TOXICOLOGICAL PROFILE FOR
 

1,2-DICHLOROPROPANE
 

Agency for Toxic Substances and Disease Registry (ATSDR)
 

U.S. Public Health Service
 

In collaboration with
 

U.S. Environmental Protection Agency (EPA)
 

December 1989
 
ii

DISCLAIMER
 

Mention of company name or product does not constitute endorsement by the
 

Agency for Toxic Substances and Disease Registry.
 










1
 

1. PUBLIC HEALTH STATEMENT
 

1.1 WHAT IS 1,2-DICHLOROPROPANE?
 

1,2-Dichloropropane is a colorless liquid belonging to a class of
 

chemicals called volatile organic compounds (VOCs). It has a chloroform-like
 

odor and evaporates quickly at room temperature. It is a man-made chemical
 

and people are probably responsible for all releases of 1,2- dichloropropane
 

into the environment. 1,2-Dichloropropane is now used in the United States only in
 

research and industry. Before the early 1980s, 1,2-dichloropropane was used in farming
 

as a soil fumigant and was found in some paint strippers, varnishes, and furniture
 

finish removers. Most of the 1,2-dichloropropane released into the environment finally
 

ends up in the air or groundwater. When applied to soil in one experiment, all but 1%
 

dispersed in 10 days. Breakdown in both the air and groundwater is slow. The rate at
 

which a chemical breaks down is usually explained by how long it takes for half the
 

chemical to disappear (half-life). The half-life of 1,2- dichloropropane in air is not
 

known exactly, but it is longer than 23 days, which means that 1,2-dichloropropane can
 

spread to areas far from where it is released. In groundwater, the half-life of 1,2­

dichloropropane is estimated to be between 6 months and 2 years. For more information
 

refer to Chapters 4 and 5 of this document.
 

1.2 HOW MIGHT I BE EXPOSED TO 1,2-DICHLOROPROPANE?
 

Air levels of 1,2-dichloropropane are usually quite low. In city areas
 

of the United States, the average amount in air is about 22 parts per
 

trillion (ppt). 1,2-Dichloropropane is found in a few drinking water
 

supplies, and most of those are from groundwater sources. A nationwide
 

survey of groundwater supplies showed that 1.4% of these supplies contained
 

1,2-dichloropropane levels at around 1 part per billion (ppb). The highest
 

amount of 1,2-dichloropropane in the survey was 21 ppb. Private wells in
 

farming areas where 1,2-dichloropropane was once used as a soil fumigant
 

have the greatest risk for contamination. Occupational exposure to 1,2­

dichloropropane may result during its production, its use in chemical
 

reactions and as an industrial solvent, and evaporation from wastewater
 

that contains the chemical. Workers involved in cleaning up hazardous waste
 

or spill sites that contain 1,2-dichloropropane may also be exposed. A
 

national survey conducted by the National Institute for Occupational Safety
 

and Health (NIOSH) in 1981-1983 estimated that 2119 workers outside of the
 

farming sector were exposed to 1,2-dichloropropane. Use of this chemical
 

has recently decreased very much, however, so that the number of exposed
 

workers may now be much lower. According to industry spokesmen, levels of
 

exposure among exposed workers range from less than 1 part per million (ppm)
 

to less than 25 ppm, depending on the industry. 1,2-Dichloropropane was
 

found in 26 of the 1177 hazardous waste sites on the National Priority List
 

(NPL) and gases from these sites may contain low levels of 1,2­

dichloropropane. For more information on levels of 1,2-dichloropropane in
 
2
 

1. PUBLIC HEALTH STATEMENT
 

the environment and potential exposure to it, please refer to Chapter 5 of
 

this document.
 

1.3 HOW CAN l,2-DICHLOROPROPANE ENTER AND LEAVE MY BODY?
 

1,2-Dichloropropane can enter the body if a person breathes air or
 

drinks water contaminated with it, or if a person's skin comes in contact
 

with it. If 1,2-dichloropropane is present at a waste site near homes that
 

use wells as a source of water, the well water could be contaminated. A
 

route of major exposure in the past was by accidentally or intentionally
 

drinking cleaning products that contained 1,2-dichloropropane, but these
 

cleaning materials are no longer produced in the United States. Experiments
 

with animals have shown that when 1,2-dichloropropane enters the body
 

through eating or drinking, it is quickly removed in the urine and feces and
 

by the lungs when the animal breathes out. 1,2-Dichloropropane may enter the
 

lungs of workers exposed where it is used indoors as a solvent. If 1,2­

dichloropropane is released at a waste site and evaporates into the air, a
 

person may breathe in 1,2-dichloropropane for a short time before it
 

disperses. When the chemical was a part of some paint strippers,
 

varnishes, and furniture finish removers, exposure of the skin through
 

contact with these products occurred; however, the amount of 1,2­

dichloropropane that entered through the skin is unknown. Soil around a
 

waste site may be contaminated with 1,2-dichloropropane, but it is not known
 

how much 1,2-dichloropropane enters the body through the skin upon contact
 

with contaminated soil. For more information on how 1,2-dichloropropane
 

enters and leaves the body, see Chapter 2.
 

1.4 HOW CAN 1,2-DICHLOROPROPANE AFFECT MY HEALTH?
 

Drinking 1,2-dichloropropane by humans (i.e., drinking cleaning
 

solutions) has produced poisoning. At these high levels of exposure,
 

effects include dizziness, headache, nausea, injury to the liver and
 

kidneys, anemia, coma and, ultimately, death. Breathing high levels of 1,2­

dichloropropane by humans, as in deliberate breathing of vapors from
 

cleaning solutions, produces similar effects. No reports have been made of
 

any health effects in humans following low-level exposure to 1,2­

dichloropropane for either short or long time periods.
 

In animal experiments, low amounts of 1,2-dichloropropane breathed in
 

over short- and long-term periods result in damage to the liver, kidney,
 

and respiratory systems, while high amounts resulted in death. Short-term
 

exposure to high levels of vapors also causes irritation to the eyes and
 

throat. When 1,2-dichloropropane is given by mouth to animals over short-


or long-term periods, damage to the liver and kidneys is seen at low doses,
 

and death occurs at high doses.
 

1,2-Dichloropropane breathed or eaten for a short time has not been
 

reported to produce cancer in humans, but long-term exposure by mouth in
 

animals has produced evidence of liver cancer in mice and breast cancer in
 
3

1. PUBLIC HEALTH STATEMENT
 

female rats. The significance of the animal cancer studies to humans is not
 

well understood. Irritation of the skin after contact with 1,2­

dichloropropane has been seen in both humans and rabbits. 1,2­

Dichloropropane has not been shown to cause birth defects in humans or
 

animals, but a delay in the growth of bones has been seen in fetal rats
 

following exposure of the mother rats. For more information on the health
 

effects of 1,2-dichloropropane in humans and animals, see Chapter 2.
 

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


 1,2-DICHLOROPROPANE?
 

Tests are available to detect 1,2-dichloropropane in the urine and the
 

blood. The available methods can predict the concentration of 1,2­

dichloropropane in the air from levels in the urine, but not from levels in
 

the blood. The levels of 1,2-dichloropropane in the urine, however, cannot
 

predict specific health effects. The method for testing the urine is
 

simple, but because special equipment is needed, the test is not yet
 

routinely available. Because 1,2-dichloropropane leaves the body quickly,
 

it is best to test for it soon after exposure. For more information on the
 

medical tests available to detect exposure to 1,2-dichloropropane, see
 

Chapter 2.
 

1.6 WHAT LEVELS OF EXPOSURE HAVE RESULTED IN HARMFUL HEALTH EFFECTS?
 

The amounts of 1,2-dichloropropane in air, drinking water and food
 

that cause known health effects in humans and animals are shown in Tables
 

l-l, l-2, l-3 and l-4. The idea of "dose-response" is important when
 

assessing the effect of a chemical on humans or animals. Dose-response
 

refers to the increase in adverse health effects that are observed as the
 

amount of the chemical to which you are exposed increases. The exact
 

amounts that result in the harmful effects in humans (see Section 1.4) are
 

not known because no amounts of 1,2-dichloropropane were determined when the
 

individuals were poisoned.
 

Minimal Risk Levels (MRLs) are included in Tables 1-l and l-3. These
 

MRLs were derived from animal data for short-term and long-term exposure
 

from breathing 1,2-dichloropropane and for short-term and longer-term
 

exposure from eating or drinking 1,2-dichloropropane, as described in
 

Chapter 2 and in Tables 2-l and 2-2. The MRLs provide a basis for
 

comparison to levels which people might encounter either in the air or in
 

food or drinking water. If a person is exposed to 1,2-dichloropropane at an
 

amount below the MRL, it is not expected that harmful (noncancer) health
 

effects will occur. Since these levels are based on information that it
 

currently available, there is always some uncertainty associated with them.
 

Also, since the method for deriving MRLs does not use any information about
 

cancer, a MRL does not imply anything about the presence, absence, or level
 

of risk of cancer.
 




8
 

1. PUBLIC HEALTH STATEMENT
 

The Occupational Safety and Health Administration (OSHA) believes that
 

75 ppm 1,2-dichloropropane is acceptable for a normal 8-hour workday and a
 

40-hour workweek and that 110 ppm 1,2-dichloropropane is acceptable for a
 

15-minute exposure period. OSHA feels that nearly all workers may be
 

repeatedly exposed to 1,2-dichloropropane at these levels, day after day,
 

without harmful effects (see Section 1.7). The amount at which the smell of
 

1,2-dichloropropane is first noticed is 0.25 ppm; therefore, most people
 

would probably smell 1,2-dichloropropane before it reached a harmful level.
 

Continued exposure to the odor may reduce the ability to smell 1,2­

dichloropropane at 0.25 ppm. For more information on the amounts of 1,2­

dichloropropane that cause effects in humans and animals, see Chapter 2.
 

1.7 WHAT RECOMMENDATIONS HAS THE FEDERAL GOVERNMENT MADE TO PROTECT HUMAN


 HEALTH?
 

The Occupational Safety and Health Administration (OSHA) regulates
 

levels of 1,2-dichloropropane in the workplace. The limit for an 8-hour
 

workday, 40-hour workweek is an average of 75 ppm and the limit for a 15­

minute exposure is an average of 110 ppm. The Environmental Protection
 

Agency (EPA) requires a notice when discharges or spills of 1000 pounds or
 

more of 1,2-dichloropropane are made into the environment. For more
 

information on Federal and State recommendations, see Chapter 7.
 

1.8 WHERE CAN I GET MORE INFORMATION?
 

If you have further questions or concerns, 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
 
9
 

2. HEALTH EFFECTS
 

2.1 INTRODUCTION
 

This chapter contains descriptions and evaluations of studies and
 

interpretation of data on the health effects associated with exposure to
 

1,2-dichloropropane. Its purpose is to present levels of significant
 

exposure for 1,2-dichloropropane based on toxicological studies,
 

epidemiological investigations, and environmental exposure data. This
 

information is presented to provide public health officials, physicians,
 

toxicologists, and other interested individuals and groups with (1) an
 

overall perspective of the toxicology of 1,2-dichloropropane and (2) a
 

depiction of significant exposure levels associated with various adverse
 

health effects.
 

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 data in this section are
 

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,
 

intermediate, and chronic.
 

Levels of significant exposure for each exposure route and duration
 

(for which data exist) are presented in tables and illustrated in figures.
 

The points in the figures showing no-observed-adverse-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, determine whether or not the
 

intensity of the effects varies 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 on the tables and graphs
 

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

concerned with the interpretation of clinical findings in exposed persons or
 

with the identification of persons with the potential to develop such
 

disease may be interested in levels of exposure associated with "serious
 

effects." Public health officials and project managers concerned with
 

response actions at Superfund 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) are of interest to health professionals and citizens alike.
 
10
 

2. HEALTH EFFECTS
 

For certain chemicals, levels of exposure associated with carcinogenic
 

effects may be indicated in the figures. These levels reflect the actual
 

doses associated with the tumor incidences reported in the studies cited.
 

Because cancer effects could occur at lower exposure levels, the figures
 

also show estimated excess risks, ranging from a risk of one in 10,000 to
 

one in 10,000,000 (10m4

 to 10m7), as developed by EPA.
 

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

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

noncancer end point for each exposure duration. MRLs include adjustments to
 

reflect human variability and, where appropriate, the uncertainty of
 

extrapolating from laboratory animal data to humans. Although methods have
 

been established to derive these levels (Barnes et al. 1987; EPA 1980),
 

uncertainties are associated with the techniques.
 

2.2.1 Inhalation Exposure
 

2.2.1.1 Death
 

No studies were located regarding lethal effects in humans following
 

inhalation exposure to 1,2-dichloropropane.
 

The lethality after a single exposure by inhalation to 1,2­

dichloropropane has been determined in rats and mice. Smyth et al. (1969)
 

and Pozzani et al. (1959) reported LC50 values of 2000 ppm and 3029 ppm,
 

respectively, after a single n-hour exposure in rats. Carpenter et al.
 

(1949) determined that 2000 ppm resulted in the death of 2/6, 3/6 or 4/6
 

rats after a single 4-hour exposure to 1,2-dichloropropane; Heppel et al.
 

(1946) reported the death of 3/12 rats after a single 7-hour exposure of
 

1600 ppm; Highman and Heppel (1946) reported the death of 6/24 rats several
 

hours after one 7-hour exposure to 2200 ppm; and Nitschke and Johnson (1983)
 

found no mortality in rats exposed to 1000 ppm 1,2-dichloropropane for 6
 

hours. Dow Chemical (1982) reported an LC50 value of 480 ppm in mice after
 

a single 10-hour exposure to 1,2-dichloropropane. All mice (22-26 animals)
 

died after a single exposure of four hours to 1000 ppm or 1500 ppm, while
 

3/10 mice died after a single two-hour exposure to 1500 ppm. Nitschke and
 

Johnson (1983) reported the death of all mice within 24 hours of a 6-hour
 

exposure to 1500 ppm 1,2-dichloropropane and, following a 6-hour exposure to
 

500 mm, mice became lethargic and 2/5 mice died within 3 days of exposure.
 

The concentration of 480 ppm in air from the Dow Chemical (1982) study is
 

presented in Table l-2.
 

Lethality was observed in rats, mice, guinea pigs and rabbits 

repeatedly exposed by inhalation to 1,2-dichloropropane for 14 days or less 

(acute exposure is defined as treatment for ≤14 calendar days). Exposures 

of 7 hours/day, 5 days/week for 2-10 exposures in the Heppel et al. (1946) 

study resulted in the deaths of 8/39 rats exposed to 1000 ppm; 3/18 rats and 

3/18 guinea pigs exposed to 1500 ppm; and 8/20 rats, 11/16 guinea pigs and 

2/4 rabbits exposed to 2200 ppm. Five consecutive days of -/-hour exposures 
11

2. HEALTH EFFECTS
 

of 1600 ppm resulted in the death of 0/13 rats, 0/10 guinea pigs and l/2 

rabbits (Heppel et al. 1946). Highman and Heppel (1946) reported the death 

of 7/20 guinea pigs after 2-3 exposures of 7 hours to 2200 ppm 1,2­

dichloropropane. Heppel et al. (1948) observed no lethality in rats or 

guinea pigs following l-9, -7-hour exposures to 400 ppm 1,2-dichloropropane. 

Nitschke and Johnson (1983) reported no compound-related mortality in rats 

and rabbits intermittently exposed for 2 weeks to ≤1000 ppm or in mice 

exposed to <300 ppm 1,2-dichloropropane (6 hours/day, 4 to 5 days/week). 

The concentrations of 1000 ppm in air for rats and 1500 ppm in air for 

guinea pigs (Heppel et al. 1946) are presented in Table l-2. 

The lethality of 1,2-dichloropropane inhaled repeatedly over an 

intermediate time period (intermediate exposure is defined as treatment for 

15 to 364 calendar days) was reported for rats, mice, guinea pigs, rabbits 

and dogs. Exposures of 7 hours/day, 5 days/week for 11 to 128 exposures in 

the Heppel et al. (1946) study resulted in the death of 17/45 rats, 3/12 

guinea pigs, 0/4 rabbits and 4/8 dogs exposed to 1000 ppm; and 4/18 rats, 

2/18 guinea pigs and l/4 rabbits exposed to 1500 ppm. Heppel et al. (1948) 

observed no lethality in rats, dogs and guinea pigs exposed to 12-140, 

7-hour exposures to 400 ppm 1,2-dichloropropane. Nitschke et al. (1988) 

reported no compound-related mortality in rats and mice intermittently 

exposed for 13 weeks to ≤150 ppm or in rabbits exposed to <1000 ppm 1,2­

dichloropropane (6 hours/day, 5 days/week). Heppel et al. (1948) determined 

that 37 exposures of 4-7 hours at 400 ppm resulted in the death of 77/80 

mice. The cause of death was not given, but some of the mice that died 

after receiving 14-28 exposures showed moderate to marked congestion and 

fatty degeneration of the liver, extensive centrolobular coagulation 

necrosis of the liver, and slight to moderate fatty degeneration of the 

kidney. The concentrations of 400 ppm in air for mice (Heppel et al. 1948) 

and 1000 ppm in air for rats, guinea pigs and dogs (Heppel et al. 1946) are 

presented in Table l-2. 

