TOXICOLOGICAL PROFILE FOR 

1,2-DIBROMO-3-CHLOROPROPANE 

Agency for Toxic Substances and Disease Registry

U.S. Public Health Service 

September 1992 
ii 

DISCLAIMER 

The use of company or product name(s) is for identification only and

does not imply endorsement by the Agency for Toxic Substances and Disease

Registry. 










1 

1. PUBLIC HEALTH STATEMENT 

This Statement was prepared to give you information about 1,2-dibromo3-chloropropane and to emphasize the human health effects that may result from

exposure to it. The Environmental Protection Agency (EPA) has identified

1,177 sites on its National Priorities List (NPL) sites. 1,2-Dibromo3-chloropropane has been found at 8 of these sites. However, we do not know

how many of the 1,177 NPL sites have been evaluated for 1,2-dibromo3-chloropropane. As EPA evaluates more sites, the number of sites at which

1,2-dibromo-3-chloropropane is found may change. This information is

important for you because 1,2-dibromo-3-chloropropane may cause harmful health

effects and because these sites are potential or actual sources of human

exposure to 1,2-dibromo-3-chloropropane. 

When a chemical 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 as a chemical emission. This emission, which is also called a

release, does not always lead to exposure. You are exposed to a chemical only

when you come into contact with that chemical. You may be exposed to it in

the environment by breathing, eating, or drinking substances containing the

chemical or from skin contact with it. 

If you are exposed to a hazardous substance such as 1,2-dibromo3-chloropropane, several factors will determine whether harmful health effects

will occur and what the type and severity of those health effects will be.

These factors include the dose (how much), the duration (how long), the route

or pathway by which you are exposed (breathing, eating, drinking, or skin

contact), the other chemicals to which you are exposed, and your individual

characteristics such as age, sex, nutritional status, family traits, life

style, and state of health. 

1.1 WHAT IS 1,2-DIBROMO-3-CHLOROPROPANE? 

1,2-Dibromo-3-chloropropane is a colorless liquid with a sharp smell.

It can be smelled in air at 2 parts chemical in 1 million parts of air. It

evaporates about as fast as water does, which is not very quickly.

1,2-Dibromo-3-chloropropane will dissolve in water to a very limited extent.

It can be tasted in water when 0.01 mg chemical is present in 1 liter of

water. It is a man-made chemical not found naturally in the environment. We

do not know exactly how much of it is currently made or used by industry, but

it is probably a small amount. Some industries use 1,2-dibromo-3-chloropropane

to make a chemical that is used to make materials resistant to 

burning. Large amounts of 1,2-dibromo-3-chloropropane were used in the past

on certain farms to kill pests that were harmful to the crops. Farmers in

Hawaii stopped using this chemical in 1985; use in other states stopped in

1979. 
2 

1. PUBLIC HEALTH STATEMENT 

1,2-Dibromo-3-chloropropane breaks down slowly in the air. Most of the

1,2-dibromo-3-chloropropane that is released to the air disappears within

several months. Most of this chemical that enters surface water evaporates

into the air within several days or a week. It does not stick to the soil at

the bottom of rivers, lakes, or ponds. We do not expect fish or other seafood

from water containing 1,2-dibromo-3-chloropropane to build up large amounts of

this chemical in their bodies. Some of what is spilled on or applied to soil

moves through the soil into the groundwater, where it may remain for a long

time. Some of the 1,2-dibromo-3-chloropropane in soil evaporates from the

surface of the soil into the air. Small amounts may stay in the soil for

several years. This chemical also breaks down slowly to simpler chemicals in

water and soil. 

You will find more information in Chapters 3, 4, and 5 on the properties

of 1,2-dibromo-3-chloropropane. 

1.2 HOW MIGHT I BE EXPOSED TO 1,2-DIBROMO-3-CHLOROPROPANE? 

1,2-Dibromo-3-chloropropane is not usually found in the environment

(air, water, and soil). Sometimes, however, it is found in the soil and

underground water from cropland where it has been used as a pesticide. It has

been found in well-water near farms where 1,2-dibromo-3-chloropropane was

used. It has been found in food grown on farms that used the chemical and at

some hazardous waste sites. Foods today most likely do not contain this

chemical. 

1,2-Dibromo-3-chloropropane can enter the environment while it is being

made or used in industry and research. Because this chemical is not used very

much, the releases are probably small. Releases and disposal of 1,2-dibromo3-chloropropane at waste sites can lead to higher than usual levels in the

nearby air, water, and soil. 

We do not know exactly what amounts of 1,2-dibromo-3-chloropropane are

usually found in the air, surface water, and soil. However, based on the

limited usage in the past 5-10 years, we expect that levels where the chemical

has not been used or discarded are either low or nonexistent. In areas where 

the chemical has been used as a soil fumigant, it may still be present in soil

and groundwater at low levels. 

You can be exposed to 1,2-dibromo-3-chloropropane by drinking water or

eating certain foods that may still contain the compound. You might also be

exposed to 1,2-dibromo-3-chloropropane by breathing air containing it.

Exposure may happen if you live near a hazardous waste site that has released

1,2-dibromochloropropane to the air, water, or soil. Exposure can also occur

in the workplace from spills or other accidents or even during routine

handling. We do not know how much 1,2-dibromo-3-chloropropane the general

public or workers are exposed to or how often they are exposed to it. 
3
 

1. PUBLIC HEALTH STATEMENT 

However, the limited use of 1,2-dibromo-3-chloropropane in recent years

suggests that exposure is minimal and infrequent. 

You can find more information in Chapter 5 on how much 1,2-dibromo3-chloropropane is in the environment and how you can be exposed to it. 

1.3 HOW CAN 1,2-DIBROMO-3-CHLOROPROPANE ENTER AND LEAVE MY BODY? 

1,2-Dibromo-3-chloropropane can enter your body through the lungs if you

breathe air contaminated with it. It can also enter your body if you drink

contaminated water or eat contaminated food. It can enter through your skin

if it comes into contact with your skin. We do not know exactly how much or

how fast 1,2-dibromo-3-chloropropane enters your body through your lungs after

breathing it or through your skin after skin contact with it. Studies in

animals show- that almost all the 1,2-dibromo-3-chloropropane that they

swallowed entered the bloodstream quickly. Inside the body, 1,2-dibromo3-chloropropane is carried by the blood to many organs and breaks down into

other chemicals also called breakdown products. These breakdown products can

attach to some chemicals inside the cells of your body and may cause harmful

effects in the liver, kidneys, or male reproductive organs. Most of the

breakdown products are removed from your body quickly, but they may stay in

fatty tissue for a longer period of time. The breakdown products of

1,2-dibromo-3-chloropropane leave the body in urine and in the air you breathe

out. Only a small amount leaves in the stool. You can find more information

in Chapter 2 on the movement of 1,2-dibromo-3-chloropropane in the body. 

1.4 HOW CAN 1,2-DIBROMO-3-CHLOROPROPANE AFFECT MY HEALTH? 

Studies of workers in chemical factories that produced 1,2-dibromo3-chloropropane showed that its main harmful effect is on male reproductive

organs. Men exposed to 1,2-dibromo-3-chloropropane in the air may have more

girl children than boy children, produce fewer sperm, and eventually become

unable to father children. We do not know the exact levels of 1,2-dibromo3-chloropropane in air that cause these effects. Studies of workers have also

suggested that 1,2-dibromo-3-chloropropane may cause headache, nausea,

lightheadedness, and weakness. No adverse effect on reproduction was seen in

people who drank water contaminated with small amounts (0.004-5.75 parts in a

billion parts of water) of 1,2-dibromo-3-chloropropane. Studies in animals

show that 1,2-dibromo-3-chloropropane may cause birth defects in the offspring

of adult rats exposed to large amounts. However, human exposure to

1,2-dibromo-3-chloropropane that occurred at work or by drinking contaminated

water has not been linked with birth defects. Some people have smelled the

sharp odor of 1,2-dibromo-3-chloropropane when only small amounts were

present, 2 parts in 1 million parts of air (2 ppm). 

Some laboratory animals died after they breathed in, received large amounts in

their food, or had skin contact with 1,2-dibromo-3-chloropropane. Rats and

mice that survived breathing in or eating large amounts of 1,2-dibromo-
4
 

1. PUBLIC HEALTH STATEMENT
 

3-chloropropane had damaged stomachs, livers, and kidneys. Incoordination and

sleepiness were seen in animals that breathed or took large amounts of 1,2-

dibromo-3-chloropropane by mouth. Animals that breathed large amounts of this

chemical also had damaged brains. In addition, rats and mice that breathed

large amounts in 1,2-dibromo-3-chloropropane had damaged air passages and

lungs. Some laboratory animals that breathed large amounts of 1,2-dibromo-3-

chloropropane had damaged spleens, low blood cell production in the bone

marrow, or decreased amounts of blood cells in the blood. Rabbits that had

1,2-dibromo-3-chloropropane placed in contact with their eyes and skin had

irritated eyes, cloudy corneas, and damaged skin. Female rats mated with male

rats that received low-to-moderate doses of 1,2-dibromo-3-chloropropane in

their food for 5 days had miscarriages. Rats and rabbits that breathed in or

received low doses of 1,2-dibromo-3-chloropropane in their food for less than

1 year had harmful effects on their reproductive organs. Male offspring of

rats that were exposed to 1,2-dibromo-3-chloropropane while they were pregnant

also had harmful effects on their reproductive organs. Laboratory animals

that were exposed to low-to-moderate amounts of 1,2-dibromo-3-chloropropane

through breathing, swallowing, or skin contact for a long time period

developed cancer. Cancerous tumors on the inside of the nose were seen after

animals breathed 1,2-dibromo-3-chloropropane for long periods. Cancer of the

stomach and kidneys was seen after animals were given this chemical by mouth

for long periods. Cancer of the stomach and skin was seen after animals had

skin contact with this chemical for long periods. The Department of Health

and Human Services has determined that 1,2-dibromo-3-chloropropane may

reasonably be anticipated to be a carcinogen. The International Agency for

Research on Cancer has determined that 1,2-dibromo-3-chloropropane is possibly

carcinogenic to humans. 

You can find a more complete discussion in Chapter 2 of the effects of

1,2-dibromo-3-chloropropane on health. 

1.5 IS THERE A MEDICAL TEST TO DETERMINE WHETHER I HAVE BEEN EXPOSED TO 

1,2-DIBROMO-3-CHLOROPROPANE? 

1,2-Dibromo-3-chloropropane can be measured in exhaled air, blood, and

samples of tissues from the body. Samples must be collected shortly after

exposure because 1,2-dibromo-3-chloropropane leaves your body rapidly after

exposure. If a large exposure has occurred, levels may be detected for longer

after exposure than if a small exposure has occurred. The levels of 1,2-

dibromo-3-chloropropane cannot be used to predict whether or not you will

experience adverse health effects. These tests are probably not available

through your doctor's office, but your doctor can refer you to a place where

they can be done. Biological changes in the human body have been studied

after 1,2-dibromo-3-chloropropane exposure, but they have not been used to

tell whether exposure occurred. 

Exposure to 1,2-dibromo-3-chloropropane causes lower production of

sperm. Therefore, sperm counts and the blood levels of certain hormones 
5
 

1. PUBLIC HEALTH STATEMENT
 

(follicular stimulating hormone, luteinizing hormone) can be checked in

exposed men to find out whether harmful effects have occurred. However, these

changes have,not been linked with exposure levels of the chemical or lengths

of exposure to the chemical. Furthermore, the hormonal changes are not

sensitive enough to detect minor changes in sperm counts. See Chapters 2 and

6 for more information about tests for exposure to 1,2-dibromo-3-

chloropropane. 

1.6 WHAT RECOMMENDATIONS HAS THE FEDERAL GOVERNMENT MADE TO PROTECT HUMAN 

HEALTH? 

The Enviromental Protection Agency (EPA) recommends that the amount of

1,2-dibromo-3-chloropropane that is found in underground drinking water be

kept to low levels. The highest recommended level is 100 micrograms of 1,2-

dibromo-3-chloropropane per liter of water (pg/L). Furthermore, EPA requires

that industries report spills of 1 pound or more of 1,2-dibromo-3-

chloropropane. EPA banned the use of this chemical as a pesticide in the

United States in the early 1980s. 

The Occupational Safety and Health Administration (OSHA) recommends that

the amount of 1,2-dibromo-3-chloropropane in workplace air be kept to low

levels. The highest level allowed in the workplace is 1 part in one billion

parts of air (ppb), for an 8-hour workday and a 40-hour workweek. 

1.7 WHERE CAN I GET MORE INFORMATION? 

If you have any more questions or concerns not covered here, please

contact your state health or environmental department or: 

Agency for Toxic Substances and Disease Registry

Division of Toxicology

1600 Clifton Road, E-29

Atlanta, Georgia 30333 

This agency can also provide you with information on the location of the

nearest occupational and environmental health clinic. Such clinics specialize

in recognizing, evaluating, and treating illness that result from exposure to

hazardous substances. 

7 

2. HEALTH EFFECTS 

2.1 INTRODUCTION 

The primary purpose of this chapter is to provide public health

officials, physicians, toxicologists, and other interested individuals and

groups with an overall perspective of the toxicology of 1,2-dibromo-3-chloropropane

and a depiction of significant exposure levels associated with various

adverse health effects. It contains descriptions and evaluations of studies

and presents levels of significant exposure for 1,2-dibromo-3-chloropropane

based on toxicological studies and epidemiological investigations. 

2.2 DISCUSSION OF HEALTH EFFECTS BY ROUTE OF EXPOSURE 

To help public health professionals address the needs of persons living

or working near hazardous waste sites, the information in this section is

organized first by route of exposure--inhalation, oral, and dermal--and then

by health effect--death, systemic,,immunological, neurological, developmental,

reproductive, genotoxic, and carcinogenic effects. These data are discussed

in terms of three exposure periods--acute (less than 15 days), intermediate

(15-364 days), and chronic (365 days or more). 

Levels of significant exposure for each route and duration are presented

in tables and illustrated in figures. The points in the figures showing no-observedadverse-effect levels (NOAELs) or lowest-observed-adverse-effect

levels (LOAELs) reflect the actual doses (levels of exposure) used in the

studies. LOAELs have been classified into "less serious" or "serious" 

effects. These distinctions are intended to help the users of the document

identify the levels of exposure at which adverse health effects start to

appear. They should also help to determine whether or not the effects vary

with dose and/or duration, and place into perspective the possible

significance of these effects to human health. 

The significance of the exposure levels shown in the tables and figures

may differ depending on the user's perspective. For example, physicians

concerned with the interpretation of clinical findings in exposed persons may

be interested in levels of exposure associated with "serious" effects. Public

health officials and project managers concerned with appropriate actions to

take at hazardous waste sites may want information on levels of exposure

associated with more subtle effects in humans or animals (LOAEL) or exposure

levels below which no adverse effects (NOAEL) have been observed. Estimates

of levels posing minimal risk to humans (Minimal Risk Levels, MRLs) may be of

interest to health professionals and citizens alike. 

Estimates of exposure levels posing minimal risk to humans (MRLs) have

been made, where data were believed reliable, for the most sensitive noncancer

effect for each exposure duration. MRLs include adjustments to reflect human

variability from laboratory animal data to humans. 
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2. HEALTH EFFECTS
 

Although methods have been established to derive these levels (Barnes et

al. 1988; EPA 1989a), uncertainties are associated with these techniques.

Furthermore, ATSDR acknowledges additional uncertainties inherent in the

application of the procedures to derive less than lifetime MRLs. As an

example, acute inhalation MRLs may not be protective for health effects that

are delayed in development or are acquired following repeated acute insults,

such as hypersensitivity reactions, asthma, or chronic bronchitis. As these

kinds of health effects data become available and methods to assess levels of 

significant human exposure improve, these MRLs will be revised. 

2.2.1 Inhalation Exposure 

Occupational exposure to 1,2-dibromo-3-chloropropane probably involves

both inhalation and dermal exposure. Thus, many of the effects reported in

occupational studies in this section may be due, in part, to dermal exposure

to l-,2-dibromo-3-chloropropane. 

2.2.1.1 Death 

No studies were located regarding death in humans after inhalation

exposure to 1,2-dibromo-3-chloropropane. 

Inhalation LC50 values in rats were 103 ppm after 8 hours of exposure,

154 ppm after 4 hours, 232 ppm after 2 hours, and 368 ppm after 1 hour of

exposure (Torkelson et al. 1961). No increase in mortality above control

levels was observed in Sprague-Dawley rats observed for up to 12 months after

2 weeks of continuous exposure to concentrations up to 10 ppm 1,2-dibromo3-chloropropane (Saegusa et al. 1982). 

Mortality data for intermittent intermediate-duration exposures in

animals are conflicting. Increased mortality occurred in Fischer-344 rats

exposed to 25 ppm 1,2-dibromo-3-chloropropane for 13 weeks (NTP 1982) and in

an unspecified strain of rats exposed to 10 ppm for 10 weeks (Torkelson et al.

1961). The cause of death was not reported; however, renal, respiratory,

and/or splenic effects observed under histopathological examination might have

contributed to increased mortality. In contrast, no deaths were observed in

Sprague-Dawley rats exposed to concentrations up to 10 ppm for 14 weeks (Rao

et al. 1983). Increased mortality from pneumonia was observed among male New

Zealand rabbits exposed to 10 ppm 1,2-dibromo-3-chloropropane for 8 weeks (Rao

et al. 1982), but no deaths were reported in an unspecified strain of rabbits

exposed to 12 ppm for 13 weeks (Torkelson et al. 1961). The above-mentioned

discrepancies may be due to differences in strain sensitivity to the chemical

or to differences in the general health of animals from different animal

colonies. Increased mortality was also observed in B6C3F1 mice exposed to

25 ppm for 13 weeks (NTP 1982). No deaths were reported in guinea pigs

exposed to 12 ppm 1,2-dibromo-3-chloropropane for 13 weeks (Torkelson et al.

1961). 
9 

2. HEALTH EFFECTS 

During a chronic-duration exposure experiment, a significant increase in

mortality from cancer occurred in both sexes of Fischer 344 rats and in female

B6C3Fl mice intermittently exposed to 3 ppm 1,2-dibromo-3-chloropropane. The

surviving animals were killed after 76-84 weeks of exposure. However, it

should be noted that the survival of male mice was low in all groups,

including the control group (NTP 1982). 

The LC50 values, the highest NOAEL values, and all reliable LOAEL values

in each species and duration category are recorded in Table 2-1 and plotted in

Figure 2-l. 

2.2.1.2 Systemic Effects 

The systemic effects of 1,2-dibromo-3-chloropropane following inhalation

exposure are discussed below. No studies were located regarding

musculoskeletal effects of 1,2-dibromo-3-chloropropane in humans or animals

after inhalation exposure. The highest NOAEL values and all reliable LOAEL

values for each effect in each species and duration category are recorded in

Table 2-l and plotted in Figure 2-l. 

Respiratory Effects. No studies were located regarding respiratory

effects in humans after inhalation exposure to 1,2-dibromo-3-chloropropane. 

Studies in animals demonstrate that 1,2-dibromo-3-chloropropane affects

the respiratory system. Pulmonary irritation was reported in rats after an

acute (l-7 hours) exposure to 60 ppm or more 1,2-dibromo-3-chloropropane

(Torkelson et al. 1961). Bronchial and bronchiolar epithelial cytomegalosis

and focal necrosis were observed in rats continuously exposed to 10 ppm for

2 weeks (Saegusa et al. 1982). Pathological changes (emphysema and

bronchopneumonia) were seen in lungs of rats exposed to 10 ppm or more

1,2-dibromo-3-chloropropane for 7 hours/day, 5 days/week, for lo-12 weeks

(Torkelson et al. 1961). Cytomegaly and hyperplasia were found in the nasal

cavity in rats exposed to 1 ppm and mice exposed to 5 ppm 1,2-dibromo-3­

chloropropane for 6 hours/day, 5 days/week, for 13 weeks (NTP 1982; Reznik et

al. 1980a). In addition, rats and mice exposed to 25 ppm had more severe

respiratory effects, including inflammatory and proliferative changes in the

nasal cavity, necrosis of the trachea, and necrosis or metaplasia of the

bronchial epithelium. Nonneoplastic changes (hyperplasia) were found in the

respiratory system of rats and mice after intermittent chronic-duration

exposure to 0.6 ppm or 3 ppm. In addition, neoplasms of the respiratory tract

also occurred in both species (NTP 1982) (Section 2.2.1.8). 

Cardiovascular Effects. No conclusive evidence was located to indicate 

that inhalation exposure to 1,2-dibromo-3-chloropropane causes cardiovascular

effects in humans. Although higher mortality from arteriosclerotic heart

disease was observed in workers in the production of trimethylene

chlorobromide where 1,2-dibromo-3-chloropropane was a potential trace 












22 

2. HEALTH EFFECTS 

contaminant (Wong et al. 1984). It is not possible to conclude from this

information that 1,2-dibromo-3-chloropropane exposure is associated with heart

disease in humans. 

The effect of 1,2-dibromo-3-chloropropane on the heart has been tested

in a few animal studies. Continuous exposure of rats to 10 ppm 1,2-dibromo-3-

chloropropane did not result in cardiac lesions (Saegusa et al. 1982). No

histopathological changes were observed in hearts of rats or rabbits following

intermittent exposure to 10 ppm or less for 14 weeks (Rao et al. 1982), in

rats or mice intermittently exposed to 25 ppm for 13 weeks, or in rats or mice

intermittently exposed to 3 ppm or less for up to 103 weeks (NTP 1982). 

Gastrointestinal Effects. No studies were located regarding

gastrointestinal effects in humans after inhalation exposure to 1,2-dibromo-3-

chloropropane. 

Unspecified lesions in the intestinal mucosa were reported in rats after 

exposure to ≥10ppm 1,2-dibromo-3-chloropropane for 7 hours/day, 5 days/week,

for 10 weeks (Torkelson et al. 1961), but no gastrointestinal lesions were

reported in rats or mice exposed to 25 ppm or less for 6 hours/day,

5 days/week, for 13 weeks (NTP 1982). In a chronic-duration study, however,

epithelial hyperplasia and hyperkeratosis were found in the stomachs of rats

exposed to 3.0 ppm and in mice exposed to 0.6 ppm for 6 hours/day,

5 days/week, for 80-107 weeks (NTP 1982). 

Hematological Effects. No hematological effects were found in workers

at a pesticide factory who were exposed to 1,2-dibromo-3-chloropropane

(Whorton et al. 1977). Airborne concentrations, measured by personal airsampling

devices at the time of the study, were approximately 0.4 ppm

(averaged for an 8-hour day); however, airborne levels prior to the study were

not presented. 

Splenic atrophy was observed in rats exposed continuously to 10 ppm 1,2-

dibromo-3-chloropropane for 2 weeks, but only on the 1st day after the

exposure was terminated. No changes were observed after a 16-day recovery

period (Saegusa et al. 1982). A significant increase in neutrophil count and

a significant decrease in white blood cell count were seen in rats

intermittently exposed to 12 or 20 ppm, respectively, for 10-12 weeks

(Torkelson et al. 1961); however, concurrent pneumonia in the rats may have

influenced this outcome. No hematological changes were found in rats or

rabbits intermittently exposed to 10 ppm 1,2-dibromo-3-chloropropane for up to

14 weeks (Rao et al. 1982, 1983; Torkelson et al. 1961). Aplastic anemia and

leukopenia were found in two monkeys intermittently exposed to 12 ppm for

10 weeks; this condition was attributed to severe infections, to which the

animals were rendered more susceptible by 1,2-dibromo-3-chloropropane exposure

(Torkelson et al. 1961). Furthermore, rats intermittently exposed to 25 ppm

for 13 weeks had hypocellularity of the bone marrow. No changes in formed 
23
 

2. HEALTH EFFECTS 

elements of the blood were reported in rats or mice after a chronic

intermittent exposure to 3 ppm 1,2-dibromo-3-chloropropane. Splenic atrophy

was found in mice but not in rats (NTP 1982). 

Hepatic Effects. No studies were located regarding hepatic effects of

1,2-dibromo-3-chloropropane in humans after inhalation exposure. 

1,2-Dibromo-3-chloropropane appears to produce minor hepatic effects in

animals. No histopathological changes were reported in livers of rabbits or

rats after intermittent exposure to 10 ppm 1,2-dibromo-3-chloropropane for

14 weeks (Rao et al. 1982, 1983). Hydropic changes in hepatocytes were

observed in rats intermittently exposed to 1 or 5 ppm 1,2-dibromo3-chloropropane for 13 weeks, while focal necrosis of the liver together with

hepatic regenerative changes was seen in the 25-ppm exposure group (NTP 1982).

In contrast, hydropic changes in hepatocytes were observed only in the highest

(25 ppm) exposure group in mice (NTP 1982). Sinusoidal dilatation and other

unspecified lesions were reported in the livers of rats intermittently exposed

to 10 or 12 ppm 1,2-dibromo-3-chloropropane for lo-12 weeks (Torkelson et al.

1961). Fatty metamorphosis of livers was found in guinea pigs exposed to

12 ppm for the same duration. There were no statistically significant

differences between changes found in the livers of rats or mice chronically

exposed to 1,2-dibromo-3-chloropropane concentrations as high as 3 ppm and

those found in their matching controls (NTP 1982). 

Renal Effects. Urinalysis parameters were within normal limits in

workers exposed occupationally to 1,2-dibromo-3-chloropropane (Whorton et al.

1977). The average airborne concentration, measured by personal air-sampling

devices at the time of the study, was approximately 0.4 ppm (averaged for an

8-hour day); however, airborne levels prior to the study were not presented.

No other studies were located regarding renal effects in humans after

inhalation exposure to 1,2-dibromo-3-chloropropane. 

The kidney is a target organ of 1,2-dibromo-3-chloropropane in animals.

Permanent scarring of the kidneys was observed in rats exposed to 50 ppm or

more 1,2-dibromo-3-chloropropane for several hours (Torkelson et al. 1961).

Necrotic changes in the proximal tubules were found in rats exposed

continuously to 10 ppm 1,2-dibromo-3-chloropropane for 2 weeks (Saegusa et al,

1982). 

Nephritis and lesions of the kidneys (cloudy swelling in epithelial

cells of the proximal tubules and an increase of interstitial tissue) were

observed in rats after intermittent exposure to 12 or 20 ppm 1,2-dibromo3-chloropropane for 10-12 weeks (Torkelson et al. 1961). Epithelial

hyperplasia in tubules and nephrotic changes were found in the 1-ppm exposure

group of rats and in the 25-ppm exposure group of mice after 13 weeks (NTP

1982). No renal histopathological changes or changes in urinalysis parameters

were detected in rats and rabbits after an intermediate-duration intermittent 
24
 

2. HEALTH EFFECTS 

exposure to 10 ppm 1,2-dibromo-3-chloropropane (Rao et al. 1982, 1983). The

apparent discrepancy in concentrations resulting in renal lesions in rats is

possibly attributable to strain differences. NTP (1982) used Fischer 344

rats, while Rao et al. (1983) used Sprague-Dawley rats. 

