafness, speech difficulties, and constriction of the visual

field. (1,2,8)

! The RfD for methyl mercury is 0.0001 mg/kg/d based on CNS effects in humans. (13)

! EPA has medium confidence in the RfD due to: (1) medium confidence in the studies on

which the RfD was based because the benchmark dose approach allowed use of the entire

dose-response assessment, and the results of laboratory studies with nonhuman primates

support the quantitative estimate of the no-observed-adverse-effect level (NOAEL)/

lowest-observed-adverse-effect level (LOAEL) range of the benchmark dose that was

indicated by the human studies; and (2) medium confidence in the database. (13)

! EPA has not established an RfC for methyl mercury. (13)

Reproductive/Developmental Effects:

Elemental Mercury

! Studies on the reproductive and developmental effects of elemental mercury in humans

have shown mixed results. One study did not see an association between mercury

exposure and miscarriages, while another revealed an increase in the rate of spontaneous

abortions. Another study showed a higher than expected frequency of birth defects, which

was not confirmed in a fourth study. (1,9)

Inorganic Mercury

! No information is available on the reproductive or developmental effects of inorganic

mercury in humans.

! Animal studies have reported effects including alterations in testicular tissue, increased

resorption rates, and abnormalities of development. (1,7,9)

Methyl Mercury

! A large number of human studies on the systemic effects of methyl mercury have been

carried out. This is the result of two large scale poisoning incidents in Japan and Iraq and

several epidemiologic studies investigating populations that consume large quantities of

fish. (1,2)
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! Oral exposure to methyl mercury has been observed to produce significant developmental

effects in humans. Infants born to women who ingested high concentrations of methyl

mercury exhibited CNS effects, such as mental retardation, ataxia, deafness, constriction

of the visual field, blindness, and cerebral palsy. At lower methyl mercury concentrations,

developmental delays and abnormal reflexes were noted. (1,2,8)

! Considerable new data on the health effects of methyl mercury are becoming available.

Large studies of fish and marine mammal consuming populations in Seychelles and Faroe

Islands are being carried out. Smaller scale studies also describe effects around the U.S.

Great Lakes. (1,2)

Cancer Risk:

Elemental Mercury

! Several studies have been carried out regarding elemental mercury and cancer in humans.

These studies are inconclusive due to lack of valid exposure data and confounding

factors. (1,2,9)

! EPA has classified elemental mercury as a Group D, not classifiable as to human

carcinogenicity. (12)

Inorganic Mercury

! No studies are available on the carcinogenic effects of inorganic mercury in humans.

! A chronic study on mercuric chloride in rats and mice reported an increased incidence of

forestomach and thyroid tumors in rats, and an increased incidence of renal tumors in

mice. (14)

! EPA has classified inorganic mercury as Group C, possible human carcinogen. (12)

Methyl Mercury

! No studies are available on the carcinogenic effects of methyl mercury in humans, and the

one available animal study reported renal tumors in mice. (1,2,13)

! EPA has classified methyl mercury as Group C, possible human carcinogen. (13)
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Mercury

0.0001

0.001

0.01

0.1

1

10

100

Health numbers

a Regulatory, advisory

numbersb

Ref.

11

Ref.

11

Ref.

15

Ref.

15

Ref.

16,15

Ref.

15 Ref.

16

Ref.

17,

16,

15

LOAELc (CNS)

(0.025 mg/m3)

RfC (element al)

(0.0003 mg/ m3)

NIOSH IDLH (all except organoalkyl)

(10 mg/m3)

NIOSH IDLH (organoalkyl)

(2 mg/m3)

ACGIH TLV (aryl) NIOSH REL (all except

organoalkyl) (0.1 mg/m3)

NIOSH REL (all except organoalkyl)

(0.05 mg/m3)

ACGIH TLV (inorganic)

(0.025 mg/m3)

(organoalkyl)

(0.01

mg/m3)

OSHA PEL, ACGIH

TLV, NIOSH REL

Conversion Factors:

To convert from ppm to mg/m3: mg/m3 = (ppm) x (molecular weight of the compound)/(24.45).

For elemental mercury: 1 ppm = 8.2 mg/m3. For mercuric chloride: 1 ppm = 11.1 mg/m3. For

methyl mercuric chloride: 1 ppm = 10.3 mg/m3.

Health Data from Inhalation Exposure

ACGIH TLV – American Conference of Governmental and Industrial Hygienists' threshold

limit value expressed as a time-weighted average; the concentration of a substance to which most

workers can be exposed without adverse effect.

NIOSH IDLH – National Institute of Occupational Safety and Health's immediately dangerous

to life or health value; the maximum environmental concentration of a contaminant from which

one could escape within 30 min without any escape-impairing symptoms or irreversible health
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effects.

NIOSH REL – National Institute of Occupational Safety and Health's recommended exposure

limit; NIOSH-recommended exposure limit for an 8- or 10-h time-weighted-average exposure

and/or ceiling.

OSHA PEL – Occupational Safety and Health Administration's permissible exposure limit

expressed as a time-weighted average; the concentration of a substance to which most workers

can be exposed without adverse effect averaged over a normal 8-h workday or a 40-h workweek.

a

 Health numbers are toxicological numbers from animal testing or risk assessment values

developed by EPA.

b

 Regulatory numbers are values that have been incorporated in Government regulations, while

advisory numbers are nonregulatory values provided by the Government or other groups as

advice.

c

 The LOAEL is from the critical study used as the basis for the EPA RfC for elemental mercury.

References

1. Agency for Toxic Substances and Disease Registry (ATSDR). Toxicological Profile for

Mercury. Public Health Service, U.S. Department of Health and Human Services,

Atlanta, GA. 1999.

2. U.S. Environmental Protection Agency (EPA). Mercury Study Report to Congress.

Volume V: Health Effects of Mercury and Mercury Compounds. Office of Air Quality

Planning and Standards, Office of Research and Development. 1997

3. U.S. Environmental Protection Agency (EPA). Locating and Estimating Air Emissions

from Sources of Mercury and Mercury Compounds. EPA-453/R-93-023. Office of Air

Quality Planning and Standards, Research Triangle Park, NC. 1993.

4. U.S. Environmental Protection Agency (EPA). National Emissions Inventory of Mercury

and Mercury Compounds: Interim Final Report. EPA-453/R-93-048. Office of Air

Quality Planning and Standards, Research Triangle Park, NC. 1993.

5. U.S. Public Health Service. Dental Amalgams: A Public Health Service Strategy for

Research, Education, and Regulation. Final Report. Committee to Coordinate

Environmental Health and Related Programs, Washington, DC. 1993.

6. U.S. Environmental Protection Agency (EPA). Deposition of Air Pollutants to the Great

Waters. First Report to Congress. EPA-453/R-93-055. Office of Air Quality Planning

and Standards, Research Triangle Park, NC. 1994.

7. U.S. Environmental Protection Agency (EPA). Summary Review of Health Effects

Associated with Mercuric Chloride: Health Issue Assessment. EPA/600/R-92/199. Office

of Health and Environmental Assessment, Washington, DC. 1994.
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8. World Health Organization (WHO). Methyl Mercury. Volume 101. Distribution and Sales

Service, International Programme on Chemical Safety, Geneva, Switzerland. 1990.

9. World Health Organization (WHO). Inorganic Mercury. Volume 118. Distribution and

Sales Service, International Programme on Chemical Safety, Geneva, Switzerland. 1991.

10. U.S. Environmental Protection Agency (EPA). Drinking Water Criteria Document for

Inorganic Mercury. (Final). PB 89-19A 2207. Environmental Criteria and Assessment

Office, Cincinnati, OH. 1988.

11. U.S. Environmental Protection Agency (EPA). Integrated Risk Information System (IRIS)

on Elemental Mercury. National Center for Environmental Assessment, Office of

Research and Development, Washington, DC. 1999.

12. U.S. Environmental Protection Agency (EPA). Integrated Risk Information System (IRIS)

on Mercuric chloride. National Center for Environmental Assessment, Office of Research

and Development, Washington, DC. 1999.

13. U.S. Environmental Protection Agency (EPA). Integrated Risk Information System (IRIS)

on Methyl mercury. National Center for Environmental Assessment, Office of Research

and Development, Washington, DC. 1999.

14. National Toxicology Program (NTP). Toxicology and Carcinogenesis Studies of

Mercuric Chloride in F344 Rats and B6C3F1 Mice (Gavage Studies). U.S. Department

of Health and Human Services, Public Health Service, National Institutes of Health,

Bethesda, MD. 1991.

15. National Institute for Occupational Safety and Health (NIOSH). Pocket Guide to

Chemical Hazards. U.S. Department of Health and Human Services, Public Health

Service, Centers for Disease Control and Prevention. Cincinnati, OH. 1997.

16. American Conference of Governmental Industrial Hygienists (ACGIH). 1999 TLVs and

BEIs. Threshold Limit Values for Chemical Substances and Physical Agents, Biological

Exposure Indices. Cincinnati, OH. 1999.

17. Occupational Safety and Health Administration (OSHA). Occupational Safety and

Health Standards, Toxic and Hazardous Substances. Code of Federal Regulations. 29

CFR 1910.1000. 1998.
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METHYLENE CHLORIDE

75-09-2

Hazard Summary

Methylene chloride is predominantly used as a solvent. The acute (short-term) effects of

methylene chloride inhalation in humans consist mainly of nervous system effects

including decreased visual, auditory, and motor functions, but these effects are reversible

once exposure ceases. The effects of chronic (long-term) exposure to methylene chloride

suggest that the central nervous system (CNS) is a potential target in humans and

animals. Limited animal studies have reported developmental effects. Human data are

inconclusive regarding methylene chloride and cancer. Animal studies have shown

increases in liver and lung cancer and benign mammary gland tumors following the

inhalation of methylene chloride. The U.S. Environmental Protection Agency (EPA) has

classified methylene chloride as a Group B2, probable human carcinogen.

Please Note: The main sources of information for this fact sheet are the Agency for Toxic Substances and Disease

Registry's (ATSDR's) Toxicological Profile for Methylene Chloride and EPA's Integrated Risk Information System

(IRIS), which contains information on oral chronic toxicity and the reference dose (RfD), and the carcinogenic

effects of methylene chloride including the unit cancer risk for inhalation exposure.

Physical Properties

! A common synonym for methylene chloride is dichloroethane. (1,4)

! Methylene chloride is a colorless liquid with a sweetish odor. (1,6)

! The chemical formula for methylene chloride is CH2Cl2, and the molecular weight is

84.93 g/mol. (1)

! The vapor pressure for methylene chloride is 349 mm Hg at 20 EC, and it has an

octanol/water coefficient (log Kow) of 1.30. (1)

! Methylene chloride has an odor threshold of 250 ppm. (7)

! Methylene chloride is slightly soluble in water and is nonflammable. (1,6)

Uses

! Methylene chloride is predominantly used as a solvent in paint strippers and removers; as

a process solvent in the manufacture of drugs, pharmaceuticals, and film coatings; as a

metal cleaning and finishing solvent in electronics manufacturing; and as an agent in

urethane foam blowing. (1)

! Methylene chloride is also used as a propellant in aerosols for products such as paints,

automotive products, and insect sprays. (1)

! It is used as an extraction solvent for spice oleoresins, hops, and for the removal of

caffeine from coffee. However, due to concern over residual solvent, most decaffeinators

no longer use methylene chloride. (1)
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! Methylene chloride is also approved for use as a postharvest fumigant for grains and

strawberries and as a degreening agent for citrus fruit. (1)

Sources and Potential Exposure

! The principal route of human exposure to methylene chloride is inhalation of ambient air.

(1)

! Occupational and consumer exposure to methylene chloride in indoor air may be much

higher, especially from spray painting or other aerosol uses. People who work in these

places can breathe in the chemical or it may come in contact with the skin. (1)

! Methylene chloride has been detected in both surface water and groundwater samples

taken at hazardous waste sites and in drinking water at very low concentrations. (1)

Assessing Personal Exposure

! Several tests exist for determining exposure to methylene chloride. These tests include

measurement of methylene chloride in the breath, blood, and urine. It is noted that

smoking and exposure to other chemicals may affect the results of these tests. (1)

Health Hazard Information

Acute Effects:

! Case studies of methylene chloride poisoning during paint stripping operations have

demonstrated that inhalation exposure to extremely high levels can be fatal to humans.

(1,2)

! Acute inhalation exposure to high levels of methylene chloride in humans has resulted in

effects on the CNS including decreased visual, auditory, and psychomotor functions, but

these effects are reversible once exposure ceases. Methylene chloride also irritates the

nose and throat at high concentrations. (1,2)

! Tests involving acute exposure of animals, such as the LD50 and LC50 tests in rats, have

shown methylene chloride to have moderate acute toxicity from oral and inhalation

exposure. (3)

Chronic Effects (Noncancer):

! The major effects from chronic inhalation exposure to methylene chloride in humans are

effects on the CNS, such as headaches, dizziness, nausea, and memory loss. (1,2)

! Animal studies indicate that the inhalation of methylene chloride causes effects on the

liver, kidney, CNS, and cardiovascular system. (1,2)

! EPA has calculated a provisional reference concentration (RfC) of 3 mg/m3 based on liver

effects in rats. The RfC is an estimate (with uncertainty spanning perhaps an order of

magnitude) of a continuous inhalation exposure to the human population (including

sensitive subgroups) that is likely to be without appreciable risk of deleterious noncancer

effects during a lifetime. It is not a direct estimator of risk but rather a reference point to
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gauge the potential effects. At exposures increasingly greater than the RfC, the potential

for adverse health effects increases. Lifetime exposure above the RfC does not imply that

an adverse health effect would necessarily occur. (5)

! The RfD for methylene chloride is 0.06 mg/kg/d based on liver toxicity in rats. (4)

! EPA has medium confidence in the RfD based on: high confidence in the study on which

the RfD is based because a large number of animals of both sexes were tested in four dose

groups, with a large number of controls, many effects were monitored, and a dose-related

increase in severity was observed; and medium to low confidence in the database because

only a few studies support the no-observed-adverse-effect level (NOAEL). (4)

Reproductive/Developmental Effects:

! No studies were located regarding developmental or reproductive effects in humans from

inhalation or oral exposure. (1,2)

! Animal studies have demonstrated that methylene chloride crosses the placental barrier,

and minor skeletal variations and lowered fetal body weights have been noted. (1,2)

Cancer Risk:

! Several studies did not report a statistically significant increase in deaths from cancer

among workers exposed to methylene chloride. (1,2)

! Animal studies have shown an increase in liver and lung cancer and benign mammary

gland tumors following inhalation exposure to methylene chloride. (1,2,4)

! EPA has classified methylene chloride as a Group B2, probable human carcinogen. (4)

! EPA uses mathematical models, based on human and animal studies, to estimate the

probability of a person developing cancer from breathing air containing a specified

concentration of a chemical. EPA calculated an inhalation unit risk estimate of 4.7 x 10-7

(μg/m3)

-1. EPA estimates that, if an individual were to continuously breathe air containing

methylene chloride at an average of 2.0 μg/m3 (0.002 mg/m3) over his or her entire

lifetime, that person would theoretically have no more than a one-in-a-million increased

chance of developing cancer as a direct result of breathing air containing this chemical.

Similarly, EPA estimates that breathing air containing 20 μg/m3 (0.02 mg/m3) would

result in not greater than a one-in-a-hundred thousand increased chance of developing

cancer, and air containing 200 μg/m3 (0.2 mg/m3) would result in not greater than a

one-in-ten thousand increased chance of developing cancer. For a detailed discussion of

confidence in the potency estimates, please see IRIS. (4)

! EPA calculated an oral cancer slope factor of 7.5 x 10-3 (mg/kg/d)-1. (4)

Conversion Factors:

To convert from ppm to mg/m3: mg/m3 = (ppm) x (molecular weight of the compound)/(24.45). 