No studies were found which determined the toxicity of 1,2­

dichloropropane after inhalation for a chronic period of time (chronic 

exposure is defined as treatment for ≥365 calendar days). 

The highest reliable NOAEL value and all reliable LOAEL values for
 

lethal effects in each species and duration category are reported in Table
 

2-l and plotted in Figure 2-l. The Carpenter et al. (1949) study cannot be
 

used as the basis for a LOAEL in rats since a small number of animals were
 

evaluated (six), and it is not clear if controls were used. The data
 

evaluating the lethal effects of 1,2-dichloropropane on rabbits in the
 

Heppel et al. (1946) study and on rats and mice in the Nitschke and Johnson
 

(1983) study cannot be used as a basis for NOAELs and LOAELs since so few
 

animals were used (four rabbits, five mice, five rats).
 









21
 

2. HEALTH EFFECTS
 

2.2.1.2 Systemic Effects
 

Respiratory Effects. Rubin (1988) described the health effects in
 

humans resulting from exposure to an accidental spill of 2000 gallons of
 

1,2-dichloropropane. The exposure resulted in chest discomfort, dyspnea,
 

and a cough in some of the patients, indicating that 1,2-dichloropropane is
 

a respiratory tract irritant. Air concentrations of 1,2-dichloropropane
 

were not measured or estimated.
 

The effects of 1,2-dichloropropane on the respiratory systems of 

animals acutely exposed (1-14 days) were determined for rats, mice, and 

rabbits, Degeneration of the nasal mucosa was found in rats and mice 

exposed to ≥100 ppm and in rabbits exposed to 1000 ppm 1,2-dichloropropane 

for 2 weeks (6 hours/day, 4 to 5 days/week) (Nitschke and Johnson 1983). In 

the rats, the severity of the nasal mucosa degeneration was concentration 

related and the effects occurred at the lowest exposure level. In the mice, 

no adverse respiratory effects were found at an exposure level of 30 ppm and 

the effects found at 100 ppm were less severe than those found in the rat. 

In the rabbits, no adverse respiratory effects were found at an exposure 

level of 300 ppm. Therefore, rats appear to be the most sensitive species 

to the respiratory effects of 1,2-dichloropropane exposure. The 

concentrations of 100 ppm in air for rats and mice and of 1000 ppm in air 

for rabbits (Nitschke and Johnson 1983) are presented in Table l-2. 

The effects of 1,2-dichloropropane on the respiratory systems of 

animals exposed for an intermediate time period (15-364 days) were 

determined for rats, mice and rabbits. Rabbits exposed to 1000 ppm and rats 

exposed to ≥50 ppm had slight degeneration of the olfactory epithelium; rats 

exposed to ≥15 ppm also had slight degeneration of the respiratory 

epithelium (Nitschke et al. 1988). No adverse effects on the respiratory 

system were found in rabbits exposed to ≤500 ppm or in mice exposed to ≤150 

ppm (Nitschke et al. 1988). The concentration of 15 ppm in air (Nitschke 

et al. 1988) is presented in Table 1-2. 

The highest reliable NOAEL value and all reliable LOAEL values for
 

respiratory effects in each species and duration category are reported in
 

Table 2-1 and plotted in Figure 2-1. Both the acute study of Nitschke and
 

Johnson (1983) and the intermediate study of Nitschke et al. (1988)
 

determined that rats are the most sensitive species to the respiratory
 

effects of 1,2-dichloropropane. Therefore, the LOAEL of 100 ppm for
 

respiratory effects in rats in the acute study (Nitschke and Johnson 1983)
 

and the LOAEL of 15 ppm for respiratory effects in rats in the intermediate
 

study (Nitschke et al. 1988) will be used as the basis for the acute and
 

intermediate MRL, respectively. Based on the LOAEL of 100 ppm (Nitschke and
 

Johnson 1983), an acute MRL of 50 ppb (0.05 ppm) was calculated and based
 

on the LOAEL of 15 ppm (Nitschke et al. 1988), an intermediate MRL of 7 ppb
 

(0.007 ppm) was calculated. These calculations are described in the
 

footnote in Table 2-l.
 
22
 

2. HEALTH EFFECTS
 

Cardiovascular Effects. No studies were located regarding
 

cardiovascular effects in humans following inhalation exposure to 1,2­

dichloropropane.
 

No adverse effects of 1,2-dichloropropane on the cardiovascular system 

were found following histological examination of the heart and aorta of rats 

and mice exposed to ≤150 ppm and of rabbits exposed to ≤1000 ppm, 6 

hours/day, 5 days/week for 13 weeks (Nitschke et al. 1988). These NOAEL 

values for rats, mice and rabbits are reported on Table 2-l and plotted on 

Figure 2-1. 

Heppel et al. (1946) observed fatty degeneration of the heart in dogs
 

that were exposed to 1000 ppm 1,2-dichloropropane for 7 hours/day, 5
 

days/week for 27-128 exposures. This effect occurred only in animals that
 

died (the dogs died after 27-96 exposures); therefore, it is inappropriate
 

to consider this concentration a LOAEL for cardiovascular effects in dogs.
 

Gastrointestinal Effects. Pozzi et al. (1985) reported vomiting and
 

abdominal pain in a young woman who had been sniffing a stain remover,
 

consisting primarily (98%) of 1,2-dichloropropane, to alleviate nervousness,
 

but no dose was determined. The woman sniffed the chemical four times in
 

one night and the symptoms appeared the next morning. ,The woman recovered
 

completely after 3 weeks of hospitalization.
 

No adverse effects of 1,2-dichloropropane on the gastrointestinal 

system were found following histological examination of the stomach, large 

intestine, and small intestine of rats and mice exposed to ≤150 ppm and of 

rabbits exposed to ≤1000 ppm, 6 hours/day, 5 days/week for 13 weeks 

(Nitschke et al. 1988). These NOAEL values for rats, mice, and rabbits are 

reported on Table 2-l and plotted on Figure 2-l. 

Hematological Effects. Pozzi et al. (1985) discussed two case studies
 

in which 1,2-dichloropropane, at unreported concentrations, was inhaled over
 

a short period of time. One case involved the inhalation of 1,2­

dichloropropane over the course of one evening, and the second case involved
 

the inhalation over 6 hours while a woman was using a solvent containing
 

1,2-dichloropropane to. clean. Effects of exposure included epistaxis
 

(nosebleed), hemolytic anemia and disseminated intravascular coagulation
 

(DIC). Both patients recovered.
 

No hematological effects were observed in rats that were acutely
 

exposed to 433 ppm 1,2-dichloropropane (Sidorenko et al. 1979).
 

Hematological effects as a result of exposure to 1,2-dichloropropane 

for intermediate durations have been evaluated in rabbits, mice, and rats. 

No hematological effects were observed in rats or mice exposed to ≤150 ppm 

(Nitschke et al. 1988). A dose-related increased severity of anemia 
23
 

2. HEALTH EFFECTS
 

occurred in rabbits exposed to ≥150 ppm (Nitschke et al. 1988). The 

concentration of 150 ppm in air (Nitschke et al. 1988) is presented in Table 

1-2. 

The highest reliable NOAEL value and all reliable LOAEL values for
 

hematological effects in each species and duration category are reported in
 

Table 2-l and plotted in Figure 2-l. The Sidorenko et al. (1979) study
 

cannot be considered a reliable study since the number of animals used was
 

not reported.
 

Musculoskeletal Effects. No studies were located regarding
 

musculoskeletal effects in humans following inhalation exposure to 1,2­

dichloropropane.
 

No adverse effects of 1,2-dichloropropane on the musculoskeletal 

system were found following histological examination of the bone of rats and 

mice exposed to ≤150 ppm and of rabbits exposed to ≤1000 ppm, 6 hours/day, 5 

days/week for 13 weeks (Nitschke et al. 1988). These NOAEL values for rats, 

mice, and rabbits are reported on Table 2-l and plotted on Figure 2-l. 

Hepatic Effects. The liver is one of the main target organs for the
 

toxic effects of 1,2-dichloropropane. Pozzi et al. (1985) discussed two
 

human case studies where 1,2-dichloropropane was inhaled, leading to hepatic
 

failure in one case and hepatic damage in the other. In the first case, a
 

55-year-old woman was already suffering from membrano-proliferative
 

glomerulonephritis and undergoing home dialysis 3 times a week. The patient
 

was hospitalized with abdominal pain after inhaling cleaning solution which
 

contained 60% 1,2-dichloropropane for 6 hours; the remaining 40% of the
 

solution was a mixture of acetone, isobutyl alcohol, and n-butyl acetate.
 

Laboratory tests (aspartate aminotransferase (AST), alanine aminotransferase
 

(ALT), lactate dehydrogenase (LDH), prothrombin) showed severe hepatic
 

failure but the woman recovered after a week of hospitalization. In the
 

second case, a 20-year-old woman deliberately inhaled Trielina (98% 1,2­

dichloropropane), over the course of one evening, as a means of sedation and
 

was admitted to the hospital. Laboratory tests (AST, ALT, total bilirubin,
 

prothrombin) showed acute liver damage. The woman recovered after 3 weeks
 

of hospitalization. Concentrations were not reported for these chemical
 

exposures so that a LOAEL cannot be determined.
 

Hepatic effects of acute inhalation exposure to 1,2-dichloropropane
 

were evaluated in guinea pigs, mice, rabbits, and rats. Fatty degeneration
 

of the liver occurred in guinea pigs and rats acutely exposed to 2200 ppm
 

(Heppel et al. 1946; Highman and Heppel 1946); adverse effects were not
 

observed in guinea pigs and rats acutely exposed to 400 ppm (Heppel et al.
 

1948) or in rats exposed to 1000 ppm (Heppel et al. 1946). Drew et al.
 

(1978) found no alterations of serum levels of liver enzymes, which would
 

indicate liver damage, in rats that were exposed to 1000 ppm for 4 hours.
 

Nitschke and Johnson (1983) found no histopathologic effects on the liver in
 

rats treated with a single 6-hour exposure of 1500 ppm 1,2-dichloropropane
 
24
 

2. HEALTH EFFECTS
 

or in rats and rabbits exposed to 1000 ppm for 2 weeks (6 hours/day, 4-5
 

days/week). In mice, extensive hemorrhagic necrosis was found in animals
 

exposed for 6 hours to 500 ppm 1,2-dichloropropane. Following intermittent
 

exposure to 300 ppm for 2 weeks (6 hours/day, 4-5 days/week), increased
 

liver weight and hepatocellular hypertrophy were observed in mice (Nitschke
 

and Johnson 1983).
 

The hepatic effects of the inhalation of 1,2-dichloropropane 

administered for intermediate time periods were studied in rats, mice, 

rabbits, guinea pigs, and dogs. Adverse effects on the liver were not 

observed in dogs, rats and guinea pigs exposed to 400 ppm (Heppel et al. 

1948); in rats, guinea pigs, rabbits or dogs exposed to 1000 ppm; and in 

guinea pigs and rabbits exposed to 1500 ppm (Heppel et al. 1946). Nitschke 

et al. (1988) observed no histopathologic effects on the liver in rats or 

mice exposed to ≤150 ppm or in rabbits exposed to ≤1000 ppm 1,2­

dichloropropane 6 hours/day, 5 days/week for 13 weeks. 

The highest reliable NOAEL value and all reliable LOAEL values for
 

hepatic effects in each species and duration category are reported in Table
 

2-l and plotted in Figure 2-l. The data regarding hepatic effects in
 

rabbits in the Heppel et al. (1946) study are not reliable since a small
 

number of animals (3-4) was used for evaluation.
 

Renal Effects. Pozzi et al. (1985) reported a case study of a 20-year-old
 

female who deliberately inhaled an unknown amount of Trielina (98% 1,2­

dichloropropane) over the course of one evening. Laboratory tests (serum
 

creatine, blood urea nitrogen (BUN)) showed severe renal failure. Scant
 

urine output (oliguria) and blood in the urine (hematuria) were also seen.
 

Renal biopsy findings showed acute tubular necrosis. Other systems, such as
 

the liver, were similarly effected. The woman recovered after 3 weeks of
 

hospitalization.
 

Renal effects as a result of acute inhalation exposure to 1,2­

dichloropropane were evaluated in rats, mice, and guinea pigs. Fatty
 

degeneration of the kidney occurred in rats and guinea pigs acutely exposed
 

to 2200 ppm (Highman and Heppel 1946); adverse effects were not observed in
 

rats and guinea pigs acutely exposed to 400 ppm (Heppel et al. 1948) or in
 

rats exposed to 1000 ppm (Heppel et al. 1946). The renal effects observed
 

after acute exposure in rats and guinea pigs are similar to the effects seen
 

in the liver (Highman and Heppel 1946). No adverse effects on the kidneys
 

were found following histopathologic examination in rats and mice exposed
 

for 6 hours to 1500 ppm 1,2-dichloropropane or in rats and rabbits exposed
 

to 1000 ppm and in mice exposed to 300 ppm for 2 weeks (6 ,hours/day, 4-5
 

days/week) (Nitschke and Johnson 1983).
 

Renal effects for intermediate inhalation exposure to 1,2­

dichloropropane were evaluated in rats, guinea pigs, rabbits, and dogs.
 

Adverse effects on the kidney were not observed in dogs, guinea pigs and
 

rats exposed to 400 ppm (Heppel et al. 1948), in guinea pigs, rats, rabbits
 
25
 

2. HEALTH EFFECTS
 

and dogs exposed to 1000 ppm, and in guinea pigs and rabbits exposed to 1500 

ppm (Heppel et al. 1946). Nitschke et al. (1988) observed no 

histopathologic effects on the kidneys in rats and mice exposed to ≤150 ppm 

and in rabbits exposed to ≤1000 ppm 1,2-dichloropropane for 13 weeks (6 

hours/day, 5 days/week). 

The highest reliable NOAEL value and all reliable LOAEL values for
 

renal effects in each species and duration category are reported in Table
 

2-l and plotted in Figure 2-1. The data regarding renal effects in rabbits
 

in the Heppel et al. (1946) study are not reliable since a small number of
 

animals (3-4) were used for evaluation.
 

Dermal/Ocular Effects. Periorbital and conjunctival hemorrhages were
 

seen in a patient that was admitted to a hospital after exposure to vapors
 

of 1,2-dichloropropane (Pozzi et al. 1985). It was not clear if the
 

hemorrhages resulted from inhalation of 1,2-dichloropropane or from direct
 

exposure of the eye to the 1,2-dichloropropane vapor. No concentration
 

information was provided.
 

Severe conjunctivitis occurred in guinea pigs acutely exposed to 2200
 

ppm of 1,2-dichloropropane vapor (Heppel et al. 1946). This concentration
 

of 1,2-dichloropropane also produced death; 5 exposures of 7 hours each
 

resulted in the deaths of 11/16 of the animals. The paper did not clearly
 

state at what point, during the 5 exposures, the conjunctivitis was first
 

observed. This concentration represents a LOAEL for ocular effects and is
 

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

No adverse effects on the eye were found following gross and 

histopathologic examination of the eyes of rats and mice exposed to ≤150 ppm 

and in rabbits exposed to ≤1000 ppm 1,2-dichloropropane for 13 weeks (6 

hours/day, 5 days/week) (Nitschke et al. 1988). These NOAEL values are 

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

2.2.1.3 Immunological Effects
 

No studies were located regarding immunological effects in humans
 

following inhalation exposure to 1,2-dichloropropane.
 

Histologic examination of the bone marrow and thymus revealed no
 

adverse effects on the organs of the immune system in rats and rabbits
 

exposed to 1000 ppm of 1,2-dichloropropane 6 hours/day, 4-5 days/week for 2
 

weeks (Nitschke and Johnson 1983). In mice exposed to 300 ppm 1,2­

dichloropropane for 2 weeks (6 hours/day, 4-5 days/week), a decrease in the
 

absolute and relative thymus weight and a decrease in cortical lymphoid
 

cells were observed (Nitschke and Johnson 1983). Following 13 weeks of
 

exposure to 1,2-dichloropropane (6 hours/day, 5 days/week), no
 

histopathologic effects on the organs of the immune system (bone marrow,
 

thymus) were found in rats (150 ppm), mice (150 ppm), or rabbits (1000 ppm)
 
26
 

2. HEALTH EFFECTS
 

(Nitschke et al. 1988). Parameters of immunological function, however, were
 

not assessed in either study so that NOAELs or LOAELs cannot be defined.
 

2.2.1.4 Neurological Effects
 

Rubin (1988) described health effects in people who were exposed to
 

unknown concentrations of 1,2-dichloropropane from a tank truck that leaked
 

2000 gallons of the chemical. Fatigue, possibly attributable to CNS
 

depression, was among the symptoms observed in the exposed people.
 

Anesthesia was observed in rats during exposure to 1500 ppm 1,2­

dichloropropane for 6 hours (Nitschke and Johnson 1983). The rats
 

recovered within an hour after exposure, but remained lethargic. All mice
 

exposed to 1500 ppm for 6 hours appeared anesthetized during exposure and
 

died within 24 hours. Mice exposed to 500 ppm did not exhibit neurological
 

effects during the exposure but became lethargic after the exposure period,
 

and 2/5 of the animals died within 3 days.
 