Tubular cell hyperplasia at 0.6 ppm and toxic tubular nephropathy at

3 ppm were found in both rats and mice after intermittent chronic inhalation

exposure to 1,2-dibromo-3-chloropropane (NTP 1982). 

Dermal/Ocular Effects. No studies were located regarding dermal/ocular

effects of 1,2-dibromo-3-chloropropane in humans after inhalation exposure. 

At relatively high concentrations, exposure to the vapors of

1,2-dibromo-3-chloropropane causes eye irritation. This is probably due to

direct contact of the vapor with the eyes rather than an ocular cytotoxic

effect of inhaled vapor. Eye irritation was reported in rats exposed to

60 ppm or more 1,2-dibromo-3-chloropropane for several hours (Torkelson et al.

1961). Clouding of the cornea and lens also occurred in rats during an

intermediate-duration exposure to 20 ppm (Torkelson et al. 1961). No

histopathological dermal or ocular changes were found in rats or mice after

chronic-duration exposure to 3 ppm 1,2-dibromo-3-chloropropane (NTP 1982). 

Other Systemic Effects. Adrenal necrosis, body weight loss, and hair

loss were reported in Fischer 344 rats after an intermittent 13-week exposure

to 25 ppm 1,2-dibromo-3-chloropropane. These effects were not noted after

exposure to 5 ppm (NTP 1982). Adrenal cortical necrosis was also seen in

female Sprague-Dawley rats after intermittent exposure to 1 ppm (but not

0.1 ppm) for 14 weeks (Rao et al. 1983). 

Decreased weight gain was found in mice after intermittent exposure to

1 ppm for 13 weeks. Decreased weight gain was also reported in rats and mice

after intermittent chronic exposure to 3 ppm (but not 0.6 ppm) 1,2-dibromo3-chloropropane (NTP 1982). 

2.2.1.3 Immunological Effects 

No studies were located regarding immunological effects of 1,2-dibromo3-chloropropane in humans after inhalation exposure. 

Several intermediate-duration studies suggest that 1,2-dibromo3-chloropropane has immunological effects in animals. Hypocellularity of the

bone marrow was observed in rats intermittently exposed to 25 ppm for 13 weeks

(NTP 1982). Severe lung infections were found in rabbits (Rao et al 1982),

rats, and monkeys (Torkelson et al. 1961) intermittently exposed for up to

14 weeks. The hypocellularity of bone marrow may represent decreased

granulopoiesis, and the presence of infection in the exposed animals (but not

in control or animals exposed to lower concentrations) suggests that exposure 
25
 

2. HEALTH EFFECTS 

to 1,2-dibromo-3-chloropropane caused a decreased resistance to disease. The

highest NOAEL values and all reliable LOAEL values for immunological effects

in each species for the intermediate-duration category are recorded in

Table 2-1 and plotted in Figure 2-1. 

2.2.1.4 Neurological Effects 

Information regarding neurological effects in humans after inhalation

exposure to 1,2-dibromo-3-chloropropane is limited. Subjective neurological

symptoms such as headache, nausea, lightheadedness, and weakness were reported

by workers occupationally exposed to 1,2-dibromo-3-chloropropane (Whorton et

al. 1977). The average airborne concentration, measured by personal airsampling

devices at the time of the study, was approximately 0.4 ppm (averaged

for an 8-hour day); however, airborne levels prior to the study were not

presented. 

Neurological effects have been observed in animals exposed to

1,2-dibromo-3-chloropropane by inhalation. Depression of the central nervous

system, expressed by apathy, sluggishness, and ataxia, was observed in rats

exposed to 60 ppm or more 1,2-dibromo-3-chloropropane for several hours, but

complete narcosis was not achieved (Torkelson et al. 1961). Rats

intermittently exposed to 10 ppm 1,2-dibromo-3-chloropropane for 14 weeks had

focal mineralized deposits in the brain (Rao et al. 1983). In contrast, no

histopathological changes were found in the brains of rabbits under the same

exposure conditions (Rao et al. 1982). Meningoencephalitis was reported in

rats after intermittent intermediate-duration exposure to 25 ppm 1,2-dibromo3-chloropropane; no such effect was reported in mice (NTP 1982). Cerebral

necrosis was observed in rats after an intermittent chronic exposure to 3 ppm

1,2-dibromo-3-chloropropane, but not in mice. 

The highest NOAEL values and all reliable LOAEL values for neurological

effects in each species and duration category are recorded in Table 2-1 and

plotted in Figure 2-1. 

2.2.1.5 Developmental Effects 

No increase in gross congenital malformations and no cytogenetic

abnormalities were found in a cohort of 34 children conceived during or after

paternal exposure to 1,2-dibromo-3-chloropropane, as compared with the control

group that was conceived before the exposure (Goldsmith et al. 1984; Potashnik

and Abeliovich 1985; Potashnik and Phillip 1988). Exposure levels were not

specified in these reports. 

No studies were located regarding developmental effects of 1,2-dibromo3-chloropropane in animals after inhalation exposure. 
26
 

2. HEALTH EFFECTS 

2.2.1.6 Reproductive Effects 

The toxicity of 1,2-dibromo-3-chloropropane to the human male

reproductive system has been assessed in cohorts of occupationally exposed

factory workers (Cortes-Gallegos et al. 1980; Egnatz et al. 1980; Lipshultz et

al. 1980; Potashnik et al. 1978; Scharnweber 1979; Whorton et al. 1977, 1979)

and in cohorts of farmers or pesticide applicators (Glass et al. 1979;

Sandifer et al. 1979; Takahashi et al. 1981). An epidemiological approach to

the assessment of occupationally linked sperm count reduction was considered

in some reports (Milby and Whorton 1980; Levine et al. 1981). Follow-up

studies were performed in some of the original cohorts (Eaton et al. 1986;

Lantz et al. 1981; Olsen et al. 1990; Potashnik 1983; Potashnik and YanaiInbar 1987; Schenker et al. 1988). Changes in sperm counts ranging from

oligospermia (deficient or low sperm levels) to azoospermia (absences of

sperm) were found among exposed workers. Histopathological changes observed

after testicular biopsy revealed atrophy of the seminiferous epithelium (Biava

et al. 1978; Potashnik et al. 1978) or tubular hyalinization with sparsity of

germ cells; in some tubules, only Sertoli cells persisted (Lantz et al. 1981).

Histopathological changes in testes were associated with elevated plasma

levels of luteinizing hormone (IX) (Cortes-Gallegos et al. 1980) and follicle

stimulating hormone (FSH) (Eaton et al. 1986; Lantz et al. 1981; Potashnik et

al. 1978). Furthermore, decreased testicular size tended to be associated

with lower sperm counts (Egnatz et al. 1980; Lantz et al. 1981; Olsen et al.

1990). In individuals whose sperm counts returned to normal, testicular

atrophy was also found to be reversible (Olsen et al. 1990). 

Those men who showed decreased spermatogenesis with normal FSH levels

showed greater recovery of spermatogenesis during an 8-year postexposure

recovery period than men whose FSH and/or LH levels were elevated throughout

the 8-year period (Potashnik 1983; Potashnik and Yanai-Inbar 1987). The

results suggest that 1,2-dibromo-3-chloropropane-induced sterility can persist

for at least 8 years (Eaton et al. 1986; Potashnik 1983). 

A standardized fertility ratio for the period when workers were exposed

was depressed compared with the period prior to exposure (Levine et al. 1981). 

The changes in sperm count appear to be associated with workplace

airborne concentrations of less than 1 ppm of 1,2-dibromo-3-chloropropane

(Whorton et al. 1977, 1979). A correlation was found between the severity of

testicular effects and the length of exposure calculated either in years

(Whorton et al. 1979) or in hours of direct 1,2-dibromo-3-chloropropane

exposure (Potashnik et al. 1978). Lack of spermatogenesis recovery was found

to be job (e.g., exposure) and possibly, age related (Olsen et al. 1990). In

contrast, cross-sectional (Coye et al. 1983) and longitudinal (Coye et al.

1990) studies in pineapple workers who were exposed to lower levels of

1,2-dibromo-3-chloropropane (around 1 ppb) did not find any effects on sperm

counts. The exposure levels were not clearly defined in any of the human

studies. This was because either the historical data regarding workplace 
27 

2. HEALTH EFFECTS 

levels were lacking or, in the case of pineapple workers, exposure levels were

so low that they were undetectable in some samples. Furthermore, most human

studies were conducted in small cohorts with a low participation of exposed

individuals. 

Effects on the male reproductive system have also been found in animals.

Atrophy of seminiferous tubules was found in rats continuously exposed to 3 or

8 ppm 1,2-dibromo-3-chloropropane for 2 weeks; no changes were found after

exposure to 1 ppm (Saegusa et al. 1982). 

Testicular atrophy was observed in rats intermittently exposed to 10 ppm

1,2-dibromo-3-chloropropane for 10 weeks (Torkelson et al. 1961). At 5 ppm,

epithelial changes in the testes were observed. Testicular atrophy with

hypospermatogenesis was also observed in rats intermittently exposed to 25 ppm

1,2-dibromo-3-chloropropane for 13 weeks; no changes were reported after 5 ppm

exposure to 5 ppm (NTP 1982). Testicular atrophy and ovarian cysts, probably

follicular in origin, were found in rats intermittently exposed to 10 ppm for

14 weeks (Rao et al. 1983). Dominant lethality was observed when the exposed

males were mated with unexposed females but returned to normal after the

recovery period. No changes in fertility were found in exposed females. No

reproductive effects were seen in either sex after 1 ppm exposure. Increased

serum FSH levels together with testicular atrophy were seen in rabbits

intermittently exposed to 1 and 10 ppm 1,2-dibromo-3-chloropropane for 8-14

weeks (Rao et al. 1982). The changes after exposure to 1 ppm were reversible.

No evidence of gonadotoxicity was found in rabbits exposed to 0.1 ppm. Based

on this value, an intermediate inhalation MRL of 0.0002 ppm was calculated as

described in the footnote in Table 2-l. Rabbit data were used to calculate 

the MRL value because this species appears to be more sensitive to the

reproductive effects of 1,2-dibromo-3-chloropropane than rats. 

The highest NOAEL values and all reliable LOAEL values for reproductive

effects in each species and duration category are recorded in Table 2-l and

plotted in Figure 2-l. 

2.2.1.7 Genotoxic Effects 

A predominance of the female sex among the offspring of male workers

occupationally exposed to 1,2-dibromo-3-chloropropane was reported in one

epidemiological study. In the cohort studied, 52.9% male infants were born

during the pre-exposure period, while 35.2% males were born during the

exposure. When the group with paternal azoospermia and oligospermia was

evaluated separately, the percentage of newborn boys was only 16.6. The

change in sex ratio indicates the lower fertility potential of sperm bearing

the Y-chromosome (Goldsmith et al. 1984; Potashnik et al. 1984). 

Dominant lethality was observed after an intermediate-duration exposure

of male rats to 10 ppm 1,2-dibromo-3-chloropropane, but it was reversed after 
28
 

2. HEALTH EFFECTS 

a recovery period (Rao et al. 1983). This implies that male fertility, and in

particular, spermatids, may be affected. 

Other genotoxicity studies are discussed in Section 2.4. 

2.2.1.8 Cancer 

In an epidemiological study of workers exposed to 1,2-dibromo3-chloropropane, no increase in the incidence of mortality from cancer of the

lungs, stomach, liver, kidney, testes, or skin was found. The workers were

exposed to airborne concentrations lower than 1 ppm 1,2-dibromo3-chloropropane during the 2 years preceding the study, but the exposure

levels in previous years were not known (Hearn et al. 1984). 

When rats were exposed by inhalation (6 hours/day, 5 days/week, for

84-103 weeks) to 0.6 or 3 ppm 1,2-dibromo-3-chloropropane, multiple-site

tumors developed. The most common were carcinomas and squamous cell

carcinomas of the nasal cavity (squamous cell papilloma, adenocarcinoma, and

adenomatous polyps also observed) and squamous cell papillomas of the tongue

in both sexes; fibroadenomas of the mammary gland and adenomas of the adrenal

cortex in females; and trichoadenomas of the skin and mesotheliomas of the

tunica vaginalis in males. Adenomas, squamous cell carcinomas, and carcinomas

of the respiratory tract also developed in mice after intermittent chronicduration

exposure to 0.6 or 3 ppm 1,2-dibromo-3-chloropropane (NTP 1982). The

cancer effect level is recorded in Table 2-l and plotted in Figure 2-l. 

2.2.2 Oral Exposure 

2.2.2.1 Death 

No studies were located regarding death in humans after oral exposure to

1,2-dibromo-3-chloropropane. 

After a single dose of 400 mg/kg 1,2-dibromo-3-chloropropane, all

treated rats died within 24 hours. These rats were given a known lethal dose

in order to study the relationship between 1,2-dibromo-3-chloropropane-induced

hepatotoxicity and death (Kato et al. 1980). Reported LD50 values for male 

rats were 170 and 300 mg/kg (results from two independent laboratories)

(Torkelson et al. 1961). For female mice, LD50 values were reported to be 340

(Moody et al. 1984), 260, and 410 mg/kg (Torkelson et al. 1961); the latter

two values were results from two independent laboratories. Oral LD50 values 

for rabbits and guinea pigs were 180 and 210 mg/kg, respectively (Torkelson et

al. 1961). A 14-day LD50 of 205 mg/kg/day was determined in male and female

mice by probit analysis (Reel et al. 1984). 

Increased mortality was observed in female rats dosed 5 days/week by

gavage with 1,2-dibromo-3-chloropropane at 40 mg/kg/day and in mice at

251 mg/kg/day for 6 weeks. No deaths were reported in rats at 25 mg/kg/day or 
29 

2. HEALTH EFFECTS 

in mice at 160 mg/kg/day (NC1 1978). Increased mortality in rats was also

found at an equivalent dose of 67.5 mg/kg/day 1,2-dibromo-3-chloropropane that

was administered in the diet for 90 days (Torkelson et al. 1961). The cause

of death was not reported in intermediate-duration studies. In a chronic

study, mortality due to cancer was increased after treatment with 15 mg/kg/day

in rats and 110 mg/kg/day in mice (NC1 1978). The survival of rats was also

decreased because of cancer after dietary exposure to 1,2-dibromo3-chloropropane at a dose of 3 mg/kg/day for 104 weeks (Hazleton 1977, 1978a),

while no increase in mortality was found in mice that ingested 4.6 mg/kg/day

for 78 weeks (Hazleton 1978b). 

The LD50 values, the highest NOAEL values, and all reliable LOAEL values

in each species and duration category are recorded in Table 2-2 and plotted in

Figure 2-2. 

2.2.2.2 Systemic Effects

The systemic effects of 1,2-dibromo-3-chloropropane after oral exposure

are described below. The highest NOAEL values and all reliable LOAEL values

for each species and duration category are recorded in Table 2-2 and plotted

in Figure 2-2. 

Respiratory Effects. No studies were located regarding respiratory

effects in humans after oral exposure to 1,2-dibromo-3-chloropropane.

Pulmonary metastases occurred in rats chronically exposed by gavage with

15 or 29 mg/kg 1,2-dibromo-3-chloropropane and in mice gavaged with

110-219 mg/kg (NC1 1978). No treatment-related respiratory effects were found

in rats exposed to 1,2-dibromo-3-chloropropane in the diet at a dose of

3 mg/kg/day for 104 weeks (Hazleton 1977, 1978a) or in mice that ingested

4.6 mg/kg/day in the diet for 78 weeks (Hazleton 1978b). 

Cardiovascular Effects. No studies were located regarding

cardiovascular effects in humans after oral exposure to 1,2-dibromo3-chloropropane. 

No histopathological changes were found in the hearts of rats or mice

that were gavaged daily with doses as high as 29 or 219 mg/kg 1,2-dibromo3-chloropropane, respectively, for 47-78 weeks (NC1 1978). Similarly, no

changes were observed in the hearts of rats that received 3 mg/kg/day in the

diet for 104 weeks (Hazleton 1977, 1978a). 

Gastrointestinal Effects. No correlation was observed between gastric

cancer incidence in humans and the contamination of drinking water with 1,2­

dibromo-3-chloropropane (Wong et al. 1989) (also discussed in

Section 2.2.2.8). 










40
 

2. HEALTH EFFECTS
 

Gastrointestinal effects have been observed in rats treated orally with

1,2-dibromo-3-chloropropane for acute, intermediate, and chronic durations.

Cell proliferation and hyperkeratosis of the forestomach were observed in rats

after 2 weeks of treatment with 29 mg/kg/day 1,2-dibromo-3-chloropropane by

gavage; no changes were detected after treatment with 15 mg/kg/day (Ghanayem

et al. 1986). No histopathological changes were found in the gastrointestinal

tracts of rats that were maintained for 60 days on drinking water that

contained 1,2-dibromo-3-chloropropane equivalent to a dose of 19.43 mg/kg/day

(Johnston et al. 1986). Intestinal edema was reported in rats that were fed

diets containing an equivalent dose of 67.5 mg/kg/day 1,2-dibromo-3-chloropropane

for 90 days (Torkelson et al. 1961); necrosis of the gastric mucosa

was observed in rats treated by gavage with 70 mg/kg for 6 weeks

(Rakhmatullayev 1969). Acanthosis and hyperkeratosis of the stomach were

reported as nonneoplastic gastrointestinal lesions in rats after chronic

treatment with 15 mg/kg/day by gavage (NC1 1978). However, a high incidence

of gastric cancer occurred in treated animals (see discussion of Cancer in

Section 2.2.2.8). Similar findings were also observed in rats chronically

exposed to doses as low as 1 mg/kg/day (Hazleton 1977, 1978a) and in mice

chronically exposed to 4.6 mg/kg/day 1,2-dibromo-3-chloropropane in their diet

(Hazleton 1978b). 

Hematological Effects. Investigators who analyzed the frequency of

leukemia in a population in Fresno County, California, where the drinking

water supply was contaminated with 1,2-dibromo-3-chloropropane, found no

increase in leukemia incidence (Wong et al. 1989). Levels in the drinking

water ranged from 0.004 to 5.75 ppb during 1978-1982. 

Limited information suggests that 1,2-dibromo-3-chloropropane induces

adverse hematological effects in rats after high-level oral exposure.

Decreased hemoglobin concentration and erythrocyte and leukocyte counts were

reported in rats after gavage with 70 mg/kg/day for 6 weeks (Rakhmatullayev

1969). Decreased reticulocytes and leukocytes were reported at doses as low

as 0.5 mg/kg/day after 8 months of exposure of rats to 1,2-dibromo-3­

chloropropane (Rakhmatullaev 1971). At 5 mg/kg/day hemoglobin and red blood

cell count were also decreased. However, interpretation of this study is

limited because data supporting these conclusions was not presented. No

hematological changes were found in rats or mice after a chronic exposure to

29 or 219 mg/kg/day, respectively (NCI 1978). Furthermore, no hematological

effects were reported in rats (Hazleton 1977, 1978a) or mice (Hazleton 1978b)

chronically exposed to 3 or 4.6 mg/kg/day 1,2-dibromo-3-chloropropane,

respectively, in the diet. 

Musculoskeletal Effects. No studies were located regarding

musculoskeletal effects in humans after oral exposure to 1,2-dibromo3-chloropropane. 
41 

2. HEALTH EFFECTS 

No histopathological changes in skeletal muscle were found in rats

chronically exposed to 29 mg/kg/day 1,2-dibromo-3-chloropropane or in mice

exposed to 219 mg/kg/day (NC1 1978). Similarly, no changes were observed in

rats chronically exposed to 3 mg/kg/day 1,2-dibromo-3-chloropropane (Hazleton

1977, 1978a). 

Hepatic Effects. No studies were located regarding hepatic effects in

humans after oral exposure to 1,2-dibromo-3-chloropropane. 

Degeneration and focal necrosis of centrilobular hepatocytes were

observed in rats that died within 24 hours after a single gavage dose of

400 mg/kg 1,2-dibromo-3-chloropropane (Kato et al. 1980). The rats in this

study were deliberately given a lethal dose so that the relationship between

hepatotoxicity and death could be studied. Mild periportal hepatocellular

swelling and increased cytoplasmic basophilia were noted in male rats

following gavage with 40 mg/kg/day 1,2-dibromo-3-chloropropane for 4 days

(Kluwe 1981). This study is limited because only one dose was tested. No

histopathological changes were found in livers of rats after intermediateduration

oral exposure to drinking water that delivered 19.45 mg/kg/day 1,2­

dibromo-3-chloropropane (Johnston et al. 1986), or to diets that delivered

67.5 mg/kg/day (Torkelson et al. 1961). Also, there were no effects on enzyme

markers for hepatic toxicity (serum glutamic-oxaloacetic transaminase [SGOT],

serum glutamic-pyruvic transaminase [SGPT], sorbitan dehydrogenase) in male

rats that were exposed to 0.4-9.7 mg/kg/day 1,2-dibromo-3-chloropropane in

drinking water for 64 days (ad libitum) (Heindel et al. 1989). In contrast,

necrosis and cirrhosis were found in livers of rats treated by gavage with

70 mg/kg/day for 6 weeks (Rakhmatullayev 1969). Hepatic toxicity was reported

to have been manifested as increased prothrombin time, decreased urea, and

increased coproporphyrin in the urine of rats after gavage with 0.5 mg/kg/day

1,2-dibromo-3-chloropropane for 8 months in a poorly documented study by

Rakhmatullaev (1971). The absence of liver effects in the rats that were

administered a similar dose in the diet may reflect the different modes of

administration, that is, diet versus bolus, and the resulting differences in

absorption kinetics. No statistically significant changes were reported in

livers of rats or mice chronically gavaged with doses as high as 29 or 219

mg/kg/day, respectively (NC1 1978). In contrast, a dose-related increased

incidence of poliosis hepatitis was found in rats that ingested 0.3 mg/kg/day

or more 1,2-dibromo-3-chloropropane for 104 weeks (Hazleton 1977, 1978a). No

such changes were reported in matching controls. No hepatic changes were

reported in mice exposed chronically to 4.6 mg/kg/day 1,2-dibromo-3-chloropropane

(Hazleton 1978b). 

Renal Effects. No studies were located regarding renal effects in

humans after oral exposure to 1,2-dibromo-3-chloropropane. 

The kidney is a target organ of 1,2-dibromo-3-chloropropane in

experimental animals. Renal effects have been observed in studies of acute, 
42 

2. HEALTH EFFECTS 

intermediate, and chronic durations. Degeneration of renal tubules was found

in rats that died after treatment with a single dose of 400 mg/kg 1,2-dibromo3-chloropropane (Kato et al. 1980). Acute renal insufficiency with tubular

necrosis was reported in rats after a single dose of 200 mg/kg 1,2-dibromo3-chloropropane (Russell 1989). The insufficiency reversed with time, but 

focal glomerulosclerosis persisted 28 weeks postexposure. Increased blood

urea nitrogen levels, decreased urine specific gravity, increased kidney

weight to brain weight ratio, proximal kidney tubule necrosis, and increased

basophilia were noted in male rats following gavage with 40 mg/kg/day

1,2-dibromo-3-chloropropane for 4 days (Kluwe 1981). This study is limited

because only one dose was tested. 

While no histopathological changes were found in kidneys of rats after

intermediate-duration ingestion of as much as 19.45 mg/kg/day 1,2-dibromo3-chloropropane in drinking water (Johnston et al. 1986) or 67.5 mg/kg/day

1,2-dibromo-3-chloropropane in the diet (Torkelson et al. 1961), necrosis and

signs of regeneration were found in rats after gavage treatment with

70 mg/kg/day for 6 weeks (Rakhmatullayev 1969). The difference in response

between rats treated by gavage and rats exposed in the diet to an equivalent

dose is probably a function of the dosing regimen mode and consequent

differences in absorption kinetics. There was no effect on blood urea

nitrogen levels, but there was a slight increase in the number of cells in the

proximal convoluted tubules was noted at doses of 5.4-9.7 mg/kg/day

1,2-dibromo-3-chloropropane given in drinking water for 64 days (Heindel et

al. 1989). Although the increased number of cells was not significant, this

effect may be an indication of increased turnover of proximal tubular cells.

Toxic nephropathy was observed in rats and mice chronically exposed by gavage

with doses as low as 15 or 110 mg/kg/day, respectively (NC1 1978). Tubular

epithelial hyperplasia and megalocytosis were found in the kidneys of rats

chronically treated with 3 mg/kg/day 1,2-dibromo-3-chloropropane in the diet,

while no changes were reported in rats exposed to 1 mg/kg/day (Hazleton 1977,

1978a). In contrast, no renal effects were found in mice chronically treated

with 4.6 mg/kg/day (Hazleton 1978b). 

Dermal/Ocular Effects. No studies were located regarding dermal/ocular

effects in humans after oral exposure to 1,2-dibromo-3-chloropropane. 

No histopathological changes were found in the skin or eyes of rats or

mice chronically gavaged with as much as 29 or 219 mg/kg/day 1,2-dibromo3-chloropropane, respectively (NC1 1978). Similarly, no changes were found in

rats chronically exposed to 3 mg/kg/day by ingestion (Hazleton 1977, 1978a). 

Other Systemic Effects. Depressed growth occurred when rats were given

1,2-dibromo-3-chloropropane in drinking water at 19.43 mg/kg/day for 60 days

(Johnston et al. 1986) or 9.7 mg/kg/day for 64 days (Heindel et al. 1989), in

the diet at 7.5 mg/kg/day -for 90 days (Torkelson et al. 1961), or by gavage at

3.75 mg/kg/day for 77 days (Amann and Berndtson 1986) or 15 mg/kg/day for 
43
 

2. HEALTH EFFECTS
 

64-78 weeks (NC1 1978). Although no effect on body weight was seen in rabbits

given 15 mg/kg/day 1,2-dibromo-3-chloropropane by gavage for 10 weeks (Foote

et al. 1986b), or in mice given up to 631 mg/kg/day by gavage for 6 weeks (NC1

1978) or up to 219 mg/kg/day by gavage for 47-60 weeks (Hazleton 1978b; NC1

1978), decreased body weight gain was a consistent finding in rats. Decreased

body weight gain was observed in male rats exposed to 3 mg/kg/day for

104 weeks but not in rats exposed to 1 mg/kg/day (Hazleton 1977, 1978a). The

reduced body weight gain after dietary or drinking water exposure to 1,2-

dibromo-3-chloropropane was probably the result of decreased food or water

consumption due to taste aversion. 

2.2.2.3 Immunological Effects 

No studies were located regarding immunological effects in humans after

oral exposure to 1,2-dibromo-3-chloropropane. 

An impaired ability of neutrophils to phagocytize bacteria was reported

following gavage administration of 0.05 mg/kg/day of 1,2-dibromo-3-

chloropropane to rats for 8 months in a poorly documented study by

Rakhmatullaev (1971). However, no abnormalities were observed after

histological evaluation of bone marrow, mesenteric lymph nodes, or spleens

from rats chronically given 3 mg/kg/day 1,2-dibromo-3-chloropropane in their

diet (Hazleton 1977, 1978a). This value is recorded as the NOAEL level for

immunological effects after oral exposure in Table 2-2 and plotted in

Figure 2-2. 

