Public Health Statement for Benzidine
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This Public Health Statement is the
summary chapter from the Toxicological
Profile for Benzidine. It is one in a series of Public
Health Statements about hazardous substances and their health
effects. A shorter version, the ToxFAQs™,
is also available. This information is important because this
substance may harm you. The effects of exposure to any hazardous
substance depend on the dose, the duration, how you are exposed,
personal traits and habits, and whether other chemicals are
present. For more information, call the ATSDR Information
Center at 1-888-422-8737.
This public health statement tells you
about benzidine and the effects of exposure. The Environmental
Protection Agency (EPA) identifies the most serious hazardous
waste sites in the nation. These sites make up the National
Priorities List (NPL) and are the sites targeted for long-term
federal cleanup activities. Benzidine has been found in at
least 28 of the 1,585 current or former NPL sites. However,
the total number of NPL sites evaluated for benzidine is not
known. As more sites are evaluated, the sites at which benzidine
is found may increase. This information is important because
exposure to benzidine may harm you and because these sites
may be sources of exposure.
When a substance is released from a large
area, such as an industrial plant, or from a container, such
as a drum or bottle, it enters the environment. This release
does not always lead to exposure. You are exposed to a substance
only when you come in contact with it. You may be exposed
by breathing, eating, or drinking the substance, or by skin
contact. If you are exposed to benzidine, many factors determine
whether you'll be harmed. These factors include the dose (how
much), the duration (how long), and how you come in contact
with it. You must also consider the other chemicals you're
exposed to and your age, sex, diet, family traits, lifestyle,
and state of health.
What is benzidine?
Benzidine is a manufactured chemical
that does not occur naturally. It is a crystalline (sandy
or sugar-like) solid that may be grayish-yellow, white, or
reddish-gray. It will evaporate slowly from water and soil.
Its flammability, smell, and taste have not been described.
Benzidine also has other names, such as 4,4'-diphenylenediamine
or Fast Corinth Base B (a registered trade name). In the environment,
benzidine is found in either its "free" state (as an organic
base), or as a salt (for example, benzidine dihydrochloride
or benzidine sulfate). In air, benzidine is found attached
to suspended particles or as a vapor.
In the past, industry used large amounts
of benzidine to produce dyes for cloth, paper, and leather.
However, it has not been made for sale in the United States
since the mid-1970s. Major U.S. dye companies no longer make
benzidine-based dyes. Benzidine is no longer used in medical
laboratories or in the rubber and plastics industries. However,
small amounts of benzidine may still be manufactured or imported
for scientific research in laboratories or for other specialized
uses. Some benzidine-based dyes (or products dyed with them)
may also still be brought into the United States.
See Chapters 4 and 5 of the toxicological
profile for more information on the properties and uses of
What happens to benzidine when it enters the environment?
In the past, benzidine entered the environment
largely when it was being made or used to produce dyes. Industry
released it to waterways in the form of liquids and sludges,
and transported benzidine-containing solids to storage or
waste sites. Benzidine was sometimes accidentally spilled,
and it was released to the air as dust or fumes. For the most
part, companies no longer make or use benzidine, and the government
strictly regulates these activities. Today, most benzidine
still entering the environment probably comes from waste sites
where it had been disposed. Some may also come from the chemical
or biological breakdown of benzidine-based dyes, or from other
dyes where it may exist as an impurity. Only very small amounts
of free benzidine will dissolve in water at moderate environmental
temperatures. When released into waterways, it will sink and
become part of the bottom sludge. Benzidine salts can dissolve
more easily in water than free benzidine. Only a very small
portion of dissolved benzidine will pass into the air. Benzidine
exists in the air as very small particles or as a vapor, which
may be brought back to the earth's surface by rain or gravity.
In soil, most benzidine is likely to be strongly attached
to soil particles, so it does not easily pass into underground
Benzidine can slowly be destroyed by
certain other chemicals, light, and some microorganisms (for
example, bacteria). Certain fish, snails, algae, and other
forms of water life may take up and store very small amounts
of benzidine, but accumulation in the food chain is unlikely.
See Chapters 5 and 6 of the toxicological
profile for more information about how benzidine behaves in
How might I be exposed to benzidine?
The general population is not likely
to be exposed to benzidine through contaminated air, water,
soil, or food. Benzidine is a manufactured chemical that does
not occur naturally in the environment. Today, U.S. industry
makes and uses very little (if any) benzidine, and no releases
to air, water, or soil are reported on the Toxic Release Inventory
(TRI). Only rarely has benzidine been detected in areas other
than waste sites, and it has not been found in food. Some
dyes used to color foods or drinks may contain impurities
that can be broken down to benzidine once inside the body.