No adverse effects on the nervous system were found following 

observation for overt signs of toxicity (tremors, convulsions, salivation, 

lacrimination, diarrhea, lethargy) or following histopathologic examination 

of the brain, spinal cord, and peripheral nerve of rats and mice exposed to 

<150 ppm and of rabbits exposed to ≤1000 ppm 1,2-dichloropropane 6 

hours/day, 5 days/week for 13 weeks (Nitschke et al. 1988). No specialized 

staining methods were used for examination of the tissues of the nervous 

system. 

Sidorenko et al. (1976) described the sequence of signs of intoxication
 

in mice that were acutely exposed by inhalation to 1,2-dichloropropane.
 

General agitation and decreased coordination of movements occurred
 

initially, followed by sluggishness, amyotonia and sporadic clonic spasms,
 

and subsequently by loss of righting reflex. The loss of the righting
 

reflex occurred at the lowest concentration given, 1000 ppm. Sidorenko et
 

al. (1979) evaluated the neurological effects in rats resulting from acute
 

and intermediate duration exposure to 1,2-dichloropropane. A total
 

threshold indicator (TTI) was used to assess the effects on the CNS, but the
 

details of the TTI were not explained in the study. In addition, control
 

data and numbers of treated rats and mice were not reported, Due to these
 

inadequacies, it is inappropriate to identify LOAELs and NOAELs for
 

neurological effects from these studies.
 

The highest reliable NOAEL value and all reliable LOAEL values for
 

neurological effects in each species and duration category are reported in
 

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

2.2.1.5 Developmental Effects
 

No studies were located regarding developmental effects in humans or
 

animals following inhalation exposure to 1,2-dichloropropane.
 
27
 

2. HEALTH EFFECTS
 

2.2.1.6 Reproductive Effects
 

Pozzi et al. (1985) reported the case of a woman who was hospitalized
 

with metrorrhagia (bleeding from the uterus between menstrual periods) after
 

acute inhalation of 1,2-dichloropropane. The metrorrhagia was a transient
 

effect. No information regarding concentration was given.
 

No histological changes in the testes of rats and rabbits exposed to
 

1000 ppm 1,2-dichloropropane and of mice exposed to 300 ppm 1,2­

dichloropropane for 2 weeks (6 hours/day, 4 to 5 days/week) were observed
 

(Nitschke and Johnson 1983).
 

No histological changes in the epididymis, prostate, or testes of males 

and in the oviduct, uterus, cervix, ovaries, or mammary glands of females 

were observed in rats and,mice exposed to ≤150 ppm and in rabbits exposed to 

≤1000 ppm 1,2-dichloropropane for 13 weeks (6 hours/day, 5 days/week) 

(Nitschke et al. 1988). 

The NOAEL values for each species and duration of exposure are
 

reported on Table 2-l and plotted on Figure 2-l.
 

2.2.1.7 Genotoxic Effects
 

No studies were located regarding genotoxic effects in humans or
 

animals following inhalation exposure to 1,2-dichloropropane.
 

2.2.1.8 Cancer
 

No studies were located regarding carcinogenic effects in humans
 

following inhalation exposure to 1,2-dichloropropane.
 

Heppel et al. (1948) examined the hepatocarcinogenic effects of 1,2­

dichloropropane resulting from intermediate inhalation exposure. It was not
 

clear if tissues other than the liver were examined. In the study,
 

hepatomas were seen in 3 out of 80 mice exposed 37 times to 400 ppm for 4-7
 

hours. High mortality occurred throughout the study; only three mice
 

survived all exposures plus a 7-month observation period. The hepatomas
 

were observed in the three mice that survived. The morphology of the
 

hepatomas was inadequately characterized and the incidence in controls was
 

not reported, therefore, this study was not used as a basis for a Cancer
 

Effect Level (CEL) in mice after intermediate inhalation exposure.
 

2.2.2 Oral Exposure
 

2.2.2.1 Death
 

There are several cases in the literature of lethality in humans
 

resulting from ingestion of 1,2-dichloropropane. The most common method of
 
28

2. HEALTH EFFECTS
 

oral exposure was the accidental or intentional ingestion of 1,2­

dichloropropane in the form of commercial solvents (Pozzi et al. 1985,
 

Larcan et al. 1977, Perbellini et al. 1985, Zedda et al. (n.d.), Chiappino,
 

and Secchi 1968). The quantity ingested cannot be determined accurately
 

because of factors such as immediate vomiting after ingestion and unknown
 

extent of absorption of 1,2-dichloropropane from the gastrointestinal tract.
 

Typically, clinical signs of 1,2-dichloropropane overexposure in these
 

incidences included primary effects on the CNS, liver, and kidney. Effects
 

on the respiratory system, heart, and blood were also described. Specific
 

causes of death included cardiac arrest and septic shock. No data on the
 

lethal effects of 1,2-dichloropropane in humans resulting from repeated oral
 

exposures, including chronic low-level exposure, were located.
 

The lethal effects of orally-administered 1,2-dichloropropane in
 

animals have been reported by several investigators. Statistically
 

determined oral LD50 values of 1942 mg/kg/day (Pozzani et al. 1959) and 2196
 

mg/kg/day (Smyth et al. 1969) have been determined for rats. An oral LD50
 

of approximately 2000 mg/kg/day in rats is reported in Table 2-2 and plotted
 

in Figure 2-2.
 

Rats and mice were administered daily doses of 125-2000 mg/kg/day by 

gavage for 14 days (NTP 1986). All rats given 2000 mg/kg/day orally died 

but there was no mortality at ≤1000 mg/kg/day. In mice, increased mortality 

occurred at ≥500 mg/kg/day, but not at ≤250 mg/kg/day. No short-term 

studies of 1,2-dichloropropane administered in food were located; therefore, 

the dose level of 500 mg/kg/day in mice and 2000 mg/kg/day in rats, which 

were administered by gavage in corn oil (NTP 1986), were converted to an 

equivalent concentration of 3850 ppm in food for mice and 40,000 ppm in 

food for rats, for presentation in Table l-4. 

Bruckner et al. (1989) reported no lethality in rats treated with up to
 

1000 mg/kg/day 1,2-dichloropropane by gavage in corn oil for 1, 5, or 10
 

consecutive days. In a 13-week study reported along with the acute study,
 

50% of the rats treated with 750 mg/kg/day (the highest dose) died within 10
 

days and the remaining animals in the treatment group were sacrificed.
 

Also, 50% of the animals treated with 500 mg/kg/day died during the course
 

of the 13-week study. The authors did not attempt to explain this apparent
 

discrepancy in the lethal dose so that no NOAEL or LOAEL values for
 

lethality will be defined.
 

In intermediate duration oral studies conducted by NTP (1986), rats and 

mice were administered doses in the range of 30-1000 mg/kg/day by gavage on 

5 days/week for 13 weeks. Death was observed at the dose of 500 mg/kg/day 

but there was no mortality at ≤250 mg/kg/day for both rats and mice. 

In chronic (103 weeks) gavage studies conducted by the NTP (1986), 

increased mortality occurred in female rats and female mice that were 

treated with 250 mg/kg/day (5 days/week). No increase in mortality occurred 

in rats or mice that were similarly treated with ≤125 mg/kg/day. No 







36
 

2. HEALTH EFFECTS
 

long-term studies of 1,2-dichloropropane administered in food were located;
 

therefore, the dose level of 250 mg/kg/day in mice and rats, which were
 

administered by gavage in corn oil (NTP 1986), were converted to an
 

equivalent concentration of 1900 ppm in food in mice and 5000 ppm in rats,
 

for presentation in Table 1-4.
 

The highest reliable NOAEL value and all reliable LOAEL values for lethal effects
 

in each species and duration category are reported in Table 2-2 and plotted in Figure 2­

2.
 

2.2.2.2 Systemic Effects
 

Respiratory Effects. No studies were located regarding respiratory
 

effects in humans following oral exposure to 1,2-dichloropropane.
 

No histopathologic changes in the lungs were observed in rats treated
 

by gavage in corn oil with up to 1000 mg/kg/day 1,2-dichloropropane for 1,
 

5, or 10 consecutive days, or with up to 500 mg/kg/day for 13 weeks (5
 

days/week) (Bruckner et al. 1989). In the gavage studies conducted by NTP
 

(19861, no compound-related histopathological lesions were observed in
 

lungs, bronchi, and trachea of F344/N rats treated with up to 1000 mg/kg/day
 

of 1,2-dichloropropane for 13 weeks, B6C3Fl mice treated with up to 500
 

mg/kg/day for 13 weeks, or rats and mice treated with up to 250 mg/kg/day
 

for 103 weeks.
 

The highest reliable NOAEL values for respiratory effects in each
 

species and duration category are reported in Table 2-2 and plotted in
 

Figure 2-2.
 

Cardiovascular Effects. Death resulting from cardiac failure occurred
 

in two humans 30 and 36 hours after ingestion of single unknown doses of
 

1,2-dichloropropane (Larcan et al. 1977, Perbellini et al. 1985). A
 

patient in the Perbellini et al. (1985) report showed ecchymoses (a purplish
 

patch caused by extravasation of blood into the skin) on the cheeks, trunk
 

and limbs, and epistaxis (nosebleed) after ingestion of an unknown dose of
 

1,2-dichloropropane.
 

Histological examination of the hearts of rats and mice that were
 

treated with doses as high as 250 mg/kg/day (5 days/week) for 103 weeks
 

revealed no compound-related lesions (NTP 1986). The dose of 250 mg/kg/day
 

is reported in Table 2-2 and plotted in Figure 2-2 as a NOAEL for
 

cardiovascular effects in rats and mice as a result of chronic oral
 

exposure.
 

Gastrointestinal Effects. Chiappino and Secchi (1968) reported a case
 

of acute overexposure by ingestion of 1,2-dichloropropane in which a 59­

year-old man experienced an immediate burning sensation in the oropharynx,
 

esophagus, and stomach, followed by vomiting for some time which became
 

biliary vomiting. Nausea, vomiting, and intense anorexia subsided but
 
37
 

2. HEALTH EFFECTS
 

persisted over the next 4 days, and the patient ultimately recovered.
 

Perbellini et al. (1985) reported reversible necrotic hemorrhagic lesions in
 

the oral cavity of a man who ingested 1,2-dichloropropane. Thorel et al.
 

(1986) observed reversible erosive esophagitis and esophageal varices in a
 

man who ingested 1,2-dichloropropane in a suicide attempt. The exposures in
 

the above cases were single, but doses were not reported.
 

Gross pathological lesions were not observed in the gastrointestinal
 

tract of mice or rats that were treated by gavage with 1,2-dichloropropane
 

doses as high as 2000 mg/kg/day for 2 weeks (NTP 1986). The fact that the
 

rats and mice in this study were not examined histologically precludes the
 

use of 2000 mg/kg/day as a NOAEL. Bruckner et al. (1989) observed no
 

histological effects on the stomach in rats treated with 1000 mg/kg/day for
 

1, 5, or 10 consecutive days.
 

Rats that were treated with 1,2-dichloropropane doses as high as 1000
 

mg/kg/day (5 days/week) for 13 weeks and mice similarly treated with up to
 

500 mg/kg/day did not have histopathological alterations in the
 

gastrointestinal tract (NTP 1986). Similarly, rats treated with up to 500
 

mg/kg/day for 13 weeks (5 days/week) showed no histopathologic changes in
 

the stomach (Bruckner et al. 1989).
 

Rats that were treated with 1,2-dichloropropane doses as high as 250
 

mg/kg/day (5 days/week) for 103 weeks did not have histological alterations
 

in the gastrointestinal tract (NTP 1986). In female mice that were treated
 

by gavage with 1,2-dichloropropane doses of 125 or 250 mg/kg/day (5
 

days/week) for 103 weeks, increased incidences of acanthosis of the forestomach
 

occurred. In male mice similarly treated, this effect was only
 

observed in the high-dose group. Because it is uncertain whether the
 

acanthosis is compound-related, a LOAEL or NOAEL for gastrointestinal
 

effects as a result of chronic oral exposure to 1,2-dichloropropane cannot
 

be determined for mice.
 

The highest reliable NOAEL value and all reliable LOAEL values for
 

gastrointestinal effects in each species and duration category are reported
 

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

Hematological Effects. Anemia, leukopenia and disseminated
 

intravascular coagulation (DIC) occurred in humans after accidental
 

ingestion of 1,2-dichloropropane (Pozzi et al. 1985; Perbellini et al.
 

1985). One of the patients recovered, one died 7 days after poisoning from
 

septic shock, and one died 30 hours after poisoning from cardiac arrest.
 

These overexposures resulted from a single deliberate ingestion of 1,2­

dichloropropane, but doses were not reported.
 

A dose-related increase in the severity of anemia was found in rats
 

treated with 250 mg/kg/day 1,2-dichloropropane by gavage in corn oil for 1,
 

5, or 10 consecutive days, and in rats treated with 100 mg/kg/day for 13
 

weeks (5 days/week) (Bruckner et al. 1989). No anemia was found in rats
 
38
 

2. HEALTH EFFECTS
 

treated with 100 mg/kg/day in the acute study. In the intermediate study,
 

anemia was found at the lowest dose level so that a LOAEL of 100 mg/kg/day
 

is defined. No short-term or long-term studies of 1,2-dichloropropane
 

administered in food were located; therefore, the dose level of 250
 

mg/kg/day in the acute study and of 100 mg/kg/day in the intermediate study
 

were converted to equivalent concentrations of 5000 and 2000 ppm in food,
 

respectively, for presentation in Table l-4. The LOAEL of 100 mg/kg/day for
 

rats in the intermediate study is the lowest effect level (LOAEL or NOAEL)
 

found for any species following intermediate exposure. A LOAEL of 100
 

mg/kg/day for decreased body weight in rats was also found. Based on the
 

LOAEL of 100 mg/kg/day, an intermediate oral MRL of 0.07 mg/kg/day was
 

calculated as described in the footnote to Table 2-2. This MEL has been
 

converted to an equivalent concentration in food (2.5 ppm) for presentation
 

in Table l-3. The MRL can be compared with existing state and federal
 

criteria levels (see Chapter 7) or to amounts of the chemical encountered in
 

environmental or occupational situations (see Chapter 5).
 

No compound-related histopathological lesions were observed in the
 

hematopoietic tissues of F344/N rats and B6C3Fl mice treated for 5 days/week
 

with 1,2-dichloropropane at doses of 30-1000 mg/kg/day for 13 weeks or 62­

125 mg/kg/day for 103 weeks (NTP 1986). Since clinical hematological tests
 

were not performed, the highest doses in these studies cannot be considered
 

NOAELs for hematological effects.
 

Musculoskeletal Effects. No studies were located regarding
 

musculoskeletal effects in humans or animals following oral exposure to 1,2­

dichloropropane.
 

Hepatic Effects. Damage to the liver has been reported in people who
 

deliberately drank 1,2-dichloropropane. Liver damage included
 

centrolobular hepatic necrosis (Pozzi et al. 1985), centro- and mediolobular
 

acute hepatic necrosis (Larcan et al. 1977), and acute icteric liver
 

disease in which histological examination and electron microscopy showed
 

diffuse, turbid degeneration in the liver cells, and evident ultrastructural
 

changes in the mitochondria, the endoplasmic reticulum, and the Golgi
 

apparatus (Chiappino and Secchi 1968). Perbellini et al. (1985) reported
 

unspecified liver damage in a man orally overexposed. Thorel et al. (1986)
 

found portal hypertension and histologically, dense, irregular portal
 

fibrosis, which damaged the hepatic parenchyma in a man who ingested 1,2­

dichloropropane in a suicide attempt. The aforementioned overexposures
 

resulted from ingestion of a single large dose, but specific amounts were
 

not reported.
 

In animal studies, the liver has been shown to be affected by acute, 

intermediate, and chronic oral exposure to 1,2-dichloropropane. Bruckner et 

al. (1989) reported adverse hepatic effects in rats treated orally for an 

acute and intermediate period of time. Liver necrosis, characterized by 

degenerative effects on the centrilobular hepatocytes and mild to moderate 

hepatitis, was observed in animals treated by gavage with ≥250 mg/kg/day 
39
 

2. HEALTH EFFECTS
 

1,2-dichloropropane in corn oil for 1, 5, or 10 consecutive days. Similar 

effects (periportal vacuolization and fibroplasia) were found in animals 

treated with ≥500 mg/kg/day for 13 weeks (5 days/week). No adverse effects, 

on the rats were found at 100 mg/kg/day in the acute study and at 250 

mg/kg/day in the intermediate study. No short-term studies of 1,2­

dichloropropane administered in food were located; therefore, the dose 

level of 250 mg/kg/day in rats, which was administered by gavage in corn oil 

(Bruckner et al. 1989), was converted to an equivalent concentration of 

5000 ppm in food in rats, for presentation in Table l-4. The NTP study 

(1986) found fatty changes, centrilobular necrosis, and congestion of the 

liver in rats given 1,2-dichloropropane orally at doses of 1000 mg/kg/day, 

but not ≤500 mg/kg/day for 13 weeks. Liver lesions were not observed in 

mice that were similarly treated with doses as high as 500 mg/kg/day (NTP 

1986). 