2.2.2.4 Neurological Effects 

No studies were located regarding neurological effects in humans after

oral exposure to 1,2-dibromo-3-chloropropane. 

Lethargy, ptosis, ataxia, and convulsions were among the signs in mice

that died after administration of 130 mg/kg/day 1,2-dibromo-3-chloropropane

for 2 weeks (Reel et al. 1984). Decreased activity was observed in rats

during dietary exposure to 67.5 mg/kg/day 1,2-dibromo-3-chloropropane for

90 days (Torkelson et al. 1961). Impaired acquisition of conditioned reflexes

by rats receiving gavage doses of 1,2-dibromo-3-chloropropane as low as

0.05 mg/kg/day for 8 months was reported (Rakhmatullaev 1971). However, no

data were presented to support this conclusion. Histological examination of

brain and spinal cord tissues in other studies failed to reveal any structural

lesions (Hazleton 1977, 1978a; Johnston et al. 1986; NC1 1978). 

The highest NOAEL values and all reliable LOAEL values for neurological

effects in each species and duration category are recorded in Tab,le 2-2 and

plotted in Figure 2-2. 
44
 

2. HEALTH EFFECTS 

2.2.2.5 Developmental Effects 

No correlation between low birth weights or birth defects and

1,2-dibromo-3-chloropropane contamination of drinking water was found in a

population exposed in Fresno County, California, during 1978-1982 (Whorton et

al. 1989). Potential exposure concentrations of 1,2-dibromo-3-chloropropane

in the water system ranged from 1~10-~to 1.6x10m4mg/kg/day. 

Developmental effects of 1,2-dibromo-3-chloropropane in animals have

been seen only in the presence of maternal toxicity. No teratogenicity was

observed in rats after dams were treated with doses up to 50 mg/kg/day

1,2-dibromo-3-chloropropane during gestation, but an increase in embryonic

lethality occurred in the highest dose group (Ruddick and Newsome 1979).

Maternal toxicity was manifested as severely decreased body weight gain. A

statistically significant decrease in average litter weight was found after

parental treatment for 60 days with 19.45 mg/kg/day 1,2-dibromo-3-chloropropane

in drinking water (Johnston et al. 1986). The dams had decreased bc

weight gain during pregnancy. 

The highest NOAEL values and reliable LOAEL values for developmental

effects in rats in each duration category are recorded in Table 2-2 and

plotted in Figure 2-2. 

2.2.2.6 Reproductive Effects 

No change in birth ratios was found in a population of Fresno County,

California, during the years 1978-1982 when the drinking water system was

contaminated with 1,2-dibromo-3-chloropropane at concentrations ranging from

0.004 to 5.75 ppb (Wong et al. 1988). 

1,2-Dibromo-3-chloropropane is a reproductive toxicant in male rats and

rabbits. Increased postimplantation loss, as a result of genetic damage to

sperm, was observed in rats after males were treated for 15 days with 10

mg/kg/day and mated to nonexposed females (Teramoto et al. 1980). The peak

incidence was observed after mating during weeks 4-5 postexposure, which

suggests that the spermatids were the most likely target. In contrast, no

increase in postimplantation loss was observed in mice after the treatment of

males with 150 mg/kg/day for 5 days. 

Histological examination revealed destruction of the architecture of the

seminiferous tubules, severe degenerative changes and sloughing into the

tubular lumen of the epididymis, and lowered sperm density in male rats

following gavage with 40 mg/kg/day 1,2-dibromo-3-chloropropane for 4 days

(Kluwe 1981). This study is limited because only one dose was tested. There

was no significant change in testes weight, relative to body weight and no

there were no effects on sperm count; levels of LH, FSH, or testicular

testosterone in serum; histopathology of the seminiferous tubules; or

spermatozoa1 development in male rats that were exposed to 0.4-9.7 mg/kg/day 
45
 

2. HEALTH EFFECTS
 

1,2-dibromo-3-chloropropane in drinking water for 64 days (ad libitum)

(Heindel et al. 1989). Histological evaluation of the testes from rats

gavaged with 15 mg/kg/day 1,2-dibromo-3-chloropropane for 77 days revealed a

reduced ratio of leptotene spermatocytes to Sertoli cells and reduced diameter

of seminiferous tubules; this is evidence of reduced production of sperm.

There was an increased incidence of dead embryos when the exposed males were

allowed to mate with unexposed females during the last days of exposure (Amann

and Berndtson 1986). Testicular necrosis was observed in rats after gavage

dosing with 70 mg/kg/day for 6 weeks (Rakhmatullayev 1969). Decreased

generative function (possibly referring to spermatogenesis or fertility) was

reported at doses as low as 0.05 mg/kg/day in rats given gavage doses of 1,2-

dibromo-3-chloropropane for 8 months (Rakhmatullaev 1971). At 0.5 mg/kg/day,

pathomorphology (unspecified) and decreased fertility were observed, and at

the highest dose tested, 5 mg/kg/day, decreased sperm motility and complete

infertility were observed. This study is limited in that no data were

presented to support these conclusions. No changes in fertility, gestation,

or survival, however, were observed in rats when both males and females

consumed up to 19.45 mg/kg/day 1,2-dibromo-3-chloropropane in drinking water

for 60 days and were then allowed to mate (Johnston et al. 1986). 

Dose-related adverse reproductive effects were reported in rabbits given

1,2-dibromo-3-chloropropane in drinking water for 10 weeks (Foote et al.

1986a, 1986b). Abnormalities in sperm morphology were observed after

treatment with 1.88 mg/kg/day or more in the drinking water for 10 weeks

(Foote et al. 1986b). Testicular atrophy occurred after exposure to

15 mg/kg/day. Increases in serum FSH levels, which are indicative of impaired

spermatogenesis, were detected after exposure to 7.50 or 15.0 mg/kg/day but

were significant only at the higher dose. Serum levels of LH and testosterone

were not affected at any dose. Fertility was not affected when the exposed

males were allowed to mate during the last week of the exposure. Decreased

spermatogenesis was also noted in rabbits following exposure to

1.88-15.0 mg/kg/day 1,2-dibromo-3-chloropropane in drinking water (Foote et

al. 1986a). The high dose also induced testicular atrophy in this study. A

NOAEL of 0.94 mg/kg/day was not derived from this study because the data

suggest that decreased spermatogenesis may occur at this dose. 

Reproductive toxicity expressed as a reduction of number of litters was

also observed after male and female mice were treated with 25 mg/kg/day

1,2-dibromo-3-chloropropane for 128 days (Reel et al. 1984). Complete

azoospermia without recovery developed in monkeys within 45 days of

1,2-dibromo-3-chloropropane treatment. The initial concentration of 650 ppm

in drinking water was gradually reduced to 10 ppm over 27 days (Overstreet et

al. 1988). 

Statistically significant increased incidences of testicular atrophy

were observed in rats chronically gavaged with 15 or 29 mg/kg/day as compared

with control groups. In contrast, no increase in testicular atrophy was found

in chronically dosed mice (NC1 1978). Furthermore, no testicular changes were 
46
 

2. HEALTH EFFECTS 

found in rats (Hazleton 1977, 1978a) or mice (Hazleton 1978b) chronically

exposed to 3 or 4.6 mg/kg/day 1,2-dibromo-3-chloropropane in the diet,

respectively. 

The highest NOAEL values and all reliable LOAEL values for reproductive

effects in each species and duration category are recorded in Table 2-2 and

plotted in Figure 2-2. 

2.2.2.7 Genotoxic Effect& 

No effects on sex ratios of human newborns were found in Fresno County,

California (1978-1982), where the drinking water was contaminated with

1,2-dibromo-3-chloropropane (Whorton et al. 1989). 

An increased incidence of dominant lethality was observed in rats after

5 days of paternal treatment with 10 mg/kg/day 1,2-dibromo-3-chloropropane.

In contrast, no induction of dominant lethality was observed in mice after the

treatment of males with 150 mg/kg/day for 5 days (Teramoto et al. 1980). 

Other genotoxicity studies are discussed in Section 2.4. 

2.2.2.8 Cancer 

An environmental epidemiological study did not find any correlation

between mortality rates for gastric cancer and leukemia and 1,2-dibromo3-chloropropane drinking water contamination in Fresno County, California,

during the years 1960-1983 (Wong et al. 1989). Similarly, case-control

analysis of gastric cancer and leukemia incidences revealed no correlations

with exposure. 

Increased carcinogenicity has been observed in animals that have

chronically ingested 1,2-dibromo-3-chloropropane. Multiple-site carcinomas

were found in rats chronically treated with 1,2-dibromo-3-chloropropane by

gavage (NC1 1978). An increased incidence of carcinomas, squamous cell

carcinomas, and papillomas of the forestomach was observed in rats of both

sexes treated with 15 or 29 mg/kg/day 1,2-dibromo-3-chloropropane.

Hemangiomas were detected in the spleens of both sexes treated with the lower

dose, while mammary adenocarcinomas were found in both groups of females.

Squamous cell carcinomas of the stomach were observed in mice chronically

administered 114 mg/kg/day (males) or 110 mg/kg/day (females) 1,2-dibromo3-chloropropane by gavage (NC1 1978). Increased incidences of squamous cell

carcinoma of the forestomach, hepatocellular carcinoma, and adenoma and/or

carcinoma of the kidneys were observed in rats that ingested 3 mg/kg/day 1,2-

dibromo-3-chloropropane for 104 weeks in their diet (Hazleton 1977, 1978a).

Squamous cell papillomas and carcinomas also developed in the stomachs of mice

chronically exposed to 4.6 mg/kg/day (Hazleton 1978b). Metastatic lesions of

these tumors were observed in livers, kidneys, and other viscera. The cancer

effect levels are recorded in Table 2-2 and plotted in Figure 2-2. 
47 

2. HEALTH EFFECTS 

2.2.3 Dermal Exposure 

Dermal exposure of humans to 1,2-dibromo-3-chloropropane can occur in

occupational settings. It is often difficult to clearly separate dermal from

inhalation exposures in many studies. Thus, many of the findings from

occupational studies described in Section 2.2.1 regarding inhalation exposure

are repeated here. 

2.2.3.1 Death 

No studies were located regarding death in humans after dermal exposure

to 1,2-dibromo-3-chloropropane. 

The local effects after application of 1,2-dibromo-3-chloropropane on

the skin of rabbits increased in severity over time from erythema to extensive

necrosis. The LD50 in rabbits after 1,2-dibromo-3-chloropropane application

to shaven skin for 24 hours under a rubber sleeve was 1,400 mg/kg (Torkelson

et al. 1961). This LD50 level is recorded in Table 2-3. 

2.2.3.2 Systemic Effects 

No studies were located regarding respiratory, gastrointestinal,

musculoskeletal, or hepatic effects in humans or animals after dermal exposure

to 1,2-dibromo-3-chloropropane. 

Cardiovascular Effects. No conclusive evidence was located to indicate 

that dermal exposure to 1,2-dibromo-3-chloropropane causes cardiovascular

effects in humans. Higher mortality from arteriosclerotic heart disease was

observed in workers who may have had skin contact with 1,2-dibromo-3­

chloropropane during the production of trimethylene chlorobromide (1,2­

dibromo-3-chloropropane is a potential trace contaminant of trimethylene

chlorobromide) (Wong et al. 1984). However, it is not possible to conclude

from this information that dermal 1,2-dibromo-3-chloropropane exposure is

associated with heart disease in humans. 

No studies were located regarding cardiovascular effects of 1,2-dibromo3-chloropropane in animals after dermal exposure. 

Hematological Effects. No hematological effects were found in workers

at a pesticide factory who may have had skin contact with 1,2-dibromo3-chloropropane (Whorton et al. 1977). Estimates of dermal exposure were not

presented. 

No studies were located regarding hematological effects of 1,2-dibromo3-chloropropane in animals after dermal exposure. 

49
 

2. HEALTH EFFECTS 

Renal Effects. Urinalysis parameters were within normal limits in

workers who may have had skin contact with 1,2-dibromo-3-chloropropane during

its production (Whorton et al. 1977). Estimates of dermal exposure were not

presented in this study. No other studies were located regarding renal

effects in humans after dermal exposure to 1,2-dibromo-3-chloropropane. 

No studies were located regarding renal effects of 1,2-dibromo-3­

chloropropane in animals after dermal exposure. 

Dermal/Ocular Effects. No studies were located regarding dermal/ocular

effects of 1,2-dibromo-3-chloropropane in humans after dermal exposure. 

The local effects after application of 0.5 mL 1,2-dibromo-3-chloropropane

on the skin of rabbits increased in severity over time from erythema

after 1 day of treatment to extensive necrosis of the dermis and subcutaneous

tissue after 20 days of treatment. Application of a 1% solution of 1,2­

dibromo-3-chloropropane in propylene glycol to the eyes of rabbits caused

irritation of the conjunctiva and iris (Torkelson et al. 1961). The LOAEL

values for dermal/ocular effects in rabbits in each duration category are

recorded in Table 2-3. 

No studies were located regarding the following health effects in humans

or animals after dermal exposure to 1,2-dibromo-3-chloropropane: 

2.2.3.3 Immunological Effects 

2.2.3.4 Neurological Effects 

2.2.3.5 Developmental Effects 

2.2.3.6 Reproductive Effects 

2.2.3.7 Genotoxic Effects 

Genotoxicity studies are discussed in Section 2.4. 

2.2.3.8 Cancer 

No studies were located regarding cancer in humans after dermal exposure

to 1,2-dibromo-3-chloropropane. 

Benign lung papillomas and stomach carcinomas and papillomas were found

in mice after dermal application of 390 mg/kg, 3 days/week for up to 85 weeks

(11.7 mg/mouse/day) (Van Dureen et al. 1979). 1,2-Dibromo-3-chloropropane was

also active as a skin-tumor initiator in a two-stage carcinogenicity assay.

Phorbol myristate acetate was used as a promoter. The median survival time

for mice was 342-468 days. The cancer effect level is recorded in Table 2-3. 
50
 

2. HEALTH EFFECTS 

2.3 TOXICOKINETICS 

2.3.1 Absorption 

2.3.1.1 Inhalation Exposure 

No studies were located regarding absorption by humans or animals after

inhalation exposure to 1,2-dibromo-3-chloropropane. Evidence that

1,2-dibromo-3-chloropropane can be absorbed by this route of exposure is

provided by toxicity studies (Section 2.2.1). 

2.3.1.2 Oral Exposure 

No studies were located regarding absorption by'humans after oral

exposure to 1,2-dibromo-3-chloropropane. 

Animal studies show that 1,2-dibromo-3-chloropropane is rapidly and

extensively absorbed from the gastrointestinal tract. The absorption of 1,2­

dibromo-3-chloropropane followed first-order kinetics in rats after oral

administration by gavage in a water vehicle. No dose dependence in absorption

was observed with doses up to 10 mg/kg/day 1,2-dibromo-3-chloropropane, and

peak blood levels were reached within 5-40 minutes. The rate of absorption

was slower and more erratic with the oil vehicle, but the extent of absorption

remained approximately the same (i.e., 68% with corn oil versus 78% with

water) (Gingell et al. 1987a). Absorption from the gastrointestinal tract was

99% of the originally administered dose of radiolabeled (14C)-1,2-dibromo3-chloropropane; only 0.223% radioactivity was recovered in the feces of bile

duct-cannulated rats (Kato et al. 1979a). 

2.3.1.3 Dermal Exposure 

No studies were located regarding absorption in humans or animals after

dermal exposure to 1,2-dibromo-3-chloropropane. Evidence that

1,2-dibromo-3-chloropropane can be absorbed by this route of exposure is

provided by the observation that death occurred following a 24-hour dermal

exposure to this chemical (Torkelson et al. 1961). 

2.3.2 Distribution 

2.3.2.1 Inhalation Exposure 

No studies were located regarding distribution in humans or animals

after inhalation exposure to 1,2-dibromo-3-chloropropane. 

2.3.2.2 Oral Exposure 

No studies were located regarding distribution in humans after oral

exposure to 1,2-dibromo-3-chloropropane. 
51 

2. HEALTH EFFECTS 

Following absorption in rats, 1,2-dibromo-3-chloropropane, which was

administered by corn oil gavage for 10 consecutive days to pregnant rats, was

rapidly and widely distributed to tissues and tended to remain longest in fat

(Ruddick and Newsome 1979). The concentration of 1,2-dibromo-3-chloropropane

in pooled fetuses and in spleens, brains, hearts, kidneys, and livers of dams

was highest within 3 hours of the exposure to the last dose of 1,2-dibromo3-chloropropane. The peak level in fat occurred after 6 hours, and

1,2-dibromo-3-chloropropane was still detectable after 24 hours. The

elimination of unchanged 1,2-dibromo-3-chloropropane from other tissues was

much faster. The detection in tissues of pooled fetuses provides evidence

that 1,2-dibromo-3-chloropropane crossed the placenta. 

In rats administered 14C-1,2-dibromo-3-chloropropane in corn oil by

gavage , unchanged 1,2-dibromo-3-chloropropane accumulated only in the adipose

tissues, while the unextractable metabolites were found in kidneys and livers

(Kato et al. 1979a). The unextractable metabolites were detected in most

tissues, possibly as reactive metabolites bound to tissue macromolecules. The

highest level of radioactivity was found in livers and kidneys (Kato et al.

1980) 6 and 20 hours postexposure. These are the organs where

histopathological changes were apparent (Section 2.2.2.2). 

2.3.2.3 Dermal Exposure 

No studies were located regarding distribution in humans or animals

after dermal exposure to 1,2-dibromo-3-chloropropane. 

2.3.3 Metabolism 

No studies were located regarding metabolism of 1,2-dibromo-3-chloropropane

in humans. 

The metabolism of 1,2-dibromo-3-chloropropane was studied in rats. The

proposed metabolic pathway is shown in Figure 2-3. According to this scheme,

1,2-dibromo-3-chloropropane is converted to epoxy derivatives, which are

further hydrolyzed and debrominated. Bromide accumulates in the kidneys.

Beside other metabolites, epichlorohydrin and epibromohydrin were found, which

can be further metabolized to oxalic acid. Mercapturic acids were detected in

urine and this indicates that metabolic intermediates reacted with nonprotein

sulfhydryl (NPS) groups (Jones et al. 1979). 

Conjugation of the epoxide intermediates with NPS groups can occur in

the liver, kidneys, lungs, stomach, and testes of rats after treatment with

2,3-dibromo-3-chloropropane (Kato et al. 1980; Kluwe et al. 1981, 1982). The

greater depletion of hepatic NPS suggests that the liver is the major site of

glutathione (GSH) conjugation with 1,2-dibromo-3-chloropropane metabolites

(Kluwe et al. 1982). GSH pretreatment protected rats from 1,2-dibromo3-chloropropane-induced liver necrosis (Kato et al. 1980), indicating that

conjugation is a detoxifying mechanism in the liver. 

53
 

2. HEALTH EFFECTS
 

GSH levels were depleted in the liver and kidney, but not in the testes,

after intraperitoneal administration of 1,2-dibromo-3-chloropropane in rats

(Lag et al. 1989a). Since both testes and kidneys are target organs of

1,2-dibromo-3-chloropropane toxicity, a correlation between GSH depletion in

these tissues and induced organ toxicity is lacking. Furthermore, there was

no preferential accumulation of 1,2-dibromo-3-chloropropane metabolites in

testes in another study (Shemi et al. 1987). Studies of the mechanism of

1,2-dibromo-3-chloropropane induced testicular toxicity suggest that in the

testes, conjugation with glutathione with subsequent metabolism to a reactive

metabolite represents a toxifying mechanism (Kluwe 1983; Omichinski et al.

1988a, 1988b). 

The interspecies differences in 1,2-dibromo-3-chloropropane

gonadotoxicity are probably due to interspecies differences in metabolism

within the testicular cells to convert 1,2-dibromo-3-chloropropane to more

reactive forms. After a single intraperitoneal injection of 1,2-dibromo3-chloropropane, atrophy of seminiferous epithelium was more severe in rats

and guinea pigs than in hamsters and mice. Furthermore, testicular

deoxyribonucleic acid (DNA) damage was observed only in rats and guinea pigs

(Lag et al. 1989a). These findings suggest that rats and guinea pigs are

sensitive to 1,2-dibromo-3-chloropropane because their testicular cells more

readily activate 1,2-dibromo-3-chloropropane to a DNA-damaging

intermediate(s). Species differences in metabolism were also found in

in vitro experiments with tissues from rats and mice. Rats metabolized 1,2­

dibromo-3-chloropropane in liver, kidney, testes, and stomach preparations

much faster than mice, as measured by GSH-dependent debromination in cytosolic

fractions (MacFarland et al. 1984). 

2.3.4 Excretion 

2.3.4.1 Inhalation Exposure 

No studies were located regarding the excretion in humans or animals

following inhalation exposure to 1,2-dibromo-3-chloropropane. 

2.3.4.2 Oral Exposure 

No studies were located regarding excretion in humans following oral

exposure to 1,2-dibromo-3-chloropropane. 

Excretion after administration of radioactively labeled 1,2-dibromo3-chloropropane in rats occurred via several routes, including exhalation and

biliary and urinary elimination. Radioactivity was primarily expired as

carbon dioxide; only a trace of unchanged 1,2-dibromo-3-chloropropane was

detected. Mercapturic acids were detected in the urine; biliary excretion

accounted for approximately 23% of the administered dose (Kato et al. 1979a).

Within 3 days of gavage administration of radioactively labeled 1,2-dibromo3-chloropropane to rats, 55% of the radioactivity was found in the urine, 18% 
2.4 

54
 

2. HEALTH EFFECTS 

in the feces, and 19.5% in the exhaled air as carbon dioxide. Less than 1%

was exhaled as unchanged 1,2-dibromo-3-chloropropane (Gingell et al. 198717). 

2.3.4.3 Dermal Exposure 

No studies were located regarding excretion in humans or animals after

dermal exposure to 1,2-dibromo-3-chloropropane. 

RELEVANCE TO PUBLIC HEALTH 

Information regarding health effects of 1,2-dibromo-3-chloropropane in

humans and animals is available for the inhalation and oral routes of 

exposure. Inhalation is the main route of exposure to 1,2-dibromo-3-chloropropane

in occupational settings, while oral exposure most often results from

ingestion of contaminated drinking water. Until 1977, 1,2-dibromo3-chloropropane was used in the United States as a nematocide (Section 4.3). 

Epidemiological studies have indicated that the testes are the main

targets of 1,2-dibromo-3-chloropropane toxicity following occupational

exposures. Decreased spermatogenesis, atrophy of the seminiferous epithelium

with azoospermia, and possible sex ratio differences in offspring were

observed in exposed workers. Studies indicate that the testicular damage can

be permanent. Other effects reported by exposed workers include headache,

nausea, lightheadedness, and weakness. No reproductive or carcinogenic

effects were detected in a population exposed to concentrations of 1,2­

dibromo-3-chloropropane ranging from 0.004 ppb to 5.75 ppb in drinking water

(Wong et al. 1988, 1989). 

In animals, effects after inhalation and oral exposures include

increased mortality, fetotoxicity, hepatic and renal lesions, gonadal atrophy,

and cancer. Respiratory lesions and carcinomas of the respiratory tract were

observed after inhalation exposure, while gastrointestinal lesions and stomach

carcinomas were seen after oral exposure. In addition, anemia, central

nervous system depression, and brain lesions were observed in animals after

inhalation exposures. 

After dermal exposure, 1,2-dibromo-3-chloropropane was reported to cause

ocular and dermal irritation and stomach cancer in experimental animals. 

Studies in humans did not provide sufficient data regarding exposure

levels and their correlation with observed effects. Therefore, animal studies

were used for the derivation of MRLs. 

Sufficient information was not available on the health effects of 

1,2-dibromo-3-chloropropane to derive an MRL for acute-duration inhalation

exposure. In one study, reproductive effects were noted in rats following

acute inhalation exposure to 1,2-dibromo-3-chloropropane (Saegusa et al.

1982). Although this is the most sensitive end point for 1,2-dibromo-
55
 

2. HEALTH EFFECTS 

3-chloropropane toxicity, the data are only available for rats. Reproductive

toxicity data are needed for acute inhalation exposures in rabbits and humans

since these appears to be more sensitive species than the rat for such

effects. 

An intermediate-duration inhalation MRL of 0.0002 ppm was derived from a NOAEL

value of 0.1 ppm for changes in spermatogenesis and testicular atrophy in rabbits

(Rao et al. 1982). The ratio of the blood/gas partition coefficients was assumed to

be 1. The dose was adjusted for intermittent exposure by multiplying the NOAEL by

6/24 to correct for less than a full day of exposure and by 5/7 to correct for less

than a full week of exposure. The result was then divided by an uncertainty factor of

100 (10 for extrapolation from animals to humans and 10 for human variability). The

lowest human equivalent concentration from the available intermediate-duration

inhalation studies and the most sensitive (reproductive) end point were used.

Intermediate-duration exposure to 1 ppm induced, decreased spermatogenesis,

sperm abnormalities, and testicular atrophy (Rao et al. 1982); and infertility

occurred at 10 ppm (Rao et al. 1982). Testicular atrophy was also noted at 10 or 25

ppm in rats (NTP 1982; Torkelson et al. 1961) Other effects included nephrosis at 1

ppm in rats (NTP 1982), decreased weight gain at 1 ppm in mice, and bronchial

hyperplasia at 5 ppm in mice (NTP 1982). 

Information regarding effects following chronic inhalation exposure to

1,2-dibromo-3-chloropropane was limited to carcinogenicity studies in rats and mice

(NTP 1982). The data were not suitable for the MRL development because no NOAEL value

for the most sensitive (reproductive) system was available from the studies.

Considering a NOAEL or a LOAEL value from any other end points would result in a

chronic-duration inhalation MRL higher than the intermediate-duration inhalation MRL.

In addition, systemic effects occurred in various organs of rats and mice at the same

exposure levels that tumors were observed in these organs. 

Several studies provided information on LD50 values and systemic effects

following acute oral exposure to 1,2-dibromo-3-chloropropane. However, no acute oral

MRL was derived for 1,2-dibromo-3-chloropropane because dominant lethality was

observed at the lowest dose tested (10 mg/kg/day) (Teramoto et al. 1980) from all

available studies. 

An intermediate-duration oral MRL was derived from information for 

reproductive effects noted in rabbits (Foote et al. 1986a, 1986b). Decreased

spermatogenesis and abnormal sperm morphology were observed in rabbits at the

end of a 10-week exposure to concentrations of 1,2-dibromo-3-chloropropane as

low as 1.88 mg/kg/day (Foote et al. 1986a, 1986b). These effects increased

with dose. At the highest dose tested, 15 mg/kg/day, testicular atrophy and

increased serum FSH levels were observed. No NOAEL was identified in this 

study. An intermediate-duration oral MRL of 0.002 mg/kg/day was derived from

the LOAEL value of 1.88 mg/kg/day for effects on spermatogenesis and sperm

morphology (Foote 1986a, 1986b). The MRL value was obtained by dividing the 
56
 

2. HEALTH EFFECTS
 

LOAEL by an uncertainty factor of 1000 (10 for use of a LOAEL, 10 for

extrapolation from animals to humans, and 10 for human variability).