If you live near a hazardous waste site,
you could be exposed to benzidine by drinking contaminated
water or by breathing or swallowing contaminated dust and
soil. Benzidine can also enter the body by passing through
the skin. Some quantities of dyes made from benzidine may
still be brought into the United States. These may contain
small amounts of benzidine as a contaminant, or chemicals
that may be broken down in the body to benzidine. If you use
such dyes to dye paper, cloth, leather, or other materials,
you may be exposed by breathing or swallowing dust, or through
skin contact with dust. You may be exposed in a similar way
if you work at or near hazardous waste sites.
See Chapter 6 of the toxicological profile
for more information on how you can be exposed to benzidine
and benzidine based dyes.
How can benzidine enter and leave my
Benzidine can enter your body if you
breathe air that has small particles of benzidine or dust
to which benzidine is attached. It can also enter your body
if you drink water or eat food that has become contaminated
with benzidine. If your skin comes in contact with benzidine,
it could also enter your body. Generally, it will take only
a few hours for most of the benzidine to get into your body
through the lungs and intestines. It may take several days
for most of the benzidine to pass through your skin. Breathing,
eating, or drinking benzidine-based dyes may also expose you
to benzidine. Your intestines contain bacteria that can break
down these dyes into benzidine.
Once in your body, only a small portion
of benzidine will leave as waste in your urine and feces.
Your body will change most of the benzidine into many different
chemical forms (called metabolites), which dissolve readily
in your bodily fluids and are easy for your body to remove.
Some of these changed forms of benzidine appear to cause many
of the chemical's harmful effects. Studies show that after
benzidine has entered your body, most of it (and its changed
forms) will be removed within a week.
See Chapter 3 of the toxicological profile
for more information on how benzidine can enter, be changed
in, and leave your body.
How can benzidine affect my health?
Very little information is available
on the noncancer health effects that may be caused by exposure
to benzidine. Benzidine contact with your skin could possibly
cause a skin allergy. Except for the cancer discussed next,
benzidine has not been definitely shown to cause major adverse
health effects in humans.
To protect the public from the harmful
effects of toxic chemicals and to find ways to treat people
who have been harmed, scientists use many tests. One way to
see if a chemical will hurt people is to learn how the chemical
is absorbed, used, and released by the body; for some chemicals,
animal testing may be necessary. Animal testing may also be
used to identify health effects such as cancer or birth defects.
Without laboratory animals, scientists would lose a basic
method to get information needed to make wise decisions to
protect public health. Scientists have the responsibility
to treat research animals with care and compassion. Laws today
protect the welfare of research animals, and scientists must
comply with strict animal care guidelines.
Benzidine can cause cancer. This has
been shown in studies of workers who were exposed for many
years to levels much higher than the general population would
experience. It is important to note that most of the workers
did not develop cancer, even after such high exposures. When
cancer does occur, most often it is cancer of the urinary
bladder. Some evidence suggests that other organs, such as
the stomach, kidney, brain, mouth, esophagus, liver, gallbladder,
bile duct, and pancreas, may also be affected. Experiments
with animals have also shown benzidine to be a carcinogen
(a cancer causing substance). The Department of Health and
Human Services (DHHS), the International Agency for Research
on Cancer (IARC), and the EPA have determined that benzidine
is a human carcinogen. In addition, dyes made from benzidine,
such as Direct Blue 6, Direct Black 38, and Direct Brown 95,
have been shown to cause cancer in animals, and there is some
evidence that they may cause bladder cancer in humans. DHHS
has determined that Direct Black 38 and Direct Blue 6 cause
cancer in animals, and IARC has also determined that Direct
Black 38, Direct Blue 6, and Direct Brown 95 cause cancer
See Chapter 3 of the toxicological profile
for more information on the health effects of benzidine.
How can benzidine affect children?
This section discusses potential health
effects from exposures during the period from conception to
maturity at 18 years of age in humans. Potential effects on
children resulting from exposures of the parents are also
considered. Children might be exposed to benzidine if they
eat small amounts of soil contaminated with benzidine. However,
studies suggest that it is difficult to release benzidine
once it becomes attached to most types of soils. Exposure
by contaminated soil may occur if the children live in an
area near a source of the chemical (such as a hazardous waste
site that contains benzidine). There are no studies on health
effects in children exposed to benzidine. There is no information
on whether benzidine causes birth defects in children. It
is unknown whether birth defects would occur in the newborn
babies of animals that breathed or ate benzidine, or had it
on their skin while they were pregnant. There is no information
to determine whether children differ from adults in their
sensitivity to the health effects of benzidine. There is indirect
evidence that benzidine or its breakdown products can cross
the placenta, but it is not known whether it can be transferred
to the young through the mother's milk. More information regarding
children's health and benzidine can befound in Section 3.7
of the toxicological profile.
How can families reduce the risk of
exposure to benzidine?