The NTP study (1986) found liver necrosis in female rats given 250 

mg/kg/day 1,2-dichloropropane by gavage for 103 weeks, but not in females at 

≤125 mg/kg/day or in males at any of the doses. The NTP study (1986) found 

necrosis of the liver in male mice, but not females, that were administered 

125 or 250 mg/kg/day 1,2-dichloropropane by gavage for 103 weeks (5 

days/week); lower doses were not tested. No long-term studies of 1,2­

dichloropropane administered in food were located; therefore, the dose level 

of 125 mg/kg/day in mice and 250 mg/kg/day in rats, which were administered 

by gavage in corn oil (NTP 1986), were converted to an equivalent 

concentration of 960 ppm in food in mice and 5000 ppm in food in rats for 

presentation in Table l-4. The LOAEL of 125 mg/kg/day for hepatic effects 

in mice is the lowest LOAEL reported following chronic oral exposure to 1,2­

dichloropropane (NTP 1986). A NOAEL of 62 mg/kg/day for effects on body 

weight in rats is reported (NTP 1986), but factors other than chemical 

toxicity may affect body weight; therefore, it will not be used as the 

basis for the MRL. Based on the LOAEL of 125 mg/kg/day, a chronic oral MRL 

of 0.09 mg/kg/day was calculated as described in the footnote to Table 2-2. 

The NTP study (1986) denoted that a significant dose-related increase in 

liver adenomas occurred in male mice treated with 250 mg/kg/day (P=0.017) 

and in female mice treated with the 125 and 250 mg/kg/day (P=0.102 at both 

doses) (see Section 2.2.2.8 on carcinogenic effects by oral exposure). 

The highest reliable NOAEL value and all reliable LOAEL values for
 

hepatic effects in each species and duration category are reported in Table
 

2-2 and plotted in Figure 2-2.
 

Renal Effects. Renal failure was observed in three patients after
 

ingestion of 1,2-dichloropropane (Perbellini et al. 1985, Pozzi et al. 1985,
 

Zedda et al. n.d.). Two of the patients died but renal failure did not
 

appear to be the cause of death; one death was attributed to cardiac arrest
 

and the other to septic shock. Dose information on 1,2-dichloropropane was
 

not provided.
 
40
 

2. HEALTH EFFECTS
 

Gross pathologic examinations showed reddened renal medullae in almost
 

all rats that were treated with 2000 mg/kg/day by gavage for 2 weeks, but
 

not at 1000 mg/kg/day or lower doses (NTP 1986). This effect was also
 

observed in mice that were similarly treated at doses of >125 mg/kg/day;
 

lower doses were not tested, Histological examinations were not performed.
 

NTP (1986) considered the reddened medullae to be a compound-related, but
 

not an adverse effect. The reddened medullae may have been transient since
 

no effects on the kidney, including the reddened renal medullae, were
 

observed grossly or histologically in mice or rats in the 13-week study or
 

in the 103-week study.
 

No adverse histopathologic effects on the kidneys were found in rats 

treated with ≤500 mg/kg/day 1,2-dichloropropane by gavage in corn oil 

following exposure for 1, 5, or 10 consecutive days or exposure for 13 weeks 

(5 days/week) (Bruckner et al. 1989). Increased BUN levels, however, were 

found in animals treated with 1000 mg/kg/day in the acute study. 

No treatment-related histopathological kidney lesions were observed in
 

rats or mice treated by gavage with 1,2-dichloropropane doses as high as
 

1000 mg/kg/day for rats and 500 mg/kg/day for mice in the 13 week study and
 

as high as 250 mg/kg/day for both species in the 103 week study (NTP 1986).
 

The highest reliable NOAEL value and all reliable LOAEL values for
 

renal effects in each species and duration category are reported in Table
 

2-2 and plotted in Figure 2-2. Since no histological examination of the
 

kidney was done in the 2 week studies in rats and mice (NTP 1986), it would
 

be inappropriate to consider this study as the basis for a NOAEL.
 

Dermal/Ocular Effects. No studies were located regarding
 

dermal/ocular effects in humans following oral exposure to 1,2­

dichloropropane. .
 

No treatment-related skin lesions were observed histologically in rats
 

or mice treated with 1,2-dichloropropane by gavage for 13 or 103 weeks (NTP
 

1986). The highest doses (1000 mg/kg/day for rats, 500 mg/kg/day for mice
 

in the 13-week study; 250 for both species in the 103-week study) are
 

indicated in Table 2-2 and Figure 2-2 as NOAELs for dermal effects as a
 

result of intermediate and chronic oral exposure to 1,2-dichloropropane.
 

Other Effects. Mean body weight gain was depressed by <10% in male
 

rats treated with >500 mg/kg/day, but not <250 mg/kg/day, and in female rats
 

treated with >1OOO mg/kg/day, but not <500 mg/kg/day, for 2 weeks; in male
 

rats treated with >500 mg/kg/day, but not <250 mg/kg/day, and not in female
 

rats treated with >500 mg/kg/day, for 13 weeks; and in male rats treated
 

with >125 mg/kg/day, but not 62 mg/kg/day, and in female rats treated with
 

<250 mg/kg/day, but not 125 mg/kg/day, for 103 weeks (NTP 1986). Body
 

weight gain was not affected in mice similarly treated (<2000 mg/kg/day for
 

2 weeks, <500 mg/kg/day for 13 weeks, <250 mg/kg/day for 103 weeks) in the
 

NTP (1986) study, A significant dose-related decrease in body weight gain
 
41
 

2. HEALTH EFFECTS
 

was observed in rats treated with >100 mg/kg/day by gavage in corn oil for
 

13 weeks (5 days/week) (Bruckner et al. 1989). Since 100 mg/kg/day was the
 

lowest dose tested, no NOAEL for body weight gain was defined. The LOAELs
 

and NOAELs for the three durations are reported in Table 2-2 and plotted in
 

Figure 2-2. No short- or long-term studies of 1,2-dichloropropane
 

administered in food were located; therefore, the dose levels of 250
 

mg/kg/day (short-term) and 100 mg/kg/day (long-term) in rats, which were
 

administered by gavage in corn oil (Bruckner et al. 1989), were converted to
 

an equivalent concentration of 5000 ppm (short-term) and 2000 ppm (longterm) in food for presentation in Table l-4.
 

2.2.2.3 Immunological Effects
 

No studies were located regarding immunological effects in humans
 

following oral exposure to 1,2-dichloropropane.
 

Histological examination of organs and tissues of the immune system
 

revealed no treatment-related effects in rats or mice treated by gavage with
 

1,2-dichloropropane on 5 days/week with doses >30 mg/kg/day for 13 weeks or
 

>62 mg/kg/day for 103 weeks (NTP 1986). Reduced survival of the high-dose
 

females in the 103-week study (see section 2.2.1) may have been due partly
 

to infections of the reproductive system; of the animals that died during
 

the study, 5/11 controls, 9/14 at 125 mg/kg/day, and 14/22 at 250 mg/kg/day
 

had inflammation of the reproductive system. However, it is not known if
 

1,2-dichloropropane caused an increased susceptibility to infections. No
 

specific immunological tests of rats and mice treated with 1,2­

dichloropropane were performed in the NTP (1986) studies. Therefore, LOAELs
 

and NOAELs for immunological effects cannot be determined.
 

2.2.2.4 Neurological Effects
 

Symptoms observed in patients lethally exposed to 1,2-dichloropropane
 

include dizziness, headache, disorientation and coma (Larcan et al. 1977;
 

Perbellini et al. 1985; Thorel et al. 1986). The overexposure resulted from
 

a single ingestion, but no doses were determined.
 

Gorzinski and Johnson (1989) performed a neurotoxicological
 

examination, including a Functional Observational Battery, on rats exposed
 

daily to 1,2-dichloropropane by gavage in corn oil for 2 weeks. After the
 

first dose, clinical signs (blinking, lacrimation, salivation and lethargy)
 

were observed in the treated groups, but by the fifth dose, the treated
 

animals were indistinguishable from the controls. Decreased locomotion in
 

males and a trend towards decreased activity in females were found at >300
 

mg/kg/day. Histological examination of the brain was not done. Bruckner et
 

al. (1989) found a dose-related increase in the severity of CNS depression
 

in rats treated with 100 mg/kg/day 1,2-dichloropropane by gavage in corn
 

oil for 1, 5, or 10 consecutive days. No histopathologic lesions were found
 

in the brain. Therefore, a LOAEL of 100 mg/kg/day from the Bruckner et al.
 

(1989) study and a LOAEL of 300 mg/kg/day from the Gorzinski and Johnson
 
42
 

2. HEALTH EFFECTS
 

(1989) study can be defined. No short-term studies -of 1,2-dichloropropane
 

administered in the food were located; therefore, the dose level of 100
 

mg/kg/day in rats, which was administered by gavage in corn oil (Bruckner,
 

et al. 1989), was converted to an equivalent concentration of 2000 ppm in
 

food for presentation in Table l-4. Bruckner et al. (1989) also observed
 

pronounced CNS depression in rats treated with 500 mg/kg/day by gavage for
 

13 weeks (5 days/week). The existence of CNS depression at the next lower
 

dose (250 mg/kg/day) was not reported, but 250 mg/kg/day cannot be defined
 

as a NOAEL for neurological effects following intermediate exposure since a
 

LOAEL of 100 mg/kg/day was defined by Bruckner et al. (1989) in the acute
 

study. The LOAEL of 100 mg/kg/day for rats is the lowest adverse effect
 

level for any species following acute oral exposure. Based on this value,
 

an acute oral MRL of 0.1 mg/kg/day was calculated, as described in the
 

footnote in Table 2-2. This MRL has been converted to an equivalent
 

concentration in food (3.6 ppm) for presentation in Table l-3. The MRL can
 

be compared with existing state and federal criteria levels (see Chapter 7)
 

or to amounts of the chemical encountered in environmental or occupational
 

situations (see Chapter 5).
 

Kirk et al. (1989) performed an observational battery on pregnant 

female rats that were exposed by gavage to 1,2-dichloropropane during days 

6-21 of gestation. The observational battery included observations in 

pupil size, respiration, movement, skin and hair coat, salivation, 

lacrimation, and urine and fecal staining. No adverse effects were found in 

dams exposed to ≤30 mg/kg/day, but at 125 mg/kg/day, decreased movement, 

muscle tone and extensor thrust reflex, and increased salivation and 

lacrimation were observed. 

NTP (1986) found no treatment-related lesions histologically in the 

brains of rats and mice treated with doses ≥30 mg/kg/day for 13 weeks or ≥62 

mg/kg/day for 103 weeks. Specific tests for neurological effects were not 

performed, however, precluding the determination of LOAELs and NOAELs from 

this study. 

2.2.2.5 Developmental Effects
 

No studies were located regarding developmental effects in humans
 

following oral exposure to 1,2-dichloropropane.
 

An increased incidence of delayed ossification of the bones of the 

skull was observed in the fetuses of dams treated with 125 mg/kg/day 1,2­

dichloropropane by gavage in corn oil during gestation days 6-21 (Kirk 

et al. 1989). No adverse effects were found in the fetuses of dams treated 

with ≤30 mg/kg/day. The NOAEL of 30 mg/kg/day and the LOAEL of 125 

mg/kg/day are reported on Table 2-2 and plotted on Figure 2-2. No long-term 

(≥14 days) studies of 1,2-dichloropropane administered in food were located; 

therefore, the dose level of 125 mg/kg/day in rats, which was administered 

by gavage in corn oil (Bruckner et al. 1989), was converted to an equivalent 

concentration of 2500 ppm in food for presentation in Table l-4. 
43
 

2. HEALTH EFFECTS
 

2.2.2.6 Reproductive Effects
 

No studies were located regarding reproductive effects in humans
 

following oral exposure to 1,2-dichloropropane.
 

Kirk et al. (1989) administered 1,2-dichloropropane by gavage to
 

pregnant rats during gestation days 6-21. No dose-related effects on the
 

number of pregnancies, the number of implantation sites, the number of
 

resorptions, the gravid uterine weight, or the number of fetuses were found
 

at the highest dose level (125 mg/kg/day).
 

Testicular degeneration was found in rats treated with 500 mg/kg/day by 

gavage in corn oil for 1, 5, or 10 consecutive days or for 13 weeks (5 

days/week) (Bruckner et al. 1989). The degeneration included reduced sperm 

production, increased numbers of degenerate sperm and reduced numbers of 

sperm in the epididymis. These effects were not found at dose levels of 

≤250 mg/kg/day. No short-term studies of 1,2-dichloropropane administered 

in food were located; therefore, the dose level of 500 mg/kg/day in rats, 

which was administered by gavage in corn oil, was converted to an equivalent 

concentration of 10,000 ppm in food for presentation in Table l-4. 

Increased incidences of suppurative infection of the ovary, uterus, or
 

other organs were found in the female mice treated by gavage with doses of
 

125 and 250 mg/kg/day for 103 weeks (NTP 1986), but it is not known if these
 

infections were related to 1,2-dichloropropane treatment since controls were
 

also infected. Histological examination of the reproductive organs of the
 

male rats and mice in the 103-week study, and of the higher dosed animals in
 

the 13-week study, revealed no compound-related lesions.
 

The NOAEL of 125 mg/kg/day (Kirk et al. 1989) for effects on the
 

female reproductive system following intermediate exposure and the NOAEL of
 

250 mg/kg/day and the LOAEL of 500 mg/kg/day for effects on the male
 

reproductive system following intermediate exposure are reported in Table
 

2-2 and plotted in Figure 2-2. Since no tests of reproductive function were
 

performed in the NTP (1986) study, it is not appropriate to regard the
 

levels that produced no histopathological lesions as NOAELs.
 

2.2.2.7 Genotoxic Effects
 

No studies were located regarding genotoxic effects in humans
 

following oral exposure to 1,2-dichloropropane.
 

In a dominant-lethal study, male rats were continuously exposed to 1,2­

dichloropropane in the drinking water for at least 10 weeks prior to
 

breeding and for 1 week after breeding (Hanley et al. 1989). Two days after
 

exposure was ended, the males were bred with untreated females. No effects
 

on mating performance or fertility in the males, or on the number of
 
44

2. HEALTH EFFECTS
 

implantations, resorptions, and litter sizes were observed at the highest
 

dose (162 mg/kg/day).
 

2.2.2.8 Cancer
 

No studies were located regarding carcinogenic effects in humans
 

following oral exposure to 1,2-dichloropropane.
 

A marginal but statistically significant increased incidence of
 

adenocarcinomas of the mammary gland was observed in female rats given 250
 

mg/kg/day 1,2-dichloropropane by gavage for 103 weeks (NTP 1986). NTP
 

(1986) considered this to be equivocal evidence for carcinogenicity. 1,2­

Dichloropropane was not found to be carcinogenic in other tissues in the
 

females or in any tissues in similarly treated (62 and 125 mg/kg/day) male
 

rats. The 250 mg/kg/day dose is indicated as a Cancer Effect Level (CEL) in
 

rats in Table 2-2 and is plotted in Figure 2-2.
 

A dose-related increase in liver adenomas for both male and female mice
 

was observed when treated with 125 or 250 mg/kg/day 1,2-dichloropropane by
 

gavage for 103 weeks (NTP 1986). The incidences were significantly greater
 

than control incidences in high-dose male (34% in treated vs. 14% in
 

control) and in low- and high-dose female groups (10% in both treated groups
 

vs. 2% in control). The incidences of hepatocellular carcinoma were
 

increased in the dosed animals although the increase was not significant.
 

NTP (1986) concluded that there was some evidence for carcinogenicity in
 

male and female mice based on the increased incidences of hepatocellular
 

neoplasms, primarily adenomas. The dose of 125 mg/kg/day is presented as a
 

Cancer Effect Level (CEL) in mice in Table 2-2 and is plotted in Figure 2-2.
 

EPA (1987a) classified 1,2-dichloropropane in Group B2 (i.e., a probable
 

human carcinogen), and derived a ql* of 6.8 x 10-2 (mg/kg/day)-1 from the
 

data in male mice. This ql* corresponds to upper bound individual lifetime
 

cancer risks at 10-4 to 10-7 risk levels of 1.5 x 10-3 to 1.5 x 10-6
 

mg/kg/day. The EPA plans to recalculate the ql * taking into consideration
 

the life table adjustments; therefore, the cancer risk levels are not
 

plotted in Figure 2-2.
 

2.2.3 Dermal Exposure
 

2.2.3.1 Death
 

No studies were located regarding lethal effects in humans following
 

dermal exposure to 1,2-dichloropropane.
 

A dermal LD50 of 8.75 mL/kg was calculated for rabbits (Smyth et al.
 

1969). The treatment site was covered with an impervious plastic film for
 

24 hours following application and the animals were observed for 14 days.
 

The LOAEL of 8.75 mL/kg is reported in Table 2-3.
 

46
 

2. HEALTH EFFECTS
 

2.2.3.2 Systemic Effects
 

Grzywa and Rudzki (1981) reported 2 cases of dermatitis resulting from
 

dermal exposure to aerosols containing 1,2-dichloropropane [7.4-12.7% 2­

dichloropropane, with the remainder consisting of methysilicone oils (3.6­

8.5%) and freons 11 and 12 in a 1:l proportion (83.6-84.1%)] in the
 

workplace. In one case, a woman with no family history of allergy was
 

dermally exposed to 1,2-dichloropropane by repeated spraying it during the
 

course of her work. Dermatitis appeared on her right hand after several
 

months of work and recurred several times during 6 years of employment.
 