For methylene chloride: 1 ppm = 3.5 mg/m3. To convert from μg/m3 to mg/m3: mg/m3 = (μg/m3)

x (1 mg/1,000 μg).
National Air Toxics Program: The Integrated Urban Strategy

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Methylene Chloride

0.001

0.01

0.1

1

10

100

1000

10000

100000

1000000

Health numbersa Regulatory, advisory

numbersb

Ref.

3 Ref.

3

Ref.

5

Ref.

5

Ref.

8 Ref.

9

LC50 (rat s) (88,000 mg/ m3)

LC50 (mice) (50,020 mg/m3)

NOAELc (liver) (695 mg/ m3)

Provisional RfC

(3 mg/m3)

Cancer Risk Level

1 in a million risk

(0.002 mg/ m3)

ACGIH TLV (174 mg/ m3

)

OSHA PEL (88 mg/m3) Ref.

11

Ref.

11

Ref.

10

NIOSH IDLH (7980 mg/ m3)

AIHA ERPG-2 (2602 mg/ m3)

AIHA ERPG-1 (694 mg/m3)

Ref.

4

Health Data from Inhalation Exposure

ACGIH TLV – American Conference of Governmental and Industrial Hygienists' threshold

limit value expressed as a time-weighted average; the concentration of a substance to which most

workers can be exposed without adverse effects.

AIHA ERPG – American Industrial Hygiene Association's emergency response planning

guidelines. ERPG 1 is the maximum airborne concentration below which it is believed nearly all

individuals could be exposed up to one hour without experiencing other than mild transient

adverse health effects or perceiving a clearly defined objectionable odor; ERPG 2 is the

maximum airborne concentration below which it is believed nearly all individuals could be

exposed up to one hour without experiencing or developing irreversible or other serious health

effects that could impair their abilities to take protective action.

LC50 (Lethal Concentration50)--A calculated concentration of a chemical in air to which

exposure for a specific length of time is expected to cause death in 50% of a defined

experimental animal population.
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NIOSH IDLH – National Institute of Occupational Safety and Health's immediately dangerous

to life or health concentration; NIOSH recommended exposure limit to ensure that a worker can

escape from an exposure condition that is likely to cause death or immediate or delayed

permanent adverse health effects or prevent escape from the environment.

NOAEL – No-observed-adverse-effects level.

OSHA PEL – Occupational Safety and Health Administration's permissible exposure limit

expressed as a time-weighted average: the concentration of a substance to which most workers

can be exposed without adverse effect averaged over a normal 8-h workday or a 40-h workweek.

a

 Health numbers are toxicological numbers from animal testing or risk assessment values

developed by EPA.

b

 Regulatory numbers are values that have been incorporated in Government regulations, while

advisory numbers are nonregulatory values provided by the Government or other groups as

advice.

c

 The NOAEL is from the critical study used as the basis for the provisional RfC.

References

1. Agency for Toxic Substances and Disease Registry (ATSDR). Toxicological Profile for

Methylene Chloride (Update). Draft for Public Comment. Public Health Service, U.S.

Department of Health and Human Services, Atlanta, GA. 1998.

2. U.S. Department of Health and Human Services. Hazardous Substances Data Bank

(HSDB, online database). National Toxicology Information Program, National Library of

Medicine, Bethesda, MD. 1993.

3. U.S. Department of Health and Human Services. Registry of Toxic Effects of Chemical

Substances (RTECS, online database). National Toxicology Information Program,

National Library of Medicine, Bethesda, MD. 1993.

4. U.S. Environmental Protection Agency (EPA). Integrated Risk Information System (IRIS)

on Methylene Chloride. National Center for Environmental Assessment, Office of

Research and Development, Washington, DC. 1999.

5. U.S. Environmental Protection Agency (EPA). Health Effects Assessment Summary

Tables. FY 1997 Update. Solid Waste and Emergency Response, Office of Emergency

and Remedial Response, Cincinnati, OH. EPA/540/R-97-036. 1997.

6. The Merck Index. An Encyclopedia of Chemicals, Drugs, and Biologicals. 11th ed. Ed. S.

Budavari. Merck and Co. Inc., Rahway, NJ. 1989.

7. J.E. Amoore and E. Hautala. Odor as an aid to chemical safety: Odor thresholds

compared with threshold limit values and volatilities for 214 industrial chemicals in air

and water dilution. Journal of Applied Toxicology, 3(6):272-290. 1983.
National Air Toxics Program: The Integrated Urban Strategy

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8. American Conference of Governmental Industrial Hygienists (ACGIH). 1999 TLVs and

BEIs. Threshold Limit Values for Chemical Substances and Physical Agents, Biological

Exposure Indices. Cincinnati, OH. 1999.

9. Occupational Safety and Health Administration (OSHA). Occupational Safety and

Health Standards, Toxic and Hazardous Substances. Code of Federal Regulations 29

CFR 1910.1052. 1998.

10. National Institute for Occupational Safety and Health (NIOSH). Pocket Guide to

Chemical Hazards. U.S. Department of Health and Human Services, Public Health

Service, Centers for Disease Control and Prevention. Cincinnati, OH. 1997.

11. American Industrial Hygiene Association (AIHA). The AIHA 1998 Emergency Response

Planning Guidelines and Workplace Environmental Exposure Level Guides Handbook.

1998.
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NICKEL COMPOUNDS

Hazard Summary

Nickel occurs naturally in the environment at low levels. Nickel is an essential element

in some animal species, and it has been suggested it may be essential for human

nutrition. Nickel dermatitis, consisting of itching of the fingers, hands, and forearms, is

the most common effect in humans from chronic (long-term) skin contact with nickel. 

Respiratory effects have also been reported in humans from inhalation exposure to

nickel. No information is available regarding the reproductive or developmental effects

of nickel in humans, but animal studies have reported reproductive and developmental

effects. The U.S. Environmental Protection Agency (EPA) has not evaluated soluble salts

of nickel as a class of compounds for potential human carcinogenicity. Human and

animal studies have reported an increased risk of lung and nasal cancers from exposure to

nickel refinery dusts and nickel subsulfide. EPA has classified nickel refinery dust and

nickel subsulfide as Group A, human carcinogens. Animal studies of soluble nickel

compounds (i.e., nickel carbonyl) have reported lung tumors. EPA has classified nickel

carbonyl as a Group B2, probable human carcinogen.

Please Note: The main sources of information for this fact sheet are EPA's Integrated Risk Information System

(IRIS), which contains information on oral chronic toxicity and the reference dose (RfD), and the carcinogenic

effects of nickel including the unit cancer risk for inhalation exposure, EPA's Health Assessment Document for

Nickel, and the Agency for Toxic Substances and Disease Registry's (ATSDR's) Toxicological Profile for Nickel.

Physical Properties

! Nickel is a silvery-white metal that is found in nature as a component of silicate, sulfide,

or arsenide ores. (1)

! In the environment, nickel is found primarily combined with oxygen or sulfur as oxides

or sulfides. (1)

! Each form of nickel exhibits different physical properties. (1,6)

! Soluble nickel salts include nickel chloride, nickel sulfate, and nickel nitrate. (6)

! Nickel carbonyl, a highly unstable form, is not found naturally and decomposes rapidly.

(1)

! The chemical symbol for nickel is Ni, and it has an atomic weight of 58.71 g/mol. (1)

Uses

! Nickel is used for nickel alloys, electroplating, batteries, coins, industrial plumbing, spark

plugs, machinery parts, stainless-steel, nickel-chrome resistance wires, and catalysts. (1,6)

! Nickel carbonyl has severely limited use in nickel refining. (1)
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Sources and Potential Exposure

! Nickel is a natural element of the earth's crust; therefore, small amounts are found in

food, water, soil, and air. (6)

! Food is the major source of nickel exposure, with an average intake for adults estimated

to be approximately 100 to 300 μg/d. (1,6)

! Individuals also may be exposed to nickel in occupations involved in its production,

processing, and use, or through contact with everyday items such as nickel-containing

jewelry and stainless steel cooking and eating utensils, and by smoking tobacco. (1)

! Nickel is found in ambient air at very low levels as a result of releases from oil and coal

combustion, nickel metal refining, sewage sludge incineration, manufacturing facilities,

and other sources. (2,6)

! Given its high instability, nickel carbonyl exposure is extremely rare.

Assessing Personal Exposure

! Laboratory tests can detect nickel in blood, urine, feces, and hair samples. (1,6)

Health Hazard Information

Acute Effects:

! One person exposed to an extremely high level of nickel by inhalation suffered severe

damage to the lungs and kidneys. (6)

! Gastrointestinal distress (e.g., nausea, vomiting, diarrhea) and neurological effects were

reported in workers who drank water on one shift that was contaminated with nickel as

nickel sulfate and nickel chloride. (1,6)

! Pulmonary fibrosis and renal edema were reported in humans and animals following

acute (short-term) exposure to nickel carbonyl. (1)

! Acute animal tests, such as the LD50 test in rats, have shown nickel compounds to exhibit

acute toxicity values ranging from low to high. The soluble compounds, such as nickel

acetate, were the most toxic, and the insoluble forms, such as nickel powder, were the

least toxic. (6)

Chronic Effects (Noncancer):

! Dermatitis is the most common effect in humans from chronic dermal exposure to nickel.

Cases of nickel dermatitis have been reported following occupational and

non-occupational exposure, with symptoms of eczema (rash, itching) of the fingers,

hands, wrists, and forearms. (1,2,6,7)

! Chronic inhalation exposure to nickel in humans also results in respiratory effects,

including a type of asthma specific to nickel, decreased lung function, and bronchitis.

(6,7)
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! Animal studies have reported effect on the lungs and immune system from inhalation

exposure to soluble and insoluble nickel compounds (nickel oxide, subsulfide, sulfate

heptahydrate). (1,6)

! Soluble nickel compounds are more toxic to the respiratory tract than less soluble

compounds. (6)

! EPA has not established a reference concentration (RfC) for nickel. (2-5)

! The RfD for nickel (soluble salts) is 0.02 mg/kg/d based on decreased body and organ

weights in rats. The RfD is an estimate (with uncertainty spanning perhaps an order of

magnitude) of a daily oral exposure to the human population (including sensitive

subgroups) that is likely to be without appreciable risk of deleterious noncancer effects

during a lifetime. It is not a direct estimator of risk, but rather a reference point to gauge

the potential effects. At exposures increasingly greater than the RfD, the potential for

adverse health effects increases. Lifetime exposure above the RfD does not imply that an

adverse health effect would necessarily occur. (5)

! EPA has medium confidence in the RfD due to: low confidence in the study on which the

RfD for nickel (soluble salts) was based because, although it was properly designed and

provided adequate toxicological endpoints, high mortality occurred in the controls; and

medium confidence in the database because it provided adequate supporting subchronic

studies, one by gavage and the other in drinking water, but inadequacies in the remaining

reproductive data. (5)

! Nickel is an essential nutrient for some mammalian species and has been suggested to be

essential for human nutrition. By extrapolation from animal data, it is estimated that a

70-kg person would have a daily requirement of 50 μg per kg diet of nickel. (6)

! The California Environmental Protection Agency (CalEPA) has calculated a chronic

inhalation reference exposure level of 0.00005 mg/m3 for nickel based on respiratory and

immune system effects reported in rats exposed to a soluble nickel salt. The CalEPA

reference exposure level is a concentration at or below which adverse health effects are

not likely to occur. (7)

! ATSDR has calculated a chronic-duration inhalation minimal risk level (MRL) of 0.0002

mg/m3 for nickel based on respiratory effects reported in rats exposed to a soluble nickel

salt. The MRL is an estimate of the daily human exposure to a hazardous substance that is

likely to be without appreciable risk of adverse noncancer health effects over a specified

duration of exposure. (6)

Reproductive/Developmental Effects:

! No information is available regarding the reproductive or developmental effects of nickel

in humans. (6)

! Animal studies have reported reproductive and developmental effects, such as a

decreased number of live pups per litter, increased pup mortality, and reduction in fetal

body weight, and effects to the female from oral exposure to soluble salts of nickel. (5,6)

! Sperm abnormalities and decreased sperm count have been reported in animals exposed

to nickel nitrate orally and nickel oxide by inhalation, respectively. (6)
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Cancer Risk:

Nickel Salts

! Nickel sulfate via inhalation and nickel acetate in drinking water were not carcinogenic in

either rats or mice. (6)

! EPA has not evaluated soluble salts of nickel as a class of compounds for potential

human carcinogenicity. (5)

Nickel Refinery Dust and Nickel Subsulfide

! Human studies have reported an increased risk of lung and nasal cancers among nickel

refinery workers exposed to nickel refinery dust. Nickel refinery dust is a mixture of

many nickel compounds, with nickel subsulfide being the major constituent. (3,4,6)

! Animal studies have also reported lung tumors from inhalation exposure to nickel

refinery dusts and to nickel subsulfide. (3,4)

! EPA has classified nickel refinery dust and nickel subsulfide as Group A, human

carcinogens. (3,4)

! EPA uses mathematical models, based on human and animal studies, to estimate the

probability of a person developing cancer from breathing air containing a specified

concentration of a chemical. EPA calculated an inhalation unit risk estimate of 2.4 x 10-4

(μg/m3)

-1 for nickel refinery dusts. EPA estimates that, if an individual were to

continuously breathe air containing nickel refinery dusts at an average of 0.004 μg/m3 (4

x 10-6 mg/m3) over his or her entire lifetime, that person would theoretically have no more

than a one-in-a-million increased chance of developing cancer as a direct result of

breathing air containing this chemical. Similarly, EPA estimates that continuously

breathing air containing 0.04 μg/m3 would result in not greater than a one-in-a-hundred

thousand increased chance of developing cancer, and air containing 0.4 μg/m3 would

result in not greater than a one-in-ten thousand increased chance of developing cancer.

For a detailed discussion of confidence in the potency estimates, please see IRIS. (3)

! For nickel subsulfide, EPA calculated an inhalation unit risk estimate of 4.8 x 10-4

(μg/m3)

-1. EPA estimates that, if an individual were to continuously breathe air containing

this nickel compound at an average of 0.002 μg/m3 (2 x 10-6 mg/m3) over his or her entire

lifetime, that person would theoretically have no more than a one-in-a-million increased

chance of developing cancer as a direct result of breathing air containing this chemical.

Similarly, EPA estimates that continuously breathing air containing 0.02 μg/m3 would

result in not greater than a one-in-a-hundred thousand increased chance of developing

cancer, and air containing 0.2 μg/m3 would result in not greater than a one-in-ten

thousand increased chance of developing cancer. (4)

Nickel Carbonyl

! Nickel carbonyl has been reported to produce lung tumors in rats exposed via inhalation.

(2)

! EPA has classified nickel carbonyl as a Group B2, probable human carcinogen. (2)
National Air Toxics Program: The Integrated Urban Strategy

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Nickel

0.000001

0.00001

0.0001

0.001

0.01

0.1

1

10

100

Health numbers

a Regulatory, advisory

numbersb

NOAELc respiratory effects

(0.03 mg/ m3)

ATSDR chronic MRL

(2 x 10-4 mg/ m3)

CalEPA reference exposure

level 5 x10-5 mg/ m3)

ACGIH TLV (metal compounds) (1.5 mg/m3)

OSHA PEL (metal compounds) (1 mg/m3)

ACGIH TLV (soluble nickel) (0.1 mg/ m3)

ACGIH TLV (insoluble nickel)

(0.2 mg/ m3)

NIOSH REL (metal

compounds)

(0.015 mg/ m3)

OSHA PEL,

NIOSH REL

(nickel carbonyl) (0.007

mg/ m3)

Cancer Risk Level

1 in a million risk

(nickel refinery dusts

(4 x 10-6 mg/ m3)

Cancer Risk

Level 1 in a

million risk

(nickel subsulfide

(2 x 10-6 mg/ m3)

Ref.

4

NIOSH IDLH (10 mg/ m3)

Ref.