If your doctor finds that you have been
exposed to significant amounts of benzidine, ask whether your
children might also be exposed. Your doctor might need to
ask your state health department to investigate. Benzidine
has no agricultural or food chemical uses, so exposure to
it by eating contaminated food is not likely. Impurities in
certain food dyes can be transformed inside the body to benzidine.
Children may be exposed to benzidine if they eat small amounts
of soil contaminated with benzidine. Children should be prevented
from eating soil; make sure they wash their hands frequently,
and before eating. Discourage your children from putting their
hands in their mouths or from doing other hand-to-mouth activities.
More information regarding exposure to benzidine can be found
in Sections 6.5, 6.6, and 6.7 of the toxicological profile.
Is there a medical test to determine
whether I have been exposed to benzidine?
Several tests have been developed to
help determine whether you have been exposed to benzidine.
Although these tests must be performed by experts in special
laboratories, your doctor can collect the blood or urine samples
and send them to an appropriate testing facility. Benzidine
and its breakdown products can be detected in your urine,
but only within about 2 weeks after your last exposure. Benzidine
and some of its changed forms will bind to proteins within
your red blood cells, and this can be detected for up to 4
months after your last exposure. Benzidine in some of its
forms can bind to the DNA found in most of your cells. There
are extremely sensitive tests that can detect such binding;
scientists continue to investigate whether these tests can
detect benzidine only or other similar chemicals too. None
of these tests, however, can predict whether harmful effects
will occur later.
See Chapters 3 and 7 of the toxicological
profile for more information on tests that can help determine
whether you have been exposed to benzidine.
What recommendations has the federal
government made to protect human health?
The federal government develops regulations
and recommendations to protect public health. Regulations
can be enforced by law. Federal agencies that develop
regulations for toxic substances include the Environmental
Protection Agency (EPA), the Occupational Safety and Health
Administration (OSHA), and the FDA. Recommendations provide
valuable guidelines to protect public health but cannot
be enforced by law. Federal organizations that develop recommendations
for toxic substances include the Agency for Toxic Substances
and Disease Registry (ATSDR) and the National Institute for
Occupational Safety and Health (NIOSH). Regulations and recommendations
can be expressed in not-to-exceed levels in air, water, soil,
or food that are usually based on levels that affect animals;
then they are adjusted to help protect people. Sometimes these
not-to-exceed levels differ among federal organizations because
of different exposure times (an 8-hour workday or a 24-hour
day), the use of different animal studies, or other factors.
Recommendations and regulations are also periodically updated
as more information becomes available. For the most current
information, check with the federal agency or organization
that provides it. Some regulations and recommendations for
benzidine include the following: Because benzidine can cause
cancer, the EPA has issued regulations that list it as a "priority"
chemical, subject to rigid inspection and control. EPA allows
0.10 parts of benzidine per million parts of waste (0.10 ppm)
that is brought to waste disposal sites. EPA also requires
that any release of one pound or more of benzidine or its
salts to the environment must be reported to the federal government's
National Response Center. EPA's Office of Water also has water
quality guidelines to protect human health. These guidelines
suggest that benzidine concentration limits should be maintained
at less than 1 part benzidine in a trillion parts of water
(ppt). Although zero benzidine is preferred, lifetime exposure
to these concentrations is estimated to result in no more
than one additional case of cancer in a million persons exposed.
OSHA considers benzidine to be a carcinogen, and has issued
regulations to reduce the risk of exposure in any workplace
in which it might still be found. These regulations include
entry controls, housekeeping and disposal rules, other rules
on operating and handling procedures, and requirements that
employers make showers and dressing rooms available. NIOSH
recommends that worker exposure to benzidine-based dyes be
kept to the lowest feasible concentration, and it considers
benzidine to be an occupational carcinogen. EPA's Office of
Water has set a discharge limit for benzidine-based dye applicators
of 10 micrograms per liter (10 µg/L) (one µg is one millionth
of a gram) over any calendar month or not more than 25 µg/L
in any working day. FDA allows a maximum of 1 part of benzidine
per billion parts (ppb) of some color additives for foods.
More information on regulations and advisories
is presented in Chapter 8 of the toxicological profile.
Agency for Toxic Substances and Disease
Registry (ATSDR). 2001. Toxicological
profile for Benzidine. Update. Atlanta, GA: U.S.
Department of Health and Human Services, Public Health Service.
Where can I get more information?
If you have questions or concerns, please contact your community or state health or environmental quality department or:
For more information, contact:
Agency for Toxic Substances and Disease Registry
Division of Toxicology and Human Health Sciences
4770 Buford Highway
Chamblee, GA 30341-3717
Phone: 1-800-CDC-INFO 888-232-6348 (TTY)
Email: Contact CDC-INFO
ATSDR can also tell you the location of occupational and environmental health clinics. These clinics specialize in recognizing, evaluating, and treating illnesses resulting from exposure to hazardous substances.