After stopping work, there was no improvement in her condition; and new
 

areas of dermatitis appeared on her left hand and right foot. Patch tests
 

showed a strongly positive reaction to Siliform AR-1 (an aerosol containing
 

1,2-dichloropropane) and to 1,2-dichloropropane. Twenty-one other workers
 

who were similarly exposed in her workplace did not develop dermatitis. In
 

the second case, a woman with no family history of allergy was dermally
 

exposed to 1,2-dichloropropane in a similar manner; after 4 years of work,
 

dermatitis appeared on the dorsa of her feet and continued for at least 10
 

years. The dermatitis was exacerbated in the summer and occasionally
 

appeared on her neck. After 13 years of work, the woman developed hand
 

dermatitis, which receded after she changed her work and was no longer
 

exposed to 1,2-dichloropropane. Patch tests showed a positive response to
 

1,2-dichloropropane and a negative response to Siliform AR-l. Skin changes
 

were seen in two of 39 other persons exposed in her workplace, but these
 

cases were not documented. No dose information was available for either of
 

the above cases.
 

No studies were located regarding any other systemic effects in humans
 

following dermal exposure to 1,2-dichloropropane.
 

No studies were located regarding hepatic, renal, musculoskeletal, or
 

cardiovascular system effects in animals following dermal exposure to 1,2­

dichloropropane.
 

No respiratory, gastrointestinal, or hematological effects were
 

observed upon gross examination of rabbits treated dermally with a single
 

dose of 3.16 g/kg 1,2-dichloropropane (Exxon 1982a). Erythema was observed
 

in rabbits treated in the same experiment. The treatment site was occluded
 

for 24 hours following application, and the animals were examined 14 days
 

following treatment. Since tissues of the respiratory, gastrointestinal and
 

hematological systems were only grossly examined, it would be inappropriate
 

to consider the dose of 3.16 g/kg a reliable NOAEL for these effects. The
 

dose of 3.16 g/kg, however, can be considered a LOAEL for dermal effects in
 

rabbits since erythema was observed upon gross examination (see Table 2-3).
 

Ocular irritation (redness, iridial irritation, cornea1 ulceration) was
 

seen when an unspecified amount of 1,2-dichloropropane was instilled in the
 

conjunctival sac of rabbits (Exxon 1982b). The 1,2-dichloropropane was
 
47
 

2. HEALTH EFFECTS
 

placed in the eye, the upper and lower lids were held together for one
 

second to prevent loss of material, and the animals were observed from 1
 

hour to 14 days after administration. Since no dose information was
 

available for this study, it would be inappropriate to consider it the basis
 

for a LOAEL.
 

No studies were located regarding the following effects in humans or
 

animals following dermal exposure to 1,2-dichloropropane:
 

2.2.3.3 Immunological Effects
 

2.2.3.4 Neurological Effects
 

2.2.3.5 Developmental Effects
 

2.2.3.6 Reproductive Effects
 

No studies were located regarding reproductive effects in humans
 

following dermal exposure to 1,2-dichloropropane.
 

No effects on the ovaries were observed upon gross examination of
 

rabbits dermally treated with a single dose of 3.16 g/kg 1,2-dichloropropane
 

(Exxon 1982a). The treatment site was occluded for 24 hours following
 

application and the animals were examined 14 days following treatment.
 

Since the ovaries were only grossly examined, the dose of 3.16 g/kg cannot
 

be considered a NOAEL for reproductive effects.
 

2.2.3.7 Genotoxic Effects
 

No studies were located regarding genotoxic effects in humans or
 

animals following dermal exposure to 1,2-dichloropropane.
 

2.2.3.8 Cancer
 

No studies were located regarding carcinogenic effects in humans or
 

animals following dermal exposure to 1,2-dichloropropane.
 

2.3 RELEVANCE TO PUBLIC HEALTH
 

Death. The few deaths observed in humans as a result of deliberate
 

ingestion of 1,2-dichloropropane were apparently due to toxic effects on the
 

central nervous system, liver, and kidney (Pozzi et al. 1985; Larcan et al.
 

1977; Zedda et al. (n.d.); Perbellini et al. 1985). The ultimate cause of
 

death has been reported to be cardiac arrest and septic shock. No deaths
 

have been reported resulting from inhalation or dermal exposure to 1,2­

dichloropropane. All of the documented human overexposures resulted from
 

ingestion or inhalation of 1,2-dichloropropane in the form of a cleaning
 

solvent. Since the use of 1,2-dichloropropane as a consumer cleaning
 

solvent has been curtailed, documented overexposures may be rare in the
 
48
 

2. HEALTH EFFECTS
 

future. Information on human lethality resulting from repeated exposures to
 

1,2-dichloropropane has not been reported.
 

Doses causing death in animals have been reported for acute and
 

intermediate inhalation exposures, for acute, intermediate, and chronic oral
 

exposure, and for acute dermal exposure. In general, mice were more
 

sensitive to the lethal effects of acute oral exposure to 1,2­

dichloropropane than are other laboratory animals. This difference in
 

sensitivity was not found following acute inhalation exposure. During
 

intermediate or chronic oral or inhalation exposure, mice and rats were
 

equally sensitive (NTP 1986; Nitschke et al. 1988). The reason for this
 

difference in sensitivity is not known; and it is not clear if humans are
 

more or less sensitive to 1,2-dichloropropane in relation to other animals,
 

since dose information is not available for the cases of human overexposure.
 

Conventionally, it is assumed that humans are as sensitive as the most
 

sensitive species tested when assessing the risk of 1,2-dichloropropane
 

lethally to humans. The concentrations associated with death in animals are
 

much higher than would be found in the environment, in occupational
 

settings, or in water or soil surrounding waste sites; therefore, it is
 

unlikely that humans would die from noncancer effects after brief or
 

prolonged exposure to 1,2-dichloropropane in air, food, water, or soil.
 

1,2-Dichloropropane has been rated a B2 carcinogen, however, so prolonged
 

exposure could result in death from cancer.
 

Systemic Effects. Systemic effects of 1,2-dichloropropane include
 

respiratory effects due to irritation of the respiratory tract,
 

hematological effects, and hepatic and renal alterations manifested
 

primarily as fatty degeneration.
 

Respiratory effects, including chest discomfort, dyspnea and cough,
 

were reported in humans as a consequence of inhalation exposure to 1,2­

dichloropropane (Rubin 1988); respiratory effects have not been observed in
 

humans following oral or dermal exposure. Similarly, respiratory effects
 

in animals were seen only as a result of inhalation exposure. Following
 

inhalation exposure, rats appeared to be more sensitive to the effects of
 

1,2-dichloropropane on the nasal tissues than mice (Nitschke et al. 1988).
 

This sensitivity was observed following both acute and intermediate exposure
 

(Nitschke and Johnson 1983; Nitschke et al. 1988).
 

Cardiac failure was the cause of death for 2 patients who ingested a
 

single dose of 1,2-dichloropropane (Larcan et al. 1977; Perbellini et al.
 

1985). It is likely, however, that the cardiac failure in humans is a
 

result of toxicity to the CNS. Oral studies in animals did not show
 

cardiovascular effects resulting from 1,2-dichloropropane, but this may be a
 

consequence of the limited scope of pathological examination in the high
 

dose acute studies. Human inhalation studies did not report adverse
 

effects on the cardiovascular system. Animal inhalation studies by Heppel
 

et al. (1946), however, reported some fatty degeneration of the heart, but
 

this effect was only seen in the animals that died. Similar effects,
 
49
 

2. HEALTH EFFECTS
 

however, were not observed in more recent studies by Nitschke and coworkers
 

(Nitschke and Johnson 1983; Nitschke et al. 1988).
 

Adverse gastrointestinal effects were seen in humans after deliberate
 

inhalation and ingestion of 1,2-dichloropropane (Pozzi et al. 1985;
 

Chiappino and Secchi 1968; Perbellini et al. 1985). These effects included
 

nausea, vomiting and gastrointestinal tract lesions. Nausea and vomiting
 

are general effects that could very well be due to CNS toxicity.; therefore,
 

it is difficult to determine if these effects are secondary to the
 

gastrointestinal irritation/corrosion or CNS toxicity. Acanthosis of the
 

forestomach was seen in mice in a chronic oral study done by NTP (1986), but
 

no effects on the gastrointestinal system were seen in any inhalation
 

studies. The acanthosis may be a consequence of repeated ingestion of an
 

irritant which is consistent with the gastrointestinal effects of 1,2­

dichloropropane on humans. It was not clear that the acanthosis was
 

specifically due to 1,2-dichloropropane.
 

Disseminated intravascular coagulation (DIC) and hemolytic anemia were 

found in humans as a result of overexposure to 1,2-dichloropropane 

(Perbellini et al. 1985; Pozzi et al. 1985). This finding, somewhat unusual 

in cases of solvent exposure, was reported in a total of five patients 

between the two studies regardless of route of exposure (inhalation or 

ingestion). Perbellini et al. (1985) suggested that hemolysis resulting 

from 1,2-dichloropropane may trigger DIC, but the mechanism has yet to be 

proven. In animal studies, a dose-related increase in the severity of 

anemia was found in rabbits exposed to 1,2-dichloropropane by inhalation 

(≥150 ppm, 6 hours/day, 5 days/week, 13 weeks) (Nitschke et al. 1988) and in 

rats treated orally with 1,2-dichloropropane (≥250 mg/kg/day for up to 10 

consecutive days and at ≥100 mg/kg/day, 5 days/week for 13 weeks) (Bruckner 

et al. 1989). These results are consistent with the anemia observed in 

humans as a result of both inhalation and ingestion of 1,2-dichloropropane. 

One of the principal target organs, in both animals and humans, for the
 

toxicity of 1,2-dichloropropane is the liver. The major effects in both
 

animals and humans resulting from both inhalation and oral exposure are
 

fatty degeneration and necrosis. The hepatic effects of 1,2-dichloropropane
 

on humans result from unknown, but apparently high, doses either ingested in
 

a single bolus dose or inhaled over a short period of time.
 

Secchi and Alessio (1968, 1971) reported increases in hepatic enzymes
 

found in human serum as an indicator of hepatic damage resulting from
 

ingestion of 1,2-dichloropropane (mixture of 70% 1,2-dichloropropane and 30%
 

trichloroethylene). Cytoplasmic liver enzymes found in the serum indicated
 

less severe damage to hepatocytes, while mitochondrial and lysosomal liver
 

enzymes found in the serum indicated severe hepatic damage, usually
 

associated with death (3/6 subjects died). Compound-related damage to
 

mitochondrial structures results in the depression of metabolic processes
 

related to the production of energy, and damage to the lysosomes results in
 

the release of hydrolytic enzymes into the cell which is responsible for
 
50
 

2. HEALTH EFFECTS
 

fatal cellular necrosis. In this study, histological examination of the
 

liver of the patients positively correlated with the serum-enzymological
 

findings.
 

Bonashevskaya et al. (1976) discussed a proposed mechanism of action of
 

1,2-dichloropropane on the rat liver based on work done on chlorinated
 

aromatic compounds. The centrolobular region of the liver was reported as
 

the focus for detoxification of lipophilic substances, while the peripheral
 

region of the liver manages the elimination of toxins with the bile. The
 

toxic effects of 1,2-dichloropropane are generally localized in the
 

centrolobular region of the liver. The 1,2-dichloropropane penetrates the
 

plasma membranes in the centrolobular region and is metabolically
 

transformed because of the activity of microsomal enzymes. This system of
 

microsomal enzymes is also described by Van Dyke and Wineman (1971) (see
 

section 2.3.1.3 on Metabolism). The activation of the enzyme system results
 

in hyperplasia of the endoplasmic reticulum, resulting in the loss of
 

ribosomes. The loss of the ribosomes results in a decrease in protein
 

synthesis and, therefore, an inhibition of lipoprotein formation.
 

Consequently, lipid inclusions appear in the cytoplasm of the cells,
 

resulting in fatty degeneration of the liver. This mechanism has been
 

proposed in the literature but has yet to be completely proven, and the
 

relevance of the mechanism to humans remains unknown.
 

Renal failure has occurred in people exposed to 1,2-dichloropropane
 

orally and by inhalation (Pozzi et al, 1985; Zedda et al. (n.d.); Perbellini
 

et al. 1985). Fatty degeneration of the kidney was seen in animals exposed
 

by inhalation to 1,2-dichloropropane (Highman and Heppel 1948). Reddened
 

renal medullae were found in animals treated by gavage for 2 weeks, but was
 

not found in animals treated for longer time periods (NTP 1986). The
 

reddened medullae may be transient lesions that disappear after initial
 

exposure to 1,2-dichloropropane. The animal inhalation and oral studies
 

suggest that kidney toxicity may be a consequence of single and repeated
 

exposure to 1,2-dichloropropane.
 

Dermal/ocular effects of 1,2-dichloropropane have occurred in humans;
 

these include periorbital and conjunctival hemorrhages following vapor
 

exposure (Pozzi et al. 1985) and dermatitis after dermal exposure (Grzywa
 

and Rudzki 1981). Conjunctivitis was seen in guinea pigs exposed to 1,2­

dichloropropane vapor (Heppel et al. 1946), but no dermal/ocular effects
 

were seen as a result of oral exposure. These local irritative effects of
 

1,2-dichloropropane are consistent with the gastrointestinal tract data; the
 

chemical appears to be a local irritant by all routes, as might be expected.
 

The reported systemic effects of 1,2-dichloropropane in humans have
 

resulted from inhalation or ingestion of 1,2-dichloropropane in the form of
 

a cleaning solvent, or from dermal contact with aerosols in the workplace.
 

Since 1,2-dichloropropane is no longer available as a consumer solvent, and
 

its use as an industrial solvent involves closed systems, the potential for
 

human exposure is minimal. The concentrations associated with systemic
 
51
 

2. HEALTH EFFECTS
 

effects in animals are much higher than those found in the environment, in
 

occupational settings, or in water or soil surrounding waste sites, so it is
 

not likely that harmful, noncancer effects would result from brief or
 

prolonged human exposure to 1,2-dichloropropane in air, food, water, or
 

soil. 1,2-Dichloropropane has been rated a B2 carcinogen, however, so
 

prolonged exposure may result in cancer.
 

Immunological Effects. Sensitization has occurred in humans dermally
 

exposed to 1,2-dichloropropane in the workplace (Grzywa and Rudzki 1981)
 

(see Section 2.2.3.2). Immunological effects in humans have not been
 

observed as a result of oral or inhalation exposure. An in vitro study on
 

the toxicity of 1,2-dichloropropane on human lymphocytes was conducted by
 

Perocco et al. (1983). The cellular parameters studied included tritiated
 

thymidine uptake and viability in cells grown with or without the S-9 rat
 

liver metabolizing system. The S-9 liver system is included to provide
 

mammalian liver enzymes that may be necessary to metabolize the compound
 

being tested into a more or less toxic chemical, simulating events in vivo.
 

No cytotoxic action against human lymphocytes was seen as a result of
 

exposure to 1,2-dichloropropane. Dermal exposure in humans may result in
 

immunological effects, but it is inappropriate to draw any conclusions
 

regarding other routes of exposure due to the limited data. In mice, a
 

decrease in the absolute and relative thymus weight and a decrease in
 

cortical lymphoid cells were found in animals exposed by inhalation to 300
 

ppm 1,2-dichloropropane (6 hours/day, 5 days/week, 2 weeks) (Nitschke and
 

Johnson 1983). Except for the acutely exposed mice described above
 

(Nitschke and Johnson 1983), no changes in the immunological organs or
 

tissues were observed in animals exposed by inhalation (acute or
 

intermediate exposure periods) or treated orally (intermediate and chronic
 

exposure periods). Tests of immunological function were not performed
 

following any route of exposure in animals.
 

Neurological Effects. The CNS is a principal target for 1,2­

dichloropropane toxicity. Dizziness, disorientation, and coma are some of
 

the effects on the central nervous system which have occurred in humans
 

after overexposure by ingestion (Larcan et al. 1977; Perbellini et al. 1985;
 

Thorel et al. 1986). The dose-response relationship for this effect cannot
 

be characterized due to lack of quantitative dose information. Reported
 

neurological effects resulting from inhalation exposure were less pronounced
 

than the effects resulting from oral exposure, probably due to different
 

exposure levels. Since only two case studies of inhalation overexposure are
 

available (Pozzi et al. 1985; Rubin 1988) and since CNS effects as a result
 

of oral overexposure to high levels are severe, it is reasonable to assume
 

that inhalation exposures (at concentrations that would result in the same
 

internal dose as in the oral studies), may produce CNS effects of similar
 

severity to those found in the oral studies. The mechanism of action on the
 

CNS has not been determined, but Perbellini et al. (1985) found a high
 

concentration of 1,2-dichloropropane in the brain of a woman who died
 

following ingestion of 1,2-dichloropropane. In animal studies, neurological
 

effects (lethargy, CNS depression, decreased activity) were found following
 
52

2. HEALTH EFFECTS
 

acute inhalation exposure (Nitschke and Johnson 1983) and following acute
 

and intermediate oral exposure (Gorzinski and Johnson 1989; Bruckner et al.
 

1989). These observations are consistent with the effects found in humans
 

following both inhalation and ingestion of 1,2-dichloropropane.
 