6,7

Ref.

7

Ref.

6

Ref.

8

Ref.

10

Ref.

8

Ref.

8

Ref.

9 Ref.

9,10

Ref.

3

Ref.

9

Conversion Factors:

To convert from ppm to mg/m3: mg/m3 = (ppm) x (molecular weight of the compound)/(24.45).

For nickel: 1 ppm = 2.4 mg/m3.

To convert from μg/m3 to mg/m3: mg/m3 = (μg/m3) x (1 mg/1,000 μg).

Health Data from Inhalation Exposure

ACGIH TLV – American Conference of Governmental and Industrial Hygienists' threshold

limit value expressed as a time-weighted average; the concentration of a substance to which most

workers can be exposed without adverse effects.

NIOSH REL – National Institute of Occupational Safety and Health's recommended exposure

limit; NIOSH-recommended exposure limit for an 8- or 10-h time-weighted-average exposure

and/or ceiling.
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NIOSH IDLH – NIOSH's immediately dangerous to life or health concentration; NIOSH

recommended exposure limit to ensure that a worker can escape from an exposure condition that

is likely to cause death or immediate or delayed permanent adverse health effects or prevent

escape from the environment.

NOAEL – No-observed-adverse-effect level.

OSHA PEL – Occupational Safety and Health Administration's permissible exposure limit

expressed as a time-weighted average; the concentration of a substance to which most workers

can be exposed without adverse effect averaged over a normal 8-h workday or a 40-h workweek.

a

 Health numbers are toxicological numbers from animal testing or risk assessment values

developed by EPA.

b

 Regulatory numbers are values that have been incorporated in Government regulations, while

advisory numbers are nonregulatory values provided by the Government or other groups as

advice.

c

 The NOAEL is from the critical study used as the basis for both the ATSDR chronic MRL and

CalEPA chronic reference exposure level. 

References

1. U.S. Environmental Protection Agency (EPA). Health Assessment Document for Nickel.

EPA/600/8-83/012F. National Center for Environmental Assessment, Office of Research

and Development, Washington, DC. 1986.

2. U.S. Environmental Protection Agency (EPA). Integrated Risk Information System (IRIS)

on Nickel Carbonyl. National Center for Environmental Assessment, Office of Research

and Development, Washington, DC. 1999.

3. U.S. Environmental Protection Agency (EPA). Integrated Risk Information System (IRIS)

on Nickel Refinery Dust. National Center for Environmental Assessment, Office of

Research and Development, Washington, DC. 1999.

4. U.S. Environmental Protection Agency (EPA). Integrated Risk Information System (IRIS)

on Nickel Subsulfide. National Center for Environmental Assessment, Office of Research

and Development, Washington, DC. 1999.

5. U.S. Environmental Protection Agency (EPA). Integrated Risk Information System (IRIS)

on Nickel, Soluble Salts. National Center for Environmental Assessment, Office of

Research and Development, Washington, DC. 1999.

6. Agency for Toxic Substances and Disease Registry (ATSDR). Toxicological Profile for

Nickel (Update). Public Health Service, U.S. Department of Health and Human Services,

Altanta, GA. 1997.
National Air Toxics Program: The Integrated Urban Strategy

Report to Congress

A-175

7. California Environmental Protection Agency (CalEPA). Technical Support Document for

the Determination of Noncancer Chronic Reference Exposure Levels. Draft for Public

Comment. Office of Environmental Health Hazard Assessment, Berkeley, CA. 1997.

8. American Conference of Governmental Industrial Hygienists (ACGIH). 1999 TLVs and

BEIs. Threshold Limit Values for Chemical Substances and Physical Agents, Biological

Exposure Indices. Cincinnati, OH. 1999.

9. National Institute for Occupational Safety and Health (NIOSH). Pocket Guide to

Chemical Hazards. U.S. Department of Health and Human Services, Public Health

Service, Centers for Disease Control and Prevention. Cincinnati, OH. 1997.

10. Occupational Safety and Health Administration (OSHA). Occupational Safety and

Health Standards, Toxic and Hazardous Substances. Code of Federal Regulations 29

CFR 1910.1000. 1998.
National Air Toxics Program: The Integrated Urban Strategy

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A-177

POLYCHLORINATED BIPHENYLS (PCBs)

1336-36-3

Hazard Summary

PCBs are a group of chemicals that contain 209 individual compounds (known as

congeners) with varying harmful effects. Information on specific congener toxicity is very

limited. Most toxicity testing has been done on specific commercial mixtures; however,

PCB mixtures found in the environment will differ in composition from the commercial

mixtures because of biotransformation and bioaccumulation. The U.S. Environmental

Protection Agency (EPA) treats all PCBs as being potentially hazardous based on results

from some formulations. However, this can have large uncertainty for any given mixture

situation.

PCBs are no longer produced or used in the U.S. today; the major source of exposure to

PCBs today is the redistribution of PCBs already present in soil and water. No

information is available on the acute (short-term) effects of PCBs in humans, and animal

studies have reported effects on the liver, kidney, and central nervous system (CNS) from

oral exposure to PCBs. Chronic (long-term) exposure to some PCB formulations by

inhalation in humans results in respiratory tract symptoms, gastrointestinal effects, mild

liver effects, and effects on the skin and eyes such as chloracne, skin rashes, and eye

irritation. Epidemiological studies suggest an association between dietary PCB exposures

and developmental effects; human reproductive studies are inconclusive. Human studies

provide inconclusive, yet suggestive, evidence of an association between PCBs exposure

and liver cancer. Animal studies have reported an increase in liver tumors in rats and

mice exposed orally to some PCB formulations. EPA has classified PCBs as a Group B2,

probable human carcinogen.

Please Note: The main sources of information for this fact sheet are EPA's Integrated Risk Information System

(IRIS), which contains information on the carcinogenic effects of PCBs including the unit cancer risk for oral

exposure, and the Agency for Toxic Substances and Disease Registry's (ATSDR's) Toxicological Profile for PCBs.

Physical Properties

! PCBs are a class of industrial chemicals that contain 209 individual compounds or

congeners. (1)

! PCBs made in the U.S. were marketed under the trade name Aroclor and are identified by

a four-digit numbering code in which the first two digits indicate that the parent molecule

is a biphenyl and for the 1200 series Aroclors the last two digits indicate the chlorine

content by weight. For example, Aroclor 1260 has 60 percent chlorine. (1)

! Commercial trade names for PCBs not manufactured in the U.S. include Kanechlor,

Clophen, Fenclor, and Phenoclor. (1)

! PCBs are either oily liquids or solids and are colorless to light yellow in color with no

known smell or taste. (1)
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! The molecular weight for one particular PCB (Aroclor 1260) is 375.7 g/mol; the vapor

pressure is 4.05 x 10-5 mm Hg at 25 EC; the octanol/water partition coefficient (log Kow)

is 6.8. (1)

! PCB mixtures found in environmental media (air, water, sediment, foods) will differ in

composition from the commercial mixtures due to differential biotransformation and

bioaccumulation among the individual compounds. (1)

Uses

! Before 1974, PCBs were used in capacitors, transformers, plasticizers, surface coatings,

inks, adhesives, pesticide extenders, and carbonless duplicating paper. After 1974, use of

PCBs was restricted to the production of capacitors and transformers, and after 1979

PCBs were no longer used in the production of capacitors and transformers. (1)

Sources and Potential Exposure

! PCBs are no longer produced in the U.S. and are no longer used in the manufacture of

new products; the major source of air exposure to PCBs today is the redistribution of

PCBs already present in soil and water. Smaller amounts of PCBs may be released to the

air from disposal sites containing transformers, capacitors, and other PCB wastes,

incineration of PCB-containing wastes, and improper disposal of the compounds to open

areas. (1)

! PCBs have been detected in indoor air at concentrations of an order of magnitude greater

than ambient air. It has been suggested that certain electrical appliances and devices, such

as fluorescent lighting ballasts, which have PCB-containing components, may emit PCBs

to the indoor air. (1)

! In the past, PCBs were released to wastewater from its industrial uses. Today, PCBs are

still detected in water due to the environmental recycling of the compound. Most of the

PCBs in water are bound to the soil and sediments and may be released to the water

slowly over a long period of time. (1)

! PCBs have been detected in food; they bioaccumulate through the food chain, with some

of the highest concentrations found in fish. (1)

! PCBs have been listed as a pollutant of concern to EPA's Great Waters Program due to

their persistence in the environment, potential to bioaccumulate, and toxicity to humans

and the environment. (3)

Assessing Personal Exposure

! Laboratory analyses can detect PCBs in blood, body fat, and breast milk. (1)

Health Hazard Information

Acute Effects:

! No reports of effects in humans following acute exposure to PCBs are available. (1)
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A-179

! Animal studies have reported acute effects on the liver, kidney, and CNS from oral

exposure to PCBs. (1)

! Acute animal tests, such as the LD50 test in rats, have shown PCBs to have moderate

acute toxicity from oral exposure. (1,4)

Chronic Effects (Noncancer):

! Chronic inhalation exposure of workers to PCBs has been reported to result in respiratory

tract symptoms, such as cough and tightness of the chest, gastrointestinal effects

including anorexia, weight loss, nausea, vomiting, and abdominal pain, mild liver effects,

and effects on the skin and eyes, such as chloracne, skin rashes, and eye irritation. (1,5)

! EPA has not established a reference concentration (RfC) or a reference dose (RfD) for all

PCB mixtures. (6)

! The RfD for Aroclor 1016 is 0.00007 mg/kg/d based on reduced birth weights in

monkeys. The RfD is an estimate (with uncertainty spanning perhaps an order of

magnitude) of a daily oral exposure to the human population (including sensitive

subgroups) that is likely to be without appreciable risk of deleterious noncancer effects

during a lifetime. It is not a direct estimator of risk, but rather a reference point to gauge

the potential effects. At exposures increasingly greater than the RfD, the potential for

adverse health effects increases. Lifetime exposure above the RfD does not imply that an

adverse health effect would necessarily occur. (7)

! EPA has medium confidence in the RfD based on: medium confidence in the study on

which the RfD was based because this was a well-conducted study, but only one group of

monkeys was examined; and medium confidence in the database because an extensive

amount of data are available but mixtures of PCBs in the environment do not match the

pattern of congeners found in Aroclor 1016. (7)

! The RfD for Aroclor 1254 is 0.00002 mg/kg/d based on immunological effects in

monkeys. (8)

! EPA has medium confidence in the RfD based on: (1) medium confidence in the study on

which the RfD was based because groups of monkeys were tested at four dose levels and

a lowest-observed-adverse-effect level (LOAEL) was established; and (2) medium

confidence in the database because an extensive number of laboratory animal and human

studies were available for review, but human data are available for PCB mixtures in

general but not specifically for Aroclor 1254. (8)

! EPA has not established an RfC for Aroclor 1016 or Aroclor 1254. (7,8)

Reproductive/Developmental Effects:

! An epidemiological study of women occupationally exposed to high levels of PCBs

suggested a relationship between PCB exposure and reduced birth weight and shortened

gestational age of their babies; however, limitations of the study limit the strength of the

conclusion. (1)

! Two human studies that investigated exposure to PCBs through the consumption of

contaminated fish suggest that exposure to PCBs may cause developmental effects in

humans. Both studies reported an association between consumption of fish with high
National Air Toxics Program: The Integrated Urban Strategy

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PCB levels by pregnant women and an increased incidence of neurodevelopmental

effects, such as motor deficits at birth, impaired psychomotor index, impaired visual

recognition, and deficits in short-term memory in infants. (1)

! Human studies are not conclusive on the reproductive effects of PCBs. One study of men

who were occupationally exposed to PCBs showed no fertility abnormalities, while

another study of men with low sperm counts found elevated levels of PCBs in the blood

and an association between certain PCB compounds in semen and decreased sperm

motility. (1)

! Animal studies have reported developmental effects, such as learning deficits, impaired

immune functions, focal liver necrosis, and cellular alterations of the thyroid, in the

offspring of animals exposed orally to PCBs. Reproductive effects, such as decreased

fertility, decreased conception, and prolonged menstruation have also been noted in

animal studies of dietary PCB exposures. (1)

Cancer Risk:

! Human studies provide inconclusive, yet suggestive evidence of an association between

PCBs' exposure and liver cancer. Several studies have reported an increase in liver cancer

among persons occupationally exposed to some PCB formulations. However, the studies

are inconclusive due to confounding exposures and lack of exposure quantification. (1,6)

! Oral exposure studies in animals show an increase in liver tumors in rats and mice

exposed to several commercial mixtures of PCBs and to several specific congeners. (1,6)

! No animal inhalation studies are available on PCBs. (1)

! EPA has classified PCBs as a Group B2, probable human carcinogen. (6)

! EPA uses mathematical models, based on human and animal studies, to estimate the

probability of a person developing cancer from ingesting water containing a specified

concentration of a chemical. EPA calculated an upper bound inhalation unit cancer risk

estimate of 1.0 x 10-4 (μg/m3)

-1 for inhalation of evaporated PCB congeners. EPA

estimates that, if an individual were to continuously breathe air containing PCBs at an

average of 0.01 μg/m3 (1 x 10-5 mg/m3) over his or her entire lifetime, that person would

theoretically have no more than a one-in-a-million increased chance of developing cancer

as a direct result of breathing air containing this chemical. Similarly, EPA estimates that

breathing air containing 0.1 μg/m3 (1 x 10-4 mg/m3) would result in not greater than a

one-in-a-hundred thousand increased chance of developing cancer, and air containing 1.0

μg/m3 (1 x 10-3 mg/m3) would result in not greater than a one-in-ten thousand increased

chance of developing cancer. For a detailed discussion of confidence in the potency

estimates, please see IRIS. (6)

! EPA has calculated an upperbound oral cancer slope factor of 0.4 (mg/kg/d)-1 for

ingestion of water soluble congeners, an upperbound oral cancer slope factor of 2.0

(mg/kg/d)-1 for food chain exposure, and an upperbound oral cancer slope factor of 0.07

(mg/kg/d)-1 for PCB exposures where congeners with more than 4 chlorines comprise less

than 5 percent of the total. (6)
National Air Toxics Program: The Integrated Urban Strategy

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Conversion Factors:

To convert from ppm to mg/m3: mg/m3 = (ppm) x (molecular weight of the compound)/(24.45).

For Aroclor 1260: 1 ppm = 15.4 mg/m3. To convert from μg/m3 to mg/m3: mg/m3 = (μg/m3) x (1

mg/1,000 μg).
National Air Toxics Program: The Integrated Urban Strategy

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Polychlorinated biphenyls

0.00001

0.0001

0.001

0.01

0.1

1

10

100

Health numbersa Regulatory, advisory

numbersb

Ref.

6

Ref.

9,10 Ref.

9,10

Ref.

11

Cancer Risk Level

1 in a million risk

(1 x 10-5 mg/m3)

OSHA PEL, ACGIH TLV (42% chlorine) (1 mg/m3

)

OSHA PEL, ACGIH TLV

(54% chlorine) (0.5 mg/m3)

NIOSH REL

(0.001 mg/m3)

Health Data from Inhalation Exposure

ACGIH TLV – American Conference of Governmental and Industrial Hygienists' threshold

limit value expressed as a time-weighted average; the concentration of a substance to which most

workers can be exposed without adverse effects.

NIOSH REL – National Institute of Occupational Safety and Health's recommended exposure

limit; NIOSH-recommended exposure limit for an 8- or 10-h time-weighted-average exposure

and/or ceiling.

OSHA PEL – Occupational Safety and Health Administration's permissible exposure limit

expressed as a time-weighted average; the concentration of a substance to which most workers

can be exposed without adverse effect averaged over a normal 8-h workday or a 40-h workweek.
National Air Toxics Program: The Integrated Urban Strategy

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A-183

a

 Health numbers are toxicological numbers from animal testing or risk assessment values

developed by EPA.

b

 Regulatory numbers are values that have been incorporated in Government regulations, while

advisory numbers are nonregulatory values provided by the Government or other groups as

advice.