Intermediate-duration oral exposure to 1,2-dibromochloropropane has also been

reported to result in testicular degeneration in rats at 15 mg/kg/day (Amann

and Berndtaon 1986), testicular necrosis in rats at 70 mg/kg/day

(Rakhmatullayev 1969); reduced litters in mice at 25 mg/kg/day (Reel et al.

1984), and azoospermia in monkeys (Overstreet et al. 1988). Adverse

reproductive effects in rats were also reported after intermediate-duration

exposure to 0.05 mg/kg/day of 1,2-dibromo-3-chloropropane (Rakhmatullaev

1971). However, the effects were poorly described and very few study details

were given. Therefore, this value was not used to derive an MRL. 

Toxicity information from chronic oral exposure to 1,2-dibromo3-chloropropane cannot be used to derive an MRL because reproductive toxicity,

which may be the most sensitive end point, was tested at levels that also

induced cancer or death. Systemic toxicity data in rats cannot be used for

MRL derivation because the statistical significance of the effects was not

reported for the available LOAEL values (Hazleton 1977, 1978a). Additional

data are needed to determine whether hepatic toxicity, which was noted at the

lowest LOAEL of 0.3 mg/kg/day (Hazleton 1977, 1978a), is the primary end point

following chronic oral exposure. 

Death. No studies were located regarding death in humans after exposure

to 1,2-dibromo-3-chloropropane. Mortality was induced in experimental animals

by all routes of exposure and corresponding LC50 and LD50 values were derived 

(Moody et al. 1984; Torkelson et al. 1961). Increased mortality was also

observed in rats and mice after intermediate- and chronic-duration oral 

exposure (Hazleton 1977, 1978b; NC1 1978) and chronic-duration inhalation

exposure (NTP 1982). The risk of shortened lifespan may be of concern for

people who are exposed to substantial amounts over extended periods of time. 

Systemic Effects 

Respiratory Effects. No studies were located regarding respiratory

effects in humans after exposure to 1,2-dibromo-3-chloropropane by any route.

1,2-Dibromo-3-chloropropane-induced toxicity in the respiratory tract

(inflammatory and proliferative changes in the nasal cavity, necrosis of the

trachea and bronchial epithelium, nasal cavity carcinomas) was observed in

animals after inhalation exposure (NTP 1982), but not after oral exposure (NC1

1978). Irritation of the upper respiratory tract of the rat occurred after

acute high-level exposure (Torkelson et al. 1961). Histopathological changes

such as epithelial cytomegaly and focal necrosis occurred after more prolonged

exposure (Saegusa et al. 1982). Inflammatory and proliferative changes were

seen in the nasal cavity, trachea, and bronchial epithelium of rats and mice

in an intermediate-duration study with exposures up to 25 ppm 1,2-dibromo3-chloropropane for 90 days (NTP 1982). Rats exposed to 10 and 20 ppm 1,2­

dibromo-3-chloropropane for 10 weeks had emphysema and bronchopneumonia 
57
 

2. HEALTH EFFECTS
 

(Torkelson et al. 1961). However, infection from stress-induced lowered

immunity cannot be ruled out in the case of the rodents. Chronic exposure of

rats and mice resulted in tumors of the respiratory tracts. Epithelial

hyperplasia was listed among nonneoplastic effects (NTP 1982). The animal

studies show a correlation between the severity of induced respiratory changes

and exposure concentrations and durations, and suggest the potential of

respiratory effects in people exposed by inhalation to 1,2-dibromo3-chloropropane. 

Cardiovascular Effects. The only epidemiological data available cannot

provide definitive conclusions regarding cardiovascular effects in humans

(Wong et al. 1984). No histopathological changes were associated with the

cardiovascular system in experimental animals by any exposure route (Hazleton

1977, 1978a; NC1 1978; NTP 1982; Rao et al. 1982). Based on the possible

association in occupationally exposed humans, a potential for increased

incidence of cardiovascular disease in humans exposed to 1,2-dibromo3-chloropropane in the environment or at hazardous waste sites may exist. 

Gastrointestinal Effects. No studies were located regarding

nonneoplastic gastrointestinal effects in humans after exposure to

1,2-dibromo-3-chloropropane by any route. One study examined the correlation

between ingestion of drinking water containing 0.004-5.75 ppb 1,2­

dibromochloropropane and gastric cancer and found no correlation (Wong et

a1.1989). Gastrointestinal effects occurred in experimental animals mainly

after oral exposure to 1,2-dibromo-3-chloropropane. Cell proliferation and

hyperkeratosis were observed in stomachs of rats after acute-duration exposure

(Ghanayem et al. 1986). Changes varied from edema to necrosis after

intermediate-duration exposure (Rakhmatullajev 1969; Torkelson et al. 1961).

Acanthosis and hyperkeratosis of the stomach were seen in rats after chronic

exposure; however, after chronic exposure, the most significant effect was

stomach cancer in both rats and mice (Hazleton 1977, 1978a, 1978b; NC1 1978).

Therefore, people who are orally exposed to substantial amounts of 1,2­

dibromo-3-chloropropane (i.e., by ingestion of heavily contaminated drinking

water) may experience adverse gastrointestinal effects. 

Hematological Effects. No studies were located regarding hematological

effects in humans after exposure to 1,2-dibromo-3-chloropropane by the oral

route. No hematological effects were found in workers exposed to 1,2-dibromo3-chloropropane (Whorton et al. 1977). A marked decrease in the white blood

cell count was reported in monkeys after an intermediate duration inhalation

exposure to 1,2-dibromo-3-chloropropane (Torkelson et al. 1961). Splenic

atrophy was observed in rats after an acute inhalation exposure (Saegusa et

al. 1982) and in mice after a chronic inhalation exposure (NTP 1982). Rats

exposed by inhalation developed hypocellularity of the bone marrow (NTP 1982).

These findings may indicate a hematological effect of 1,2-dibromo3-chloropropane exposure. However, no hematological changes were observed in

several other inhalation experiments in rats, mice, guinea pigs, or rabbits

(NTP 1982; Rao et al. 1982, 1983; Torkelson et al. 1961). No changes were 
58
 

2. HEALTH EFFECTS 

found after oral exposure. The possibility that 1,2-dibromo-3-chloropropane

could cause hematological effects in humans cannot be ruled out. 

Hepatic Effects. No studies were located regarding hepatic effects in

humans after exposure to 1,2-dibromo-3-chloropropane by any route. Hydropic

hepatocytes and focal necrosis were found in rats and mice after intermediateduration inhalation exposure. No changes were found after chronic exposure of

either species to lower concentrations (NTP 1982). Focal centrilobular

necrosis and hydropic hepatocytes (Kato et al. 1980) and hepatocellular

swelling and increased cytoplasmic basophilia (Kluwe 1981) were also reported

in rats after acute oral exposure. Poliosis hepatitis was observed in rats

after chronic oral exposure (Hazleton 1977, 1978a). The hepatic toxicity of

1,2-dibromo-3-chloropropane was supported by results in rats treated with 1,2-

dibromo-3-chloropropane by injection. Dose-related changes that ranged from

hepatocellular swelling to necrosis were observed (Kluwe 1981; Kluwe et al.

1985; Saegusa 1986, 1987). There were no differences in the incidence or

severity of hepatocytic effects in rats regardless of whether exposure was

conducted by oral gavage, intraperitoneal injection, or subcutaneous injection

(Kluwe 1981). 

The mechanism of 1,2-dibromo-3-chloropropane-induced hepatic toxicity

has been investigated in several studies. The role of microsomal metabolism

was demonstrated by the enhancement of macromolecular binding after

pretreatment of rats with phenobarbital (Kato et al. 1980). However,

pretreatment of rats with phenobarbital was shown to reduce 1,2-dibromo3-chloropropane-induced hepatic toxicity (Kluwe 1983). Thus, the role of the

microsomal system in the hepatic toxicity induced by 1,2-dibromo3-chloropropane or its metabolites is not clear. An in vitro study

demonstrated DNA damage and a depletion of hepatocellular GSH after liver

cells were exposed to 1,2-dibromo-3-chloropropane (Holme et al. 1989). The

initial metabolism of 1,2-dibromo-3-chloropropane to reactive epoxide

metabolites that bind to DNA and other macromolecules may be responsible for

the hepatotoxicity. 

The demonstration of hepatic effects in animals indicates that

1,2-dibromo-3-chloropropane has the potential to cause liver injury in humans. 

Renal Effects. No studies were located regarding renal effects in humans after

exposure to 1,2-dibromo-3-chloropropane by the oral route. No renal effects were

detected from the urinalysis of workers exposed to 1,2-dibromo-3-chloropropane

(Whorton et al. 1977). Renal toxicity of 1,2-dibromo-3-chloropropane in animals,

however, was apparent after inhalation and oral exposures, as well as after injection

of experimental animals. Necrotic changes in the proximal tubules were reported after

an acute inhalation exposure (Saegusa et al. 1982), while nephritis and nephrosis

were observed after intermediate-duration (NTP 1982; Torkelson et al. 1961) and

chronic exposures (NTP 1982). Similarly, acute renal insufficiency and/or

tubular necrosis were reported after an acute oral exposure (Kato et al. 1980; 
59
 

2. HEALTH EFFECTS
 

Kluwe 1981; Russell 1989). Renal function recovered, but focal

glomerulosclerosis persisted (Russell 1989). Increased turnover of proximal

tubular cells was noted in rats following intermediate exposure (Heindel et

al. 1989). Tubular epithelial changes were observed in the kidneys of rats

after chronic oral exposure (Hazleton 1977, 1978a). Furthermore, increased

incidence of renal carcinomas occurred in these exposed rats. Acute tubular

necrosis was also observed in rats that were injected with 1,2-dibromo3-chloropropane (Kluwe 1981; Kluwe et al. 1985; Saegusa 1986, 1987). There

were no differences in the incidence or severity of kidney tubular necrosis in

rats regardless of whether exposure was conducted by oral gavage,

intraperitoneal injection, or subcutaneous injection (Kluwe 1981). 

A recent study in rats indicates that renal DNA damage correlates with

renal necrosis after injection of 1,2-dibromo-3-chloropropane (Omichinski et

al. 1987). The.involvement of oxidative metabolism in producing the

nephrotoxic effect seems to be unlikely because deuteration of the parent

compound did not decrease the DNA damaging effect. (Deuterium substitution

can often decrease the extent of a compound's toxicity that is due to a

reactive metabolite formed by oxidation of the carbon-hydrogen bond because of

the high activation energy required to break the carbon-deuterium bond.) An

accumulation of 1,2-dibromo-3-chloropropane metabolites in the kidneys was

observed together with the depletion of renal GSH concentrations after an oral

exposure of rats (Kato et al. 1980); however, the results of experiments with

modulators of NPS conjugate formation indicated that this mechanism is not

rate-limiting in 1,2-dibromo-3-chloropropane-induced nephrotoxicity

(Omichinski et al. 1987). Experiments with methylated analogs of 1,2-dibromo3-chloropropane suggested the importance of a dibromo-ethyl group to the toxic

effects. Although the mechanism is not clear, the demonstration of renal

effects in rats and mice in several studies suggests the potential for renal

effects in humans who are substantially exposed to 1,2-dibromo3-chloropropane. 

Dermal/Ocular Effects. Eye irritation and clouding of the cornea and

lens were observed in rats after an inhalation exposure to high concentrations

of 1,2-dibromo-3-chloropropane (Torkelson et al. 1961). Changes varying from

erythema to necrosis were seen in rabbits after dermal application.

1,2-Dibromo-3-chloropropane that was applied to the skin caused death in

exposed animals, indicating that it was dermally absorbed. It is evident that

1,2-dibromo-3-chloropropane can be absorbed through the skin of humans. There

is, therefore, a potential for systemic and local effects to occur following

1,2-dibromo-3-chloropropane contact with the skin. 

Immunological Effects. No data were located regarding immunological

effects of 1,2-dibromo-3-chloropropane in humans after inhalation exposure.

No histopathological changes were observed in bone marrow, lymph nodes, or

spleen of rats after chronic oral exposure (Hazleton 1977, 1978a). However,

reversible atrophy and depletion of lymphocytes in the thymus, spleen, and 
60
 

2. HEALTH EFFECTS
 

lymphatic nodules were reported in rats after a single subcutaneous injection

of 1,2-dibromo-3-chloropropane (Saegusa 1986). In addition, hypocellularity

of bone marrow was observed in rats exposed by inhalation (NTP 1982). Severe

respiratory infections were found in rats (Torkelson et al. 1961) and monkeys

and rabbits (Rao et al. 1982) that were exposed to 1,2-dibromo-3-chloropropane;

control animals did not have infections. These findings suggest that

1,2-dibromo-3-chloropropane may have caused a decreased resistance to

infection. The possibility of immunological effects in humans exposed to

1,2-dibromo-3-chloropropane cannot be ruled out. 

Neurological Effects. No studies were located regarding neurological

effects in humans after exposure to 1,2-dibromo-3-chloropropane by the oral

route. Subjective symptoms (nausea, headache, and weakness) were reported by

workers exposed occupationally to 1,2-dibromo-3-chloropropane (Whorton et al.

1977). Inhalation is the primary route of exposure in industrial settings,

although dermal exposure is also likely. Neurological effects of 1,2-dibromo3-chloropropane have been described after inhalation and oral exposures of

experimental animals. Depression of the central nervous system was reported

in rats after an acute inhalation exposure, but without complete narcosis

(Torkelson et al. 1961). Histopathological changes found in the brains of

exposed animals include focal mineralization, meningoencephalitis and cerebral

necrosis. The severity increased with increasing exposure (NTP 1982; Rao et

al. 1983). No histopathological changes in brains of rats or mice were

reported after oral treatment with 1,2-dibromo-3-chloropropane (Hazleton 1977,

1978a; Johnston et al. 1986; NCI 1978); however, depression of the central

nervous system was observed after oral treatment with high doses

(Rakhmatullaev 1969; Reel et al. 1984). The findings in animals suggest a

potential for neurological effects in humans who are exposed to very large

amounts of 1,2-dibromo-3-chloropropane. 

Developmental Effects. No developmental effects were found among the

offspring of workers occupationally exposed to 1,2-dibromo-3-chloropropane

(Goldsmith et al. 1984; Potashnik and Abeliovich 1985; Potashnik and Phillip

1988). Negative results were also obtained after examining the offspring of a

population in Fresno County, California, who were exposed to drinking water

contaminated with 1,2-dibromo-3-chloropropane (Whorton et al. 1989). 

No teratogenicity was observed in the offspring of rats after oral

exposure of the dams to 1,2-dibromo-3-chloropropane during gestation (Ruddick

and Newsome 1979), or after exposure of both parents to drinking water that

contained 1,2-dibromo-3-chloropropane (Johnston et al. 1986). Effects on pup

weight and litter size were attributed to maternal toxicity manifested as

decreased body weight gain. Testicular degeneration was observed in male rats

postexposure in utero when their dams had been injected with 1,2-dibromo3-chloropropane during gestation (Warren et al. 1988). Although 1,2-dibromo3-chloropropane does not appear to cause developmental effects in animals at 
61 

2. HEALTH EFFECTS 

doses that are not toxic to the dams, developmental effects after inhalation

or oral exposure in humans cannot be ruled out. 

Reproductive Effects. 1,2-Dibromo-3-chloropropane toxicity to the human

male reproductive system was demonstrated in numerous studies. 1,2-Dibromo-3­

chloropropane-induced changes were found in cohorts of workers exposed in

factories that produced this nematocide (Potashnik et al. 1978; Whorton et al.

1979) and in 1,2-dibromo-3-chloropropane applicators and farmers exposed to

1,2-dibromo-3-chloropropane (Glass et al. 1979; Sandifer et al. 1979). The

actual levels of exposure were not established in most studies, but the

testicular toxicity can apparently occur upon inhalation of concentrations in

air of less than 1 ppm (Whorton et al. 1977). When the cohorts were divided

according to their length of exposure either by years (Whorton et al. 1979) or

by hours when they were directly involved in 1,2-dibromo-3-chloropropane

production (Potashnik et al. 1978), a correlation was found between the length

of exposure and the severity of changes. Exposure to levels of about 1 ppb

1,2-dibromo-3-chloropropane did not cause any effects in pineapple workers in

Hawaii (Coye et al. 1983, 1990). Azoospermia or oligospermia found by

analysis of sperm counts was a reflection of the measure of damage

demonstrated in histopathological examinations at biopsy (Lantz et al. 1981;

Potashnik et al. 1978). Depletion of germ cells in seminiferous tubules with

intact Sertoli cells was seen in most cases of azoospermia. Azoospermia was

accompanied with an increase in plasma FSH levels (Eaton et al. 1986; Lantz et

al. 1981). The hormonal changes were more'pronounced in unrecovered workers

after a nonexposure period (Potashnik and Yanai-Inbar 1987). The FSH assay

alone, however, was not sensitive enough to detect oligospermia (Whorton et

al. 1979). A depressed fertility rate resulted as a direct consequence of

testicular changes in these workers who were exposed to 1,2-dibromo3-chloropropane. 

Oral exposure to 1,2-dibromo-3-chloropropane through contaminated

drinking water occurred in Fresno County, California (Wong et al. 1988);

however, the concentrations of 1,2-dibromo-3-chloropropane in the water were

low (0.004-5.75 ppb), and no changes in birth rates were detectable. 

1,2-Dibromo-3-chloropropane-induced testicular toxicity has been

demonstrated in several animal studies. Atrophy of the seminiferous tubules

was reported in rats after acute- or intermediate-duration inhalation

exposures (NTP 1982; Rao et al. 1983; Saegusa et al. 1982). Similar changes

were also found in exposed rabbits, together with an increase of plasma FSH

levels (Rao et al. 1982). Testicular damage was reversible in rabbits (Rao et

al. 1982), and humans (Olson et al. 1990). In addition, dominant lethality

recorded in rats was reversed after a recovery period (Rao et al. 1983).

Following oral exposures, the induction of dominant lethality was also

observed after in rats (Amann and Berndtson 1986; Teramoto et al. 1980) but

not in mice (Teramoto et al. 1980). Dominant lethality was not induced in

mice after intraperitoneal injections of 1,2-dibromo-3-chloropropane (Generoso 
62 

2. HEALTH EFFECTS 

et al. 1985). Histopathological changes found in testes of rats and/or

rabbits after oral exposure to 1,2-dibromo-3-chloropropane were similar to

those found after inhalation exposure (Amann and Berndtson 1986; Foote et al.

1986b; Kluwe 1981). The changes were dose-related and accompanied by elevated

FSH levels in rabbits (Foote et al. 1986b). Impaired spermatogenesis was also

noted in rabbits under identical exposure conditions (Foote et al. 1986a). No

changes in fertility were recorded in these rabbits (Foote et al. 1986b).

There were no differences in the incidence or severity of testicular effects

in rats regardless of whether exposure was conducted by oral gavage,

intraperitoneal injection, or subcutaneous injection (Kluwe 1981). 

A high incidence of testicular atrophy was observed in rats (but not in

mice) after chronic gavage dosing with 1,2-dibromo-3-chloropropane (NC1 1978);

however, no effects were found in rats after administration of lower doses

(Hazleton 1977, Hazleton 1978a). No statistically different changes from the '

controls were seen in reproductive organs of rats or mice after chronic

inhalation exposure (NTP 1982). Interspecies differences have been shown

between rats and rabbits; rabbits were found to be more susceptible to male

reproductive effects (Rao et al. 1982, 1983). The interspecies differences

for testicular effects induced in rats or mice were also apparent after

parenteral exposure. While testicular changes were found in rats after 1,2-

dibromo-3-chloropropane injections (Ahmad et al. 1988; Kluwe et al. 1985; Lui

and Wysocki 1987; Warren et al. 1984), no changes were observed in mice

(Oakberg and Cummings 1984). 

The difference in susceptibility between immature and adult rats was

also investigated (Kluwe et al. 1985; Lui and Wysocki 1987). Sexually mature

male rats seemed to be less susceptible to 1,2-dibromo-3-chloropropane-induced

testicular toxicity. Changes that were induced in neonates or in utero were

carried on to adulthood (Kluwe et al. 1985; Warren et al. 1988). These

results are in contrast with a report that found degenerative testicular

changes in the adult group of rats and not in the immature group (Saegusa

1987). 

The mechanism of 1,2-dibromo-3-chloropropane testicular toxicity has

been investigated in several studies in vitro. The inhibition of sperm

carbohydrate metabolism, probably at the step of nicotinamide adenine

dinucleotide (NADH) dehydrogenase activity in the mitochondrial electron

transport chain, was suggested to be the cause of the toxicity (Bartoov et al.

1987; Greenwell et al. 1987). Alternatively, well-conducted toxicokinetic

studies have indicated that the severity of testicular necrosis is directly

related to DNA damage (Omichinski et al. 1988a, 1988b; Soderlund et al. 1988).

Metabolism via a cytochrome P-450-dependent pathway is probably not involved

in the DNA-damaging effects because the use of deuterated analogs of the

parent compound, which interfere with cytochrome P-450 metabolism, did not

decrease the amount of the damage. Investigators have suggested that the

testicular genotoxicity of 1,2-dibromo-3-chloropropane may involve conjugation

with glutathione, with subsequent formation of a reactive episulphonium ion 
63 

2. HEALTH EFFECTS 

that can cause.direct alkylation of target molecules. If so, in contrast to

the apparent detoxifying role of glutathione conjugation in the liver,

conjugation,with glutathione in the testes may be a toxifying mechanism. 

1,2-Dibromo-3-chloropropane-induced toxicity to the female reproductive

system is not so obvious. No histological changes were found in female

reproductive organs after an intermediate- or chronic-duration inhalation

exposure (NTP 1982) or chronic oral exposure in rats or mice (NC1 1978).

Ovarian cysts were recorded in rats exposed to 10 ppm 1,2-dibromo-3-chloropropane

for 14 weeks; fertility, however, was not affected (Rao et al. 1983).

No changes in fertility were found in female rats exposed to 1,2-dibromo-3­

chloropropane in drinking water (Johnston et al. 1986). In contrast, only 60%

of treated females became pregnant after mating when the proestrus rats were

given a single injection of 1,2-dibromo-3-chloropropane so that cells in the

first meiotic division could be targeted (Shaked et al. 1988). No effect on

dominant lethality or fertility was observed in female mice after a single

intraperitoneal injection of 1,2-dibromo-3-chloropropane (Generoso et al.

1985). 

Evidence that the male reproductive system is a target of 1,2-dibromo-3­

chloropropane in humans and some laboratory animals is overwhelming. Recovery

is possible, but with higher doses and/or longer exposure, the changes may

become permanent. 

Genotoxic Effects. 1,2-Dibromo-3-chloropropane has been tested for

genotoxicity in a number of in vivo and in vitro studies (Tables 2-4 and 2-5). 

The mutagenic potential of 1,2-dibromo-3-chloropropane was demonstrated

in humans by the evidence of a change in sex ratio among the offspring of

exposed workers (Potashnik et al. 1984). In contrast, no alterations in sex

ratios of newborns were found in Fresno County (1978-1982), California, where

the drinking water Kas contaminated with 1,2-dibromo-3-chloropropane (Whorton

et al. 1989). However, total exposure via drinking water was probably much

lower than that experienced by occupationally exposed workers. 

Increased dominant lethality was reported in rats after inhalation (Rao

et al. 1983) and oral exposures to 1,2-dibromo-3-chloropropane (Teramoto et

al. 1980). In contrast, no dominant lethal effect was observed in mice

treated either orally for 5 days (Teramoto et al. 1980) or intraperitoneally

or subcutaneously with a single injection of 1,2-dibromo-3-chloropropane

(Generoso et al. 1985). Positive results were obtained in mice in the spot

test (Sasaki et al. 1986) but not in the specific-locus gene mutation test

(Russell et al. 1986). 

Positive results were found in the reverse mutation assay in Salmonella

typhimurium TA1535, TAlOO, and TA98 with metabolic activation but not without 


66
 

2. HEALTH EFFECTS 

activation (Ratpan and Plauman 1988; Stolzenberg and Hine 1979). Purified

1,2-dibromo-3-chloropropane was considered a potent indirect mutagen. 

In in vitro studies with eukaryotic systems, 1,2-dibromo-3-chloropropane

induced an increased incidence of sister chromatid exchanges in Chinese

hamster V79 cells (Tezuka et al. 1980) and in sister chromatid exchanges and

chromosomal aberrations in Chinese hamster ovary cells (Loveday et al. 1989). 

1,2-Dibromo-3-chloropropane was mutagenic in the recessive lethal assay

in Drosophila melanogaster (Inoue et al. 1982; Zimmering 1983). In contrast,

the increased lethality was observed only when male flies were treated as

embryos (Kale and Baum 1982b). A positive response was also obtained in the

induction of genetic crossing-over (Kale and Baum 1982b), chromosome loss

(Zimmering 1983), and heritable translocations (Zimmering 1983). 

1,2-Dibromo-3-chloropropane induced unscheduled DNA synthesis in the

premeiotic germ cells after a single injection to prepubertal mice (Lee and

Suzuki 1979). Unscheduled DNA synthesis was also induced in spermatocytes in

adult rats (Bentley and Working 1988). 

The aforementioned results demonstrate that 1,2-dibromo-3-chloropropane

is a potent genetic toxicant. Microbial assays showed that it is capable of

inducing gene mutations, and mammalian assays showed that it can cause

chromosomal mutations in both somatic and germinal cells. The demonstrated

potential for a genotoxic effect in humans is supported by results from a

variety of experimental systems. 

Cancer. Information regarding carcinogenicity of 1,2-dibromo3-chloropropane in humans is sparse. Only two epidemiological studies

regarding cancer risk were located. One did not report any increased

incidence of cancer among exposed workers (Hearn et al. 1984). The other

study found no correlation between the risk of gastric cancer in a population

residing in an area where drinking water was contaminated with 1,2-dibromo-3­

chloropropane (Wong et al. 1989). 

There is conclusive evidence of the carcinogenicity of 1,2-dibromo3-chloropropane in experimental animals. Rats that were exposed to

1,2-dibromo-3-chloropropane by inhalation for 84-103 weeks developed multiplesite

neoplasms (NTP 1982). Adenomas and carcinomas of the respiratory tract

and tongue in both sexes, fibroadenomas of the mammary gland and adenomas of

the adrenal cortex in females, and trichoadenomas of the skin and

mesotheliomas of the tunica vaginalis in males were observed in the exposed

animals. In contrast, the development of neoplasms was restricted only to the

respiratory tract in mice exposed to the same concentrations for 76-103 weeks

(NTP 1982). When administered chronically by gavage, 1,2-dibromo-3-chloropropane

induced squamous cell carcinomas of the forestomach in rats and mice

of both sexes and carcinomas of the mammary gland in female rats (NC1 1978). 
67
 

2. HEALTH EFFECTS
 

When administered chronically in the diet, 1,2-dibromo-3-chloropropane induced

squamous cell carcinomas of the forestomach in rats and mice and adenomas

and/or carcinomas of the kidneys in rats (Hazleton 1977, 1978a, 1978b).