Since 1,2-dichloropropane is no longer available as a consumer solvent,
 

it is unlikely that other modes of human exposure (air, food, or water)
 

would result in harmful central nervous system effects.
 

Genotoxic Effects. No studies were located regarding genotoxic effects
 

in humans or animals following inhalation or dermal exposure to 1,2­

dichloropropane. In an oral dominant-lethal study in mice, no effects were
 

found on mating performance or fertility in the males, or on the number of
 

implantations, resorptions, and litter sizes (Hanley et al. 1989). Results
 

of in vitro genetic testing of 1,2-dichloropropane are presented in Table 2­

4. A number of investigators found that 1,2-dichloropropane is mutagenic
 

for various strains of Salmonella, when tested with or without S-9
 

exogenous metabolic activation preparation. Carere and Morpurgo (1981) and
 

Principe et al. (1981) found that 1,2-dichloropropane was mutagenic for
 

Aspergillus but not Streptomyces when tested without an exogenous metabolic
 

activation system. 1,2-Dichloropropane was mutagenic in mouse lymphoma
 

cells when tested with exogenous activation (Tennant et al. 1987) and in
 

Drosophila (exposed by inhalation and ingestion) (Woodruff et al. 1985).
 

Chromosomal aberrations were induced in Chinese hamster ovary cells under
 

both activated and non-activated conditions, but not in Aspergillus
 

(Crebelli et al. 1984). Since 1,2-dichloropropane is mutagenic in bacteria,
 

mouse lymphoma cells and Drosophila, and clastogenic in Chinese hamster
 

cells, it is appropriate to predict that 1,2-dichloropropane poses a
 

genotoxic threat to humans.
 

Cancer. Chronic oral exposure to 1,2-dichloropropane produced
 

significantly increased incidences of hepatocellular neoplasms in male and
 

female mice and mammary gland adenocarcinomas in female rats (NTP 1986).
 

Male mice of the strain used (B6C3Fl) in the NTP (1986) study are known to
 

have a high incidence of benign liver tumors. The normally high rate of
 

these tumors can be enhanced by various stimuli including stress, irritants,
 

carcinogenic chemicals and promoters. As discussed by NTP (1986),
 

promoters seem to enhance the incidence of liver tumors only in animals that
 

have a high spontaneous rate. Carcinogenic chemicals, however, have
 

increased the incidence of both benign and malignant liver tumors in mice,
 

regardless of whether a certain strain has a high incidence of spontaneous
 

tumors. NTP (1986) discussed the possibility that 1,2-dichloropropane was a
 

tumor promotor but could not come to a conclusion.
 

NTP (1986) regarded the increased incidences of mammary gland
 

adenocarcinoma in female rats as equivocal evidence of carcinogenicity.
 

That the increase was associated with 1,2-dichloropropane exposure is
 

strengthened by the following facts: these are relatively rare tumors in
 

the strain of rat used; the incidence was 25% in the high-dose females that
 

54
 

2. HEALTH EFFECTS
 

survived until the end of the study; and the lower body weight of the high-


dose females would be expected to decrease the spontaneous rate, rather
 

than enhance it. However, the toxicity of the high dose may have affected
 

the homeostasis of the female rats; the incidence of mammary fibroadenomas
 

was decreased in the high-dose females relative to controls, and the
 

adenocarcinomas were morphologically similar to tumors classified by some
 

pathologists as highly cellular fibroadenomas.
 

The EPA (1987b) has classified 1,2-dichloropropane as a B2 carcinogen
 

(probable human carginogen) based on the NTP (1986) study, which concluded
 

that 1,2-dichloropropane is reasonably anticipated to be a human
 

carcinogen.
 

2.4 LEVELS IN HUMAN TISSUES AND FLUIDS ASSOCIATED WITH HEALTH EFFECTS
 

No studies were located that associated human tissue levels with human
 

health effects or with environmental levels of 1,2-dichloropropane.
 

Perbellini et al. (1985) described a case of oral overexposure to 1,2­

dichloropropane where the subject died from cardiac arrest 30 hours after
 

ingestion. Symptoms of the overexposure included; initial agitation,
 

bradycardia, hypertension and anuria, followed by hypoxemia, shock, DIC and
 

cardiac arrest. Approximately 28 hours after ingestion, 7614 μg/L of 1,2­

dichloropropane was found in the subject's blood and, after 29 hours, the
 

concentration found was 6900 μg/L. At autopsy, the concentration of 1,2­

dichloropropane was determined in several tissues; brain tissue contained
 

18,005 μg/L, cerebellar tissue contained 39,890 μg/L and adipose tissue
 

contained 531,840 μg/L.
 

2.5 LEVELS IN THE ENVIRONMENT ASSOCIATED WITH LEVELS IN HUMAN TISSUES


 AND/OR HEATH EFFECTS
 

Rubin (1988) described health effects as a result of an accidental
 

spill of 2000 gallons of 1,2-dichloropropane in 1981. The complaints from
 

those exposed included chest discomfort, dyspnea, and a cough, suggesting
 

that 1,2-dichloropropane is a respiratory tract irritant. The concentration
 

of 1,2-dichloropropane in the air was not determined, so the health effects
 

cannot be correlated level.
 

Amoore and Hautala (1983) odor thresholds of 214 industrial chemicals, including
 

1,2-dichloropropane, and compared these values with the
 

Threshold Limit Values (TLV) recommended by the ACGIH. The air odor
 

threshold of 1,2-dichloropropane is 0.25 ppm. The study reported that 50­

90% of distracted persons would perceive the odor of 1,2-dichloropropane at
 

the TLV of 75 ppm. The experiment was done with distracted persons, and not
 

persons focused on detecting an odor, in order to better simulate the work
 

environment. It is likely that unacclimated people would smell 1,2­

dichloropropane before experiencing significant exposure.
 
55

 2. HEALTH EFFECTS
 

Ghittori et al. (1987) evaluated the Biological Equivalent Exposure
 

Limit (BEEL) for nine solvents, including 1,2-dichloropropane. BEEL refers
 

to the concentration of a substance in a biological compartment when the
 

environmental exposure level through the lungs equals the Threshold Limit
 

Value (TLV). Ghittori et al. (1987) used urinary concentration of 1,2­

dichloropropane as a biological indicator and correlated it with the TLV. A
 

linear relationship between breathing zone concentration and urinary
 

concentration was obtained. This relationship is displayed graphically in
 

Figure 2-3.
 

Cramer et al. (1988) introduced a method for the detection of volatile
 

compounds, including 1,2-dichloropropane, at parts per trillion (ppt) levels
 

in whole blood (see Table 6-l). This method was validated using blood
 

samples from a small population. Based on the method validation data, this
 

method appears reliable and, in the future, may be routinely used to detect
 

organic chemicals in human whole blood.
 

Wallace et al. (1982) monitored 1,2-dichloropropane and other volatile
 

organic compounds in the breathing-air zone, in drinking water and in
 

exhaled breath at a petrochemical area in Texas and in a non-industrial area
 

in North Carolina. In this study, it was determined that inhalation was the
 

main route of exposure to volatile organic compounds. No 1,2­

dichloropropane, however, was found in the ambient air or in expired breath
 

at either test site.
 

2.6 TOXICOKINETICS
 

2.6.1 Absorption
 

2.6.1.1 Inhalation Exposure
 

No studies were located regarding the rate and extent of absorption of
 

1,2-dichloropropane following inhalation exposure of humans. During the
 

first 24 hours after a 6-hour exposure of rats to 14C-1,2-dichloropropane
 

(5, 50, or 100 ppm), 71-88% of the recovered dose was found in the excreta,
 

with 55-65% of the recovered dose found in the urine and 16-23% of the
 

recovered dose found in expired air as 14CO2 (Timchalk et al. 1989). These
 

data suggested that 1,2-dichloropropane was absorbed through the lungs. The
 

data indicated that 1,2-dichloropropane was rapidly absorbed according to a
 

zero-order input, but that absorption was not linear with respect to the
 

concentration of 1,2-dichloropropane. The authors assumed that 60% of the
 

inspired concentration of 14C-1,2-dichloropropane was absorbed, but the
 

basis for this assumption was not reported (Timchalk et al. 1989). Sato and
 

Nakajima (1979) measured the blood/air partition coefficient of 10.7 for
 

1,2-dichloropropane indicating that 1,2-dichloropropane is readily absorbed
 

from the lungs.
 

57
 

2. HEALTH EFFECTS
 

2.6.1.2 Oral Exposure
 

No studies were located regarding the rate and extent of absorption of
 

1,2-dichloropropane following oral exposure of humans. Studies in rats by
 

Hutson et al. (1971) and Timchalk et al. (1989), which found that an average
 

of 74-95% of the 14C-labeled 1,2-dichloropropane dose was excreted in the
 

urine or in expired air within 24 hours of dosing, suggest that 1,2­

dichloropropane is readily and extensively absorbed from the
 

gastrointestinal tract. This is supported by the fact that only 0.5% of the
 

administered dose remained in the gut 4 days after administration (Hutson et
 

al. 1971).
 

2.6.1.3 Dermal Exposure
 

No studies were located regarding the rate and extent of absorption of
 

1,2-dichloropropane following dermal exposure of humans or animals. That
 

1,2-dichloropropane is absorbed by the skin can be inferred from the
 

lethality observed in rabbits following dermal exposure (see section 2.2.3.1
 

on Death following dermal exposure).
 

2.6.2 Distribution
 

2.6.2.1 Inhalation Exposure
 

After rats were exposed for 6 hours to 5, 50, or 100 ppm 14C-labeled
 

1,2-dichloropropane, the radioactivity was well distributed among the major
 

tissues, with the highest concentration in the liver, kidney, lung, and
 

blood (Timchalk et al. 1989).
 

2.6.2.2 Oral Exposure
 

Perbellini et al. (1985) described a case of a lethal overdose from a 

single ingestion of 1,2-dichloropropane. Death occurred 30 hours after 

ingestion. At autopsy, 18,005 μg/L 1,2-dichloropropane was found in the 

brain tissue, 39,890 μg/L was found in the cerebellar tissue, and 531,840 

μg/L was found in adipose tissue. 

Timchalk et al. (1989) observed that 48 hours after administration of
 14C-labeled 1,2-dichloropropane, the radioactivity was well distributed
 

among the major tissues, with liver having the highest concentration. The
 

distribution of radioactivity in the tissues of rats was similar following
 

inhalation and oral exposure to 1,2-dichloropropane in the Timchalk et al.
 

(1989) study, with the exception of high levels of radioactivity found in
 

the lungs only after inhalation exposure. In a study by Hutson et al
 

1971), rats were administered one dose of 4.0 mg kg 1,2-dichloro(l14C)propane. Approximately 1.5% and 3.5% of the 14C dose were found in the
 

skin and carcass, respectively, after 96 hours.
 
58

2. HEALTH EFFECTS
 

2.6.2.3 Dermal Exposure
 

No studies were located regarding the distribution of 1,2­

dichloropropane following dermal exposure.
 

2.6.3 Metabolism
 

No studies were located regarding the metabolism of 1,2-dichloropropane
 

following dermal exposure in humans or in animals.
 

Hutson et al. (1971) administered 4.8 mg/kg 1,2-dichloro(l-14C)propane
 

orally to rats and 42.4% of the given dose was measured in the expired air
 

after 96 hours. Of the 42.4%, 19.3% was expired as (14C)C02, indicating
 

that extensive metabolism of 1,2-dichloropropane had occurred.
 

Jones and Gibson (1980) administered one dose of 100 mg/kg/day
 

intraperitoneally to rats and measured the amount of 1,2-dichloropropane in
 

the expired air, They found 5% of the administered dose after 0-3 hours,
 

and 5% of the dose after 9-18 hours, indicating that the 1,2-dichloropropane
 

is transported in the blood and expired by the lungs.
 

Timchalk et al. (1989) described the time course of 1,2-dichloropropane
 

in the blood as a one-compartment open pharmacokinetic model, with zero-


order input and first-order elimination. In rats exposed to 50 or 100 ppm
 

1,2-dichloropropane vapors for 6 hours, the peak blood concentrations were
 

17- to 19- and 68- to 84-fold higher, respectively, than the peak blood
 

concentration of the 5 ppm group. This dose-dependent non-linearity of
 

blood clearance suggests that metabolism and/or elimination of 1,2­

dichloropropane becomes saturated with increasing concentrations (Timchalk
 

et al. 1989).
 

The major urinary metabolites in rats treated by gavage or exposed to 

1,2-dichloropropane vapors are N-acetyl-S-(2-hydroxypropyl)-L-cysteine, 

N-acetyl-S-(2-oxopropyl)-L-cysteine, and N-acetyl-S-(l-carboxyethyl)-Lcysteine. 

These metabolites accounted for approximately 84% of the urinary 

metabolites excreted (Timchalk et al. 1989) (see Figure 2-4). Data indicate 

that the three N-acetyl cystein conjugates result from 1,2-dichloropropane 

undergoing oxidation, either before or after conjugation with gluathione. 

The data also indicate that 1,2-dichloropropane may conjugate with lactate, 

forming CO2 and Acetyl Co-A. Acetyl Co-A may then enter the TCA cycle and 

generate more CO2 or may be utilized in various biosynthetic pathways. In 

another study, 25-35% of an oral dose of 20 mg/kg/day 1,2-dichloropropane 

administered for 4 days was excreted as N-acetyl-S-(2-hydroxypropyl)­

cysteine. β-Chloroactate and N-acetyl-S-(2,3-dihydroxypropyl)-cysteine were 

also detected in the urine (Jones and Gibson 1980). Similar urinary 

metabolites (mercapturic acids) were detected following intraperitoneal 

administration of 1,2-dichloropropane (Trevisan et al. 1988). 

60
 

2. HEALTH EFFECTS
 

Repeated exposure of rats to 1 mg kg/day 1,2-dichloropropane via gavage
 

for 7 days following a single dose of 14C-labeled compound resulted in
 

enhanced oxidative metabolism (increased CO2 formation) and reduced
 

radioactivity excreted in the urine compared to rats receiving only the
 

single-labeled dose (Timchalk et al. 1989).
 

Van Dyke and Wineman (1971) determined that 5.8% of (36Cl)1,2­

dichloropropane was enzymatically dechlorinated in vitro by an enzyme system
 

found in hepatic microsomes. This system required NADPH and oxygen and was
 

inducible by phenobarbital and benzpyrene, but not by methylcholanthrene.
 

The optimum pH of the system was 8.2.
 

2.6.4 Excretion
 

2.6.4.1 Inhalation Exposure
 

In rats exposed to 5, 50, or 100 ppm of 14C-labeled 1,2-dichloropropane
 

vapors for 6 hours, the principal routes of elimination were the urine and
 

expired air; 55-65% of the recovered does was excreted in the urine, expired
 

CO2 accounted for 16-23% of the recovered dose, and 1.7, 2.1-3.4, and 6.3­

6.7% of the recovered dose was expired as organic volatiles in the 5, 50,
 

and 100 ppm groups, respectively. The majority of the administered dose was
 

excreted within the first 24 hours after exposure (Timchalk et al. 1989).
 

2.6.4.2 Oral Exposure
 

In a study by Hutson et al. (1971), rats were administered one dose of
 

4.0 mg/kg 1,2-dichloro(1 -14C)propane by gavage. In the first 24 hours, 80­

90% of the 14C dose was excreted in the urine, feces, and expired air.
 

After 24 hours, males had excreted 48.5% of the dose in the urine and 5.0%
 

of the dose in the feces. Females had excreted 51.9% of the dose in the
 

urine and 3.8% of the dose in the feces in the same time period. Therefore,
 

the percentage of radioactivity in expired air after 24 hours ranged from
 

24.3-36.5% of the dose in both sexes. Similar results were observed in rats
 

administered 1 or 100 mg/kg of 14C-labeled 1,2-dichloropropane (Timchalk et
 

al. 1989). In a separate experiment, 42.4% of the administered 14C dose of
 

4.8 mg/kg 1,2-dichloro(l-14C)propane was detected in the expired air after
 

96 hours (Hutson et al. 1971).
 

In rats exposed to 1 mg/kg of 14C-labeled 1,2-dichloropropane, 31-36%
 

of the dose was expired as CO2 and 0.14-1.13% as volatile organics. In
 

animals treated with 100 mg/kg, 23-27% of the label was expired as CO2 and
 

10-16% as volatile organics. The differences between the two groups were
 

statistically significant. In the 100 mg/kg groups, 82% of the exhaled
 

volatile organics were identified as 1,2-dichloropropane (Timchalk et al.
 

1989).
 

Trevisan et al. (1988) administered 1,2-dichloropropane
 

intraperitoneally to rats and determined that it is excreted in the urine in
 
61
 

2. HEALTH EFFECTS
 

the form of mercapturic acids, N-acetyl-S-(2-hydroxypropyl)cysteine and N-acetylS-(2,3-dihydroxypropyl)cysteine. A non-linear, dose-dependent
 

excretion was observed with the maximum excretion seen 9 hours after
 

injection.
 

2.6.4.3 Dermal Exposure
 

No studies were located regarding the excretion of 1,2-dichloropropane
 

following dermal exposure.
 