References

1. Agency for Toxic Substances and Disease Registry (ATSDR). Toxicological Profile for

Polychlorinated Biphenyls. Public Health Service, U.S. Department of Health and Human

Services, Atlanta, GA. 1997.

2. U.S. Environmental Protection Agency (EPA). Workshop Report on Toxicity Equivalence

for PCB Congeners. EPA/625/3-91/020. 1991.

3. U.S. Environmental Protection Agency (EPA). Deposition of Air Pollutants to the Great

Waters. First Report to Congress. EPA-453/R-93-055. Office of Air Quality Planning

and Standards, Research Triangle Park, NC. 1994.

4. U.S. Department of Health and Human Services. Registry of Toxic Effects of Chemical

Substances (RTECS, online database). National Toxicology Information Program,

National Library of Medicine, Bethesda, MD. 1993.

5. U.S. Department of Health and Human Services. Hazardous Substances Data Bank

(HSDB, online database). National Toxicology Information Program, National Library of

Medicine, Bethesda, MD. 1993.

6. U.S. Environmental Protection Agency (EPA). Integrated Risk Information System (IRIS)

on PCBs. National Center for Environmental Assessment, Office of Research and

Development, Washington, DC. 1999.

7. U.S. Environmental Protection Agency (EPA). Integrated Risk Information System (IRIS)

on Aroclor 1016. National Center for Environmental Assessment, Office of Research and

Development, Washington, DC. 1999.

8. U.S. Environmental Protection Agency (EPA). Integrated Risk Information System (IRIS)

on Aroclor 1254. National Center for Environmental Assessment, Office of Research and

Development, Washington, DC. 1999.

9. Occupational Safety and Health Administration (OSHA). Occupational Safety and

Health Standards, Toxic and Hazardous Substances. Code of Federal Regulations. 29

CFR 1910.1000. 1998.
National Air Toxics Program: The Integrated Urban Strategy

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10. American Conference of Governmental Industrial Hygienists (ACGIH). 1999 TLVs and

BEIs. Threshold Limit Values for Chemical Substances and Physical Agents, Biological

Exposure Indices. Cincinnati, OH. 1999.

11. National Institute for Occupational Safety and Health (NIOSH). Pocket Guide to

Chemical Hazards. U.S. Department of Health and Human Services, Public Health

Service, Centers for Disease Control and Prevention. Cincinnati, OH. 1997.
National Air Toxics Program: The Integrated Urban Strategy

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1

 Polycyclic organic matter consists of polycyclic aromatic hydrocarbons (PAHs),

including benzo(a)pyrene (CAS#50-32-8), their nitrogen analogs, and a small number of

oxygen-containing polycyclic organic matter compounds.

A-185

POLYCYCLIC ORGANIC MATTER (POM)1

Hazard Summary

The term POM defines a broad class of compounds that includes the polycyclic aromatic

hydrocarbon compounds (PAHs), of which benzo[a]pyrene is a member. POM

compounds are formed primarily from combustion and are present in the atmosphere

predominantly in particulate form with a smaller amount as vapor. Sources of air

emissions are diverse and include cigarette smoke, vehicle exhaust, home heating, laying

tar, and grilling meat. Skin exposures to mixtures of carcinogenic PAHs cause skin

disorders in humans and animals. No information is available on the reproductive or

developmental effects of POM in humans, while animal studies have reported that

benzo[a]pyrene, via oral exposure, causes reproductive and developmental effects. Cancer

is the major concern from exposure to POM. Epidemiologic studies have reported an

increase in lung cancer in humans exposed to coke oven emissions, roofing tar emissions,

and cigarette smoke; all of these mixtures contain POM compounds. Animal studies have

reported respiratory tract tumors from inhalation exposure to benzo[a]pyrene and

forestomach tumors, leukemia, and lung tumors from oral exposure to benzo[a]pyrene. 

The U.S. Environmental Protection Agency (EPA) has classified seven PAHs

(benzo[a]pyrene, benz[a]anthracene, chrysene, benzo[b]fluoranthene,

benzo[k]fluoranthene, dibenz[a,h]anthracene, and indeno[1,2,3-cd]pyrene) as Group B2,

probable human carcinogens.

Please Note: The main sources of information for this fact sheet are EPA's Integrated Risk Information System

(IRIS), which contains information on the carcinogenic effects of benzo(a)pyrene including the unit cancer risk for

oral exposure, and the Agency for Toxic Substances and Disease Registry's (ATSDR's) Toxicological Profile for

Polycyclic Aromatic Hydrocarbons (PAHs).

Physical Properties

! The term POM generally defines a broad class of compounds that includes all organic

structures having two or more fused aromatic rings (i.e., rings that share a common

border), and that have a boiling point greater than or equal to 212 EF (100 EC). The 1990

Amendments to the Clean Air Act describes POM as including “organic compounds with

more than one benzene ring, and which have a boiling point greater than or equal to 100

degrees C.” (11)

! POM has been identified with up to seven fused rings and, theoretically, millions of POM

compounds could be formed; however, only about 100 species have been identified and

studied. (11)
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! Eight major categories of compounds have been defined by the EPA to constitute the

class known as POM. The most common category is the polycyclic aromatic

hydrocarbons (PAHs), also known as polynuclear aromatics, which include

benzo[a]pyrene. (11)

! Most POM compounds are solids with high melting and boiling points, and are extremely

insoluble in water. The PAHs are primarily planar, nonpolar compounds with melting

points considerably over 212 EF (100 EC). Phenanthrene, with a melting point of 214 EF

(101 EC), and benzo[c]phenanthrene, with a melting point of 154 EF (68 EC), are two

exceptions. (11)

! POM is present in the atmosphere predominantly in the particulate form with a smaller

amount in the vapor phase. (11)

! The chemical formula for benzo[a]pyrene is C20H12, and the molecular weight is 252.3

g/mol. (1)

! The vapor pressures of POM compounds vary, depending upon the ring size and

molecular weight, from 6.8 x 10-4 mm Hg for phenanthrene, to 1.5 x 10-12 for coronene. 

The vapor pressure for benzo[a]pyrene is 5.6 x 10-9 mm Hg at 25 EC, and it has a log

octanol/water partition coefficient (log Kow) of 6.06. (1,11)

Uses

! The majority of the polycyclic organic compounds have no commercial uses. (11)

! Solutions containing mixtures of some PAHs are used to treat some skin disorders in

humans. (1)

Sources and Potential Exposure

! The primary source of POM is formation during combustion. A less significant formation

mechanism is the volatilization of lightweight POM compounds, which occurs in the

production and use of naphthalene. (11)

! Polycyclic organic compounds have been detected in ambient air from sources including

cigarette smoke, vehicle exhausts, asphalt road paving, coal burning, application of coal

tar, agricultural burning, residential wood burning, and hazardous waste sites. The

compounds present in POM and their relative amounts differ among different sources

(e.g, POM from diesel exhaust is chemically different than POM from wood burning).

(1,2)

! Benzo[a]pyrene, one of the more commonly monitored PAHs, has been detected in urban

air at levels approximately twice as high as those in rural areas (e.g., 0.6 ng/m3 versus 0.3

ng/m3). Seasonal variations have also been observed from monitoring in the Northeast

U.S. during the early 1980's, with mean benzo[a]pyrene concentrations during the winter

more than an order of magnitude greater than during the summer. (11)

! PAHs have been found in some drinking water supplies. (1)

! Cooking meat or other foods at high temperatures increases the amount of PAHs in the

food. (1)

! Occupational exposure to PAHs may occur in coal tar production plants, coking plants,

coal-gasification sites, smokehouses, municipal trash incinerators, and other facilities. (1)
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! POM has been listed as a pollutant of concern in EPA's Great Waters Program due to its

persistence in the environment, potential to bioaccumulate, and toxicity to humans and

the environment (2).

Assessing Personal Exposure

! PAHs or their breakdown products can be measured in urine, blood, or body tissues. (1)

Health Hazard Information

Acute Effects:

! No reports of effects to humans following acute (short-term) exposure to POM are

available.

! Acute animal tests, such as the LD50 test in rats, have shown benzo[a]pyrene to have high

acute toxicity from oral exposure. (3)

Chronic Effects (Noncancer):

! Skin exposures to mixtures of carcinogenic PAHs cause skin disorders in humans and

animals, and adverse skin effects have been noted in humans and animals following

application of solutions containing benzo[a]pyrene. (1)

! An epidemiological study of workers exposed by inhalation to benzo[a]pyrene and other

particulate matter reported some respiratory effects. The role of benzo[a]pyrene in this

association, however, is unclear. (1)

! Animal studies have reported effects on the blood and liver from oral exposure to

benzo[a]pyrene and a slight hypersensitivity response from dermal exposure to

benzo[a]pyrene. (1)

! EPA has not established a reference concentration (RfC) or a reference dose (RfD) for

POM or for benzo[a]pyrene. (4,5)

Reproductive/Developmental Effects:

! No information is available on the reproductive or developmental effects of POM in

humans.

! Animal studies have indicated that benzo[a]pyrene, via oral exposure, induces

reproductive toxicity, including a reduced incidence of pregnancy and decreased fertility.

Developmental effects, such as a reduced viability of litters and reduced mean pup

weight, have also been noted from oral exposure to benzo[a]pyrene in animals. (1,6)

Cancer Risk:

! Epidemiologic studies have reported an increase in lung cancer in humans exposed to

coke oven emission, roofing tar emissions, and cigarette smoke. Each of these mixtures

contains a number of POM compounds (e.g., certain PAHs). (1,6)
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! Animal studies have reported respiratory tract tumors from inhalation exposure to

benzo(a)pyrene and forestomach tumors, leukemia, and lung tumors from oral exposure

to benzo[a]pyrene. (1,5,7)

! EPA has classified seven PAHs (benzo[a]pyrene, benz[a]anthracene, chrysene,

benzo[b]fluoranthene, benzo[k]fluoranthene, dibenz[a,h]anthracene, and

indeno[1,2,3-cd]pyrene) as Group B2, probable human carcinogens. (4,5,12-17)

! EPA uses mathematical models, based on human and animal studies, to estimate the

probability of a person developing cancer from ingesting water containing a specified

concentration of a chemical. Although a quantitative cancer risk estimate for the mixture

of POM has not been derived, EPA has calculated an oral cancer slope factor of 7.3

(mg/kg/d)-1 for benzo[a]pyrene, one of the many constituents of POM. For a detailed

discussion of the confidence in the potency estimates, please see IRIS. (5)

! The California Environmental Protection Agency (CalEPA) has calculated an inhalation

unit risk estimate of 1.1 x 10-3 (μg/m3)

-1 for benzo[a]pyrene, one of the many constituents

of POM. (7)

Conversion Factors:

To convert from ppm to mg/m3: mg/m3 = (ppm) x (molecular weight of the compound)/(24.45).

For benzo(a)pyrene: 1 ppm = 10.3 mg/m3.

To convert from μg/m3 to mg/m3: mg/m3 = (μg/m3) x (1 mg/1,000 μg).
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Health Data from Inhalation Exposure

ACGIH TLV – American Conference of Governmental and Industrial Hygienists' threshold

limit value expressed as a time-weighted average; the concentration of a substance to which most

workers can be exposed without adverse effects.

NIOSH REL – National Institute of Occupational Safety and Health's recommended exposure

limit; NIOSH-recommended exposure limit for an 8- or 10-h time-weighted-average exposure

and/or ceiling.
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NIOSH IDLH – NIOSH's recommended exposure limit; NIOSH-recommended immediately

dangerous to health level.

OSHA PEL – Occupational Safety and Health Administration's permissible exposure limit

expressed as a time-weighted average; the concentration of a substance to which most workers

can be exposed without adverse effects averaged over a normal 8-h workday or a 40-h

workweek.

a

 These chemicals, a subset of POM, are emitted from the application of hot coal tar pitch.

b

 Regulatory numbers are values that have been incorporated in Government regulations, while

advisory numbers are nonregulatory values provided by the Government or other groups as

advice.

References

1. Agency for Toxic Substances and Disease Registry (ATSDR). Toxicological Profile for

Polycyclic Aromatic Hydrocarbons (PAHs). Public Health Service, U.S. Department of

Health and Human Services, Atlanta, GA. 1995.

2. U.S. Environmental Protection Agency (EPA). Deposition of Air Pollutants to the Great

Waters. First Report to Congress. EPA-453/R-93-055. Office of Air Quality Planning

and Standards, Research Triangle Park, NC. 1994.

3. U.S. Department of Health and Human Services. Registry of Toxic Effects of Chemical

Substances (RTECS, online database). National Toxicology Information Program,

National Library of Medicine, Bethesda, MD. 1993.

4. U.S. Environmental Protection Agency (EPA). Integrated Risk Information System (IRIS)

on Polycyclic Organic Matter. National Center for Environmental Assessment, Office of

Research and Development, Washington, DC. 1999.

5. U.S. Environmental Protection Agency (EPA). Integrated Risk Information System (IRIS)

on Benzo(a)pyrene. National Center for Environmental Assessment, Office of Research

and Development, Washington, DC. 1999.

6. U.S. Department of Health and Human Services. Hazardous Substances Data Bank

(HSDB, online database). National Toxicology Information Program, National Library of

Medicine, Bethesda, MD. 1993.

7. California Environmental Protection Agency (CalEPA). Air Toxics Hot Spots Program

Risk Assessment Guidelines: Technical Support Document for Determining Cancer

Potency Factors. Draft for Public Comment. Office of Environmental Health Hazard

Assessment, Berkeley, CA. 1997
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8. National Institute for Occupational Safety and Health (NIOSH). Pocket Guide to

Chemical Hazards. U.S. Department of Health and Human Services, Public Health

Service, Centers for Disease Control and Prevention. Cincinnati, OH. 1997.

9. Occupational Safety and Health Administration (OSHA). Occupational Safety and

Health Standards, Toxic and Hazardous Substances. Code of Federal Regulations. 29

CFR 1910.1000. 1998.

10. American Conference of Governmental Industrial Hygienists (ACGIH). 1999 TLVs and

BEIs. Threshold Limit Values for Chemical Substances and Physical Agents, Biological

Exposure Indices. Cincinnati, OH. 1999.

11. U.S. Environmental Protection Agency (EPA). Locating and Estimating Air Emissions

from Sources of Polycyclic Organic Matter. EPA-454/R-98-014. Office of Air Quality

Planning and Standards, Research Triangle Park, NC. 1998.

12. U.S. Environmental Protection Agency (EPA). Integrated Risk Information System

(IRIS) on Benz[a]anthracene. National Center for Environmental Assessment, Office of

Research and Development, Washington, DC. 1999.

13. U.S. Environmental Protection Agency (EPA). Integrated Risk Information System

(IRIS) on Benzo[b]fluoranthene. National Center for Environmental Assessment, Office

of Research and Development, Washington, DC. 1999.

14. U.S. Environmental Protection Agency (EPA). Integrated Risk Information System

(IRIS) on Benzo[k]fluoranthene. National Center for Environmental Assessment, Office

of Research and Development, Washington, DC. 1999.

15. U.S. Environmental Protection Agency (EPA). Integrated Risk Information System

(IRIS) on Chrysene. National Center for Environmental Assessment, Office of Research

and Development, Washington, DC. 1999.

16. U.S. Environmental Protection Agency (EPA). Integrated Risk Information System

(IRIS) on Dibenz[a,h]anthracene. National Center for Environmental Assessment,

Office of Research and Development, Washington, DC. 1999.

17. U.S. Environmental Protection Agency (EPA). Integrated Risk Information System

(IRIS) on Indeno[1,2,3-cd]pyrene. National Center for Environmental Assessment,

Office of Research and Development, Washington, DC. 1999.
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QUINOLINE

91-22-5

Hazard Summary

Quinoline is used mainly as an intermediate in the manufacture of other products. 