Systemic papillomas and carcinomas developed in the lungs and stomachs of mice

after dermal application of 1,2-dibromo-3-chloropropane (Van Duuren et al.

1979). Thus, 1,2-dibromo-3-chloropropane induced cancer, not only at the

initial site of contact (respiratory tract or stomach), but also in distant

organs. It is possible that metabolites play a significant role in the

carcinogenicity of 1,2-dibromo-3-chloropropane. 

Based on the evidence in animals, 1,2-dibromo-3-chloropropane is

reasonably anticipated to be carcinogenic in humans who are exposed to

sufficient doses for long enough periods. 

2.5 BIOMARKERS OF EXPOSURE AND EFFECT 

Biomarkers are broadly defined as indicators signaling events in

biologic systems or samples. They have been classified as markers of

exposure, markers of effect, and markers of susceptibility (NAS/NRC 1989). 

A biomarker of exposure is a xenobiotic substance or its metabolite(s)

or the product of an interaction between a xenobiotic agent and some target

molecule(s) or cell(s) that is measured within a compartment of an organism

(NAS/NRC 1989). The preferred biomarkers of exposure are generally the

substance itself or substance-specific metabolites in readily obtainable body

fluid(s) or excreta. However, several factors can confound the use and

interpretation of biomarkers of exposure. The body burden of a substance may

be the result of exposures from more than one source. The substance being

measured may be a metabolite of another xenobiotic substance (e.g., high

urinary levels of phenol can result from exposure to several different

aromatic compounds). Depending on the properties of the substance (e.g.,

biologic half-life) and environmental conditions (e.g., duration and route of

exposure), the substance and all of its metabolites may have left the body by

the time biologic samples can be taken. It may be difficult to identify

individuals exposed to hazardous substances that are commonly found in body

tissues and fluids (e.g., essential mineral nutrients such as copper, zinc,

and selenium). Biomarkers of exposure to 1,2-dibromo-3-chloropropane are

discussed in Section 2.5.1. 

Biomarkers of effect are defined as any measurable biochemical,

physiologic, or other alteration within an organism that, depending on

magnitude, can be recognized as an established or potential health impairment

or disease (NAS/NRC 1989). This definition encompasses biochemical or

cellular signals of tissue dysfunction (e.g., increased liver enzyme activity

or pathologic changes in female genital epithelial cells), as well physiologic

signs of dysfunction such as increased blood pressure or decreased lung

capacity, Note that these markers are often not substance specific.

They also may not be directly adverse, but can indicate potential health impairment 
68
 

2. HEALTH EFFECTS
 

e.g., DNA adducts). Biomarkers of effects caused by 1,2-dibromo-3-chloropropane

are discussed in Section 2.5.2. 

A biomarker of susceptibility is an indicator of an inherent or acquired

limitation of an organism's ability to respond to the challenge of exposure to

a specific xenobiotic substance. It can be an intrinsic genetic or other

characteristic or a preexisting disease that results in an increase in

absorbed dose, biologically effective dose, or target tissue response. If

biomarkers of susceptibility exist, they are discussed in Section 2.7,

"POPULATIONS THAT ARE UNUSUALLY SUSCEPTIBLE." 

2.5.1 Biomarkers Used to Identify and/or Quantify Exposure to 1,2-Dibromo-3-

chloropropane 

No studies were located regarding tissue, fluid, or excreta levels of

1,2-dibromo-3-chloropropane in humans. 

Toxicokinetic studies performed in animals after acute exposures to 1,2­

dibromo-3-chloropropane indicate that this chemical preferentially partitions

to fat; however, upon termination of exposure the accumulated chemical is

rapidly lost from this tissue (Kato et al. 1979a; Ruddick and Newsom 1979).

Over 80% of adipose tissue 1,2-dibromo-3-chloropropane is lost by 24 hours

postexposure. 1,2-Dibromo-3-chloropropane was lost from other tissues more

rapidly. Thus, determination of tissue levels of 1,2-dibromo-3-chloropropane

must be made shortly after exposure. 1,2-Dibromo-3-chloropropane may be found

in exhaled air, but less than 1% of an administered dose was found in exhaled

air during the first 24 hours after dosing. At least 20 metabolites were

detected in the urine of rats following ingestion of radioactively labeled

1,2-dibromo-3-chloropropane (Gingell et al. 1987b). However, it is not known

if these metabolites occur in human urine following exposure to 1,2-dibromo-3­

chloropropane by inhalation, oral, or dermal exposures. Also, the detection

of these metabolites may not be specific for 1,2-dibromo-3-chloropropane

exposures. 

The induction of microsomal enzymes, particularly aryl hydrocarbon

hydroxylase and epoxide hydrolase, was observed in tissues of rats that were

exposed to 1,2-dibromo-3-chloropropane (Suzuki and Lee 1981). However,

microsomal enzyme induction may be caused by over 300 drugs, pesticides, and

industrial chemicals. Therefore, changes in microsomal enzyme activity does

not specifically indicate exposure to 1,2-dibromo-3-chloropropane. Increased

concentrations of serum creatinine, urea nitrogen, glutamic pyruvic

transaminase, and sorbitol dehydrogenase were detected in exposed rats (Kluwe

1983). These changes are not, however, specific for 1,2-dibromo-3­

chloropropane exposure. Increased concentrations of serum creatinine and urea

nitrogen are indicative of kidney damage and may be raised by an chemical

exhibiting renal toxicity. Likewise, increased concentrations of serum

glutamic pyruvic transaminase are indicative of liver damage and may be raised

by any chemical resulting in hepatocellular damage. 
69
 

2. HEALTH EFFECTS
 

The possible effect of 1,2-dibromo-3-chloropropane metabolites on heme

synthesis and breakdown was investigated in rats (Moody et al. 1984; Tofilon

et al. 1980). Decreased incorporation of radioactively labeled aminolevulinic

acid into liver protein and extracted heme was observed in 1,2-dibromo3-chloropropane-exposed rats (Moody et al. 1984). Furthermore, heme catalase

activity was also decreased, while increased heme oxygenase activity and

increased liver concentrations of uroporphyrin and coproporphyrin were

detected. The mechanism of this effect is unknown. Similarly, heme

concentrations were depressed in testicular microsomal fractions after oral

exposure of rats to 1,2-dibromo-3-chloropropane (Tofilon et al. 1980);

however, 1,2-dibromo-3-chloropropane administration did not alter testicular

heme oxygenase activity, indicative of a possible difference in the mechanism

of organ injury. The reason for the 1,2-dibromo-3-chloropropane-induced

changes in heme turnover, and its relationship to a lesion in the testes,

needs to be further investigated, The application as a biomarker of exposure

would involve a biopsy to obtain the liver or testicular tissue. Use of

changes in heme synthesis as a biomarker is limited because the test would not

be specific for 1,2-dibromo-3-chloropropane. 

Although inorganic bromide could be found in the serum of 1,2-dibromo-3­

chloropropane-exposed animals, its measurement was not useful in demonstrating

excessive exposure (Torkelson et al. 1961). Furthermore, elevated inorganic

bromide levels may result from occupational exposure to methyl bromide or

ingestion of inorganic bromides as sleep aids. 

Further information on distribution and excretion of 1,2-dibromo3-chloropropane and its metabolites in animal tissues can be located in

Section 2.3.2. 

2.5.2 Biomarkers Used to Characterize Effects Caused by 1,2-Dibromo3-chloropropane 

The only consistently observed effects in humans exposed to 1,2-dibromo3-chloropropane are testicular. An attempt has been made to identify early

subtle changes caused by 1,2-dibromo-3-chloropropane in the male reproductive

system. For this purpose, the measuring of FSH plasma levels in exposed

workers was proposed; however, the elevation of FSH correlates with more

serious testicular changes and azoospermia and is not sensitive enough to

detect oligospermia (Whorton et al. 1979). Foote et al. (1986a, 1986b)

suggest several tests that may be used to identify testicular effects and/or

abnormalities in spermatogenic function in males. These include decreases in

testis weight, FSH concentration in blood, seminiferous tubular diameter, and

enumeration of germ cells per Sertoli cell or per tubular Stage I cross

section. The authors concluded that the most sensitive indicator would be 

germ cell counts; changes in seminiferous tubule diameter would also be a

sensitive indicator. Sperm count analysis is a reliable method for detecting

1,2-dibromo-3-chloropropane-induced reproductive toxicity. The other methods 
70
 

2. HEALTH EFFECTS 

suggested by Foote et al. have not been tested for their reliability in

humans. 

2.6 INTERACTIONS WITH OTHER CHEMICALS 

No studies were located regarding interaction of 1,2-dibromo-3-chloropropane

with other chemicals. Workers who are occupationally exposed to

1,2-dibromo-3-chloropropane in chemical factories are also exposed to other

chemicals. In addition, technical 1,2-dibromo-3-chloropropane contains a

trace of epichlorohydrin, which is a known carcinogen (Kawabata 1981; Laskin

et al. 1980) and testicular toxicant (Cooper et al. 1974; Hahn 1970) in

animals. In contrast, reproductive effects were not found in workers

occupationally exposed to epichlorohydrin (Milby et al. 1981). However,

interpretation of this study was confounded by only partial participation of

the exposed cohort, by the lack of a matched control from the geographic area,

and the lack of exposure data. In conclusion, whether epichlorohydrin or

other chemicals have synergistic systemic, reproductive, or carcinogenic

effects in humans is not known. 

2.7 POPULATIONS THAT ARE UNUSUALLY SUSCEPTIBLE 

1,2-Dibromo-3-chloropropane toxicity to the reproductive system is

pronounced in males. Persons suffering from asthma or chronic respiratory

disease might be vulnerable to the respiratory irritant effects of

1,2-dibromo-3-chloropropane. Persons with impaired liver and kidney function

may also be more susceptible to the toxic effects of 1,2-dibromo-3­

chloropropane because these organs are involved in the detoxification and

excretion of this chemical. 

2.8 MITIGATION OF TOXICOLOGICAL EFFECTS 

This section will describe clinical practice and research concerning

methods for reducing toxic effects of exposure to 1,2-dibromo-3-chloropropane.

However, because some of the treatments discussed may be experimental and

unproven, this section should not be used as a guide for treatment of

exposures to 1,2-dibromo-3-chloropropane. When specific exposures have

occurred, poison control centers and medical toxicologists should be consulted

for medical advice. 

No specific data were located regarding the mitigation of effects of

1,2-dibromo-3-chloropropane once it has entered the bloodstream and no

specific antidotes are known. Therefore, steps should be taken to minimize

exposure to this chemical, and in the event that exposure has taken place, to

limit absorption into the bloodstream. To minimize occupational exposure,

chemical protective clothing, gloves, face shields, and goggles should be

provided for workers (NIOSH 1988). In addition, exposure levels should be

maintained below permissible exposure limits. In situations where exposure

levels may exceed these limits, respirators may also be required. Absorption 
71 

2. HEALTH EFFECTS 

by persons who have been exposed to elevated levels of 1,2-dibromo-3-

chloropropane may be limited by removing the exposed individual from the

contaminated area and by removing contaminated clothing (Bronstein and

Currance 1988; NIOSH 1988; Stutz and Janusz 1988). Exposed skin should be

washed with soapy water and contaminated eyes flushed with water.

Proparacaine hydrochloride (0.5% solution) can be used to facilitate eye

irrigation (Bronstein and Currance 1988). Water or milk should be ingested

following oral exposure (Bronstein and Currance 1988; Stutz and Janusz 1988).

Activated charcoal should be given orally to adsorb the chemical. Emetics

should not be used (Bronstein and Currance 1988). Oxygen may be administered

and ventilation assistance provided as needed and standard procedures may be

used for the treatment of cardiac arrhythmias and pulmonary edema (Bronstein

and Currance 1988; Stutz and Janusz 1988). 

Studies on the microsomal metabolism of 1,2-dibromo-3-chloropropane

showed that the chemical is converted to its epoxy derivatives that can be

further hydrolyzed or debrominated (Jones et al. 1979) (Jones et al. 1979;

Kale and Baum 1982a; Kato et al. 1979b). Some of the intermediate or end

metabolites (α-chlorohydrin, epichlorohydrin, oxalic acid, and a bromide ion)

may be responsible for observed toxic effects. The active metabolites are

able to bind covalently with nucleophilic sites of macromolecules, such as DNA

and protein. In vitro binding to liver protein was found to be enzymedependent

as demonstrated by alteration of the reaction with metabolic

modifiers (Kato et al. 1979b). The addition of nicotinamide adenine

dinucleotide phosphate (NADPH) to the system stimulated the binding, while the

addition of sesamex, an inhibitor of microsomal oxidation, inhibited the

binding (Kato et al. 1979b). Conversely, pretreatment of mice with

polybrominated biphenyls (PBB), inducers of microsomal enzymes, protected the

animals from 1,2-dibromo-3-chloropropane toxicity, perhaps by shifting the

metabolic pathway in favor of metabolites that do not bind to macromolecules

(Kluwe et al. 1981). 

In the liver, conjugation of the reactive metabolites with GSH may

represent a detoxifying mechanism. The liver was the major site of GSH

conjugation with 1,2-dibromo-3-chloropropane metabolites in vivo (Kluwe et al.

1982), and the depletion of GSH correlated with observed toxicity in the

liver. That conjugation of intermediate metabolites with GSH is a detoxifying

mechanism was further demonstrated in rats (Kluwe et al. 1982). Pretreatment

of rats with diethyl maleate, a GSH depletor, increased the renal and hepatic

toxicity of the subsequent 1,2-dibromo-3-chloropropane dose. 

In contrast, studies in animals indicated that conjugation with GSH is

not a detoxifying mechanism in the testes, but rather a toxifying mechanism

(Kluwe 1983; Lag et al. 1989a; Omichinski et al. 1988a, 1988b). 1,2-Dibromo3-chloropropane exposure causes a depletion of seminiferous epithelial germ

cells in humans (Biava et al. 1978) and in animals (Lag et al. 1989a). The

results of genotoxicity studies indicated that 1,2-dibromo-3-chloropropane

metabolites interact with the DNA of spermatogenic cells (Lee and Suzuki 
72 

2. HEALTH EFFECTS 

1979). The difference between the mechanism of toxicity in the liver and in

the testes precludes the clinical use of agents that would alter the

conjugation of metabolites with GSH. Agents that would deplete GSH could

protect against harmful effects of 1,2-dibromo-3-chloropropane in the testes

but would increase the toxicity in the liver. Agents that would prevent the

binding to germ cell DNA would decrease the toxicity in the testes. 

2.9 ADEQUACY OF THE DATABASE 

Section 104(i)(5) of CERCLA, as amended, directs the Administrator of

ATSDR (in consultation with the Administrator of EPA and agencies and programs

of the Public Health Service) to assess whether adequate information on the

health effects of 1,2-dibromo-3-chloropropane is available. Where adequate

information is not available, ATSDR, in conjunction with the National

Toxicology Program (NTP), is required to assure the initiation of a program of

research designed to determine the health effects (and techniques for

developing methods to determine such health effects) of 1,2-dibromo3-chloropropane. 

The following categories of possible data needs have been identified by

a joint team of scientists from ATSDR, NTP, and EPA. They are defined as

substance-specific informational needs that, if met, would reduce or eliminate

the uncertainties of human health assessment. In the future, the identified

data needs will be evaluated and prioritized, and a substance-specific

research agenda will be proposed. 

2.9.1 Existing Information on Health Effects of 1,2-Dibromo-3-chloropropane 

The existing data on health effects of inhalation, oral, and dermal

exposure of humans and animals to 1,2-dibromo-3-chloropropane are summarized

in Figure 2-4. The purpose of this figure is to illustrate the existing

information concerning the health effects of 1,2-dibromo-3-chloropropane.

Each dot in the figure indicates that one or more studies provide information

associated with that particular effect. The dot does not imply anything about

the quality of the study or studies. Gaps in this figure should not be

interpreted as "data needs" information. 

As seen from Figure 2-4, information regarding chronic systemic effects

(cardiovascular, hematological, and renal), neurologic, developmental and

reproductive effects, genotoxicity, and cancer exists for inhalation exposure

of humans to 1,2-dibromo-3-chloropropane. Human data regarding developmental,

reproductive, and genotoxic effects, and cancer were located for oral

exposure. No information was located regarding solely dermal exposure of

humans to 1,2-dibromo-3-chloropropane, although dermal exposure may have

contributed to the effects observed in studies of occupational exposures. 

Studies in animals regarding death, systemic effects, neurologic

effects, developmental effects, reproductive effects, genotoxicity, and cancer 

74
 

2. HEALTH EFFECTS
 

were located for inhalation exposure. Oral studies provide information about

death, systemic, neurologic, developmental, and reproductive effects,

genotoxicity, and cancer. Information about death, effects on the skin and

eyes, and cancer for dermal exposure to 1,2-dibromo-3-chloropropane in animals

is available. 

2.9.2 Data Needs 

Acute-Duration Exposure. Reliable data regarding human acute toxicity

following exposure by any route were not located. Systemic effects observed

in animals exposed to 1,2-dibromo-3-chloropropane were either route specific

or nonspecific. Data were sufficient to identify target organs and systems in

animals. Respiratory tract irritation and toxicity were observed after

inhalation exposure (Saegusa et al. 1982; Torkelson et al. 1961),

gastrointestinal toxicity was reported after oral exposure (Ghanayem et al.

1986), and dermal irritation was reported after dermal exposure (Torkelson et

al. 1961). Hepatic and renal toxicity were observed after both inhalation and

oral exposures (Kato et al. 1980; Russell 1989; Torkelson et al. 1961).

Reproductive system toxicity was also reported after acute inhalation and oral

exposures (Saegusa et al. 1982; Teramoto et al. 1980). Pharmacokinetic data

are not sufficient to identify additional target organs following dermal

exposure. Since hepatic, renal, and reproductive toxicity seem to be common

effects of oral and inhalation exposure, and dermal lethality data suggest

that absorption occurs by the dermal route, further studies on dermal exposure

investigating the target organs might be useful. Dominant lethality was

observed in the lowest dose tested in available studies (Teramoto et al.

1980); therefore, an acute oral MRL could not be derived. Reproductive

toxicity of 1,2-dibromo-3-chloropropane in humans exposed occupationally for

intermediate durations suggests the possibility of similar effects for acuteduration

exposure. Furthermore, there are populations living near hazardous

waste sites that might be exposed to 1,2-dibromo-3-chloropropane in soil or

water through dermal contact, ingestion, or inhalation for brief periods of

time. 

Intermediate-Duration Exposure. The results obtained from workers who 

were exposed for intermediate durations show that 1,2-dibromo-3-chloropropane

is toxic to the male reproductive system (Potashnik et al. 1978, 1984; Whorton

et al. 1979). Data were sufficient to identify the male reproductive system

and other organs and systems as targets in animals. Respiratory tract

irritation and toxicity were observed in mice and rats after inhalation

exposure (NTP 1982). Hepatic and renal toxicity were observed after

inhalation and oral exposures of rats and mice in several studies (NTP 1982;

Rakhmatullayev 1969; Torkelson et al. 1961). Testicular changes were also

found in various species after both routes of exposure. MRLs were derived

from the most sensitive end point (reproductive) for inhalation (Rao et al.

1982) and oral (Foote et al. 1986a, 1986b) exposures. The only information

located regarding toxicity via dermal exposure of intermediate duration was 
75
 

2. HEALTH EFFECTS
 

crustiness of the skin of rabbits. An investigation of internal effects of

intermediate-duration dermal exposure may identify target organs similar to

those of oral and inhalation exposures. Because people who work with

1,2-dibromo-3-chloropropane or people living near hazardous waste sites may

have skin contact with soil or water contaminated with 1,2-dibromo-3-chloropropane

for intermediate durations, information about 1,2-dibromo-3-chloropropane

toxicity by the dermal route is important. 

Chronic-Duration Exposure and Cancer. The evidence of reproductive

toxicity of 1,2-dibromo-3-chloropropane in humans after inhalation exposure is

substantial. One study regarding reproductive effects after oral exposure in

humans was located (Wong et al. 1988). Exposure to contaminated drinking

water probably represented not only oral exposure, but dermal and inhalation

exposure as well. Chronic oral and inhalation studies have been conducted in

rats and mice, and extensive histological examinations have identified the

target organs: respiratory after inhalation (NTP 1982); gastrointestinal,

hepatic, renal, and reproductive after oral exposure (Hazleton 1977, 1978a;

NC1 1978). No studies were located regarding 1,2-dibromo-3-chloropropane

toxicity after chronic dermal exposure. Although chronic inhalation NOAEL and

LOAEL values are available for most target organs and systems, a chronic

inhalation MRL was not derived because a reproductive NOAEL for chronic

exposure is not available, and a MRL derived for any other non-cancer end

point might not reflect adequate protection against reproductive effects. The

lowest available LOAEL cannot be used to derive an MRL because it does not 

protect against reproductive effects and the data have not been verified as

statistically significant for the observed effects. Information regarding the

internal effects of chronic dermal exposure may identify target organs and

thresholds of dermal exposure in animals. This information is important

because populations living near waste sites for long periods of time might be

continuously exposed dermally to 1,2-dibromo-3-chloropropane in contaminated

media. 

Well-conducted chronic inhalation, oral, and dermal exposure studies

provide evidence that 1,2-dibromo-3-chloropropane is carcinogenic in animals

(NC1 1978; NTP 1982; Van Duuren et al. 1979). This is supported by the

genotoxicity studies on prokaryotic and eukaryotic organisms. On the basis of

these data, IARC (1979) and EPA (1985a) concluded that there is sufficient

evidence for the carcinogenicity of 1,2-dibromo-3-chloropropane in animals.

EPA has classified 1,2-dibromo-3-chloropropane as a probable human carcinogen.

Further epidemiological studies of exposed workers would be useful to

determine the possible risk in humans. 

Genotoxicity. A 1,2-dibromo-3-chloropropane-induced genotoxic effect

was reported in humans after occupational exposure. A higher incidence of

newborn girls than boys was observed among offspring of exposed men (Goldsmith

et al. 1984; Potashnik et al. 1984). In animals, dominant lethal effects were

induced after both inhalation and oral exposures in rats (but not in mice) 
76
 

2. HEALTH EFFECTS
 

(Rao et al. 1983; Teramoto et al. 1980). 1,2-Dibromo-3-chloropropane has been

tested in a number of studies in Drosophila melanogaster (Inoue et al. 1982;

Kale and Baum 1982a; Zimmering 1983). The induction of recessive lethals.

genetic crossing-over, chromosome loss, and heritable translocations were

observed. 1,2-Dibromo-3-chloropropane was also mutagenic in a battery of

in vitro tests in prokaryotic systems and in eukaryotic systems (Biles et al.

1978; Loveday et al. 1989; Moriya et al. 1983; Ratpan and Plauman 1988; Tezuka

et al. 1980). These data sufficiently characterize the genotoxic properties

of 1,2-dibromo-3-chloropropane, but further information about genotoxic

effects of 1,2-dibromo-3-chloropropane in humans would be useful. Cytogenetic

analysis of peripheral lymphocytes and sperm examination of exposed workers

and correlation of obtained results with exposure concentrations would be

helpful. 

Reproductive Toxicity. The evidence that 1,2-dibromo-3-chloropropane is

toxic to male reproductive organs in workers who were exposed primarily by

inhalation is extensive (Eaton et al. 1986; Egnatz et al. 1980; Glass et al.

1979; Goldsmith et al. 1984; Lantz et al. 1981; NIOSH 1979; Potashnik et al.

1978, 1984; Whorton et al. 1977, 1979). The only information on reproductive

effects in low-dose orally exposed humans is that no changes in birth rates

were observed in populations that were exposed to 1,2-dibromo-3­

chloropropanecontaminated water (Wong et al. 1988). This route of exposure was not

studied in the human population sufficiently, and it might be important for

populations near the waste sites. Therefore, more studies regarding

reproductive ef.fects in humans after oral exposure from contaminated water

would be useful. The testicular toxicity of 1,2-dibromo-3-chloropropane after

inhalation and oral exposure was demonstrated in rats, but not in mice. AMRL

for intermediate-duration inhalation (Rao et al. 1982) exposure was derived

from a NOAEL for reproductive effects in the rabbit. More information for

reproductive effects from all routes of exposure and different exposure

durations, and on interspecies differences would be useful. No data were

located about reproductive toxicity of 1,2-dibromo-3-chloropropane after

dermal exposure, but skin contact with soil near hazardous waste sites, or

with contaminated water supplies may occur. Mostly negative results were

obtained for reproductive effects in experimental animals after inhalation and

oral exposure of females; however, ovarian cysts were reported in rats after

inhalation exposure (Rao et al. 1983). More data about 1,2-dibromo3-chloropropane toxicity to the female reproductive system would be useful.

More data about 1,2-dibromo-3-chloropropane reproductive toxicity in human

males might be helpful to correlate exposure levels with effects. 

Developmental Toxicity. No developmental effects were observed among

workers who were exposed to 1,2-dibromo-3-chloropropane, but the cohort was

not big enough to give reliable information (Potashnik and Abeliovich 1985;

Potashnik and Phillip 1988). Negative results were obtained after examination

of the offspring in a population exposed to 1,2-dibromo-3-chloropropane

through drinking water (Whorton et al. 1989). Reduced litter weight and size 
77
 

2. HEALTH EFFECTS 

were found in rats at doses that caused maternal toxicity (Johnston et al.

1986; Ruddick and Newsome 1979). No information about developmental toxicity

after dermal exposure is available. More data on developmental toxicity in

experimental animals would be useful to identify possible risks for humans. 

Immunotoxicity. No data were located regarding immunological effects of

1,2-dibromo-3-chloropropane in humans after inhalation, oral, or dermal

exposure of any duration. Results of animal studies suggest that bone marrow

may be a target (NTP 1982). The apparent greater susceptibility of

1,2-dibromo-3-chloropropane-exposed animals to pulmonary infections also

suggests a possible immunologic effect. A battery of immune function tests

has not been performed in humans or in animals, but would provide valuable

information to confirm or refute the suggestive evidence. Studies regarding

skin sensitization with 1,2-dibromo-3-chloropropane have not been performed. 

Neurotoxicity. Workers exposed to 1,2-dibromo-3-chloropropane

occupationally reported subjective neurological symptoms (Whorton et al.

1977). Depression of the central nervous system was observed in rats after

acute inhalation (Torkelson et al. 1961) and oral (Reel et al. 1984; Torkelson

et al. 1961) exposure. Histopathological changes in brains were detected

after intermediate and chronic inhalation exposures in animals (NTP 1982; Rao

et al. 1983). In contrast, no histopathological changes were found after oral

exposure in the same duration categories (Johnston et al. 1986; NC1 1978). No

data were located regarding neurotoxicity of 1,2-dibromo-3-chloropropane after

dermal exposure in animals. Additional neurological and neurobehavioral tests

in experimental animals would help to identify possible subtle neurological

effects and the exposures associated with them. 

Epidemiological and Human Dosimetry Studies. Several epidemiological

studies have been conducted in humans exposed to 1,2-dibromo-3-chloropropane.