2.7 INTERACTIONS WITH OTHER CHEMICALS
 

A common soil fumigant known as D-D consists of 1,2-dichloropropane
 

(27.1%), 1,3-dichloropropene (53%), related compounds and 1%
 

epichlorohydrin. Nater and Gooskens (1976) reported three incidences of
 

exposure to D-D which resulted in dermatosis. Patch testing suggested the
 

existence of a contact allergic sensitivity to D-D in one of the patients.
 

Patch tests with components of D-D suggest that the cause of the contact
 

allergy is with the dichloropropene component.
 

Shell Oil Co. (1982) studied the toxic effects of 1,2-dichloropropane
 

(light ends) which is a mixture of 65% 1,2-dichloropropane and various other
 

dichloropropane/dichloropropenes. The oral LD50 in rats was 487 mg/kg (95%
 

confidence limits, 387-613 mg/kg), which was found in fairly good agreement
 

with the LD50 value of 604 mg/kg, calculated on the basis of the additive
 

effects of the major components of the mixture, indicating that potentiation
 

of toxicity was not occurring. The 24-hour percutaneous LD50 in rats was
 

greater than 2340 mg/kg (the maximum dose volume that could be applied).
 

The Draize skin irritancy test showed necrosis of female rabbit skin with a
 

less severe effect seen in males. In both sexes, skin reactions persisted
 

at 21 days after dosing. The mixture was mildly irritating to rabbit eyes
 

with a severe initial pain reaction. The mixture was a strong sensitizer in
 

guinea pigs (19/20 positive after 24 hours, 16/20 after 48 hours).
 

Shell Oil Co. (1983) studied the genotoxic effects of a mixture of
 

dichloropropanes and dichloropropenes in which 1,2-dichloropropane was the
 

major component (65%). Compound-related effects were observed with several
 

strains of Salmonella that contained base substitution mutations, and with
 

Saccharomyces. Similar effects were found with 1,3-dichloropropene (25% of
 

mixture), indicating that the mutagenic response may have been due to 1,3­

dichloropropene. The mixture did not mutate rat liver cells (RL4) in
 

vitro.
 

Parker et al. (1982) exposed CD-1 mice and F344 rats to mixtures of D-D
 

[1,3-dichloropropene (52%)/1.2-dichloropropane (29%)] at concentrations of
 

0, 5, 15 or 50 ppm, 6 hours/day, 5 days/week for 6 or 12 weeks. Exposure-


related effects in the animals exposed to 50 ppm D-D included increased mean
 

liver/body weight ratios in male rats, increased mean kidney/body weight
 

ratios in female rats and slight to moderate diffuse hepatic enlargement in
 
62
 

2. HEALTH EFFECTS
 

male mice after 12 weeks of exposure. No exposure-related effects were
 

found at the lower exposure levels.
 

Linnett et al. (1988) studied the effects of subchronic inhalation of
 

D-D (1,3-dichloropropene (53.7%)/1,2-dichloropropane(25.6%)) on reproduction
 

in male and female rats. Exposures up to 90 ppm for 10 weeks had no effects
 

on the libido, fertility, or morphology of the reproductive tracts of male
 

or female rats.
 

In animals, the joint toxicity of 1,2-dichloropropane was assessed with
 

a variety of different compounds since environmental or occupational
 

exposures to chemicals usually occur in combination with other chemicals.
 

Pozzani et al. (1959) determined that 1,2-dichloropropane has an additive
 

toxic effect (LD50 assessed) when given orally or by inhalation to rats with
 

1,1,2-trichloroethane, and when given with both ethylene dichloride and
 

perchloroethylene. Drew et al. (1978) reported that inhalation of 1,2­

dichloropropane in combination with trichloropropane by rats did not result
 

in a greater-than-additive toxic effect (serum enzymes assessed: SGOT, SGPT,
 

G-6-phosphatase, ornithine carbamyl transferase). Tsulaya et al. (1979) and
 

Sidorenko et al. (1976, 1979) determined that inhalation of 1,2­

dichloropropane has an additive effect in rats and mice when given in
 

combination with 1,2,3-trichloropropane and perchloroethylene (effects on
 

lung, liver and nervous system assessed).
 

2.8 POPULATIONS THAT ARE UNUSUALLY SUSCEPTIBLE
 

No populations with unusual or increased susceptibility to the health
 

effects of 1,2-dichloropropane could be identified based on the available
 

literature.
 

2.9 ADEQUACY OF THE DATABASE
 

Section 104 (i) (5) of CERCLA, 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-dichloropropane is available. Where adequate information is
 

not available, ATSDR, in cooperation with the National Toxicology Program
 

(NTP), is required to assure the initiation of a program of research
 

designed to determine these health effects (and techniques for developing
 

methods to determine such health effects). The following discussion
 

highlights the availability, or absence, of exposure and toxicity
 

information applicable to human health assessment. A statement of the
 

relevance of identified data needs is also included. In a separate effort,
 

ATSDR, in collaboration with NTP and EPA, will prioritize data needs across
 

chemicals that have been profiled.
 
63

2. HEALTH EFFECTS
 

2.9.1 Existing Information on the Health Effects of 1,2-Dichloropropane
 

The existing data on health effects of inhalation, oral, and dermal
 

exposure of humans and animals to 1,2-dichloropropane are summarized in
 

Figure 2-5.
 

Data regarding the toxic effects of 1,2-dichloropropane on humans
 

result solely from case reports of people exposed by inhalation, ingestion
 

or skin exposure. The case reports contain information regarding the
 

lethal and systemic effects of acute inhalation and oral exposure to the
 

agent. These reports indicate that 1,2-dichloropropane primarily affected
 

the central nervous system, liver, and kidneys, but respiratory and
 

hematopoietic system alterations were also observed. Chronic dermal
 

exposure to 1,2-dichloropropane in aerosol form in the workplace resulted in
 

dermatitis.
 

There are data regarding the lethality and toxic effects of 1,2­

dichloropropane in animals exposed by inhalation for acute and intermediate
 

time periods. The central nervous system, respiratory system, liver, and
 

kidney are the major target organs of 1,2-dichloropropane toxicity.
 

Hematological effects are also reported. A limited study on the
 

carcinogenicity of 1,2-dichloropropane in mice after inhalation exposure
 

has been done and has suggested that 1,2-dichloropropane was carcinogenic
 

(see Section 2.2.1.8), but the study is unreliable (high mortality occurred
 

in the exposed group; tumor incidence in controls was not reported;
 

morphology of the hepatomas was inadequately characterized) so no
 

conclusions may be drawn.
 

Data are available regarding the lethality and toxic effects of 1,2­

dichloropropane in animals orally exposed for acute, intermediate and
 

chronic time periods. These data show that the liver is the main target
 

organ for the toxic effects of 1,2-dichloropropane; effects on the
 

hematological and nervous systems were also observed. An increase in the
 

incidence of a developmental effect in rats (delayed ossification of the
 

bones of the skull) was also observed. The carcinogenicity in rats and mice
 

after chronic oral exposure to 1,2-dichloropropane was assessed and
 

carcinogenic potential was found in both species: there was equivocal
 

evidence in female rats (chemically related marginal increase in
 

adenocarcinomas of the mammary gland), no evidence in male rats (no
 

chemically related increases in neoplasms), and some evidence in male and
 

female mice (chemically increased incidence of hepatocellular neoplasms).
 

Application of 1,2-dichloropropane to the skin or eye of rabbits
 

produced irritation. Application to the skin of rabbits has also produced
 

death.
 

No genotoxic effects were found in a dominant-lethal study in rats.
 

65
 

2. HEALTH EFFECTS
 

Genotoxicity data in bacteria, fungus, Drosophila and mammalian cell
 

lines was evaluated. The preponderance of data indicate that 1,2­

dichloropropane ,is mutagenic in these systems.
 

2.9.2 Data Needs
 

Single Dose Exposure. Information regarding single inhalation and oral
 

exposure of various animal species to 1,2-dichloropropane provides
 

information on lethal effect levels. The limited data available on the
 

non-lethal effects of a single dose of 1,2-dichloropropane show effects on
 

the liver and kidney. More studies that use non-lethal doses and examine
 

tissues histologically might provide information on dose-response
 

relationships and mechanisms of lethality and toxicity. Single dose dermal
 

and ocular studies in rabbits have shown that 1,2-dichloropropane is a skin
 

and eye irritant. Additional observations in other species of animals
 

dermally exposed to 1,2-dichloropropane would help to more fully
 

characterize the irritative effects of this chemical.
 

Repeated Dose Exposure. Available repeated exposure inhalation and
 

oral studies of 1,2-dichloropropane provide information on the lethal and
 

non-lethal effects in various species of animals. The major target organs
 

for the effects of 1,2-dichloropropane are the central nervous system, liver
 

and kidney, and effects on the respiratory, hematological systems and body
 

weight were also seen. Repeated dose dermal studies with animals are not
 

available but would provide information on the possible systemic effects of
 

1,2-dichloropropane. Since occupational dermal exposure has resulted in
 

dermatitis in humans, repeated dermal dose studies in animals might also
 

provide information on allergic responses as well as local irritation.
 

Chronic Exposure and Carcinogenicity. Well-conducted chronic oral
 

gavage studies provide information on the systemic and carcinogenic effects
 

of 1,2-dichloropropane in rats and mice. Chronic inhalation, oral drinking
 

water, and dermal animal studies are not available but could provide
 

information on similarity of systemic effects across routes and dose-


response data that may be useful for human health risk evaluation. These
 

studies may also help categorize the carcinogenic potential of 1,2­

dichloropropane in humans.
 

Genotoxicity. The available genotoxicity studies conducted with
 

bacteria, fungus, and mammalian cell lines indicate that 1,2-dichloropropane
 

is genotoxic in some systems. A dominant-lethal study in rats resulted in
 

no genotoxic effects, but further in vivo studies with mammals will help
 

fully characterize the genotoxic potential of 1,2-dichloropropane, with
 

regard to potential for heritable mutations, chromosomal damage, and
 

chromosomal aberrations. Cell transformation studies may also be useful to
 

augment carcinogenesis bioassays.
 
 

66
 

2. HEALTH EFFECTS
 

Reproductive Toxicity. Histological examination of the reproductive
 

organs of female rats and mice exposed orally to 1,2-dichloropropane for
 

subchronic or chronic durations, showed inflammation of the uterus and ovary
 

and hyperplasia of the mammary gland. It was not found conclusively that
 

these effects were compound-related; this uncertainty and the fact that
 

limited human data (metrorrhagia) suggest an adverse effect on the
 

reproductive system suggests that additional studies examining the effects
 

of 1,2-dichloropropane on the female reproductive organs are desirable.
 

Male and female reproductive organs in rodents were also histologically
 

examined after subchronic and chronic oral exposure but no compound-related
 

lesions were found. A 2-generation oral reproduction study is now in
 

progress, and the results of these studies will provide further information
 

regarding any reproductive effects of 1,2-dichloropropane in animals, which
 

then may be related to possible reproductive effects in humans. Studies
 

examining the reproductive effects of 1,2 dichloropropane following
 

inhalation and dermal exposure of animals would also be helpful in assessing
 

the potential effects in humans.
 

Developmental Toxicity. Toxic effects in rats (delayed ossification of
 

the bones of the skull) have been found following oral exposure to 1,2­

dichloropropane. Further studies using a greater range of doses and studies
 

testing other relevant routes of exposure would provide information on
 

possible fetotoxic and teratogenic effects in animals that might be relevant
 

to humans.
 

Immunotoxicity. Subchronic and chronic oral studies in rats and mice
 

have found no adverse effects after histological examination of organs and
 

tissues of the immunological system, but a battery of immunotoxicity tests
 

have not been performed. A decrease in thymus weight and a decrease in
 

cortical lymphoid cells were found in mice following acute inhalation
 

exposure to 1,2-dichloropropane, but no tests of immunological function were
 

performed. These studies in animals by relevant environmental routes would
 

provide a better assessment of immunotoxic effects than histological
 

examination of organs and tissues. Two case studies suggested that 1,2­

dichloropropane may sensitize humans. Testing in animals to determine the
 

dose and time of exposure needed to sensitize animals would be helpful in
 

determining levels of 1,2-dichloropropane leading to sensitization in ,
 

humans.
 

Neurotoxicity. Signs of central nervous system toxicity have been seen 

in humans after both inhalation and oral exposure. Signs of central nervous 

system toxicity were found in animals acutely exposed to 1,2-dichloropropane 

by inhalation and in animals treated orally with 1,2-dichloropropane (acute 

and subchronic exposures). Functional Observational Batteries have been 

performed on rats acutely exposed to 1,2-dichloropropane and neurological 

effects (decrease in activity) were found at ≥300 mg/kg/day. A battery of 

tests by other relevant routes of exposure and the assessment of 

neuropathology using specialized fixation methods would provide further 
67
 

2. HEALTH EFFECTS
 

information on the neurotoxicity in animals, which may relate to possible
 

neurotoxic effects in humans.
 

Epidemiological and Human Dosimetry Studies. In humans, 1,2­

dichloropropane primarily affects the central nervous system, liver and
 

kidney. This information comes from case studies where patients either
 

inhaled or ingested 1,2-dichloropropane, accidentally or as a suicide
 

attempt. The only occupational exposure was reported in a Polish study in
 

which two women out of sixty that were dermally exposed to liquid 1,2­

dichloropropane developed allergic dermatitis. The most likely routes of
 

exposure for the United States general population are through inhalation of
 

contaminated ambient air or consumption of contaminated drinking water. As
 

discussed in Chapter 5, the use of 1,2-dichloropropane as a consumer solvent
 

and as a soil fumigant has been discontinued. 1,2-Dichloropropane is now
 

used as a commercial solvent, but only in closed systems. Therefore,
 

exposure to the general population via inhalation should be much lower than
 

in the past. The most likely exposure to humans is the consumption of
 

contaminated drinking water resulting from the use of 1,2-dicholopropane
 

soil fumigant in agricultural areas. Elimination of 1,2-dichloropropane
 

from the groundwater is slow so that contamination may remain for a long and
 

indeterminate period of time. The monitoring of urine and blood levels of
 

1,2-dichloropropane in populations exposed to contaminated drinking water or
 

air (such as those living near industries using 1,2-dichloropropane as a
 

solvent, those living near hazardous waste sites, or those people
 

occupationally exposed) and the correlation of these levels with health
 

effects, may provide a basis for further epidemiological studies.
 

Biomarkers of Disease. Secchi and Alessio (1968, 1971) reported
 

differences in hepatic enzymes found in human serum as an indicator of
 

hepatic damage resulting from ingestion of 1,2-dichloropropane. It was
 

found that cytoplasmic liver enzymes found in the serum indicated less
 

severe damage to hepatocytes, while mitochondrial and lysosomal liver
 

enzymes found in the serum indicated severe liver damage, which usually
 

results in death. Further epidemiological studies may validate these
 

indices and correlate other parameters with a particular disease state
 

resulting from exposure to 1,2-dichloropropane.
 

Disease Registries. At present, the only toxicological effects of 1,2­

dichloropropane reported in humans are acute effects resulting from
 

ingestion or inhalation of cleaning solvents containing 1,2-dichloropropane.
 

If epidemiological studies identify particular diseases associated with 1,2­

dichloropropane exposure, it may be possible to determine the number of
 

people affected and the factors associated with identifying the disease in
 

certain populations, such as exposure to 1,2-dichloropropane in the ambient
 

air or in the drinking water near hazardous waste sites.
 

Bioavailability from Environmental Media. Detection of exposure to
 

1,2-dichloropropane through urinalysis, blood analysis, and odor thresholds
 

have been studied (Amoore and Hautala 1983, Ghittori et al. 1987, Cramer et
 
68
 

2. HEALTH EFFECTS
 

al. 1988). Epidemiology studies that correlate levels of 1,2­

dichloropropane in the environment with levels in human tissues, blood or
 

urine and with specific health effects would be useful. While no data on
 

the uptake of 1,2-dichloropropane in other tissue or bodily fluids are
 

available, a pilot study demonstrated that similar low molecular weight
 

chlorinated alkanes are found in human milk (Pellizzarri et al. 1982). The
 

source of these pollutants was probably ambient air. The major source of
 

human exposure to 1,2-dichloropropane could be from contaminated well water,
 

and an animal study (Hutson et al. 1971) indicates that it is readily
 

adsorbed from the GI tract. An analysis of body fluids of those people
 

whose drinking water contains 1,2-dichloropropane or who have come into
 

contact (orally or dermally) with soil contaminated with 1,2­

dichloropropane, may allow a determination of the existence of exposure and
 

bioavailability of the chemical.
 

Food Chain Bioaccumulation. 1,2-Dichloropropane has not been reported
 

in food or biota nor were any studies located in which the uptake of this
 

chemical in plants or animals was investigated. The bioaccumulation
 

potential for a chemical is most conveniently studied by measuring the
 

bioconcentration factor (BCF) or the concentration of a chemical in fish
 

divided by the concentration in water from which the chemical is taken up.
 

Lacking any data on such studies for 1,2-dichloropropane, the
 

bioaccumulation can be estimated from its partitioning behavior between
 

octanol and water which, in turn, can be estimated from structure-activity
 

relationships. Accordingly, the BCF of 1,2-dichloropropane estimated from
 

its K,, is 18 (Lyman et al. 1982, Eqn 5-2), indicating that there is a very
 

low potential for bioaccumulation in the food chain.
 