Potential exposure to quinoline may occur from the inhalation of cigarette smoke and, to

a much lesser extent, ambient air contaminated by emissions from the petroleum and coal

industries. Acute (short-term) inhalation exposure to quinoline vapors irritates the eyes,

nose, and throat and may cause headaches, dizziness, and nausea in humans. Information

on the chronic (long-term), reproductive, developmental, or carcinogenic effects of

quinoline in humans is not available. Liver damage has been observed in rats chronically

exposed to quinoline by ingestion. An increased incidence of liver vascular tumors has

been observed in rats and mice orally exposed to quinoline. The U.S. Environmental

Protection Agency (EPA) has provisionally classified quinoline as a Group C, possible

human carcinogen.

Please Note: The main source of information for this fact sheet is EPA's Health and Environmental Effects Profile

for Quinoline. Other secondary sources include the Hazardous Substances Data Bank (HSDB), a database of

summaries of peer-reviewed literature, and the Registry of Toxic Effects of Chemical Substances (RTECS), a

database of toxic effects that are not peer reviewed.

Physical Properties

! The chemical formula for quinoline is C9H7N, and it has a molecular weight of 129.15

g/mol. (7)

! Quinoline occurs as a colorless, hygroscopic liquid that darkens with age and is sparingly

soluble in water but is more easily soluble in hot water. (3,7)

! Quinoline has a penetrating, pungent odor. (3,7)

! The vapor pressure of quinoline is 0.0091 mm Hg at 25 EC and its log octanol/water

partition coefficient (log Kow) is 2.03. (3)

Uses

! Quinoline is used mainly as an intermediate in the manufacture of other products. (3)

! Quinoline is also used as a catalyst, a corrosion inhibitor, in metallurgical processes, in

the manufacture of dyes, as a preservative for anatomical specimens, in polymers and

agricultural chemicals, and as a solvent for resins and terpenes. It is also used as an

antimalarial medicine. (2,3,7)

Sources and Potential Exposure

! Workers in certain industries may be occupationally exposed to quinoline by inhalation,

ingestion of particulates, or dermal contact. (1,2)
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! A potential source of very low exposure to quinoline includes the inhalation of ambient

air contaminated by emissions from petroleum refining, coal mining, quenching and

coking, and release in shale oil, synthetic coal conversion wastewaters, and wood

preservative wastewaters. Levels of 2-7 μg/m3 have been measured in ambient air. (1,3)

! Quinoline is found at higher levels in cigarette smoke (1-20 μg/cigarette). (1,3)

! Underground coal gasification has been a source of quinoline contamination of

groundwater. Individuals may be exposed by consumption of contaminated water. (1)

Assessing Personal Exposure

! No information was located regarding the measurement of personal exposure to

quinoline.

Health Hazard Information

Acute Effects:

! Acute inhalation exposure to quinoline vapor irritates the eyes, nose, and throat, and may

cause headaches, dizziness, and nausea, and, at high concentrations, coma in humans. (3)

! Tests involving acute exposure of animals, such as the LD50 test in rats and rabbits, have

demonstrated quinoline to have high acute toxicity by oral or dermal exposure. (4)

Chronic Effects (Noncancer):

! Information on the chronic effects of quinoline in humans is not available. (3)

! Liver damage has been observed in rats chronically exposed to quinoline by ingestion. (3)

! EPA has not established a reference concentration (RfC) or reference dose (RfD) for

quinoline. (5)

Reproductive/Developmental Effects:

! No information is available on the reproductive or developmental effects of quinoline in

humans or animals. (3)

Cancer Risk:

! No human studies are available on the carcinogenicity of quinoline. (3)

! An increased incidence of liver hemangioendotheliomas (liver vascular tumors) has been

observed in rats and mice orally exposed to quinoline. (3)

! EPA has provisionally classified quinoline as a Group C, possible human carcinogen.

(3,6)

! EPA has calculated a provisional oral cancer slope factor of 12 (mg/kg/d)-1. A

provisional value is one which has not received Agency-wide review. (6)
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.

Conversion Factors:

To convert from ppm to mg/m3: mg/m3 = (ppm) x (molecular weight of the compound)/(24.45).

For quinoline: 1 ppm = 5.3 mg/m3.

Note: There are very few health numbers or regulatory/advisory numbers for quinoline; thus, a

graph has not been prepared for this compound.

References

1. U.S. Department of Health and Human Services. Hazardous Substances Data Bank

(HSDB, online database). National Toxicology Information Program, National Library of

Medicine, Bethesda, MD. 1993.

2. G.D. Clayton and F.E. Clayton, Eds. Patty's Industrial Hygiene and Toxicology. Volume

IIA, 3rd revised ed. John Wiley & Sons, New York. 1981.

3. U.S. Environmental Protection Agency (EPA). Health and Environmental Effects Profile

for Quinoline. EPA/600/x-85/355. Environmental Criteria and Assessment Office, Office

of Health and Environmental Assessment, Office of Research and Development,

Cincinnati, OH. 1985.

4. U.S. Department of Health and Human Services. Registry of Toxic Effects of Chemical

Substances (RTECS, online database). National Toxicology Information Program,

National Library of Medicine, Bethesda, MD. 1993.

5. U.S. Environmental Protection Agency (EPA). Integrated Risk Information System

(IRIS). National Center for Environmental Assessment, Office of Research and

Development, Washington, DC. 1999.

6. U.S. Environmental Protection Agency (EPA). Health Effects Assessment Summary

Tables. FY 1997 Update. Office of Research and Development, Office of Emergency

and Remedial Response, Washington, DC. EPA/540/R-97-036. 1997.

7. The Merck Index. An Encyclopedia of Chemicals, Drugs, and Biologicals. 11th ed. Ed. S.

Budavari. Merck and Co. Inc., Rahway, NJ. 1989.
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2,3,7,8-TETRACHLORODIBENZO-p-DIOXIN (2,3,7,8-TCDD)

1746-01-6

Hazard Summary

2,3,7,8-Tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) is formed as an unintentional

by-product of incomplete combustion. It may be released to the environment during the

combustion of fossil fuels and wood, and during the incineration of municipal and

industrial wastes. It causes chloracne in humans, a severe acne-like condition, and has

been shown to be very toxic in animals studies. It is known to be a developmental

toxicant in animals, causing skeletal deformities, kidney defects, and weakened immune

responses in the offspring of animals exposed to 2,3,7,8-TCDD during pregnancy. Human

studies have shown an association between 2,3,7,8-TCDD and soft-tissue sarcomas,

lymphomas, and stomach carcinomas. The U.S. Environmental Protection Agency (EPA)

has classified 2,3,7,8- TCDD as a Group B2, probable human carcinogen.

Please Note: The main source of information for this fact sheet is the Agency for Toxic Substances and Disease

Registry's (ATSDR's) Toxicological Profile for Chlorinated Dibenzo-p-Dioxins.

Physical Properties

! 2,3,7,8-TCDD is a colorless solid with no distinguishable odor. (1)

! The chemical formula for 2,3,7,8-TCDD is C12H4Cl4O2, and the molecular weight is 322

g/mol. (1)

! The vapor pressure for 2,3,7,8-TCDD is 7.4 x10-10 at 25 EC, and it has an octanol/water

partition coefficient (log Kow) of 6.8 - 7.58. (1)

Uses

! 2,3,7,8-TCDD is not intentionally produced by industry. It can be inadvertently produced

in very small amounts as an impurity during the incineration of municipal and industrial

wastes and during the manufacture of certain chemicals. (1)

! The only present use for 2,3,7,8-TCDD is in chemical research. (1)

 Sources and Potential Exposure

! 2,3,7,8-TCDD may be formed during the chlorine bleaching process used by pulp and

paper mills, and as a by-product from the manufacture of certain chlorinated organic

chemicals, such as chlorinated phenols. (1)

! 2,3,7,8-TCDD is primarily released to the environment during the combustion of fossil

fuels (including motor vehicles) and wood, and during incineration processes. (1)

! Very low levels of 2,3,7,8-TCDD are found throughout the environment, including air,

food, and soil. (1)
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! Most of the exposure of the general population to 2,3,7,8-TCDD is from food, mainly

meat, dairy products, and fish. (1)

Assessing Personal Exposure

! Body fat, blood, and breast milk may be analyzed for 2,3,7,8-TCDD. (1)

Health Hazard Information

Acute Effects:

! The major acute (short-term) effect from exposure of humans to high levels of

2,3,7,8-TCDD in air is chloracne, a severe acne-like condition that can develop within

months of first exposure. (1,2)

! Acute animal tests, such as the LD50 test in dogs, monkeys, and guinea pigs, have shown

2,3,7,8-TCDD to have extreme toxicity from oral exposure. (1)

Chronic Effects (Noncancer):

! Chloracne is also the major effect seen from chronic (long-term) exposure to

2,3,7,8-TCDD. (1)

! Animal studies have reported hair loss, loss of body weight, and a weakened immune

system from oral exposure to 2,3,7,8-TCDD. (1)

! EPA has not established a reference concentration (RfC) or a reference dose (RfD) for

2,3,7,8-TCDD.

! ATSDR has calculated a chronic oral minimal risk level (MRL) of 1 x 10-9 mg/kg/d based

on neurological effects in monkeys. The MRL is an estimate of daily exposure to a dose

of a chemical that is likely to be without appreciable risk of adverse noncancerous effects

over a specified duration of exposure. Exposure to a level above the MRL does not mean

that adverse effects will occur. The MRL is used by public health professionals as a

screening tool. (1)

Reproductive/Developmental Effects:

! The results of available reproductive and developmental studies in humans are

inconclusive. (1)

! Animal studies have reported developmental effects, such as skeletal deformities, kidney

defects, and weakened immune responses in the offspring of animals exposed to

2,3,7,8-TCDD during pregnancy. (1)

! Reproductive effects, including altered levels of sex hormones, reduced production of

sperm, and increased rates of miscarriages, have been seen in animals exposed to

2,3,7,8-TCDD. (1)
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Cancer Risk:

! Human studies, primarily of workers occupationally exposed to 2,3,7,8-TCDD by

inhalation, have found an association between 2,3,7,8-TCDD and lung cancer, soft-tissue

sarcomas, lymphomas, and stomach carcinomas, although for malignant lymphomas, the

increase in risk is not consistent. (1)

! No information is available on the carcinogenic effects of 2,3,7,8-TCDD in animals

following inhalation exposure. (1)

! Animal studies have reported tumors of the liver, lung, tongue, thyroid, and nasal

turbinates from oral exposure to 2,3,7,8-TCDD. (1)

! EPA has classified 2,3,7,8-TCDD as a Group B2, probable human carcinogen. (2,3)

! EPA has calculated a provisional inhalation cancer slope factor of 1.5x105 (mg/kg/d)-1

and an inhalation unit risk estimate of 3.3 x 10-5 (pg/m3)

-1 for 2,3,7,8-TCDD. The

provisional slope factor is a value that has had some form of Agency review, but it does

not appear on IRIS. (2,3)

! EPA has calculated a provisional oral cancer slope factor of 1.5 x 105 (mg/kg/d)-1 and an

oral unit risk factor of 4.5 (μg/L)-1 for 2,3,7,8-TCDD. (2,3)

Conversion Factors:

To convert from ppm to mg/m3: mg/m3 = (ppm) x (molecular weight of the compound)/(24.45).

For 2,3,7,8-TCDD: 1 ppm = 13.2 mg/m3.

Note: There are very few health numbers or regulatory/advisory numbers for 2,3,7,8-TCDD;

thus, a graph has not been prepared for this compound.

References

1. Agency for Toxic Substances and Disease Registry (ATSDR). Toxicological Profile for

Chlorinated Dibenzo-p-Dioxins. Public Health Service, U.S. Department of Health and

Human Services, Atlanta, GA. 1998.

2. U.S. Environmental Protection Agency (EPA). Health Effects Assessment Summary

Tables. FY 1997 Update. Environmental Criteria and Assessment Office, Office of

Health and Environmental Assessment, Office of Research and Development, Cincinnati,

OH. 1997.

3. U.S. Environmental Protection Agency (EPA). Health Assessment Document for

Polychlorinated Dibenzo-p-Dioxin. Environmental Criteria and Assessment Office,

Office of Health and Environmental Assessment, Office of Research and Development,

Cincinnati, OH. EPA 600/8-84-014F. 1985.
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1,1,2,2-TETRACHLOROETHANE

79-34-5

Hazard Summary

As 1,1,2,2-tetrachloroethane is no longer used much in the U.S., current air emissions

predominantly result from its use as a chemical intermediate during the manufacture of

other chemicals. Low levels have been detected in air. The main effects of

1,1,2,2-tetrachloroethane are liver and neurological effects. Acute (short-term) inhalation

exposure to very high levels of 1,1,2,2-tetrachloroethane has resulted in effects on the

liver and respiratory, central nervous, and gastrointestinal systems in humans. Chronic

(long-term) inhalation exposure to 1,1,2,2-tetrachloroethane in humans results in jaundice

and an enlarged liver, headaches, tremors, dizziness, numbness, and drowsiness. Animal

studies have shown a significantly increased incidence of liver tumors in mice orally

exposed to 1,1,2,2-tetrachloroethane. The U.S. Environmental Protection Agency (EPA)

has classified 1,1,2,2-tetrachloroethane as a Group C possible human carcinogen. 

Please Note: The main sources of information for this fact sheet are EPA's Integrated Risk Information System

(IRIS), which contains information on the carcinogenic effects of 1,1,2,2-tetrachloroethane, and the Agency for

Toxic Substances and Disease Registry's (ATSDR's) Toxicological Profile for 1,1,2,2-Tetrachloroethane.

Physical Properties

! 1,1,2,2-Tetrachloroethane is a colorless, dense liquid that has a sweet, chloroform like

odor. (1,6)

! The odor threshold for 1,1,2,2-tetrachloroethane is 1.5 ppm. (6)

! The chemical formula for 1,1,2,2-tetrachloroethane is C2H2Cl4, and the molecular weight

is 167.85 g/mol. (1,2)

! The vapor pressure for 1,1,2,2-tetrachloroethane is 5.95 mm Hg at 25 EC, and it has a log

octanol/water partition coefficient (log Kow) of 2.39. (1)

! The half-life in air is about 60 days. (1)

Uses

! The production of 1,1,2,2-tetrachloroethane has decreased significantly in the U.S. (1)

! In the past, 1,1,2,2-tetrachloroethane was used in large amounts to produce

trichloroethylene, tetrachloroethylene, and 1,2,-dichloroethylene. (1)

! It was also used as a solvent, in cleaning and degreasing metals, in paint removers,

varnishes and lacquers, in photographic films, as an extractant for oils and fats, and in

pesticides. (1)
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Sources and Potential Exposure

! As it is no longer used much in the U.S., present sources of 1,1,2,2-tetrachloroethane are

chemical production activities in which it is an intermediate product. (1)

! Low levels of 1,1,2,2-tetrachloroethane can be present in both indoor and outdoor air. In

the early 1980s, average ambient air concentrations were around 0.005 ppb, and average

concentrations in the indoor air of several homes measured 1.8 ppb. (1)

! 1,1,2,2-Tetrachloroethane has been found, in trace amounts, in adhesives, oils, greases,

and lubricants; these household products may contaminate indoor air. (1)

! Limited occupational exposure to 1,1,2,2-tetrachloroethane may occur through inhalation

of the vapors or through skin contact due to spills or accidents in the workplace. (1)

! 1,1,2,2-Tetrachloroethane has been detected in surface water and groundwater; however,

a nationwide survey of drinking water supplies in the 1980s did not find any supplies

containing 1,1,2,2-tetrachloroethane. (1)

Assessing Personal Exposure

! No specific medical tests are available to determine exposure to 1,1,2,2-tetrachloroethane.