Some dealt with the occurrence of cardiovascular disease and cancer in the 

exposed workers or in a population exposed to contaminated drinking water

(Hearn et al. 1984; Wong et al. 1984, 1989). The limitations of occupational

studies are coexposure to other chemicals and uncertainty about actual

1,2-dibromo-3-chloropropane concentrations in the workplace. More

retrospective studies would be useful to determine possible 1,2-dibromo3-chloropropane-induced mortality from cancer. 

Other epidemiologic studies dealt with 1,2-dibromo-3-chloropropane

toxicity on the reproductive system after occupational exposure (Eaton et al.

1986; Egnatz et al. 1980; Glass et al. 1979; Goldsmith et al. 1984; Lantz et

al. 1981; NIOSH 1979; Potashnik et al. 1978, 1984; Whorton et al. 1979) or

exposure to contaminated drinking water (Wong et al. 1988). 1,2-Dibromo3-chloropropane-induced toxicity to the human male reproductive system was

well established in several cross-sectional studies. Reliable dosimetry data

on the exposed population and its correlation with early signs of mild

oligospermia would be useful. Follow-up studies of exposed workers would be 
78
 

2. HEALTH EFFECTS
 

of value to further determine the reversibility of testicular effects. The

determination of 1,2-dibromo-3-chloropropane toxicity to the female

reproductive system would be valuable. More data about the reproductive

outcome in exposed populations and the possibility of spontaneous abortions

after exposure would be useful. The inhalation and dermal routes of exposure

are important for occupationally exposed individuals; inhalation, oral, and

dermal exposure might be of concern to populations living near hazardous waste

sites as 1,2-dibromo-3-chloropropane might get into soil and then contaminate

the source of water used for bathing or drinking. 

Biomarkers of Exposure and Effect. No biomarkers of exposure were

identified for 1,2-dibromo-3-chloropropane. Several studies indicated that

1,2-dibromo-3-chloropropane induced DNA damage and changes in the activity of

microsomal enzymes (Kluwe 1983; Suzuki and Lee 1981); however, these changes

are not.specific for 1,2-dibromo-3-chloropropane exposure and cannot be used

as biomarkers. Further studies regarding possible biochemical changes after

1,2-dibromo-3-chloropropane exposure would be useful. The identification of

1,2-dibromo-3-chloropropane metabolites in the urine and their correlation

with levels of exposure would also be useful. 

Elevated levels of FSH were found in men exposed to 1,2-dibromo3-chloropropane (Whorton et al. 1979); however, this elevation does not

usually occur after a short-term exposure. It is associated with severe

testicular degeneration and azoospermia in exposed men. It might occur after

prolonged exposure or even after a nonexposure period following exposure in

unrecovered men. This assay, however, cannot be correlated with the early

signs of testicular toxicity. Further studies for developing specific early

biomarkers of disease would be useful. Identification of biochemical changes

in sperm would be particularly useful because sampling would involve methods

that are already used to monitor occupational exposure. 

Absorption, Distribution, Metabolism, and Excretion. 1,2-Dibromo3-chloropropane can be absorbed through the lungs, gastrointestinal tract, and

skin, as indicated by toxicity studies (Gingell et al. 1987a; Kato et al.

1979a). Absorption has been studied specifically only after oral exposure

(Gingell et al. 1987a; Kato et al. 1979a). The absorption followed firstorder

kinetics, and no saturation has been observed with concentrations tested

thus far. In animals, 1,2-Dibromo-3-chloropropane is quickly distributed to

tissues throughout the body, with highest concentrations accumulating in

adipose tissue (Kato et al. 1979a, 1980). The metabolic pathway was

determined in rats (Jones et al. 1979). Excretion occurs mainly via urinary

metabolites in exposed animals, and smaller amounts are excreted in breath and

bile (Gingell et al. 1987b; Kato et al. 1979a). No comparisons have been made

regarding absorption, distribution, metabolism, and excretion via different

routes of exposure. Further studies in animals, especially after inhalation

exposure, would be useful. The determination of the urinary and breath 
79 

2. HEALTH EFFECTS 

excretion of 1,2-dibromo-3-chloropropane and its metabolites in exposed humans

with known exposure would be useful for future monitoring purposes. 

Comparative Toxicokinetics. The differences between reproductive

toxicity in mice and rats were demonstrated in several studies. Similar

differences were observed in toxicokinetics between rats and hamsters (with

high testicular toxicity) and mice and guinea pigs (with low testicular

toxicity) (Lag et al. 1989a; MacFarland et al. 1984). Also, rabbits were

found to be more susceptible to reproductive effects than rats (Rao et al.

1982, 1983). The fact that reproductive toxicity of 1,2-dibromo-3­

chloropropane was also observed in humans might suggest that rabbits, and

possibly rats, could serve as a model for 1,2-dibromo-3-chloropropane

toxicity. Further investigation of toxicokinetics in different species and

the comparison of detected metabolites with those detected in humans would be

useful. 

Mitigation of Toxicological Effects. No specific information was

located regarding mitigation of effects in 1,2-dibromo-3-chloropropane. The

characteristic effects of 1,2-dibromo-3-chloropropane-induced toxicity are

known, and nonspecific treatments for intoxicated persons have been

recommended (Bronstein and Currance 1988; NIOSH 1988; Stutz and Janusz 1988).

The mechanism of toxicity involves microsomal metabolism of 1,2-dibromo3-chloropropane to reactive intermediates that are capable of binding to

biological macromolecules such as DNA and protein. Conjugation of reactive

metabolites with GSH acts as a detoxifying mechanism in the liver (Kato et al.

1979b; Kluwe et al. 1982). In contrast, conjugation with GSH increases the

toxicity in the testes (Kluwe 1983). Agents that deplete GSH might,

therefore, decrease testicular toxicity but might also increase liver

toxicity. Therefore, the development of specific agents that prevent liver

and testicular toxicity by obstructing the binding of active metabolites to

DNA would be useful. 

2.9.3 On-going Studies 

No on-going studies were located regarding 1,2-dibromo-3-chloropropane

toxicity or toxicokinetics. 

81 

3. CHEMICAL AND PHYSICAL INFORMATION 

3.1 CHEMICAL IDENTITY 

Data pertaining to the chemical identity of 1,2-dibromo-3-chloropropane

are listed in Table 3-l. 

3.2 PHYSICAL AND CHEMICAL PROPERTIES 

The physical and chemical properties of 1,2-dibromo-3-chloropropane

are presented in Table 3-2. 



85 

4. PRODUCTION, IMPORT, USE, AND DISPOSAL 

4.1 PRODUCTION 

1,2-Dibromo-3-chloropropane was first produced commercially in the

United States in 1955 (IARC 1979). In 1969, U.S. production was 8.58 million

pounds (IARC 1979). Estimates of annual production during 1974-1975 ranged

from 18 to 20 million pounds (IARC 1979; NTP 1985). 1,2-Dibromo-3­

chloropropane is no longer commercially manufactured in the United States

(Hawley 1981; Sax and Lewis 1987). R.W. Greeff & Co., Inc., in Old Greenwich,

Connecticut, is listed as a current supplier of 1,2-dibromo-3-chloropropane

for domestic research purposes (OPD 1989). It is not known whether this

supplier produces 1,2-dibromo-3-chloropropane in the United States or imports

the chemical. Two companies were listed as producers of 1,2-dibromo-3­

chloropropane in 1977 (EPA 1989b). The production volume of Columbia Organic

Chemicals Co., in Columbia, South Carolina, was listed as less than 1,000

pounds. No production volume was listed for the other producer, Velsicol

Chemical Corp., in El Dorado, Arkansas. As 1,2-dibromo-3-chloropropane is no

longer used as a fumigant and nematocide in the United States, it is likely

that its current production volume in the United States, if any, is very low. 

4.2 IMPORT/EXPORT 

No quantitative data concerning the recent import or export of 1,2­

dibromo-3-chloropropane in the United States were found. Ameribrom Inc., in

New York, New York, was listed as an importer of 1,2-dibromo-3-chloropropane

in 1977; no import volume was listed (EPA 1989b). Because R.W. Greeff 6 Co.,

Inc., is listed as a current supplier of 1,2-dibromo-3-chloropropane (OPD

1989), it may be an importer of the chemical. It is unlikely that significant

amounts of the chemical are imported into the United States since its former

major uses as a soil fumigant and nematocide are no longer permitted in the

United States (EPA 1977, 1979, 1985b, 1985c). No significant exports are

expected since it has been reported that 1,2-dibromo-3-chloropropane is no

longer made in the United States (Hawley 1981; Sax and Lewis 1987). 

4.3 USE 

1,2-Dibromo-3-chloropropane is used as an intermediate in the synthesis

of organic chemicals, such as the brominated flame retardant tris[(2,3­

dibromopropyl)phosphate] (Verschueren 1983). Until 1977, 1,2-dibromo-3­

chloropropane was extensively used as a soil fumigant and nematocide on over

40 different crops in the United States (Anonymous 1988). The chemical was

used to protect field crops, vegetables, fruits and nuts, nursery and

greenhouse crops, and turf from pests (NTP 1985). From 1977 to 1979, EPA

suspended registration of products containing 1,2-dibromo-3-chloropropane

except for use on pineapples in Hawaii (Anonymous 1988; EPA 1977, 1979). In

1985, EPA issued an intent to cancel all registrations for 1,2-dibromo-3­

chloropropane-containing pesticide products, including use on pineapples. 
86
 

4. PRODUCTION, IMPORT, USE, AND DISPOSAL 

Subsequently, the use of existing stocks of 1,2-dibromo-3-chloropropane on

pineapples was prohibited (EPA 1985b, 1985c). 

Prior to the cancellation of pesticide uses, 1,2-dibromo-3-chloropropane

was used extensively; 9.8 million pounds of 1,2-dibromo-3-chloropropane were

applied in 1974 (NTP 1985). In California, 831,000 pounds of the chemical

were applied, mainly on grapes and tomatoes, during 1977 (NTP 1985). The

volume of 1,2-dibromo-3-chloropropane applied to pineapple fields in Hawaii

between 1979 and 1985 was probably high, since during much of that time, the

chemical was the preferred fumigant for use on pineapple fields (Albrecht

1987). 

4.4 DISPOSAL 

1,2-Dibromo-3-chloropropane has been identified as a hazardous waste by

EPA, and the disposal of this compound is regulated under the federal Resource

Conservation and Recovery Act (RCRA) (EPA 1988b, 1988c). Specific information

regarding federal regulations on the land disposal of 1,2-dibromo-3-chloropropane

is provided in the Code of Federal Regulations (EPA 1988c). No

acceptable chemical decontamination is known for 1,2-dibromo-3-chloropropane

(HSDB 1989). Dilution of the chemical with a flammable solvent is necessary

for incineration to be effective, and the products must be passed through

scrubbers to remove the hydrogen bromide and hydrogen chloride that is

produced (HSDB 1989). 
87
 

5. POTENTIAL FOR HUMAN EXPOSURE 

5.1 OVERVIEW 

There are no known natural sources of 1,2-dibromo-3-chloropropane

(IARC 1979). Although data on releases of 1,2-dibromo-3-chloropropane to the

atmosphere, water, and soil are lacking, current releases of the chemical to

the environment that result from the production and use of the chemical are

probably low because the chemical is used only as an intermediate in organic

synthesis and for research purposes. Relatively minor releases to the

environment may still occur from contaminated soil, groundwater, and surface

water. This is especially true at or near agricultural areas where

1,2-dibromo-3-chloropropane had been extensively used in the past or where a

chemical spill occurred, and from hazardous waste sites where improper

disposal techniques were used. 

1,2-Dibromo-3-chloropropane in soil is subject both to leaching into

groundwater and to volatilization to the atmosphere from near-surface soil, as

has been observed in field soil studies. Small amounts of 1,2-dibromo-3­

chloropropane may be absorbed through the soil roots and translocated to other

plant parts. 1,2-Dibromo-3-chloropropane that is present in water is expected

to volatilize to the atmosphere. 1,2-Dibromo-3-chloropropane is not expected

to adsorb significantly to sediment or suspended organic matter in water,

bioconcentrate in fish and other aquatic organisms, or to biomagnify from

lower to higher trophic levels of the food chain. The primary degradation

process for 1,2-dibromo-3-chloropropane in the atmosphere is estimated to

occur via gas-phase reaction with photochemically produced hydroxyl radicals.

Degradation of 1,2-dibromo-3-chloropropane in natural waters and soil is a

slow process. 1,2-Dibromo-3-chloropropane may be susceptible to slow

biodegradation in soil and natural waters based on the observation of

biologically mediated dehalogenation in certain soils. 1,2-Dibromo3-chloropropane residues that do not leach or volatilize appear to be very

persistent in soil based upon monitoring data. Laboratory experiments using

anoxic biofilm columns showed that biodegradation of 1,2-dibromo3-chloropropane in groundwater may occur under anaerobic conditions. 

The general population may be infrequently exposed to very small amounts

of 1,2-dibromo-3-chloropropane through the ingestion of contaminated drinking

water and food. Since 1,2-dibromo-3-chloropropane is no longer used as a

fumigant and nematocide in the United States and since such use in the past

was limited to certain agricultural areas, widespread exposure of the general

public or of workers to 1,2-dibromo-3-chloropropane is not likely. Even in

the agricultural areas, exposure is probably minor. 

EPA has identified 1,177 National Priorities list (NPL) sites.

1,2-Dibromo-3-chloropropane has been found at 8 of the sites evaluated for the

presence of this chemical (View 1990). However, we do not know how many of

the 1,177 sites have been evaluated for this chemical. As more sites are 
88 

5. POTENTIAL FOR HUMAN EXPOSURE 

evaluated by the EPA, the number may change. The frequency of these sites

within the United States can be seen in Figure 5-l. The Contract Laboratory

Program (CLP) Statistical Database did not list 1,2-dibromo-3-chloropropane

among the compounds that are most commonly found at NPL waste sites in

groundwater, surface water, or soil (CLPSD 1989). 

5.2 RELEASES TO THE ENVIRONMENT 

5.2.1 Air 

Data on releases of 1,2-dibromo-3-chloropropane to the atmosphere are

lacking. Significant releases to the atmosphere probably occurred in the past

due to the extensive manufacture and use of the chemical as a soil fumigant on

a wide variety of crops in the United States (Section 5.3.1) (Albrecht and

Chenchin 1985; Hodges and Lear 1974; NTP 1985; Peoples et al. 1980). However,

current releases of 1,2-dibromo-3-chloropropane to the atmosphere that result

from the production and use of the chemical are probably very low because the

chemical is used only as an intermediate in organic synthesis and for research

purposes. Use of 1,2-dibromo-3-chloropropane as a soil fumigant, the only

major purpose for which the chemical had been used in the past, is no longer

permitted in the United States (Anonymous 1988; EPA 1977, 1979, 1985b).

Releases to the atmosphere may continue to occur from soils that were treated

with 1,2-dibromo-3-chloropropane in the past and that still contain residues

in the soil. Further releases, may result from the use of well water and other

water sources that were contaminated with the chemical due to leaching through

soil. However, no data were found that would permit the estimation of the

amount that is currently being released to the ambient atmosphere. Additional

potential sources of release to the atmosphere include identified and

unidentified hazardous waste sites that contain 1,2-dibromo-3-chloropropane

either in surface water or in near-surface soil. 

5.2.2 Water 

Data on release of 1,2-dibromo-3-chloropropane to water are lacking.

Significant releases to water may have occurred in the past due to the

extensive manufacture and use of the chemical as a soil fumigant on a wide

variety of crops in the United States (Section 5.3.1), but current releases

are probably very low because the chemical is now used only as an intermediate

in organic synthesis and for research purposes. Its use as a soil fumigant,

the only major purpose for which the chemical was used in the past, is no

longer permitted in the United States (Section 4.3). The potential pathways

for release to surface waters include runoff from spill and hazardous waste

sites where improper disposal techniques were used, runoff from farmland that

was irrigated with contaminated well water or other water, and direct release

during manufacture and use as an intermediate for organic synthesis and

research. Releases to groundwater may occur via leaching of residues in 

90
 

5. POTENTIAL FOR HUMAN EXPOSURE 

agricultural soils that were treated with 1,2-dibromo-3-chloropropane in the

past, and via leaching through soils at hazardous waste and spill sites that

contain the chemical. 

The CLP Statistical Database (CLPSD) did not list 1,2-dibromo-3-chloropropane

among the compounds most commonly found in groundwater or surface

water at NPL waste sites (CLPSD 1989). 

5.2.3 Soil 

Data on current release of 1,2-dibromo-3-chloropropane to soils are

lacking probably because few, if any, releases to soil are currently

occurring. Significant releases to soil occurred in the past as a result of

its extensive use as a soil fumigant on a wide variety of crops in the United

States (Section 5.3.1). Current releases are probably very low because the

chemical is used only as an intermediate in organic synthesis and for research

purposes. Its use as a soil fumigant, the only major purpose for which the

chemical was used in the past, is no longer permitted in the United States

(Section 4.3). Potential pathways for release to soil include disposal at

hazardous waste sites with improper disposal techniques, spills, and

irrigation with contaminated well water or other water. The CLPSD did not

list 1,2-dibromo-3-chloropropane among the compounds most commonly found in

soil at NPL waste sites (CLPSD 1989). 

5.3 ENVIRONMENTAL FATE 

5.3.1 Transport and Partitioning 

1,2-Dibromo-3-chloropropane in soil is subject both to leaching into

groundwater and to volatilization from near-surface soil. The experimental

K,,s of approximately 149 in Lincoln fine sand (Wilson et al. 1981) and 128 in

an unspecified soil (Sabljic 1984) indicate that 1,2-dibromo-3-chloropropane

is highly mobile in soil (Swann et al. 1983). Data from field and laboratory

experiments confirm that 1,2-dibromo-3-chloropropane has a strong potential to

leach through soil to groundwater (Bomberger et al. 1983; Carter et al. 1984;

Hodges and Lear 1974; Kloos 1983; Oki and Giambelluca 1987; Wilson et al.

1981). The rate and extent that 1,2-dibromo-3-chloropropane leaches through

agricultural soil depend upon various factors that include the water-holding

capacity of the soil (which is related to the size of the air spaces in the

soil), the amount of organic matter in the soil, the amount of water applied,

and the method of 1,2-dibromo-3-chloropropane application (Hodges and Lear

1974). 

In a study using primarily clay, silt, and sandy soils, mobility was

lowest in the clay soil, which had a higher content of organic matter than

both sandy and silt soil and a lower amount of air space between particles of

soil than was found in the silt soil (Hodges and Lear 1974). Mobility was

highest in the sandy soil, which had the largest spaces between soil particles 
91 

5. POTENTIAL FOR HUMAN EXPOSURE 

(and therefore the fastest rate of water movement) and the lowest amount of

organic matter (Hodges and Lear 1974). Application of 1,2-dibromo3-chloropropane by either injection or application in irrigation water (flood

application) led to extensive and rapid penetration of the fumigant.

Application of 1,2-dibromo-3-chloropropane by injection led to greater

penetration in the clay and silt soils, compared to its flood application,

because it was retained near the soil surface in the latter case and was 

subsequently lost to the atmosphere (Hodges and Lear 1974). An illustration

of the volatilization behavior of 1,2-dibromo-3-chloropropane from soil was

obtained in a study of a pineapple field that was treated with 4 gallons per

acre of the chemical injected to a depth of 12 inches (Albrecht and Chenchin

1985). 1,2-Dibromo-3-chloropropane concentration in the air at ground level

and at 42 inches above the ground reached peaks after 2 days (approximately

0.4 and 8 ppb, respectively), dropped off to non-detectable levels after

3 days, peaked after 6 days following a 6-mm rainfall on days 5-6

(approximately 1.2 and 0.5 ppb at ground level and 42 inches, respectively),

and dropped off but remained at measurable levels for the remainder of the

30-day experiment (Albrecht and Chenchin 1985). These data support results

obtained in modeling studies that predict that volatilization of 1,2-dibromo3-chloropropane from near-surface soil is important (Bomberger et al. 1983;

Jury et al. 1987). Estimated volatilization half-lives for 1,2-dibromo3-chloropropane that was evenly distributed in the top 10 cm of soil varied

between 0.6 days in dry soil with very low soil organic content to 26.2 days

in wet soil with relatively high soil organic content (Bomberger et al. 1983).

The use of plastic coverings over 1,2-dibromo-3-chloropropane treated fields

retards volatilization loss from soil. 

Small amounts of 1,2-dibromo-3-chloropropane may be absorbed through the

roots of plants growing in 1,2-dibromo-3-chloropropane contaminated soil and

may be translocated to other parts of the plants (see Section 5.4.4.) (Carter

and Riley 1982; Newsome et al. 1977). 1,2-Dibromo-3-chloropropane was found

in peaches and in the roots and tops of carrots and radishes that were grown

in 1,2-dibromo-3-chloropropane treated soil. The generally lower amounts of

the chemical found in the foliage than in the roots of the carrot and radish

plants may have resulted from translocation from the roots or from absorption

of 1,2-dibromo-3-chloropropane that had volatilized from the soil to the air

(Newsome et al. 1977). The possibility of absorption of volatilized 1,2­

dibromo-3-chloropropane by the peaches appears to be a less likely explanation

than translocation because the 1,2-dibromo-3-chloropropane was applied to the

fields in the fall, months before the spring harvest of the peaches (Carter

and Riley 1984). 

In the atmosphere, 1,2-dibromo-3-chloropropane is expected to exist

predominantly in the vapor phase based upon its vapor pressure (Table 3-2)

(Eisenreich et al. 1981; Munnecke and VanGundy 1979). Because significant

amounts of 1,2-dibromo-3-chloropropane are not likely to be present in the

particulate phase, dry deposition to the earth's surface is not a significant

removal process. Based upon its high water solubility (Table 3-2), the small 
92 

5. POTENTIAL FOR HUMAN EXPOSURE 

amounts of 1,2-dibromo-3-chloropropane that are present in air may be removed

by wet deposition; however, much of the 1,2-dibromo-3-chloropropane removed

from the atmosphere by washout is likely to reenter the atmosphere by

volatilization. No experimental or predictive data were located in the

literature regarding the transport of 1,2-dibromo-3-chloropropane in the

atmosphere; however, the expected half-life of 36 days (Section 5.3.2.1)

indicates that it could be transported long distances in the atmosphere. 

1,2-Dibromo-3-chloropropane that is present in water 'is expected to

volatilize rapidly to the atmosphere. Using the Henry's law constant, a halflife

of 13.5 hours was calculated for evaporation from a model river l-m deep,

flowing at 1 m/second, with a wind velocity of 3 m/second, and neglecting

adsorption to sediment (Thomas 1982). A volatilization half-life of 8 days

from a model pond can be estimated using a three-compartment EXAMS model (EPA

1985d). 1,2-Dibromo-3-chloropropane is not expected to adsorb significantly

to sediment and suspended organic matter based upon a KOC ranging between 128

and 149 (Sabljic 1984; Wilson et al. 1981). It is not expected to

bioconcentrate in fish and other aquatic organisms based upon an estimated

bioconcentration factor (BCF) of 11.2 (calculated from water solubility;

Table 3-2) (Bysshe 1982; Munnecke and VanGundy 1979). No data were located

that would indicate a potential for 1,2-dibromo-3-chloropropane to biomagnify

from lower to higher trophic states of aquatic or terrestrial food chains. 

5.3.2 Transformation and Degradation 

5.3.2.1 Air 

The primary degradation process for 1,2-dibromo-3-chloropropane in the

atmosphere is likely to be a vapor-phase reaction with photochemically

produced hydroxyl radicals. The experimental rate constant for this process

is 4.4x10-13 cm3

/molecule-set (Tuazon et al. 1986). This corresponds to a

half-life of 36 days at an estimated atmospheric concentration of

5~10~ hydroxyl radicals/cm3

. Direct photolysis of 1,2-dibromo-3-chloropropane

is not expected to occur in the atmosphere since the chemical lacks a

chromophore that absorbs light at environmentally significant wavelengths

(greater than 290 nm) (Silverstein et al. 1974). 

5.3.2.2 Water 

Degradation of 1,2-dibromo-3-chloropropane in natural waters is a slow

process. It volatilizes from surface waters before significant degradation

can occur. Hydrolysis of 1,2-dibromo-3-chloropropane in natural waters is

unlikely to be an important removal process. The base hydrolysis rate

constant at 25°C of 20.6 hr-1 M-l was extrapolated from data obtained at 40°

100°C (Burlinson et al. 1982). This rate constant corresponds to half-lives

for hydrolysis of 38 years and 140 days at pH 7 and 9, respectively. Direct

photolysis of 1,2-dibromo-3-chloropropane is not likely to occur in

environmental waters since the chemical lacks a chromophore that absorbs light 
93 

5. POTENTIAL FOR HUMAN EXPOSURE 

at environmentally significant wavelengths (greater than 290 nm) (Silverstein

et al. 1974). 

No studies were located regarding the biodegradation of 1,2-dibromo3-chloropropane in natural waters. 1,2-Dibromo-3-chloropropane may be

susceptible to slow biodegradation in natural waters based upon the

observation of biologically mediated dehalogenation in certain soils amended

with a nutrient (Castro and Belser 1968). In experiments using anoxic biofilm

columns that were designed to resemble groundwater environments, 1,2-dibromo3-chloropropane was susceptible to biodegradation under conditions of

methanagenesis, denitrification, and sulfate respiration (Bouwer and Wright

1988). Although data from these experiments cannot be used to predict what

type of aquifer is likely to support biodegradation or the rate of

biodegradation to be expected, they indicate that some biodegradation of

1,2-dibromo-3-chloropropane in groundwater may occur under anaerobic

conditions. 

5.3.2.3 Soil 

1,2-Dibromo-3-chloropropane is subject to biodehalogenation in soilwater

suspensions (aerobic/anaerobic conditions not specified) in the presence

of an added nutrient (Castro and Belser 1968). Biodegradation did not occur

in the absence of the added glycerol nutrient or in suspensions of sterilized

soil. Approximately 75% of the soil samples that were tested affected

dehalogenation of 1,2-dibromo-3-chloropropane. The highest rate of

dehalogenation was 20% in 1 week at pH 8, which was measured by the rate of

bromide ion formation. The maximum observed yield of bromide from

1,2-dibromo-3-chloropropane was 63% of the theoretical yield in 4 weeks under

unspecified conditions. The data from these experiments suggest that

1,2-dibromo-3-chloropropane may be susceptible to biodegradation in soil under

certain conditions; however, it is not possible to predict the soils that will

biodegrade the chemical or what the rate of biodegradation might be (Castro

and Belser 1968). In another study, it appears that no degradation of

1,2-dibromo-3-chloropropane was observed in soil columns within 25 days under

aerobic conditions (Wilson et al. 1981). Based upon aqueous hydrolysis data,

chemical hydrolysis is not expected to be significant except in very alkaline

soils. 

Based upon monitoring data obtained years after the last known

application, 1,2-dibromo-3-chloropropane residues that do not leach or 
94 

5. POTENTIAL FOR HUMAN EXPOSURE 

volatilize appear to be very persistent in soil. For example, 1,2-dibromo3-chloropropane residues as high as 0.5 μg/kg were found in the soil at a site

6-7 years following the last known application (Nelson et al. 1981). 