(1)

Health Hazard Information

Acute Effects:

! Acute exposure to very high levels of 1,1,2,2-tetrachloroethane has caused death in

humans; the autopsies revealed severe liver destruction. (1,2)

! Respiratory and eye irritation, dizziness, nausea, and vomiting have been noted in humans

exposed to fumes in the workplace. (1)

! Animal studies have reported effects on the liver, eyes, and central nervous system (CNS)

from acute inhalation exposure to 1,1,2,2,-tetrachloroethane. (1)

! Tests involving acute exposure of animals, such as the LC50 and LD50 tests in rats and

mice, have shown 1,1,2,2-tetrachloroethane to have moderate acute toxicity. (3)

Chronic Effects (Noncancer):

! Chronic exposure of humans to high levels of 1,1,2,2-tetrachloroethane results in effects

on the liver (jaundice and an enlarged liver), central and peripheral nervous system

(headaches, tremors, dizziness, and drowsiness), and gastrointestinal effects (pain,

nausea, vomiting, and loss of appetite). (1)

! Liver effects have also been observed in animals exposed via inhalation. (1)

! EPA has not established a reference concentration (RfC) or reference dose (RfD) for

1,1,2,2-tetrachloroethane. (4)

! ATSDR has calculated an intermediate-duration inhalation minimal risk level (MRL) of

0.4 ppm (3 mg/m3) for 1,1,2,2-tetrachloroethane based on liver effects in rats. The MRL

is an estimate of the daily human exposure to a hazardous substance that is likely to be
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without appreciable risk of adverse noncancer health effects over a specified duration of

exposure. Exposure to a level above the MRL does not mean that adverse health effects

will occur. The MRL is intended to serve as a screening tool. (1)

Reproductive/Developmental Effects:

! No studies are available regarding developmental or reproductive effects in humans from

inhalation or oral exposure to 1,1,2,2-tetrachloroethane. (1)

! Animal studies have not reported reproductive effects from inhalation exposure to

1,1,2,2-tetrachloroethane, while an oral study in rats reported histopathological changes in

the testes. (1)

! No effects to the offspring of male rats exposed to 1,1,2,2-tetrachloroethane via

inhalation were reported. (1)

Cancer Risk:

! Oral exposure to 1,1,2,2-tetrachloroethane in mice resulted in an increased incidence of

hepatocellular carcinomas, while no increase in tumors was reported in rats. (1,4)

! EPA has classified 1,1,2,2-tetrachloroethane as a Group C, possible human carcinogen.

(4)

! EPA uses mathematical models, based on human and animal studies, to estimate the

probability of a person developing cancer from breathing air containing a specified

concentration of a chemical. EPA has calculated an inhalation unit risk estimate of 5.8 x

10-5 (μg/m3)

-1. EPA estimates that, if an individual were to continuously breathe air

containing 1,1,2,2-tetrachloroethane at an average of 0.02 μg/m3 (2.0 x 10-5 mg/m3) over

his or her entire lifetime, that person would theoretically have no more than a

one-in-a-million increased chance of developing cancer as a direct result of breathing air

containing this chemical. Similarly, EPA estimates that continuously breathing air

containing 0.2 μg/m3 (2.0 x 10-4 mg/m3) would result in not greater than a

one-in-a-hundred thousand increased chance of developing cancer over a lifetime, and air

containing 2.0 μg/m3 (2.0 x 10-3 mg/m3) would result in not greater than a one-in-ten

thousand increased chance of developing cancer. For a detailed discussion of confidence

in the potency estimates, please see IRIS. (4)

! EPA has also calculated an oral cancer slope factor of 0.2 (mg/kg/d)-1. (4)

Conversion Factors:

To convert from ppm to mg/m3: mg/m3 = (ppm) x (molecular weight of the compound)/(24.45).

For 1,1,2,2-tetrachloroethane: 1 ppm = 6.86 mg/m3.

To convert from μg/m3 to mg/m3: mg/m3 = (μg/m3) x (1 mg/1,000 μg).
National Air Toxics Program: The Integrated Urban Strategy

Report to Congress

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1,1,2,2-Tetrachloroethane

0.00001

0.0001

0.001

0.01

0.1

1

10

100

1000

10000

100000

Health numbersa Regulatory, advisory

numbers

b

LC50 (mice) (4,500 mg/ m3)

LOAELd (liver) (890 mg/ m3)

ATSDR int ermediat e

MRL (3 mg/ m3)

Cancer Risk

Level c 1 in a

million risk

(2 x 10-5 mg/ m3)

OSHA PEL (35 mg/m3)

ACGIH TLV,NIOSH

REL (7 mg/ m3)

Ref.

4

NIOSH IDLH (690 mg/ m3)

Ref.

3

Ref.

1

Ref.

1

Ref.

5

Ref.

7,8

Ref.

8

Health Data from Inhalation Exposure

ACGIH TLV – American Conference of Governmental and Industrial Hygienists' threshold

limit value expressed as a time-weighted average; the concentration of a substance to which most

workers can be exposed without adverse effects.

LC50 (Lethal Concentration50) – A calculated concentration of a chemical in air to which

exposure for a specific length of time is expected to cause death in 50% of a defined

experimental animal population.

LOAEL – Lowest-observed-no-adverse-affect level.

NIOSH REL – National Institute of Occupational Safety and Health's recommended exposure

limit; NIOSH-recommended exposure limit for an 8- or 10-h time-weighted-average exposure

and/or ceiling.

NIOSH IDLH – NIOSH's immediately dangerous to life or health concentration; NIOSH

recommended exposure limit to ensure that a worker can escape from an exposure condition that

is likely to cause death or immediate or delayed permanent adverse health effects or prevent

escape from the environment.
National Air Toxics Program: The Integrated Urban Strategy

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OSHA PEL – Occupational Safety and Health Administration's permissible exposure limit

expressed as a time-weighted average: the concentration of a substance to which most workers

can be exposed without adverse effect averaged over a normal 8-h workday or a 40-h workweek.

a

 Health numbers are toxicological numbers from animal testing or risk assessment values

developed by EPA.

b

 Regulatory numbers are values that have been incorporated in Government regulations, while

advisory numbers are nonregulatory values provided by the Government or other groups as

advice.

c

 These cancer risk estimates were derived from oral data and converted to provide the estimated

inhalation risk.

d

 The LOAEL is from the critical study used as the basis for the ATSDR intermediate MRL.

References

1. Agency for Toxic Substances and Disease Registry (ATSDR). Toxicological Profile for

1,1,2,2-Tetrachloroethane (Update). U.S. Public Health Service, U.S. Department of

Health and Human Services, Atlanta, GA. 1996.

2. U.S. Department of Health and Human Services. Hazardous Substances Data Bank

(HSDB, online database). National Toxicology Information Program, National Library of

Medicine, Bethesda, MD. 1993.

3. U.S. Department of Health and Human Services. Registry of Toxic Effects of Chemical

Substances (RTECS, online database). National Toxicology Information Program,

National Library of Medicine, Bethesda, MD. 1993.

4. U.S. Environmental Protection Agency (EPA). Integrated Risk Information System (IRIS)

on 1,1,2,2-Tetrachloroethane. National Center for Environmental Assessment, Office of

Research and Development, Washington, DC. 1999.

5. Occupational Safety and Health Administration (OSHA). Occupational Safety and

Health Standards, Toxic and Hazardous Substances. Code of Federal Regulations 29

CFR 1910.1000. 1998.

6. J.E. Amoore and E. Hautala. Odor as an aid to chemical safety: Odor thresholds

compared with threshold limit values and volatilities for 214 industrial chemicals in air

and water dilution. Journal of Applied Toxicology, 3(6):272-290. 1983.

7. American Conference of Governmental Industrial Hygienists (ACGIH). 1999 TLVs and

BEIs. Threshold Limit Values for Chemical Substances and Physical Agents, Biological

Exposure Indices. Cincinnati, OH. 1999.
National Air Toxics Program: The Integrated Urban Strategy

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8. National Institute for Occupational Safety and Health (NIOSH). Pocket Guide to

Chemical Hazards. U.S. Department of Health and Human Services, Public Health

Service, Centers for Disease Control and Prevention. Cincinnati, OH. 1997.
National Air Toxics Program: The Integrated Urban Strategy

Report to Congress

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TETRACHLOROETHYLENE (PERCHLOROETHYLENE)

127-18-4

Hazard Summary

Tetrachloroethylene is widely used for dry-cleaning fabrics and metal degreasing

operations. The main effects of tetrachloroethylene in humans are neurological, liver, and

kidney effects following acute (short-term) and chronic (long-term) inhalation exposure. 

Dizziness, sleepiness, and impaired coordination have been reported. Some adverse

reproductive effects, such as menstrual disorders and spontaneous abortions, have been

reported from occupational exposure to tetrachloroethylene; however, no definite

conclusions can be made because of the limitations of the studies. Results from

epidemiological studies of tetrachloroethylene and cancer incidence have been mixed;

some studies reported an increased incidence of a variety of tumors, while other studies

did not report any carcinogenic effects. Animal studies have reported an increased

incidence of liver cancer in mice, via inhalation and gavage, and kidney and mononuclear

cell leukemia in rats. The U.S. Environmental Protection Agency (EPA) considers

trichloroethylene as intermediate between a probable and possible human carcinogen

(Group B/C). The Agency is currently reassessing its potential carcinogenicity.

Please Note: The main sources of information for this fact sheet are EPA's Integrated Risk Information System

(IRIS), which contains information on oral chronic toxicity and the reference dose (RfD), and the Agency for Toxic

Substances and Disease Registry's (ATSDR's) Toxicological Profile for Tetrachloroethylene. Another secondary

source is EPA's Health Effects Assessment for Tetrachloroethylene.

Physical Properties

! Tetrachloroethylene is a nonflammable colorless liquid with a sharp sweet odor; the odor

threshold is 1 ppm. (1)

! The chemical formula for tetrachloroethylene is C2Cl4, and the molecular weight is

165.83 g/mol. (1)

! The vapor pressure for tetrachloroethylene is 18.47 mm Hg at 25 EC, and it has a log

octanol/water partition coefficient (log Kow) of 3.40. (1)

Uses

! Tetrachloroethylene is used for dry cleaning and textile processing, as a chemical

intermediate, and for vapor degreasing in metal-cleaning operations. (1)

Sources and Potential Exposure

! Prior to 1981, tetrachloroethylene was detected in ambient air at average levels of 0.16

ppb in rural and remote areas, 0.79 ppb in urban and suburban areas, and 1.3 ppb in areas

near emission sources. (1)
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! Tetrachloroethylene has also been detected in drinking water; one survey prior to 1984 of

water supplies from groundwater sources reported a median concentration of 0.75 ppb for

the samples in which tetrachloroethylene was detected, with a maximum level of 69 ppb.

(1)

! Occupational exposure to tetrachloroethylene may occur, primarily in dry cleaning

establishments and at industries manufacturing or using the chemical. (1)

Assessing Personal Exposure

! Tetrachloroethylene can be measured in the breath, and breakdown products of

tetrachloroethylene can be measured in the blood and urine. (1)

Health Hazard Information

Acute Effects:

! Acute exposure to very high levels of tetrachloroethylene in humans has caused death.

Effects noted from short-term, inhalation exposure to tetrachloroethylene vapors include

irritation of the upper respiratory tract and eyes, kidney dysfunction, and at lower

concentrations, neurological effects, such as reversible mood and behavioral changes,

impairment of coordination, dizziness, headache, sleepiness, and unconsciousness. (1)

! Animal studies have reported effects on the liver, kidney, and central nervous system

(CNS) from acute inhalation exposure to tetrachloroethylene. (1)

! Acute animal tests, such as the LC50 and LD50 tests in mice have shown

tetrachloroethylene to have low toxicity from inhalation and oral exposure. (1)

Chronic Effects (Noncancer):

! The major effects from chronic inhalation exposure to tetrachloroethylene in humans are

neurological effects, including headaches, and impairment of memory, concentration, and

intellectual function. Other effects noted in humans include cardiac arrhythmia, liver

damage, and possible kidney effects. (1,5)

! Animal studies have reported effects on the liver, kidney, and CNS from chronic

inhalation exposure to tetrachloroethylene. (1,5)

! EPA has not established a reference concentration (RfC) for tetrachloroethylene. (4)

! The RfD for tetrachloroethylene is 0.01 mg/kg/d based on hepatotoxicity in mice and

weight gain in rats. The RfD is an estimate (with uncertainty spanning perhaps an order of

magnitude) of a daily oral exposure to the human population (including sensitive

subgroups) that is likely to be without appreciable risk of deleterious noncancer effects

during a lifetime. It is not a direct estimator of risk, but rather a reference point to gauge

the potential effects. At exposures increasingly greater than the RfD, the potential for

adverse health effects increases. Lifetime exposure above the RfD does not imply that an

adverse health effect would necessarily occur. (4)

! EPA has medium confidence in the RfD based on low confidence in the study on which

the RfD was based due to the lack of complete histopathological examination at the
National Air Toxics Program: The Integrated Urban Strategy

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A-209

no-observed-adverse-effect level (NOAEL) in the mouse; and medium confidence in the

database because it is relatively complete but lacks studies of reproductive and teratology

endpoints subsequent to oral exposure. (4)

! ATSDR has calculated a chronic-duration inhalation minimal risk level (MRL) of 0.04

ppm (0.3 mg/m3) for tetrachloroethylene based on neurological effects in humans. The

MRL is an estimate of the daily human exposure to a hazardous substance that is likely to

be without appreciable risk of adverse noncancer health effects over a specified duration

of exposure. (1)

! Repeated skin contact may cause irritation. (1)

Reproductive/Developmental Effects:

! Some adverse reproductive effects, such as menstrual disorders and spontaneous

abortions, have been reported in women occupationally exposed to tetrachloroethylene. 

However, no definitive conclusions can be made because of the limitations of the studies.

(1)

! In a study of residents exposed to drinking water contaminated with solvents, including

tetrachloroethylene, there was a suggestion that birth defects were associated with

exposure. However, no firm conclusions can be drawn from this study due to multiple

chemical exposures and problems with the analysis. (1)

! Increased fetal resorptions and effects to the fetus have been reported in animals exposed

to high levels of tetrachloroethylene by inhalation. (1)

Cancer Risk:

! Epidemiological studies of dry cleaning workers exposed to tetrachloroethylene and other

solvents have shown mixed results; some studies reported an increased incidence of a

variety of tumors, while other studies did not show any carcinogenic effects. All of these

studies are complicated by potential exposure to numerous chemicals. (1,5,6)

! One human study reported that there was a potential association between drinking water

contaminated with tetrachloroethylene and other chemicals and an increased risk of

childhood leukemia. Other studies reexamined the data and did not agree with the

association because the people were exposed to multiple chemicals and the statistical

significance of the incidence of leukemia has not been resolved. (1)

! Animal studies have reported an increased incidence of liver tumors in mice, from

inhalation and gavage exposure, and kidney and mononuclear cell leukemias in rats, via

inhalation exposure. (1,5,6)

! Regardless of exposure route, less than 5 percent of absorbed tetrachloroethylene is

metabolized by humans to trichloroacetic acid (TCA), with the remainder being exhaled

unchanged. Trichloroacetic acid is classified as a Group C, possible human carcinogen

based on limited evidence of liver tumors in mice (but not rats). (4,7)

! EPA considers trichloroethylene as intermediate between a probable and possible human

carcinogen (Group B/C). The Agency is currently reassessing its potential

carcinogenicity. (10)
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! EPA uses mathematical models, based on animal studies, to estimate the probability of a

person developing cancer from breathing air containing a specified concentration of a

chemical. EPA has calculated a provisional inhalation unit risk estimate of 5.8 x 10-7

(μg/m3)

-1. A provisional value is one which has not received Agency-wide review. (7)

! EPA has calculated a provisional oral cancer slope factor of 0.051 (mg/kg/d)-1. (5)

Conversion Factors:

To convert from ppm to mg/m3: mg/m3 = (ppm) x (molecular weight of the compound)/(24.45).

For tetrachloroethylene: 1 ppm = 6.78 mg/m3.

To convert from μg/m3 to mg/m3: mg/m3 = (μg/m3) × (1 mg/1,000 μg).
National Air Toxics Program: The Integrated Urban Strategy

Report to Congress

A-211

Tetrachloroethylene

0.1

1

10

100

1000

10000

100000

Health numbersa Regulatory, advisory

numbers

b

Ref.

1

Ref.

1

Ref.

1

Ref.

9

Ref.

2

LC50 (mice) (35,268 mg/m3)

LOAELc (neurological)

(102 mg/m3)

ASDR chronic MRL

(0.3 mg/m3)

OSHA PEL, ACGIH STEL (685 mg/m3)

ACGIH TLV

(170 mg/m3)

AIHA ERPG-2 (1360 mg/m3)

NIOSH IDLH (1020 mg/m3)

AIHA ERPG-1

(680 mg/m3)

Ref.

2,3

Ref.

8

Ref.

9

Health Data from Inhalation Exposure

AIHA ERPG – American Industrial Hygiene Association's emergency response planning

guidelines. ERPG 1 is the maximum airborne concentration below which it is believed nearly all

individuals could be exposed up to one hour without experiencing other than mild transient

adverse health effects or perceiving a clearly defined objectionable odor; ERPG 2 is the

maximum airborne concentration below which it is believed nearly all individuals could be

exposed up to one hour without experiencing or developing irreversible or other serious health

effects that could impair their abilities to take protective action.

ACGIH STEL – American Conference of Governmental and Industrial Hygienists' short-term

exposure limit; 15-min time-weighted-average exposure that should not be exceeded at any time

during a workday even if the 8-h time-weighted-average is within the threshold limit value.

ACGIH TLV – American Conference of Governmental and Industrial Hygienists' threshold
National Air Toxics Program: The Integrated Urban Strategy

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A-212

limit value expressed as a time-weighted average; the concentration of a substance to which most

workers can be exposed without adverse effects.

LC50 (Lethal Concentration50) – A calculated concentration of a chemical in air to which

exposure for a specific length of time is expected to cause death in 50% of a defined

experimental animal population.

LOAEL – Lowest-observed-no-adverse-affect level.

NIOSH IDLH – National Institute of Occupational Safety and Health's immediately dangerous

to life or health concentration; NIOSH recommended exposure limit to ensure that a worker can

escape from an exposure condition that is likely to cause death or immediate or delayed

permanent adverse health effects or prevent escape from the environment.

OSHA PEL – Occupational Safety and Health Administration's permissible exposure limit

expressed as a time-weighted average; the concentration of a substance to which most workers

can be exposed without adverse effect averaged over a normal 8-h workday or a 40-h workweek.

a

 Health numbers are toxicological numbers from animal testing or risk assessment values

developed by EPA.

b

 Regulatory numbers are values that have been incorporated in Government regulations, while

advisory numbers are nonregulatory values provided by the Government or other groups as

advice.

c

 The LOAEL is from the critical study used as the basis for the ATSDR chronic inhalation MRL.

References

1. Agency for Toxic Substances and Disease Registry (ATSDR). Toxicological Profile for

Tetrachloroethylene (Update). U.S. Public Health Service, U.S. Department of Health

and Human Services, Atlanta, GA. 1997.

2. American Conference of Governmental and Industrial Hygienists (ACGIH). 1999 TLVs

and BEIs: Threshold Limit Values for Chemical Substances and Physical Agents,

Biological Exposure Indices. Cincinnati, OH. 1999.

3. Occupational Safety and Health Administration (OSHA). Occupational Safety and

Health Standards, Toxic and Hazardous Substances. Code of Federal Regulations 29

CFR 1910.1000. 1998.

4. U.S. Environmental Protection Agency (EPA). Integrated Risk Information System (IRIS)

on Tetrachloroethylene. National Center for Environmental Assessment, Office of

Research and Development, Washington, DC. 1999.

5. U.S. Environmental Protection Agency (EPA). Health Effects Assessment for

Tetrachloroethylene. EPA/600/8-89-096. Environmental Criteria and Assessment Office,

Office of Health and Environmental Assessment, Office of Research and Development,

Cincinnati, OH. 1988.
National Air Toxics Program: The Integrated Urban Strategy

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6. U.S. Environmental Protection Agency (EPA). Updated Health Assessment Document for

Tetrachloroethylene. EPA/600/8-82/005B. Environmental Criteria and Assessment

Office, Office of Health and Environmental Assessment, Office of Research and

Development, Cincinnati, OH. 1988.

7. U.S. Environmental Protection Agency (EPA). Risk Assessment Issue Paper for

Carcinogenicity Information for Tetrachloroethylene (Perchloroethylene, PERC)

(CASRN 127-18-4). Superfund Technical Support Center, National Center for

Environmental Assessment, Cincinnati, OH. nd.

8. National Institute for Occupational Safety and Health (NIOSH). Pocket Guide to

Chemical Hazards. U.S. Department of Health and Human Services, Public Health

Service, Centers for Disease Control and Prevention. Cincinnati, OH. 1997.

9. American Industrial Hygiene Association (AIHA). The AIHA 1998 Emergency Response

Planning Guidelines and Workplace Environmental Exposure Level Guides Handbook.

1998.

10. U.S. Environmental Protection Agency (EPA). National Emission Standards for

Hazardous Air Pollutants: Wood Furniture Manufacturing Operations. Federal Register

63 FR 34336-346. June 24, 1998.
National Air Toxics Program: The Integrated Urban Strategy

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TRICHLOROETHYLENE

79-01-6

Hazard Summary

Most of the trichloroethylene (TCE) used in the U.S. is released into the atmosphere from

industrial degreasing operations. Acute (short-term) and chronic (long-term) inhalation

exposure to trichloroethylene can affect the human central nervous system (CNS), with

symptoms such as dizziness, headaches, confusion, euphoria, facial numbness, and

weakness. High, short-term exposures of humans by inhalation also have been associated

with effects on the liver, kidneys, gastrointestinal system, and skin. Although several

epidemiological studies have investigated a possible link between trichloroethylene

exposure and reproductive or developmental effects, no conclusive evidence has been

identified. Similarly, the existence of a relationship between trichloroethylene exposure

and cancer is also not clear from the epidemiological studies that have been performed. 

Animal studies have reported increases in lung, liver, and testicular tumors, via inhalation

exposure. The U.S. Environmental Protection Agency (EPA) considers trichloroethylene

as intermediate between a probable and possible human carcinogen (Group B/C). The

Agency is currently reassessing its potential carcinogenicity.

Please Note: The main source of information for this fact sheet is the Agency for Toxic Substances and Disease

Registry's (ATSDR's) Toxicological Profile for Trichloroethylene. Another secondary source used is EPA's Health

Assessment Document for Trichloroethylene.

Physical Properties

! Trichloroethylene is a nonflammable colorless liquid with a sweet odor similar to ether or

chloroform. (1)

! The odor threshold for trichloroethylene is 28 ppm. (6)

! The chemical formula for trichloroethylene is C2HCl3, and the molecular weight is 131.40

g/mol. (1)

! The vapor pressure for trichloroethylene is 74 mm Hg at 25 EC, and it has a log

octanol/water partition coefficient (log Kow) of 2.42. (1)

! Trichloroethylene is not a persistent chemical in the atmosphere; its half-life in air is

about 7 days. (1)

Uses

! The main use of trichloroethylene is in the vapor degreasing of metal parts. (1)

! Trichloroethylene is also used as an extraction solvent for greases, oils, fats, waxes, and

tars, a chemical intermediate in the production of other chemicals, and as a refrigerant. (1)

! Trichloroethylene is used in consumer products such as typewriter correction fluids, paint

removers/strippers, adhesives, spot removers, and rug-cleaning fluids. (1)

! Trichloroethylene was used in the past as a general anesthetic. (1)
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Sources and Potential Exposure

! Trichloroethylene has been detected in ambient air at levels less than 1 ppb. (1)

! Drinking water supplies relying on contaminated groundwater sources may contain

trichloroethylene. A monitoring study in the early 1980s of drinking water systems

relying groundwater sources detected TCE in 10 percent of the systems sampled. The

median level among the systems where detected was 1 ppb. (1)

! Workers may be exposed to trichloroethylene in the factories where it is manufactured or

used. In addition, persons breathing air around these factories may be exposed to

trichloroethylene. (1)

! Persons may also be exposed to trichloroethylene through the use of products containing

the chemical and from evaporation and leaching from waste disposal sites. (1)

Assessing Personal Exposure

! Trichloroethylene can be measured in the breath, and breakdown products of

trichloroethylene can be measured in urine or blood. (1)

Health Hazard Information

Acute Effects:

! Acute exposure to extremely high levels of trichloroethylene (approximately 10,000 ppm)

in humans has caused death. A few of these reports have cited cardiac arrhythmias as the

cause of death, and one report noted massive liver damage. (1)

! CNS effects are the primary effects noted from acute inhalation exposure to

trichloroethylene in humans, with symptoms including sleepiness, fatigue, headache,

confusion, and feelings of euphoria. Effects on the liver, kidneys, gastrointestinal system,

and skin have also been noted. (1)

! Neurological, lung, kidney, and heart effects have been reported in animals acutely

exposed to trichloroethylene. (1)

! Tests involving acute exposure of animals, such as the LC50 and LD50 tests in rats and

mice, have shown trichloroethylene to have low toxicity from inhalation exposure and

moderate toxicity from oral exposure. (1,2)

Chronic Effects (Noncancer):

! As with acute exposure, chronic exposure to trichloroethylene by inhalation also affects

the human CNS. Case reports of intermediate and chronic occupational exposures

included effects such as dizziness, headache, sleepiness, nausea, confusion, blurred

vision, facial numbness, and weakness. (1)

! Studies have shown that simultaneous alcohol consumption and trichloroethylene

inhalation increases the toxicity of trichloroethylene in humans. (1)

! Neurological, liver, and kidney effects were reported in chronically-exposed animals. (1)
National Air Toxics Program: The Integrated Urban Strategy

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! EPA has not calculated a reference concentration (RfC) or reference dose (RfD) for

trichloroethylene. (3)

! ATSDR has calculated an intermediate-duration inhalation minimal risk level (MRL) of

0.1 ppm (0.5 mg/m3) for trichloroethylene based on neurological effects in rats. The

MRL is an estimate of the daily human exposure to a hazardous substance that is likely to

be without appreciable risk of adverse noncancer health effects over a specified duration

of exposure. Exposure to a level above the MRL does not mean that adverse health

effects will occur. The MRL is intended to serve as a screening tool. (1)

! The California Environmental Protection Agency (CalEPA) has calculated a chronic

inhalation reference exposure level of 0.6 mg/m3 based on neurological effects in humans.

The CalEPA reference exposure level is a concentration at or below which adverse health

effects are not likely to occur. (5)

Reproductive/Developmental Effects:

! A study of nurses occupationally exposed by inhalation to trichloroethylene along with

other chemicals in operating rooms, and another epidemiological study of women

exposed occupationally or nonoccupationally to trichloroethylene and other solvents,

have reported increases in the incidence of miscarriages. The presence of other chemicals,

however, limits the ability to draw conclusions specific to trichloroethylene. (1)

! An epidemiological study of 2,000 male and female workers exposed to trichloroethylene

via inhalation found no increase in malformations in babies born following exposure. (1)

! Several studies have evaluated and not found an association between adverse

reproductive effects in humans and exposure to trichloroethylene in contaminated

drinking water. An association was found between the occurrence of congenital heart

disease in children and a drinking water supply contaminated with trichloroethylene and

other similar chemicals; however, no causal relationship with trichloroethylene could be

concluded. (1)

! In one animal study, an increase in abnormal sperm morphology was observed following

very high inhalation exposures of mice; however, other animal studies have not reported

reproductive or developmental effects from either inhalation or ingestion exposures. (1,4)

Cancer Risk:

! Several human studies have investigated the relationship between inhalation exposure to

trichloroethylene and cancer, some finding weak relationships and others finding none;

however, each has limitations that restrict its usefulness. None of the studies found strong

evidence of an association between trichloroethylene exposure and cancer incidence. (1,4)

! The existence of a relationship between oral exposure to trichloroethylene and cancer

incidence is also not clear. One human study reported that there was a potential

association between drinking water contaminated with trichloroethylene and an increased

risk of childhood leukemia. Other studies reexamined the data and did not agree with the

association because the people were exposed to chemicals other than trichloroethylene,

and the statistical significance of the incidence of leukemia has not been resolved. (1)
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! Animal studies, via inhalation exposure, have reported increases in lung, liver, and

testicular tumors and increases in liver tumors via gavage. (1,4)

! EPA considers trichloroethylene as intermediate between a probable and possible human

carcinogen (Group B/C). The Agency is currently reassessing its potential

carcinogenicity. (11)

! EPA uses mathematical models, based on animal studies, to estimate the probability of a

person developing cancer from continuously breathing air containing a specified

concentration of a chemical. EPA has calculated a provisional inhalation unit risk

estimate of 1.7 x 10-6 (μg/m3)

-1. A provisional value is one which has not received

Agency-wide review. (10)

! EPA has also calculated a provisional oral cancer slope factor of 0.011 (mg/kg/d)-1. (10)

Conversion Factors:

To convert from ppm to mg/m3: mg/m3 = (ppm) x (molecular weight of the compound)/(24.45).

For trichloroethylene: 1 ppm = 5.37 mg/m3. To convert from μg/m3 to mg/m3: mg/m3 = (μg/m3) x

(1 mg/1,000 μg).
National Air Toxics Program: The Integrated Urban Strategy

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Trichloroethylene

0.1

1

10

100

1000

10000

100000

1000000

Health numbersa Regulatory, advisory

numbersb

Ref.

1,2 Ref.

1,2

Ref.

1 Ref.

5

Ref.

5

Ref.

8,9,

12 Ref.

8

Ref.

1

LC50 (rat s) (67,178 mg/ m3)

LC50 (mice) (45,412 mg/ m3)

LOAELc (neurological) (269 mg/m3)

LOAELd (neurological)

(170 mg/ m3)

CalEPA reference

exposure level

(0.6 mg/ m3)

ATSDR

int ermediat e

MRL (0.5 mg/ m3)

OSHA PEL,

ACGIH STEL,

AIHA ERPG-1

(537 mg/ m3)

ACGIH TLV

(270 mg/ m3)

AIHA ERPG-2 (2685 mg/m3)

NIOSH IDLH (5370 mg/ m3)

Ref.

7

Ref.

12

Health Data from Inhalation Exposure

ACGIH STEL – American Conference of Governmental and Industrial Hygienists' short-term

exposure limit; 15-min time-weighted-average exposure that should not be exceeded at any time

during a workday even if the 8-h time-weighted-average is within the threshold limit value.

ACGIH TLV – ACGIH's threshold limit value expressed as a time-weighted average; the

concentration of a substance to which most workers can be exposed without adverse effects.

AIHA ERPG – American Industrial Hygiene Association's emergency response planning

guidelines. ERPG 1 is the maximum airborne concentration below which it is believed nearly all

individuals could be exposed up to one hour without experiencing other than mild transient

adverse health effects or perceiving a clearly defined objectionable odor; ERPG 2 is the

maximum airborne concentration below which it is believed nearly all individuals could be

exposed up to one hour without experiencing or developing irreversible or other serious health

effects that could impair their abilities to take protective action.

LC50 (Lethal Concentration50) – A calculated concentration of a chemical in air to which
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exposure for a specific length of time is expected to cause death in 50% of a defined

experimental animal population.

LOAEL – Lowest-observed-adverse-affect level

NIOSH IDLH – National Institute of Occupational Safety and Health's immediately dangerous

to life or health concentration; NIOSH recommended exposure limit to ensure that a worker can

escape from an exposure condition that is likely to cause death or immediate or delayed

permanent adverse health effects or prevent escape from the environment.