5.4 LEVELS MONITORED OR ESTIMATED IN THE ENVIRONMENT 

5.4.1 Air 

Few data concerning the detection of 1,2-dibromo-3-chloropropane in the

atmosphere were found. Ambient air surrounding bromine industry chemical

plants in the vicinity of two cities in Arkansas were analyzed for the

presence of 1,2-dibromo-3-chloropropane in 1976 and 1977 (Pellizzari et al.

1978). In the vicinity of Magnolia, Arkansas, the maximum concentration of

the chemical found in air surrounding a Dow Chemical Company plant was

6,653 ng/m3

. The maximum concentration in the El Dorado, Arkansas, area was

187 ng/m3

 at the Velsicol Chemical Corporation (Pellizzari et al. 1978). In a

study that reported data collected primarily between 1970 and 1980, the median

concentration of 1,2-dibromo-3-chloropropane was 1.8 ng/m3

 in ambient air near 

source-dominated areas; no data were listed for rural, remote, urban, or

suburban areas (Brodzinsky and Singh 1982). This study is not comprehensive

since it involved only scattered sampling of bromine industry chemical plants

in one state. Furthermore, the data are old and were taken when the chemical

was still being manufactured and widely used as a soil fumigant. Current

releases to the atmosphere from manufacturing or research-use point sources

are not likely to be significant since only limited amounts are presumed to be

made and used (Sections 4.3 and 5.2.1). Significant concentrations of the

chemical are probably not present in the ambient atmosphere at this time;

therefore, the background level estimated for ambient air is expected to be

less than'the detection limit. Exceptions may include air near hazardous

waste sites where 1,2-dibromo-3-chloropropane has been disposed, although no

data were found concerning atmospheric concentrations at these sites. 

5.4.2 Water 

Data concerning levels of 1,2-dibromo-3-chloropropane in water are

lacking, and those available are neither current nor comprehensive

(Table 5-l). The data in Table 5-l indicate that contamination of municipal

drinking water supplies was not widespread in the past. Where contamination

was found, the concentrations had been less than 10 μg/L; however,

concentrations as high as 95 and 137 μg/L have been reported in water from

drinking water wells in California and Arizona, respectively, although no

information was provided on possible sources of contamination (Burmaster

1982). In a study of water from drinking water wells in the Fresno area of

California's Central Valley conducted between 1979 and 1983, the tested wells

generally had seasonal concentration patterns ranging from a low in winter to

highs in spring/summer months. The 1,2-dibromo-3-chloropropane concentration

also changed with daily use patterns ranging from highs at the start of

pumping with lower concentrations as pumping continued (Kloos 1983). In a 

96
 

5. POTENTIAL FOR HUMAN EXPOSURE
 

study of various waters in South Carolina sampled between 1979 and 1980,

concentrations of 1,2-dibromo-3-chloropropane in water from one of three

municipal water supplies ranged from 0.008 μg/L (detection limit) to 0.05 μg/L

in an area where 1,2-dibromo-3-chloropropane was not known to have been used

(Carter and Riley 1981). 

Few data concerning the detection of 1,2-dibromo-3-chloropropane in

surface water were found. In a study of South Carolina surface waters that

were sampled between 1979 and 1980, concentrations of 1,2-dibromo-3-chloropropane

ranged from not detected (detection limit = 0.008 μg/L) to 0.05 μg/L

in areas where 1,2-dibromo-3-chloropropane usage rates ranged from non-use to

scattered use (Carter and Riley 1981). In high-use areas, 18 of 48 sites had

concentrations exceeding the background level of 0.05 μg/L; concentrations as 

high as 0.35 μg/L were detected (Carter and Riley 1981). 1,2-Dibromo-3­

chloropropane was identified, but not quantified, in surface water at a

bromine industry chemical plant in the vicinity of Magnolia, Arkansas, which

was sampled in 1977 (Pellizzari et al. 1978). 

These data, combined with the knowledge that use of 1,2-dibromo3-chloropropane as a soil fumigant has not been permitted in the United States

for several years, suggest that widespread exposure to the chemical in

drinking water is not likely. The estimated background level for groundwater

in areas where the chemical has not been used or disposed of in the past and

in surface water is less than the detection limit. In areas where it was used 

as a soil fumigant, background levels of 0.001-0.008 μg/L can be expected

depending on the amount used and environmental conditions. 

5.4.3 Soil 

Few data concerning the detection of 1,2-dibromo-3-chloropropane in soil

were found. In a study conducted in 1980, 1,2-dibromo-3-chloropropane was

analyzed in soils and subsoils from fields at four sites that were known to

have been treated with 1,2-dibromo-3-chloropropane (the last application was

3-6 years prior to sampling) and where groundwater contamination with the

chemical had been identified (Nelson et al. 1981). The concentrations in the

soil and subsoils ranged from not detected (detection limit not stated) to

9 μg/kg (dry weight basis); higher levels were generally found in clay and

silt layers (Nelson et al. 1981). In 32 fields that had received 1,2-dibromo3-chloropropane treatments 2-4 years prior to sampling, the surface of the

topsoil contained approximately 2-5 μg/kg of the chemical (Peoples et al. 

1980). 

In another study, soil samples taken from two South Carolina peach

orchards with similar histories of 1,2-dibromo-3-chloropropane usage contained

mostly undetectable levels (detection limit 0.025 μg/kg), but up to less than 

0.1 and less than 0.5 μg/kg of the chemical was found in soil from the two

orchards (Carter et al. 1984). Soil profile samples indicated that the

residues were usually found in the upper 90 cm (Carter et al. 1984). Higher 
97
 

5. POTENTIAL FOR HUMAN EXPOSURE
 

levels of contamination in the groundwater at the first site were explained by

a spill in which a formulation containing 1,2-dibromo-3-chloropropane had

leaked from a rusting barrel (30 m from the well) leading to concentrations as

high as 7.844 μg/kg in the adjacent soil (Carter et al. 1984). 

These data, combined with the knowledge that use of 1,2-dibromo3-chloropropane as a soil fumigant has not been permitted in the United States

for several years, suggest that widespread exposure to the chemical due to

contamination of soil is unlikely. The estimated background level for ambient

soil in areas where the chemical has not been used is less than the detection 

limit. In areas where it was used as a soil fumigant or disposed, background

levels of up to 0.5 μg/kg can probably be expected. 

5.4.4 Other Environmental Media 

Few data concerning levels of 1,2-dibromo-3-chloropropane in other

environmental media were found. 1,2-Dibromo-3-chloropropane was tentatively

identified, not quantified, in sediment at a bromine industry chemical plant

in the vicinity of Magnolia, Arkansas, which was sampled in 1977 (Pellizzari

et al. 1978). 

Peaches grown in soil treated by injection into the soil of 51.4 and

137.5 L/hectare of a fumigant formulation containing 1.45 kg/L of 1,2-dibromo3-chloropropane (peaches harvested between 183 and 217 days following

treatment) contained 0.13 and 0.72 ppb 1,2-dibromo-3-chloropropane (Carter and

Riley 1984). No residues were found in peaches grown in nonfumigated soil or

in soil treated at or below the recommended treatment rate of 46.8 L/treated

hectare (Carter and Riley 1984). In another study, Carter and Riley (1982)

found levels as high as 24.7 ppb in peaches that were treated 114 days prior

to harvest (application rate not reported). Carrots grown in soil that was

treated with 12.26 pounds/acre of 1,2-dibromo-3-chloropropane by injection to

a depth of 7 inches contained up to 1.50 ppm 3 weeks after treatment, and the

residues persisted for 16 weeks when fumigation was at seeding (Newsome et al.

1977). Most of the residues were contained in the pulp of the carrots and

two-thirds of the residues in unpeeled carrots disappeared when the carrots

were boiled for 5 minutes. The maximum concentration found in radishes from 

treated fields (application rate of 12.26 pounds/acre of 1,2-dibromo-3­

chloropropane) was 0.194 ppm (Newsome et al. 1977). 

1,2-Dibromo-3-chloropropane was found at concentrations between 15 and

25 ppb in a commercial sample of sodium humate that was apparently imported

from Germany (Gabbita 1986). It was not known whether the soil from which the

humate was extracted was itself contaminated with the chemical. 
98
 

5. POTENTIAL FOR HUMAN EXPOSURE 

5.5 GENERAL POPULATION AND OCCUPATIONAL EXPOSURE 

The general population may be exposed to 1,2-dibromo-3-chloropropane

through the ingestion of contaminated drinking water and food. Contaminated

drinking water is most likely to be derived from contaminated groundwater

sources at or near locations where 1,2-dibromo-3-chloropropane had been used

as a soil fumigant. Not only are these areas limited in number and size, but

the use of 1,2-dibromo-3-chloropropane as a soil fumigant has been banned for

some time; therefore, although no current and comprehensive data were found to

calculate an estimate of general population exposure to 1,2-dibromo-3-chloropropane

from drinking water, the estimate is expected to be minimal based upon

older data concerning the presence of 1,2-dibromo-3-chloropropane in drinking

water and groundwater in the United States (Section 5.4.2). Since use of

1,2-dibromo-3-chloropropane has been prohibited for several years, it seems

unlikely that foods recently harvested would contain 1,2-dibromo-3-chloropropane:

Foods grown in fields that were irrigated with water derived from

groundwater contaminated with 1,2-dibromo-3-chloropropane may contain small

amounts of 1,2-dibromo-3-chloropropane based upon detection of the chemical in

certain foods (Carter and Riley 1982, 1984; Newsome et al. 1977). Although

data are lacking, inhalation is not expected to contribute significantly to

general population exposure to 1,2-dibromo-3-chloropropane. 

Due to the lack of recent comprehensive monitoring data, the average

daily intake of 1,2-dibromo-3-chloropropane and the relative significance of

each source of exposure cannot be determined. Since releases of 1,2-dibromo3-chloropropane to the environment are generally limited to areas where it was

used as a soil fumigant, a use which has been banned by the EPA in 1985,

widespread exposure to the chemical is not likely. 

The National Occupational Hazard Survey (NOHS) conducted by the National

Institute for Occupational Safety and Health (NIOSH) between 1972 and 1974

statistically estimated that 9,682 workers were exposed to 1,2-dibromo3-chloropropane in the workplace in 1972 (RTECS 1984). The NOHS database does

not contain information on the frequency, concentration, or duration of

exposure of workers to any of the chemicals therein. The survey provides only

an estimate of the number of workers potentially exposed to chemicals in the

workplace; furthermore, the NOHS data are no longer valid to predict current

numbers of workers exposed to 1,2-dibromo-3-chloropropane in the United States

since the use of 1,2-dibromo-3-chloropropane as a soil fumigant (by far its

major use in the past) has been banned in the United States, and since it is

presumed that only relatively small amounts are produced for research

purposes, and for use as an intermediate in chemical synthesis. 1;2-Dibromo3-chloropropane was not listed by the National Occupational Exposure Survey

(NOES) conducted by NIOSH (NIOSH 1989). 
99
 

5. POTENTIAL FOR HUMAN EXPOSURE 

5.6 POPULATIONS WITH POTENTIALLY HIGH EXPOSURES 

The highest levels of exposure may occur with workers who manufacture or

use the compound for research or as a chemical intermediate in synthesis. 

Populations with potentially higher exposure than normal for the general

population include those in areas that obtain drinking water from contaminated

groundwater sources. These areas are generally at or near agricultural

regions where 1,2-dibromo-3-chloropropane had been used as a soil fumigant,

and include, for example, the San Joaquin Valley in California (Kloos 1983),

the pineapple-growing regions of Hawaii (Oki and Giambelluca 1987), and the

peach-growing regions of South Carolina (Carter and Riley 1981). Drinking

water derived from contaminated groundwater at or near hazardous waste sites

that contain 1,2-dibromo-3-chloropropane might contain the chemical and

contribute to exposure. Inhalation of contaminated air may contribute

significantly to overall exposure of the general public, especially for

populations living at or near hazardous waste dumps where 1,2-dibromo3-chloropropane has been found. Most, if not all, of these exposures are

expected to be rare and at relatively low levels. 

5.7 ADEQUACY OF THE DATABASE 

Section 104(i)(5) of CERCLA, as amended, directs the Administrator of

ATSDR (in consultation with the Administrator of EPA and agencies and programs

of the Public Health Service) ta assess whether adequate information on the

health effects of 1,2-dibromo-3-chloropropane is available. Where adequate

information is not available, ATSDR, in conjunction with the NTP, is required

to assure the initiation of a program of research designed to determine the 3

health effects (and techniques for developing methods to determine such health

effects) of 1,2-dibromo-3-chloropropane. 

The following categories of possible data needs have been identified by

a joint team of scientists from ATSDR, NTP, and EPA. They are defined as

substance-specific informational needs that, if met, would reduce or eliminate

the uncertainties of human health assessment. In the future, the identified

data needs will be evaluated and prioritized, and a substance-specific

research agenda will be proposed. 

5.7.1 Data Needs 

Physical and Chemical Properties. Physical and chemical property data

are essential for estimating the transport and partitioning of a chemical in

the environment. Most of the essential physical and chemical properties

needed to estimate the environmental fate and transport of 1,2-dibromo3-chloropropane are available (Table 3-2) (IARC 1979; Munnecke and VanGundy

1979; Ruth 1986; Sabljic 1984; Sax and Lewis 1987; Stenger 1978; Thomas 1982;

Wilson et al. 1981; Windholz 1983). No experimental values are available for 
100
 

5. POTENTIAL FOR HUMAN EXPOSURE
 

the log octanol/water partition coefficient (log KOW) and BCF. Since an

estimated log KOW was used to estimate the KOC and BCF, the availability of an

experimentally determined log KOW would lead to less uncertainty in those

estimated properties. While the techniques used for these estimations are

reasonably accurate (Bysshe 1982; EPA 1988a), having the experimentally

determined values would eliminate uncertainty concerning the reliability of

these data. 

Production, Import/Export, Use, and Disposal. Data regarding the

production methods for 1,2-dibromo-3-chloropropane are available (Windholz

1983); however, data regarding current production volumes, release, and use

patterns are lacking. Current levels of production, release, and use are

considered relatively low due to the banning of the chemical's major use as a

soil fumigant. Use, release, and disposal data can be useful for determining

areas where environmental exposure to 1,2-dibromo-3-chloropropane may be high.

Based upon relatively outdated data, significant concentrations are expected

to be found mainly in the groundwater and drinking water derived from the

groundwater at or near areas where 1,2-dibromo-3-chloropropane was used

extensively as a soil fumigant (Burmaster 1982; Carter and Riley 1981; Cohen

1986; Kloos 1983; Kutz and Carey 1986; Nelson et al. 1981; Oki and Giambelluca

1987; Peoples et al. 1980; Westrick et al. 1984). Only general data are

available on the methods of disposal of 1,2-dibromo-3-chloropropane (HSDB

1989). Specific disposal information would be useful for determining the

effectiveness of the disposal methods. Regulations are available pertaining

to the restrictions upon the land disposal of 1,2-dibromo-3-chloropropane. 

According to the Emergency Planning and Community Right-to-Know Act of

1986, 42 U.S.C. Section 11023, industries are required to submit chemical

release and off-site transfer information to the EPA. The Toxic Release 

Inventory (TRI), which contains this information for 1987, became available in

May of 1989. This database will be updated yearly and should provide a list

of industrial production facilities and emissions. Information specifically

for 1,2-dibromo-3-chloropropane is dependent upon the current status of the

TRI. 

Environmental Fate. The ultimate environmental fate of 1,2-dibromo3-chloropropane remains unclear due to a lack of experimental data. It is

known, however, that the chemical has a tendency to partition into groundwater

and into the atmosphere (Hodges and Lear 1974; Sabljic 1984; Wilson et al.

1981). It does not bind strongly to sediment or soil, but leaches rapidly

through soil. It is subject to volatilization from surface water and near

surface soil (Albrecht and Chenchin 1985; Bomberger et al. 1983; Thomas 1982).

It degrades in the atmosphere via reaction with hydroxyl radicals (Tuazon et

al. 1986). The chemical is not expected to significantly photolyze directly

or to hydrolyze in water, but it is not known whether it biodegrades in water.

It may biodegrade in certain soils provided adequate nutrients are available

(Castro and Belser 1968). Residues of 1,2-dibromo-3-chloropropane evaporate 
101 

5. POTENTIAL FOR HUMAN EXPOSURE 

from near-surface soil and could leach through soil to groundwater.

Experimental data regarding the processes that determine the fate and

transport of 1,2-dibromo-3-chloropropane in air and soil are unavailable.

Nothing definite is known about the biodegradability of the compound in soil

or natural waters. Monitoring data obtained years after the last known

applications of 1,2-dibromo-3-chloropropane indicate that small residues of

the chemical are persistent in soil and groundwater (Carter and Riley 1981).

Experimental data concerning biodegradation in soil would aid in assessing the

ultimate environmental fate of 1,2-dibromo-3-chloropropane. This, in turn,

would aid in understanding the levels that may be found in the environment and

the observed or predicted levels of human exposure. 

Bioavailability from Environmental Media. Studies have shown that 

1,2-dibromo-3-chloropropane is absorbed through the gastrointestinal tract

(Kato et al. 1979a) (Section 2.3.1), indicating that it may be absorbed

through the ingestion of contaminated water and food. This suggests that

exposure to 1,2-dibromo-3-chloropropane may occur as the result of ingestion

of soil by children playing in hazardous waste sites. Thus, monitoring data

on the actual number of children who eat soil while playing at toxic waste

sites are needed. No data were found concerning absorption through the lungs

or through dermal contact. Knowledge of the bioavailability through the

various exposure routes is essential in assessing the potential body burdens

that may occur as a result of exposure to known environmental concentrations. 

Food Chain Bioaccumulation. Experimental data regarding the bioconcentration

of 1,2-dibromo-3-chloropropane in plants, aquatic organisms, and

animals were not located in the literature. However, based on an estimated

BCF of 11.2, it is not expected to bioconcentrate in fish and other aquatic

organisms (Bysshe 1982; Munnecke and VanGundy 1979); thus biomagnification in

aquatic food chains is unlikely. Additional information on bioconcentration

in plants and animals and biomagnification in terrestrial food chains would be

helpful in assessing the potential for exposure of terrestrial animals at

higher trophic levels. 

Exposure Levels in Environmental Media. The data concerning the

detection of 1,2-dibromo-3-chloropropane in the environment are so limited and

outdated that estimation of human intake is not possible (Brodzinski and Singh

1982; Burmaster 1982; Carter and Riley 1981; Cohen 1986; Kloos 1983;

Pellizzari et al. 1978; Peoples et al. 1980; Westrick et al. 1984). Current

and comprehensive monitoring data, especially in areas where the chemical has

been used in the past and is being used at the present time, would be helpful

to estimate human intake. This may pertain to food survey analyses since it

is difficult to ascertain whether the surveys to date tested for the presence

of 1,2-dibromo-3-chloropropane. 

Exposure Levels in Humans. No monitoring data were found indicating

that 1,2-dibromo-3-chloropropane has been found in human tissues or blood. 
102 

5. POTENTIAL FOR HUMAN EXPOSURE 

The only biological monitoring studies that were found analyzed human breath

samples for the presence of 1,2-dibromo-3-chloropropane (Pellizzari et al.

1978). 1,2-Dibromo-3-chloropropane was not found in any of the samples

tested. Data concerning the level of 1,2-dibromo-3-chloropropane in human

tissue samples would be helpful in assessing the extent of human exposure to

the chemical and in estimating its body burden. 

Exposure Registries. No exposure registries for 1,2-dibromo-3-chloropropane

were located. This compound is not currently one of the compounds for

which a subregistry has been established in the National Exposure Registry.

The compound will be considered in the future when chemical selection is made

for subregistries to be established. The information that is amassed in the

National Exposure Registry facilitates the epidemiological research needed to

assess adverse health outcomes that may be related to exposure to this

compound. Determination of the number of workers who are exposed to this

compound may be included in the information since occupational exposure may be

the major area of exposure. 

5.7.2 On-going Studies 

As part of the Third National Health and Nutrition Evaluation Survey

(NHANES III), the Environmental Health Laboratory Sciences Division of the

Center for Environmental Health and Injury Control, Centers for Disease

Control, will be analyzing human blood samples for 1,2-dibromo-3-chloropropane

and other volatile organic compounds. These data will indicate the frequency

of occurrence and background levels of these compounds in the general

population. 

Remedial investigations and feasibility studies conducted at the eight

NPL sites known to be contaminated with 1,2-dibromo-3-chloropropane will add

to the available database on exposure levels in environmental media, exposure

levels in humans, and exposure registries and will increase current knowledge

regarding the transport and transformation of 1,2-dibromo-3-chloropropane in

the environment. 
103 

6. ANALYTICAL METHODS 

The purpose of this chapter is to describe the analytical methods that

are available for detecting and/or measuring and monitoring 1,2-dibromo3-chloropropane in environmental media and in biological samples. The intent

is not to provide an exhaustive list of analytical methods that could be used

to detect and quantify 1,2-dibromo-3-chloropropane. Rather, the intention is

to identify well-established methods that are used as the standard methods of

analysis. Many of the analytical methods used to detect 1,2-dibromo3-chloropropane in environmental samples are the methods approved by federal

agencies such as EPA. Additionally, analytical methods are included that

refine previously used methods to obtain lower detection limits, and/or to

improve accuracy and precision. 

6.1 BIOLOGICAL MATERIALS 

Methods for analyzing 1,2-dibromo-3-chloropropane in biological samples

are presented in Table 6-l. All of the methods listed utilize gas

chromatography (GC) with various detectors. For most of the methods,

detection limit and recovery data are not provided. No studies that reported

the analysis of 1,2-dibromo-3-chloropropane in urine were located in the

literature. With suitable modifications, the methods used for the

determination of this chemical in water samples may be applicable for its

determination in urine samples (Section 6.2). 

6.2 ENVIRONMENTAL SAMPLES 

Methods for analyzing 1,2-dibromo-3-chloropropane in environmental

samples are presented in Table 6-2. As with the methods for the analysis of

biological samples, all of the listed methods for the analysis of

environmental samples utilize GC with various detection methods. The

preconcentration/pretreatment methods use either adsorption onto a sorbent

column for air samples, purge-and-trap methods for environmental water, soil,

and solid samples, or simple extraction for food samples. The detection

systems used, which include halogen-specific detection (e.g., Hall

electrolytic conductivity detector), electron capture detector (ECD), and mass

spectrometry (MS), generally provide excellent detection limits. An advantage

of halogen-specific detectors is that they are not only very sensitive but

also are specific to halogen compounds. The mass spectrometer, on the other

hand, provides additional confirmation of a compound's identity through its

ion fragment patterns. High-resolution gas chromatography (HRGC) with

capillary columns provides better resolution for volatile compounds than

packed columns. In this method, desorbed compounds are cryogenically trapped

onto the head of the capillary column. 



107 

6. ANALYTICAL METHODS 

6.3 ADEQUACY OF THE DATABASE 

Section 104(i)(5) of CERCLA, as amended, directs the Administrator of

ATSDR (in consultation with the Administrator of EPA and agencies and programs

of the Public Health Service) to assess whether adequate information on the

health effects of 1,2-dibromo-3-chloropropane is available. Where adequate

information is not available, ATSDR, in conjunction with the NTP, is required

to assure the initiation of a program of research designed to determine the

health effects (and techniques for developing methods to determine such health

effects) of 1,2-dibromo-3-chloropropane. 

The following categories of possible data needs have been identified by

a joint team of scientists from ATSDR, NTP, and EPA. They are defined as

substance-specific informational needs that, if met, would reduce or eliminate

the uncertainties of human health assessment. In the future, the identified

data needs will be evaluated and prioritized, and a substance-specific

research agenda will be proposed. 

6.3.1 Data Needs 

Methods for Determining Biomarkers of Exposure and Effect. No biomarker 

that can be associated quantitatively with exposure to 1,2-dibromo-3-chloropropane

has been identified (Moody et al. 1984; Suzuki and Lee 1981; Tofilon

et al. 1980) (Section 2.5). If a biomarker in a human tissue or fluid were

available, and a correlation between the level of the biomarker and exposure

existed, it could be used as an indication of the levels and extent of

exposure to this chemical. If exposure to bromine compounds is limited to

1,2-dibromo-3-chloropropane, serum bromide can be used as an indication of

exposure (Torkelson et al. 1961). There are accurate techniques available

for this analysis. 

No biomarker of effect that can be associated quantitatively and

directly attributed to 1,2-dibromo-3-chloropropane exposure has been

identified (Whorton et al. 1979) (Section 2.5). If biomarkers of effect were

available, and a correlation existed between the level or intensity of the

biomarker of effect and the level of exposure, it could be used as an

indication of the levels and extent of exposure to this chemical. 

Methods for Determining Parent Compounds and Degradation Products in

Environmental Media. Methods for the determination of 1,2-dibromo-3-chloropropane

in environmental media are generally available (Albrecht et al. 1986;

Daft 1988, 1989; EPA 1986a, 1986b; Fredrickson et al. 1985; Garman et al.

1987; Ho 1989; Kastl et al. 1981; Mann et al. 1980; Pellizzari et al. 1985a,

1985b; Tonogai et al. 1986; Wallace et al. 1986). Groundwater contaminated by

leached 1,2-dibromo-3-chloropropane and air contaminated by volatilization of

1,2-dibromo-3-chloropropane from soil are the media of most concern for 
108
 

6. ANALYTICAL METHODS
 

potential human exposure. The precision, accuracy, reliability, and

specificity of the methods for environmental waters are well documented and

well suited for the determination of low levels of 1,2-dibromo-3-chloropropane

and levels at which health effects occur; however, these data are lacking for

the soil methods. 

6.3.2 On-going Studies 

The Environmental Health Laboratory Sciences Division of the Center for

Environmental Health and Injury Control, Centers for Disease Control, is

developing methods for the analysis of 1,2-dibromo-3-chloropropane and other

volatile organic compounds in blood. These methods use purge-and-trap

methodology and magnetic sector mass spectrometry which give detection limits

in the low parts per trillion (ppt) range. 

No other on-going studies were located. 
109 

7. REGULATIONS AND ADVISORIES 

The international, national, and state regulations and guidelines

pertinent to human exposure to 1,2-dibromo-3-chloropropane are summarized in Table 7-

1. 



 

113
 

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Andrologia 20:90-94. 

*Potashnik G, Ben-Aderet N, Israeli R, et al: 1978. Suppressive effect of

1,2-dibromo-3-chloropropane on human spermatogenesis. Fertil Steril 30:444­

447. 

*Potashnik G, Goldsmith J, Insler V. 1984. Dibromochloropropane-induced

reduction of the sex-ratio in man. Andrologia 16:213-218.

Powers M, Voelker R, Page N, et al. 1975. Carcinogenicity of ethylene

dibromide (EDB) and 1,2-dibromo-3-chloropropane (DBCP) after oral

administration in rats and mice. Toxicol Appl Pharmacol 33:171-172. 

*Rakhmatullayev N. 1969. The hygienic, sanitary and toxicological

characteristics of the new nematocide nemagon, from the viewpoint of the

sanitary protection reservoirs. Meditsinskiy Zhurnal Uzbekistana 7:75-78. 