OSHA PEL – Occupational Safety and Health Administration's permissible exposure limit

expressed as a time-weighted average; the concentration of a substance to which most workers

can be exposed without adverse effect averaged over a normal 8-h workday or a 40-h workweek.

a

 Health numbers are toxicological numbers from animal testing or risk assessment values

developed by EPA.

b

 Regulatory numbers are values that have been incorporated in Government regulations, while

advisory numbers are nonregulatory values provided by the Government or other groups as

advice.

c

 The LOAEL is from the critical study used as the basis for the ATSDR intermediate MRL.

d

 The LOAEL is from the critical study used as the basis for the CalEPA chronic reference

exposure level.

References

1. Agency for Toxic Substances and Disease Registry (ATSDR). Toxicological Profile for

Trichloroethylene (Update). U.S. Public Health Service, U.S. Department of Health and

Human Services, Atlanta, GA. 1997.

2. U.S. Department of Health and Human Services. Registry of Toxic Effects of Chemical

Substances (RTECS, online database). National Toxicology Information Program,

National Library of Medicine, Bethesda, MD. 1993.

3. U.S. Environmental Protection Agency (EPA). Integrated Risk Information System (IRIS)

on Trichloroethylene. National Center for Environmental Assessment, Office of Research

and Development, Washington, DC. 1999.

4. U.S. Environmental Protection Agency (EPA). Health Assessment Document for

Trichloroethylene. EPA/600/8-82/006F. Environmental Criteria and Assessment Office,

Office of Health and Environmental Assessment, Office of Research and Development.

1985.

5. California Environmental Protection Agency (CalEPA). Technical Support Document for

the Determination of Noncancer Chronic Reference Exposure Levels. Draft for Public

Comment. Office of Environmental Health Hazard Assessment, Berkeley, CA. 1997.
National Air Toxics Program: The Integrated Urban Strategy

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6. J.E. Amoore and E. Hautala. Odor as an aid to chemical safety: Odor thresholds

compared with threshold limit values and volatilities for 214 industrial chemicals in air

and water dilution. Journal of Applied Toxicology, 3(6):272-290. 1983.

7. National Institute for Occupational Safety and Health (NIOSH). Pocket Guide to

Chemical Hazards. U.S. Department of Health and Human Services, Public Health

Service, Centers for Disease Control and Prevention. Cincinnati, OH. 1997.

8. American Conference of Governmental Industrial Hygienists (ACGIH). 1999 TLVs and

BEIs. Threshold Limit Values for Chemical Substances and Physical Agents, Biological

Exposure Indices. Cincinnati, OH. 1999.

9. Occupational Safety and Health Administration (OSHA). Occupational Safety and

Health Standards, Toxic and Hazardous Substances. Code of Federal Regulations 29

CFR 1910.1000. 1998.

10. U.S. Environmental Protection Agency (EPA). Risk Assessment Issue Paper for

Carcinogenicity Information for Trichloroethylene (TCE) (CASRN 79-01-6). Superfund

Technical Support Center, National Center for Environmental Assessment, Cincinnati,

OH. nd.

11. U.S. Environmental Protection Agency (EPA). National Emission Standards for

Hazardous Air Pollutants: Wood Furniture Manufacturing Operations. Federal Register

63 FR 34336-346. June 24, 1998.

12. American Industrial Hygiene Association (AIHA). The AIHA 1998 Emergency Response

Planning Guidelines and Workplace Environmental Exposure Level Guides Handbook.

1998.
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VINYL CHLORIDE

75-01-4

Hazard Summary

Most vinyl chloride is used to make polyvinyl chloride (PVC) plastic and vinyl products. 

Acute (short-term) exposure to high levels of vinyl chloride in air has resulted in central

nervous system(CNS) effects, such as dizziness, drowsiness, and headaches in humans. 

Chronic (long-term) exposure to vinyl chloride through inhalation and oral exposure in

humans has resulted in liver damage. There are positive human and animal studies

showing adverse effects which raise a concern about potential reproductive and

developmental hazards to humans from exposure to vinyl chloride. Cancer is a major

concern from exposure to vinyl chloride via inhalation, as vinyl chloride exposure has

been shown to increase the risk of a rare form of liver cancer in humans. The U.S.

Environmental Protection Agency (EPA) has classified vinyl chloride as a Group A,

human carcinogen. 

Please Note: The main sources of information for this fact sheet are the Agency for Toxic Substances and Disease

Registry's (ATSDR's) Toxicological Profile for Vinyl Chloride and Case Studies in Environmental Medicine. Vinyl

Chloride Toxicity.

Physical Properties

! Vinyl chloride is a colorless gas with a mild, sweet odor. (1)

! The odor threshold for vinyl chloride is 3,000 ppm. (5)

! Vinyl chloride is slightly soluble in water and is quite flammable. (1)

! The chemical formula for vinyl chloride is C2H3Cl, and the molecular weight is 62.5

g/mol. (1)

! The vapor pressure for vinyl chloride is 2,600 mm Hg at 25 EC, and it has a log

octanol/water partition coefficient (log Kow) of 1.36. (1)

! The half-life of vinyl chloride in air is a few hours. (1)

Uses

! Most of the vinyl chloride produced in the U.S. is used to make polyvinyl chloride (PVC),

a material used to manufacture a variety of plastic and vinyl products including pipes,

wire and cable coatings, and packaging materials. (1)

! Smaller amounts of vinyl chloride are used in furniture and automobile upholstery, wall

coverings, housewares, and automotive parts. (1)

! Vinyl chloride has been used in the past as a refrigerant. (1)
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Sources and Potential Exposure

! Ambient air concentrations of vinyl chloride are generally quite low, with exposure

occurring from the discharge of exhaust gases from factories that manufacture or process

vinyl chloride, or evaporation from areas where chemical wastes are stored. (1,2)

! Air inside new cars may contain vinyl chloride at higher levels than detected in ambient

air because vinyl chloride may outgas into the air from the new plastic parts. (1,2)

! Drinking water may contain vinyl chloride released from contact with polyvinyl pipes.

(1,2)

! Vinyl chloride is a microbial degradation product of trichloroethylene in groundwater,

and thus can be found in groundwater affected by trichloroethylene contamination. (3)

! Occupational exposure to vinyl chloride may occur in those workers concerned with the

production, use, transport, storage, and disposal of the chemical. (1,2)

Assessing Personal Exposure

! Vinyl chloride can be detected in urine and body tissues, but the tests are not reliable

indicators of total exposure. (1,2)

Health Hazard Information

Acute Effects:

! Acute exposure of humans to high levels of vinyl chloride via inhalation in humans has

resulted in effects on the CNS, such as dizziness, drowsiness, headaches, and giddiness.

(1,2)

! Vinyl chloride is reported to be slightly irritating to the eyes and respiratory tract in

humans. (1,2)

! Acute exposure to extremely high levels of vinyl chloride has caused loss of

consciousness, lung and kidney irritation, and inhibition of blood clotting in humans and

cardiac arrhythmias in animals. (1)

! Tests involving acute exposure of animals, such as the LC50 test in mice, have shown

vinyl chloride to have high acute toxicity from inhalation exposure. (5)

Chronic Effects (Noncancer):

! Liver damage may result in humans from chronic exposure to vinyl chloride, through

both inhalation and oral exposure. (1,2)

! A small percentage of individuals occupationally exposed to high levels of vinyl chloride

in air have developed a set of symptoms termed "vinyl chloride disease," which is

characterized by Raynaud's phenomenon (fingers blanch and numbness and discomfort

are experienced upon exposure to the cold), changes in the bones at the end of the fingers,

joint and muscle pain, and scleroderma-like skin changes (thickening of the skin,

decreased elasticity, and slight edema). (1,2)
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! CNS effects (including dizziness, drowsiness, fatigue, headache, visual and/or hearing

disturbances, memory loss, and sleep disturbances) as well as peripheral nervous system

symptoms (peripheral neuropathy, tingling, numbness, weakness, and pain in fingers)

have also been reported in workers exposed to vinyl chloride. (1)

! Animal studies have reported effects on the liver, kidney, and CNS from chronic

exposure to vinyl chloride. (1,6)

! EPA has not established a reference concentration (RfC) or a reference dose (RfD) for

vinyl chloride. (8)

! ATSDR has calculated an intermediate-duration inhalation minimal risk level (MRL) of

0.03 ppm (0.08 mg/m3) for vinyl chloride based on liver effects in rats. The MRL is an

estimate of the daily human exposure to a hazardous substance that is likely to be without

appreciable risk of adverse noncancer health effects over a specified duration of exposure.

Exposure to a level above the MRL does not mean that adverse health effects will occur.

The MRL is intended to serve as a screening tool. (1)

! The California Environmental Protection Agency (CalEPA) has calculated a chronic

inhalation reference exposure level of 0.005 mg/m3 based on liver effects in humans. The

CalEPA reference exposure level is a concentration at or below which adverse health

effects are not likely to occur. (15)

Reproductive/Developmental Effects:

! Several case reports suggest that male sexual performance may be affected by vinyl

chloride. However, these studies are limited by lack of quantitative exposure information

and possible co-occurring exposure to other chemicals. (1)

! Several epidemiological studies have reported an association between vinyl chloride

exposure in pregnant women and an increased incidence of birth defects, while other

studies have not reported similar findings. (1,2)

! Epidemiological studies have suggested an association between men occupationally

exposed to vinyl chloride and miscarriages in their wives' pregnancies although other

studies have not supported these findings. (1,2)

! Testicular damage and decreased male fertility have been reported in rats exposed to low

levels for up to 12 months. (1)

! Animal studies have reported decreased fetal weight and birth defects at levels that are

also toxic to maternal animals in the offspring of rats exposed to vinyl chloride through

inhalation. (1)

Cancer Risk:

! Inhaled vinyl chloride has been shown to increase the risk of a rare form of liver cancer

(angiosarcoma of the liver) in humans. (1,2,6)

! Vinyl chloride exposure, through inhalation, has also been associated with cancer of the

brain, CNS, lung, respiratory tract, and the lymphatic/hematopoietic system in humans.

(1,2)

! Animal studies have shown that vinyl chloride, via inhalation, increases the incidence of

angiosarcoma of the liver and cancer of the liver and brain. (1,2,6)
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! Several rat studies show a pronounced early-life susceptibility to the carcinogenic effect

of vinyl chloride, i.e., early exposures are associated with higher cancer incidence than

much longer exposures that occur after maturity. (1)

! EPA has classified vinyl chloride as a Group A, human carcinogen. (8)

! EPA uses mathematical models, based on human and animal studies, to estimate the

probability of a person developing cancer from breathing air containing a specified

concentration of a chemical. EPA has calculated a provisional inhalation unit risk

estimate of 8.4 x 10-5 (μg/m3)

-1 for vinyl chloride. A provisional value is one which has

not received Agency-wide review. (8)

! EPA has calculated a provisional oral cancer slope factor of 1.9 (mg/kg/d)-1 for vinyl

chloride. (8)

Conversion Factors:

To convert from ppm to mg/m3: mg/m3 = (ppm) x (molecular weight of the compound)/(24.45).

For vinyl chloride: 1 ppm = 2.6 mg/m3.

To convert from μg/m3 to mg/m3: mg/m3 = (μg/m3) x (1 mg/1,000 μg).
National Air Toxics Program: The Integrated Urban Strategy

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Vinyl Chloride

0.001

0.01

0.1

1

10

100

1000

10000

Health numbers

a Regulatory, advisory

numbersb

Ref.

5 Ref.

5

Ref.

1

Ref.

11

Ref.

1

Ref.

11

Ref.

9,10

Ref.

10

LC50 (rabbit s) (588 mg/m3)

LC50 (mice) (299 mg/m3)

LOAELc (liver) (26 mg/m3)

LOAELd (liver) (4 mg/m3)

ATSDR int ermediat e

MRL (0.08 mg/m3)

CalEPA reference

exposure level

(0.005 mg/m3)

ACGIH TLV, OSHA ceiling

(13 mg/m3)

OSHA PEL

(2.6 mg/m3)

Health Data from Inhalation Exposure

ACGIH TLV – American Conference of Governmental and Industrial Hygienists' threshold

limit value expressed as a time-weighted average; the concentration of a substance to which most

workers can be exposed without adverse effects.

LC50 (Lethal Concentration50) – A calculated concentration of a chemical in air to which

exposure for a specific length of time is expected to cause death in 50% of a defined

experimental animal population.

LOAEL – Lowest-observed-no-adverse-affect level.

OSHA PEL – Occupational Safety and Health Administration's permissible exposure limit

expressed as a time-weighted average: the concentration of a substance to which most workers

can be exposed without adverse effect averaged over a normal 8-h workday or a 40-h workweek.

OSHA PEL ceiling value – OSHA's permissible exposure limit ceiling value; the concentration

of a substance that should not be exceeded at any time.
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a

 Health numbers are toxicological numbers from animal testing or risk assessment values

developed by EPA.

b

 Regulatory numbers are values that have been incorporated in Government regulations, while

advisory numbers are nonregulatory values provided by the Government or other groups as

advice.

c

 The LOAEL is from the critical study used as the basis for the ATSDR intermediate-duration

inhalation MRL.

d

 The LOAEL is from the critical study used as the basis for the CalEPA chronic inhalation

reference exposure level.

References

1. Agency for Toxic Substances and Disease Registry (ATSDR). Toxicological Profile for

Vinyl Chloride (Update). Public Health Service, U.S. Department of Health and Human

Services, Atlanta, GA. 1997.

2. Agency for Toxic Substances and Disease Registry (ATSDR). Case Studies in

Environmental Medicine. Vinyl Chloride Toxicity. Public Health Service, U.S.

Department of Health and Human Services, Atlanta, GA. 1990.

3. Agency for Toxic Substances and Disease Registry (ATSDR). Toxicological Profile for

Trichloroethylene. Public Health Service, U.S. Department of Health and Human

Services, Atlanta, GA. 1992.

4. U.S. Department of Health and Human Services. Registry of Toxic Effects of Chemical

Substances (RTECS, online database). National Toxicology Information Program,

National Library of Medicine, Bethesda, MD. 1993.

5. J.E. Amoore and E. Hautala. Odor as an aid to chemical safety: Odor thresholds

compared with threshold limit values and volatilities for 214 industrial chemicals in air

and water dilution. Journal of Applied Toxicology, 3(6):272-290. 1983.

6. U.S. Department of Health and Human Services. Hazardous Substances Data Bank

(HSDB, online database). National Toxicology Information Program, National Library of

Medicine, Bethesda, MD. 1993.

7. U.S. Environmental Protection Agency (EPA). Integrated Risk Information System

(IRIS). National Center for Environmental Assessment, Office of Research and

Development, Washington, DC. 1999.

8. U.S. Environmental Protection Agency (EPA). Health Effects Assessment Summary

Tables. FY1997 Update. Environmental Criteria and Assessment Office, Office of Health

and Environmental Assessment, Office of Research and Development, Cincinnati, OH.

1997.
National Air Toxics Program: The Integrated Urban Strategy

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9. American Conference of Governmental Industrial Hygienists (ACGIH). 1999 TLVs and

BEIs. Threshold Limit Values for Chemical Substances and Physical Agents, Biological

Exposure Indices. Cincinnati, OH. 1999.

10. Occupational Safety and Health Administration (OSHA). Occupational Safety and

Health Standards, Toxic and Hazardous Substances. Code of Federal Regulations 29

CFR 1910.1017. 1998.

11. California Environmental Protection Agency (CalEPA). Technical Support Document for

the Determination of Noncancer Chronic Reference Exposure Levels. Draft for Public

Comment. Office of Environmental Health Hazard Assessment, Berkeley, CA. 1997.
National Air Toxics Program: The Integrated Urban Strategy

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