Rao K, Murray F, Crawford A, et al. 1979. Effects of inhaled 1,2-dibromo-3­

chloropropane (DBCP) on the semen of rabbits and the fertility of male and

female rats. Toxicol Appl Pharmacol 48:A137. 
129
 

8. REFERENCES 

*Rao KS, Burek JD, Murray FJ, et al. 1982. Toxicologic and reproductive

effects of inhaled 1,2-dibromo-3-chloropropane in male rabbits. Fundam Appl

Toxicol 2:241-251. 

*Rao K, Burek J, Murray F, et al. 1983. Toxicologic and reproductive effects

of inhaled 1,2-dibromo-3-chloropropane in rats. Fundam Appl Toxicol 3:104-110. 

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compounds and their methylated derivatives. (Meeting Abstract). Environ

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*Ratpan F, Plaumann H. 1988. Mutagenicity of halogenated propanes and their

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*Reel JR, Wolkowski-Tyl R, Lawton AD. 1984. Dibromochloropropane:

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Reznik G, Reznik-Schuller H, Ward J, et al. 1980b. Morphology of nasalcavity

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Rosenberg M, Feldblum P, Marshall E. 1987. Occupational influences on

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*Ruddick JA, Newsome WH. 1979. A teratogenicity and tissue distribution

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*Ruth JH. 1986. Odor thresholds and irritation levels of several chemical
 

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Schneiderman M. 1987. Mortality experience of employees with occupational

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Sod-Moriah UA, Sror U, Shemi D, et al. 1988. Long term effects of

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20:60-66. 

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Stellman J. 1986. Environmental agents and birth outcomes. Ann NY Acad Sci

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*Swann RL, Laskowski DA, McCall PJ, et al. 1983. A rapid method for the

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*Tofilon PJ, Clement RP, Piper WN. 1980. Inhibition of the biosynthesis of

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29:2563-2566. 
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8. REFERENCES 

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*Tonogai Y, It0 Y, Ogawa S, et al. 1986. Determination of dibromochloropropane

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Tsongas T, Infante P. 1984. Occupational reproductive hazards: Regulatory

concerns. Prog Clin Biol Res 160:533-539. 

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Warren DW, Ahmad N. 1986. Effect of maternal administration of 1 2 dibromo3-chloropropane on fetal testosterone production and adult sexual behavior of

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pesticide workers. Lancet 2:1259-1261. 

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Fresno County, California. Am J Public Health 78:46-51. 

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of drinking water criteria documents on 1,2-dibromo-3-chloropropane. Prepared

by Syracuse Research Corporation, Syracuse, NY for Environmental Criteria and

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Wills J. 1983. Dibromochloropropane. Encyclopedia of occupational health

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*Windholz M, ed. 1983. The Merck index. 10th ed. Rahway, NJ: Merck and

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*Wong 0, Brocker W, Davis HV, et al. 1984. Mortality of workers potentially

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DDT. Br J Ind Med 41:15-24. 
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of the relationship between DBCP contamination in drinking water and birth

rates in Fresno County, California. Am J Public Health 78:43-46. 

*Wong 0, Morgan RW, Whorton MD, et al. 1989. Ecological analyses and casecontrol

studies of gastric cancer and leukemia in relation to DBCP in drinking

water in Fresno County, California. Br J Ind Med 46:521-528. 

Yoon J, Mason J, Valencia R, et al. 1985. Chemical mutagenesis testing in

drosophila. IV. Results of 45 coded compounds tested for the National

Toxicology Program. Environ Mutagen 7:349-367. 

*Zimmering S. 1983. 1,2-dibromo-3-chloropropane (DBCP) is positive for sexlinked

recessive lethals, heritable translocations and chromosome loss in

drosophila. Mutat Res 119:287-288. 

137
 

9. GLOSSARY 

Acute Exposure -- Exposure to a chemical for a duration of 14 days or less, as

specified in the Toxicological Profiles.
 

Adsorption Coefficient (KOC) -- The ratio of the amount of a chemical adsorbed
 

per unit weight of organic carbon in the soil or sediment to the concentration

of the chemical in solution at equilibrium.
 

Adsorption Ratio (Kd) -- The amount of a chemical adsorbed by a sediment or

soil (i.e., the solid phase) divided by the amount of chemical in the solution

phase, which is in equilibrium with the solid phase, at a fixed solid/solution

ratio. It is generally expressed in micrograms of chemical sorbed per gram of

soil or sediment.
 

Bioconcentration Factor (BCF) -- The quotient of the concentration of a

chemical in aquatic organisms at a specific time or during a discrete time

period of exposure divided by the concentration in the surrounding water at

the same time or during the same period.
 

Cancer Effect Level (CEL) -- The lowest dose of chemical in a study, or group

of studies, that produces significant increases in the incidence of cancer (or

tumors) between the exposed population and its appropriate control.
 

Carcinogen -- A chemical capable of inducing cancer.
 

Ceiling Value -- A concentration of a substance that should not be exceeded,

even instantaneously.

Chronic Exposure -- Exposure to a chemical for 365 days or more, as specified

in the Toxicological Profiles.
 

Developmental Toxicity -- The occurrence of adverse effects on the developing

organism that may result from exposure to a chemical prior to conception

(either parent), during prenatal development, or postnatally to the time of

sexual maturation. Adverse developmental effects may be detected at any point

in the life span of the organism.
 

Embryotoxicity and Fetotoxicity -- Any toxic effect on the conceptus as a

result of prenatal exposure to a chemical; the distinguishing feature between

the two terms is the stage of development during which the insult occurred.

The terms, as used here, include malformations and variations, altered growth,

and in utero death.
 

EPA Health Advisory -- An estimate of acceptable drinking water levels for a

chemical substance based on health effects information. A health advisory is

not a legally enforceable federal standard, but serves as technical guidance

to assist federal, state, and local officials.
 
138
 

9. GLOSSARY 

Immediately Dangerous to Life or Health (IDLH) -- The maximum environmental 

concentration of a contaminant from which one could escape within 30 min

without any escape-impairing symptoms or irreversible health effects. 

Intermediate Exposure -- Exposure to a chemical for a duration of 15-364 days

as specified in the Toxicological Profiles. 

Immunologic Toxicity -- The occurrence of adverse effects on the immune system

that may result from exposure to environmental agents such as chemicals. 

In Vitro -- Isolated from the living organism and artificially maintained, as

in a test tube. 

In Vivo -- Occurring within the living organism. 

Lethal Concentration (LO) (LCLO )-- The lowest concentration of a chemical in 

air which has been reported to have caused death in humans or animals. 

Lethal Concentration(50) (LC50) -- 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. 

Lethal Dose(LO) (LDLO) -- The lowest dose of a chemical introduced by a route

other than inhalation that is expected to have caused death in humans or

animals. 

Lethal Dose(50) (LD50) -- The dose of a chemical which has been calculated to 

cause death in 50% of a defined experimental animal population. 

Lethal Time(50) (LT50) -- A calculated period of time within which a specific

concentration of a chemical is expected to cause death in 50% of a defined

experimental animal population. 

Lowest-Observed-Adverse-Effect Level (LOAEL) -- The lowest dose of chemical in 

a study, or group of studies, that produces statistically or biologically

significant increases in frequency or severity of adverse effects between the

exposed population and its appropriate control. 

Malformations -- Permanent structural changes that may adversely affect

survival, development, or function. 

Minimal Risk Level -- An estimate of daily human exposure to a chemical that

is likely to be without an appreciable risk of deleterious effects

(noncancerous) over a specified duration of exposure. 
139
 

9. GLOSSARY 

Mutagen -- A substance that causes mutations. A mutation is a change in the

genetic material in a body cell. Mutations can lead to birth defects,

miscarriages, or cancer. 

Neurotoxicity -- The occurrence of adverse effects on the nervous system

following exposure to chemical. 

No-Observed-Adverse-Effect Level (NOAEL)-- The dose of chemical at which 

there were no statistically or biologically significant increases in frequency

or severity of adverse effects seen between the exposed population and its

appropriate control. Effects may be produced at this dose, but they are not

considered to be adverse. 

Octanol-Water Partition Coefficient (KOW)-- The equilibrium ratio of the

concentrations of a chemical in n-octanol and water, in dilute solution. 

Permissible Exposure Limit (PEL) -- An allowable exposure level in workplace

air averaged over an 8-hour shift. 

q1* -- The upper-bound estimate of the low-dose slope of the dose-response

curve as determined by the multistage procedure. The q1* can be used to 

calculate an estimate of carcinogenic potency, the incremental excess cancer

risk per unit of exposure (usually μg/L for water, mg/kg/day for food, and 

μg/m3

 for air). 

Reference Dose (RfD) -- An estimate (with uncertainty spanning perhaps an

order of magnitude) of the daily exposure of the human population to a

potential hazard that is likely to be without risk of deleterious effects

during a lifetime. The RfD is operationally derived from the NOAEL (from

animal and human studies) by a consistent application of uncertainty factors

that reflect various types of data used to estimate RfDs and an additional

modifying factor, which is based on a professional judgment of the entire

database on the chemical. The RfDs are not applicable to nonthreshold effects

such as cancer. 

Reportable Quantity (RQ) -- The quantity of a hazardous substance that is

considered reportable under CERCLA. Reportable quantities are (1) 1 lb or

greater or (2) for selected substances, an amount established by regulation

either under CERCLA or under Sect. 311 of the Clean Water Act. Quantities are

measured over a 24-hour period. 

Reproductive Toxicity -- The occurrence of adverse effects on the reproductive

system that may result from exposure to a chemical. The toxicity may be

directed to the reproductive organs and/or the related endocrine system. The

manifestation of such toxicity may be noted as alterations in sexual behavior,

fertility, pregnancy outcomes, or modifications in other functions that are

dependent on the integrity of this system. 
140
 

9. GLOSSARY
 

Short-Term Exposure Limit (STEL) -- The maximum concentration to which workers 

can be exposed for up to 15 min continually. No more than four excursions are

allowed per day, and there must be at least 60 min between exposure periods.

The daily TLV-TWA may not be exceeded. 

Target Organ Toxicity -- This term covers a broad range of adverse effects on

target organs or physiological systems (e.g., renal, cardiovascular) extending

from those arising through a single limited exposure to those assumed over a

lifetime of exposure to a chemical. 

Teratogen -- A chemical that causes structural defects that affect the 

development of an organism. 

Threshold Limit Value (TLV) -- A concentration of a substance to which most 

workers can be exposed without adverse effect. The TLV may be expressed as a

TWA, as a STEL, or as a CL. 

Time-Weighted Average (TWA) -- An allowable exposure concentration averaged

over a normal 8-hour workday or 40-hour workweek. 

Toxic Dose (TD50) -- A calculated dose of a chemical, introduced by a route

other than inhalation, which is expected to cause a specific toxic effect in

50% of a defined experimental animal population. 

Uncertainty Factor (UF) -- A factor used in operationally deriving the RfD

from experimental data. UFs are intended to account for (1) the variation in

sensitivity among the members of the human population, (2) the uncertainty in

extrapolating animal data to the case of human, (3) the uncertainty in

extrapolating from data obtained in a study that is of less than lifetime

exposure, and (4) the uncertainty in using LOAEL data rather than NOAEL data.

Usually each of these factors is set equal to 10. 
A-l 

APPENDIX A 

USER'S GUIDE 

Chapter 1 

Public Health Statement 

This chapter of the profile is a health effects summary written in nontechnical

language. Its intended audience is the general public especially people living

in the vicinity of a hazardous waste site or substance release. If the Public

Health Statement were removed from the rest of the document, it would still

communicate to the lay public essential information about the substance. 

The major headings in the Public Health Statement are useful to find specific

topics of concern. The topics are written in a question and answer format. The

answer to each question includes a sentence that will direct the reader to

chapters in the profile that will provide more information on the given topic. 

Chapter 2 

Tables and Figures for Levels of Significant Exposure (LSE) 

Tables (2-1, 2-2, and 2-3) and figures (2-l and 2-2) are used to summarize health

effects by duration of exposure and endpoint and to illustrate graphically levels

of exposure associated with those effects. All entries in these tables and

figures represent studies that provide reliable, quantitative estimates of

No-Observed-Adverse-Effect Levels (NOAELS), Lowest-Observed- Adverse-Effect

Levels (LOAELs) for Less Serious and Serious health effects, or Cancer Effect

Levels (CELs). In addition, these tables and figures illustrate differences in

response by species, Minimal Risk Levels (MRLs) to humans for noncancer end

points, and EPA's estimated range associated with an upper-bound individual

lifetime cancer risk of 1 in 10,000 to 1 in 10,000,000. The LSE tables and

figures can be used for a quick review of the health effects and to locate data

for a specific exposure scenario. The LSE tables and figures should always be

used in conjunction with the text. 

The legends presented below demonstrate the application of these tables and

figures. A representative example of LSE Table 2-l and Figure 2-1 are shown.

The numbers in the left column of the legends correspond to the numbers in the

example table and figure. 

LEGEND 

See LSE Table 2-l 

1) Route of Exposure One of the first considerations when reviewing the

toxicity of a substance using these tables and figures should be the

relevant and appropriate route of exposure. When sufficient data exist, 
A-2
 

APPENDIX A
 

three LSE tables and two LSE figures are presented in the document. The

three LSE tables present data on the three principal routes of exposure,

i.e., inhalation, oral, and dermal (LSE Table 2-1, 2-2, and 2-3,

respectively). LSE figures are limited to the inhalation (LSE Figure 2-i)

and oral (LSE Figure 2-2) routes. 

2) Exposure Duration Three exposure periods: acute (14 days or less);

intermediate (15 to 364 days); and chronic (365 days or more) are

presented within each route of exposure. In this example, an inhalation

study of intermediate duration exposure is reported. 

3) Health Effect The major categories of health effects included in

LSE tables and figures are death, systemic, immunological,

neurological, developmental, reproductive, and cancer. NOAELs and

LOAELs can be reported in the tables and figures for all effects but

cancer. Systemic effects are further defined in the "System" column

of the LSE table. 

4) Key to Figure Each key number in the LSE table links study information

to one or more data points using the same key number in the corresponding

LSE figure. In this example, the study represented by key number 18 has

been used to define a NOAEL and a Less Serious LOAEL (also see the two

"18r" data points in Figure 2-l). 

5) Species The test species, whether animal or human, are identified in this

column. 

6) Exposure Freouencv/Duration The duration of the study and the weekly and

daily exposure regimen are provided in this column. This permits

comparison of NOAELs and LOAELs from different studies. In this case (key

number 18), rats were exposed to [substance x] via inhalation for 13

weeks, 5 days per week, for 6 hours per day. 

7) System This column further defines the systemic effects. These systems

include: respiratory, cardiovascular, gastrointestinal, hematological,

musculoskeletal, hepatic, renal, and dermal/ocular. "Other" refers to any

systemic effect (e.g., a decrease in body weight) not covered in these

systems. In the example of key number 18, one systemic effect

(respiratory) was investigated in this study. 

8) NOAEL A No-Observed-Adverse-Effect Level (NOAEL) is the highest exposure

level at which no harmful effects were seen in the organ system studied.

Key number 18 reports a NOAEL of 3 ppm for the respiratory system which

was used to derive an intermediate exposure, inhalation MRL of 0.005 ppm

(see footnote IIc"). 

9) LOAEL A Lowest-Observed-Adverse-Effect Level (LOAEL) is the lowest

exposure level used in the study that caused a harmful health effect.

LOAELs have been classified into "Less Serious" and "Serious" effects. 

These distinctions help readers identify the levels of exposure at which

adverse health effects first appear and the gradation of effects with

increasing dose. A brief description of the specific end point used to 
A-3
 

APPENDIX A 

quantify the adverse effect accompanies the LOAEL. The "Less Serious"

respiratory effect reported in key number 18 (hyperplasia) occurred at a

LOAEL of 10 ppm. 

10)	 Reference The complete reference citation is given in Chapter 8 of the

profile. 

11)	 CEL A Cancer Effect Level (CEL) is the lowest exposure level associated

with the onset of carcinogenesis in experimental or epidemiological

studies. CELs are always considered serious effects. The LSE tables and

figures do not contain NOAELs for cancer, but the text may report doses

which did not cause a measurable increase in cancer. 

12)	 Footnotes Explanations of abbreviations or reference notes for data in

the LSE tables are found in the footnotes. Footnote "c" indicates the 

NOAEL of 3 ppm in key number 18 was used to derive an MRL of 0.005 ppm. 

LEGEND 

See LSE Figure 2-l 

LSE figures graphically illustrate the data presented in the corresponding LSE

tables. Figures help the reader quickly compare health effects according to

exposure levels for particular exposure duration. 

13)	 Exposure Duration The same exposure periods appear as in the LSE table.

In this example, health effects observed within the intermediate and

chronic exposure periods are illustrated. 

14)	 Health Effect These are the categories of health effects for which

reliable quantitative data exist. The same health effects appear in the

LSE table. 

15)	 Levels of ExDosure Exposure levels for each health effect in the LSE

tables are graphically displayed in the LSE figures. Exposure levels are

reported on the log scale "y" axis. Inhalation exposure is reported in

mg/m3 or ppm and oral exposure is reported in mg/kg/day. 

16)	 NOAEL In this example, 18r NOAEL is the critical end point for which an

intermediate inhalation exposure MRL is based. As you can see from the

LSE figure key, the open-circle symbol indicates a NOAEL for the test

species (rat). The key number 18 corresponds to the entry in the LSE

table. The dashed descending arrow indicates the extrapolation from the

exposure level of 3 ppm (see entry 18 in the Table) to the MRL of 0.005

ppm (see footnote "b" in the LSE table). 

17)	 CEL Key number 38r is one of three studies for which Cancer Effect Levels

(CELs) were derived. The diamond symbol refers to a CEL for the test

species (rat). The number 38 corresponds to the entry in the LSE table. 
A-4 

APPENDIX A 

18)	 Estimated Upper-Bound Human Cancer Risk Levels This is the range

associated with the upper-bound for lifetime cancer risk of 1 in 10,000

to 1 in 10,000,000. These risk levels are derived from EPA's Human Health

Assessment Group's upper-bound estimates of the slope of the cancer dose

response curve at low dose levels (q1*). 

19)	 Key to LSE Figure The Key explains the abbreviations and symbols used in

the figure. 


A-7
 

APPENDIX A 

Chapter 2 (Section 2.4) 

Relevance to Public Health 

The Relevance to Public Health section provides a health effects summary based

on evaluations of existing toxicological, epidemiological, and toxicokinetic

information. This summary is designed to present interpretive,

weight-of-evidence discussions for human health end points by addressing the

following questions. 

1. What effects are known to occur in humans? 

2. What effects observed in animals are likely to be of concern to

humans? 

3. What exposure conditions are likely to be of concern to humans,

especially around hazardous waste sites? 

The section discusses health effects by end point. Human data are presented

first, then animal data. Both are organized by route of exposure (inhalation,

oral, and dermal) and by duration (acute, intermediate, and chronic). In vitro

data and data from parenteral routes (intramuscular, intravenous, subcutaneous,

etc.) are also considered in this section. If data are located in the

scientific literature, a table of genotoxicity information is included. 

The carcinogenic potential of the profiled substance is qualitatively evaluated,

when appropriate, using existingtoxicokinetic, genotoxic, and carcinogenic data.

ATSDR does not currently assess cancer potency or perform cancer risk

assessments. MRLs for noncancer end points if derived, and the end points from

which they were derived are indicated and discussed in the appropriate

section(s). 

Limitations to existing scientific literature that prevent a satisfactory

evaluation of the relevance to public health are identified in the Identification

of Data Needs section. 

Interpretation of Minimal Risk Levels 

Where sufficient toxicologic information was available, MRLs were derived. MRLs

are specific for route (inhalation or oral) and duration (acute, intermediate,

or chronic) of exposure. Ideally, MRLs can be derived from all six exposure

scenarios (e.g., Inhalation - acute, -intermediate, -chronic; Oral - acute, ­

intermediate, - chronic). These MRLs are not meant to support regulatory action,

but to aquaint health professionals with exposure levels at which adverse health

effects are not expected to occur in humans. They should help physicians and

public health officials determine the safety of a community living near a

substance emission, given the concentration of a contaminant in air or the

estimated daily dose received via food or water. MRLs are based largely on

toxicological studies in animals and on reports of human occupational exposure. 
A-8
 

APPENDIX A
 

MRL users should be familiar with the toxicological information on which the

number is based. Section 2.4, "Relevance to Public Health," contains basic

information known about the substance. Other sections such as 2.6, "Interactions

with Other Chemicals" and 2.7, "Populations that are Unusually Susceptible"

provide important supplemental information. 

MRL users should also understand the MRL derivation methodology. MRLs are

derived using a modified version of the risk assessment methodology used by the

Environmental Protection Agency (EPA) (Barnes and Dourson, 1988; EPA 1989a) to

derive reference doses (RfDs) for lifetime exposure. 

To derive an MRL, ATSDR generally selects the end point which, in its best

judgement, represents the most sensitive humanhealth effect for a given exposure

route and duration. ATSDR cannot make this judgement or derive an MRL unless

information (quantitative or qualitative) is available for all potential effects

(e.g., systemic, neurological, and developmental). In order to compare NOAELs

and LOAELs for specific end points, all inhalation exposure levels are adjusted

for 24hr exposures and all intermittent exposures for inhalation and oral routes

of intermediate and chronic duration are adjusted for continous exposure (i.e.,

7 days/week). If the information and reliable quantitative data on the chosen

end point are available, ATSDR derives an MRL using the most sensitive species

(when information from multiple species is available) with the highest NOAEL that

does not exceed any adverse effect levels. The NOAEL is the most suitable end

point for deriving an MRL. When a NOAEL is not available, a Less Serious LOAEL

can be used to derive an MRL, and an uncertainty factor (UF) of 10 is employed.

MRLs are not derived from Serious LOAELs. Additional uncertainty factors of 10

each are used for human variability to protect sensitive subpopulations (people

who are most susceptible to the health effects caused by the substance) and for

interspecies variability (extrapolation from animals to humans). In deriving an

MRL, these individual uncertainty factors are multiplied together. The product

is then divided into the adjusted inhalation concentration or oral dosage

selected from the study. Uncertainty factors used in developing a

substance-specific MRL are provided in the footnotes of the LSE Tables. 
B-l 

APPENDIX B 

ACRONYMS, ABBREVIATIONS, AND SYMBOLS 

ACIGH	 American Conference of Governmental Industrial Hygienists

ADME	 Absorption, Distribution, Metabolism, and Excretion

ATSDR	 Agency for Toxic Substances and Disease Registry

BCF	 bioconcentration factor 

BSC	 Board of Scientific Counselors 

CDC	 Centers for Disease Control 

CEL	 Cancer Effect Level 

CERCLA	 Comprehensive Environmental Response, Compensation, and Liability

Act 

CFR	 Code of Federal Regulations

CLP	 Contract Laboratory Program

cm	 centimeter 

CNS	 central nervous system

DHEW	 Department of Health, Education, and Welfare

DHHS	 Department of Health and Human Services

DOL	 Department of Labor

ECG	 electrocardiogram

EEG	 electroencephalogram

EPA	 Environmental Protection Agency

EKG	 see ECG 

FAO	 Food and Agricultural Organization of the United Nations

FEMA	 Federal Emergency Management Agency

FIFRA	 Federal Insecticide, Fungicide, and Rodenticide Act

f1	 first generation

fpm	 feet per minute

ft	 foot 

FR	 Federal Register

g	 gram

GC	 gas chromatography

HPLC	 high performance liquid chromatography

hr	 hour 

IDLH	 Immediately Dangerous to Life and Health

IARC	 International Agency for Research on Cancer

ILO	 International Labor Organization

in	 inch 

Kd	 adsorption ratio

Kg	 kilogram

KOC	 octanol-soil partition coefficient

KOW	 octanol-water partition coefficient

L	 liter 

LC	 liquid chromatography

LCLO	 lethal concentration low 

LC50	 lethal concentration 50 percent kill

LDLO	 lethal dose low 

LD50	 lethal dose 50 percent kill

LOAEL	 lowest-observed-adverse-effect level 
 

B-2 

LSE Levels of Significant Exposure

m meter 

mg milligram

min minute 

mL milliliter 

mm millimeters 

mmo1 millimole 

mppcf millions of particles per cubic foot

MRL Minimal Risk Level 

MS mass spectroscopy

NIEHS National Institute of Environmental Health Sciences 

NIOSH National Institute for Occupational Safety and Health

NIOSHTIC NIOSH's Computerized Information Retrieval System

nm nanometer 

ng nanogram

NHANES National Health and Nutrition Examination Survey

nmol nanomole 

NOAEL no-observed-adverse-effect level 

NOES National Occupational Exposure Survey

NOHS National Occupational Hazard Survey

NPL National Priorities List 

NRC National Research Council 

NTIS National Technical Information Service 

NTP National Toxicology Program

OSHA Occupational Safety and Health Administration

PEL permissible exposure limit

pg picogram

pmo1 picomole

PHS Public Health Service 

PMR proportional mortality ratio

ppb parts per billion

ppm parts per million

ppt parts per trillion

REL recommended exposure limit

RfD Reference Dose 

RTECS Registry of Toxic Effects of Chemical Substances

sec second 

SCE sister chromatid exchange

SIC Standard Industrial Classification 

SMR standard mortality ratio

STEL short-term exposure limit

TLV threshold limit value 

TSCA Toxic Substances Control Act 

TRI Toxic Release Inventory

TWA time-weighted average

U.S. United States 

UF uncertainty factor

WHO World Health Organization

> greater than

≥ greater than or equal to

= equal to 
B-3 

< less than ≤ less than or equal to

% percent α alpha β beta δ delta γ gamma μm micron μg microgram 
C-l 

APPENDIX C
 

PEER REVIEW
 

A peer review panel was assembled for 1,2-dibromo-3-chloropropane. The

panel consisted of the following members: Dr. James Bruckner, University of

Georgia, Athens, Georgia; Dr. Fumio Matsumura, University of California,

Davis, California; Dr. Donald Morgan, University of Iowa Medical School, Iowa

City, Iowa; Dr. Jay Silkworth, New York State Department of Health, Albany,

New York; Dr David Strayer, University of Texas, Houston, Texas. These

experts collectively have knowledge of 1,2-dibromo-3-chloropropane's physical

and chemical properties, toxicokinetics, key health end points, mechanisms of

action, human and animal exposure, and quantification of risk to humans. All

reviewers were selected in conformity with the conditions for peer review

specified in the Comprehensive Environmental Response, Compensation, and

Liability Act of 1986, Section 104. 

Scientists from the Agency for Toxic Substances and Disease Registry

(ATSDR) have reviewed the peer reviewers' comments and determined which

comments will be included in the profile. A listing of the peer reviewers'

comments not incorporated in the profile, with a brief explanation of the

rationale for their exclusion, exists as part of the administrative record for

this compound. A list of databases reviewed and a list of unpublished

documents cited are also included in the administrative record. 

The citation of the peer review panel should not be understood to imply

its approval of the profile's final content. The responsibility for the

content of this profile lies with the ATSDR.