Absorption, Distribution, Metabolism, Excretion. The only in vivo
 

toxicokinetic data of 1,2-dichloropropane are the inhalation metabolism and
 

the excretion study of Timchalk et al. (1989), oral metabolism and excretion
 

studies of Hutson et al. (1971) and Timchalk et al. (1989), the oral
 

metabolism study of Jones and Gibson (1980), and the intraperitoneal
 

excretion study of Trevisan et al. (1988). These studies indicate that
 

inhaled 1,2-dichloropropane and orally administered 1,2-dichloropropane are
 

readily and extensively absorbed by the gastrointestinal tract, is primarily
 

metabolized to N-acetyl-S-(2-hydroxypropyl)cysteine, and is rapidly excreted
 

in the urine, feces and expired air. Studies in animals of the rate and
 

extent of absorption and distribution following exposure to all three
 

routes, and metabolism and excretion following dermal exposure would provide
 

more complete characterization the pharmacokinetics of 1,2-dichloropropane,
 

Ghittori et al. (1987) and Cramer et al. (1988) reported methods for
 

detection of 1,2-dichloropropane in urine and blood. These methods may
 

provide means of monitoring human exposure and of extrapolating results from
 

animal studies,
 

Comparative Toxicokinetics. No studies were found that evaluated
 

differences in toxicokinetics between species. Toxicokinetic differences
 

may explain the increased sensitivity of mice to the toxic effects of 1,2­
69
 

2. HEALTH EFFECTS
 

dichloropropane in comparison to other species. Ethical considerations
 

limit the amount of information that can be obtained in humans, but analysis
 

of the urine of people with known exposure to the parent compound or its
 

metabolites could provide knowledge of the metabolic 'pathways in humans.
 

Qualitative and quantitative comparison of human metabolites with those of
 

animals could help identify the most appropriate species to serve as a model
 

for predicting toxic effects in humans and studying the mechanisms of
 

action.
 

2.9.3 On-going Studies
 

The EPA (1987d) issued a final rule requiring the manufacturers and
 

processors of 1,2-dichloropropane to conduct health effects studies. All of
 

the required studies have been incorporated into this profile, except for a
 

2-generation oral study, which has yet to be completed.
 

71
 

3. CHEMICAL AND PHYSICAL INFORMATION
 

3.1 CHEMICAL IDENTITY
 

Data pertaining to the chemical identity of 1,2-dichloropropane
 

are listed in Table 3-l.
 

3.2 PHYSICAL AND CHEMICAL PROPERTIES
 

The physical and chemical properties of 1,2-dichloropropane are
 

presented in Table 3-2.
 



75
 

4. PRODUCTION, IMPORT, USE AND DISPOSAL
 

4.1 PRODUCTION
 

1,2-Dichloropropane is produced by Columbia Organics in Cassatt, SC,
 

Dow Chemical in Freeport, TX and Dow Chemical in Plaquemine, LA (SRI 1988;
 

USITC 1987); however, Dow Chemical Company is the only manufacturer of the
 

isolated chemical in the United States (EPA 1986c). The total output of
 

1,2-dichloropropane by U.S. manufacturers remained relatively stable until
 

1984 when a major manufacturer, Mannsville Chemical Products Corporation,
 

discontinued production (IARC 1986). The domestic production volume of 1,2­

dichloropropane during 1984 was 59.8 million pounds (IARC 1986). Over 95%
 

of the approximately 75 million pounds produced in 1982 was used on site as
 

a captive chemical intermediate in the production of perchloroethylene and
 

other chlorinated products (EPA 1986c, Dow Chem. Co. 1983). High-purity
 

1,2-dichloropropane, marketed as a solvent, is obtained as a by-product of
 

the synthesis of propylene oxide by the chlorohydrin process. The high-


purity product may also be obtained by the reaction of propylene and
 

chlorine in the presence of an iron oxide catalyst at moderate temperature
 

(45°C) and pressure (25-30 psia). Pesticide products that contain 1,2­

dichloropropane were distillates of the chlorination of propylene (IARC
 

1986). However, Dow discontinued production of 1,2-dichloropropane for
 

agricultural use, and pesticidal formulations containing this chemical, such
 

as D-D, are unavailable in the U.S. (Meister 1987). By 1983, 1,2­

dichloropropane was no longer sold for consumer use in paint strippers,
 

paint varnish, and furniture finish removers (EPA 1986c; Dow Chem. Co.
 

1983). This indicates that production for sale, as opposed to internal
 

consumption by manufacturers, has been greatly curtailed in the early 1980s.
 

4.2 IMPORT
 

Mobay Corporation imported 1 million lbs of 1,2-dichloropropane from
 

the German Federal Republic in 1986 (EPA 1987c). Mobay currently imports
 

1,2-dichloropropane from the German Federal Republic on an as-need basis on
 

customer's request, Other data pertaining to the import of 1,2­

dichloropropane were not located in available literature.
 

4.3 USE
 

Based on 1982 production data supplied by Dow (EPA 1986c), it has been
 

estimated that over 95% of the isolated product manufactured by Dow Chemical
 

is used on-site as a captive intermediate in the production of
 

perchloroethylene and other chlorinated products by their 'per-tet' process
 

(EPA 1986c, Dow Chem. Co. 1983). Approximately 3 million pounds per year of
 

dichloropropane was marketed by Dow Chemical in 1982 for use as an
 

industrial solvent for oils, fats, resins, waxes, and rubber, in ion
 

exchange manufacture, in toluene diisocyanate (TDI) production, in
 

photographic film manufacture, for paper coating, and for petroleum catalyst
 

regeneration (HSDB 1988; IARC 1986; EPA 1986c). As of 1982, Dow Chemical no
 
76
 

4. PRODUCTION, IMPORT, USE AND DISPOSAL
 

longer sold 1,2-dichloropropane for use as a solvent in paint strippers,
 

paint, varnish, and furniture finish removers as a low-cost alternative to
 

methylene chloride. It had been a component of 10 of,these products (EPA
 

1986c). By the end of 1983, its use as a solvent for film production was to
 

be phased out in favor of l,l,l-trichloroethane (Dow 1983). According to
 

Dow (1989), the phaseout of use of 1,2-dichloropropane as a solvent for film
 

production had not occurred as of June, 1989, although it is still planned.
 

They further stated that the use of 34% in TDI production has now been
 

discontinued, Outside of its use as a chemical intermediate, Dow Chemical
 

Company's use pattern for 1,2-dichloropropane in 1982 was 41% in ion
 

exchange manufacturing, 34% in toluene diisocyanate (TDI) production, 19% in
 

photographic film production, 4% in paper coating, and 2% in petroleum
 

catalyst regeneration (Dow 1983).
 

An estimated 20 million pounds/year of dichloropropane were produced as
 

a by-product in a mixture marketed as a soil fumigant which had been used in
 

the cultivation of a variety of crops, including citrus fruits, pineapple,
 

soya beans, cotton, tomatoes, and potatoes (IARC 1986; HSDB 1988). Dow has
 

discontinued production of soil fumigants containing 1,2-dichloropropane,
 

and pesticidal formulations containing this chemical are no longer available
 

in the U.S. (Meister 1987). Other uses for 1,2-dichloropropane include an
 

intermediate in the synthesis of carbon tetrachloride, lead scavenger in
 

gasoline, textile stain remover, oil and paraffin extractant, scouring
 

compound, and metal degreasing agent, especially prior to electroplating
 

(IARC 1986). However, the largest manufacturer of 1,2-dichloropropane, Dow
 

Chemical Co. (1989), is not aware of its current uses as a lead scavenger in
 

gasoline, textiles, stain remover, oil and paraffin extractant, scouring
 

compound, and metal degreasing agent.
 

4.4 DISPOSAL
 

Incineration under controlled conditions appears to be the most viable
 

method of disposal for 1,2-dichloropropane (OHM-TADS 1988; HSDB 1988). It
 

is reported that Dow Chemical incinerates 7 million pounds of 1,2­

dichloropropane annually (EPA 1986c). Disposal through the use of a liquid
 

injection incinerator requires a temperature range of 650 to 1600°C and
 

residence time of 0.1 to 2 seconds. A rotary kiln incinerator requires a
 

temperature range of 820 to 1600°C and a residence time of seconds. A
 

fluidized bed incinerator requires a temperature range of 450 to 980°C and a
 

residence time of seconds (HSDB 1988). Where land disposal of waste residue
 

containing 1,2-dichloropropane is sought, environmental regulatory agencies
 

should be consulted on acceptable disposal practices (HSDB 1988). 1,2­

Dichloropropane may also be a constituent of wastewater streams where it
 

would be susceptible to removal by air stripping (EPA 1986c).
 

4.5 ADEQUACY OF THE DATABASE
 

Section 104 (i) (5) of CERCLA, directs the Administrator of ATSDR (in
 

consultation with the Administrator of EPA and agencies and programs of the
 
77
 

4. PRODUCTION, IMPORT, USE AND DISPOSAL
 

Public Health Service) to assess whether adequate information on the health
 

effects of 1,2-dichloropropane is available. Where adequate information is
 

not available, ATSDR, in cooperation with the National Toxicology Program
 

(NTP), is required to assure the initiation of a program of research
 

designed to determine these health effects (and techniques for developing
 

methods to determine such health effects). The following discussion
 

highlights the availability, or absence, of exposure and toxicity
 

information applicable to human health assessment. A statement of the
 

relevance of identified data needs is also included. In a separate effort,
 

ATSDR, in collaboration with NTP and EPA, will prioritize data needs across
 

chemicals that have been profiled.
 

4.5.1 Data Needs
 

Production, Import, Use, and Disposal. Production methods for 1,2­

dichloropropane are described in the literature. While former major uses of
 

1,2-dichloropropane are known, there has been a phasing out of many of the
 

applications with the greatest potential for population exposure. Current
 

information concerning production volume and use is lacking. This type of
 

information is absolutely necessary for estimating the potential for
 

environmental releases from various industries, as well as potential
 

concentrations in the environmental. Knowledge of what consumer products
 

contain 1,2-dichloropropane is essential for estimating general population
 

exposure. Unfortunately, this type of information is difficult to obtain in
 

detail since companies consider it to be confidential business information.
 

According to the Emergency Planning and Community Right to Know Act of 1986
 

(EPCRTKA), (§313), (Pub. L. 99-499, Title III, §313), industries are
 

required to submit release information to the EPA. The Toxic Release
 

Inventory (TRI), which contains release information for 1987, became
 

available in May of 1989. This database will be updated yearly and should
 

provide a more reliable estimate of industrial production and emission.
 

79
 

5. POTENTIAL FOR IITJMAN EXPOSURE
 

5.1 OVERVIEW
 

1,2-Dichloropropane is a man-made chemical whose presence in the
 

environment results from anthropogenic activity. Emission sources of 1,2­

dichloropropane include process and fugitive emissions from its production
 

and use as a chemical intermediate and industrial solvent, and evaporation
 

from wastewater streams. Many of the major uses of 1,2-dichloropropane,
 

other than as a chemical intermediate and industrial solvent, have been
 

eliminated or curtailed. Most importantly, all uses with significant
 

consumer and general population exposure may have been eliminated in the
 

U.S. 1,2-Dichloropropane is no longer used as a soil fumigant in the United
 

States, a use that has been responsible for polluting groundwater supplies
 

in some agricultural areas. Its major producer, Dow Chemical Company, has
 

recommended that it no longer be used in paint stripping formulations,
 

varnish, and furniture finish removers, uses with potential for widespread
 

consumer and occupational exposure. Dow Chemical Company asserts that
 

occupational exposure is minimal since all their processes involving the
 

production, conversion, or disposal of 1,2-dichloropropane are in closed
 

systems. Additionally, vent gas from their production process is destroyed
 

by thermal oxidation. There is evidence that there were substantial
 

releases of 1,2-dichloropropane into wastewater by industries that use 1,2­

dichloropropane as a solvent. An example of such industries are those that
 

use 1,2-dichloropropane in the manufacture of ion exchange resins.
 

The major releases of 1,2-dichloropropane will be to the atmosphere and
 

to soil. However, when 1,2-dichloropropane is spilled on soil, landfilled,
 

or applied to soil, as it formerly had been, as a fumigant, it will
 

partially volatilize, and the remainder will leach into the subsurface soil
 

and groundwater. In one experiment in which soil was treated with 1,2­

dichloropropane, immediately covered with 12 cm of untreated soil and stored
 

outdoors in open jars protected from rain, 99% of the chemical was lost
 

within 10 days. With the elimination of 1,2-dichloropropane's use in
 

agriculture, its potential for polluting groundwater has been substantially
 

reduced. In groundwater, where volatilization is unlikely, the principal
 

reactions will be hydrolysis and anaerobic biotransformation. Hydrolysis is
 

estimated to be very slow (half-life 25-200 weeks) and the potential for
 

anaerobic biotransformation has not been evaluated. Therefore groundwater
 

supplies that are contaminated with 1,2-dichloropropane may remain so for a
 

long and indeterminate period of time.
 

The dominant removal process of 1,2-dichloropropane in the atmosphere
 

is expected to be reaction with photochemically-generated hydroxyl radicals
 

(half-life >23 days). Washout in precipitation should also occur; although
 

most 1,2-dichloropropane removed by this mechanism is likely to reenter the
 

atmosphere by volatilization. Since degradation in the atmosphere is slow,
 

considerable dispersion of 1,2-dichloropropane from source areas can occur
 

before it degrades or is removed in washout. Besides dispersal, importation
 
80
 

5. POTENTIAL FOR HUMAN EXPOSURE
 

of 1,2-dichloropropane may also occur from other countries where it may be
 

more widely used. Volatilization will be the primary fate process in
 

surface water (half-life 5.8 hr in a model river). In soil, 1,2­

dichloropropane is expected to volatilize rapidly from the soil surface and.
 

to leach into the ground, where the potential for groundwater contamination
 

exists.
 

The general population may be exposed to low levels of 1,2­

dichloropropane through inhalation of contaminated ambient air, consumption
 

of contaminated drinking water, or dermal contact. With the elimination of
 

its use as a soil fumigant and curtailment of its use in paint strippers,
 

varnishes, and furniture finish removers, exposure of the general population
 

to 1,2-dichloropropane by inhalation or dermal contact should be much lower
 

than it once was. Any groundwater supplies that are already contaminated,
 

may remain so for a long time. A 1981-1983 National Occupational Exposure
 

Survey (NOES) by NIOSH estimated that 2119 non-agricultural workers,
 

including 949 females, were potentially exposed to 1,2-dichloropropane in
 

the United States. The number of exposed workers should be much lower now
 

because of the chemical's diminished use. Occupational exposure is primarily
 

by inhalation and dermal contact,
 

5.2 RELEASES TO THE ENVIRONMENT
 

5.2.1 Air
 

The total estimated annual environmental release of 1,2-dichloropropane
 

from production and industrial use, primarily in the manufacture of
 

perchloroethylene, was 1,146,OOO lbs (EPA 1986c). This figure represents
 

releases regulated by the Toxic Substances Control Act (TSCA), and therefore
 

excludes pesticidal uses of 1,2-dichloropropane. Of these releases, 772,000
 

lbs were to air, 198,000 lbs to water, and 176,000 lbs to land disposal
 

sites. They include releases from process emissions to the air, secondary
 

air emissions resulting from volatilization during wastewater treatment
 

(aeration), releases to water in wastewater effluent, emissions to air from
 

incomplete incineration, and land disposal of solid waste residues. The
 

inclusion of fugitive emissions would increase the total. Recently it has
 

been shown that a variety of chlorinated organic compounds are formed during
 

combustion of hydrocarbons when chlorine is present; two isomers of
 

dichloropropane were among the more than 100 chemicals formed during the
 

combustion of propane in the presence of HCl under oxygen deficient
 

conditions (Eklund et al. 1987). These conditions may occur in municipal
 

incinerators and, therefore, 1,2-dichloropropane may be released from
 

incinerators. A correlation of data from the EPA Air Toxics Emission
 

Inventory with industrial source categories (SIC codes), shows volatile
 

emissions of 1,2-dichloropropane from electronic components, photographic
 

equipment and supplies, and apartment building operators (SIC Codes 3679,
 

3861, 6513). (EPA 1987a).
 
81

5. POTENTIAL FOR HUMAN EXPOSURE
 

5.2.2 Water
 

The total estimated annual environmental re1eas.e of 1,2-dichloropropane
 

in wastewater from production and industrial use was 198,000 lbs (EPA
 

1986c). Table 5-l shows the types of industries that discharged 1,2­

dichloropropane, their frequency of release, and concentrations in
 

wastewater. These data come from a comprehensive wastewater survey
 

conducted by EPA's Effluent Guidelines Division. Over 4000 samples of
 

wastewater from a broad range of industrial facilities and publicly-owned
 

treatment works were analyzed in this survey. Between 1980 and 1988, 708
 

samples of wastewater in EPA's STORET database were analyzed for 1,2­

dichloropropane (STORET 1988). Ten percent of the samples were 10 parts per
 

billion (ppb) or higher with a maximum level of 910 ppb. Unfortunately, the
 

detection limit is apparently recorded when no chemical is detected, so it
 

is impossible to say whether the 90 percentile figure represents positive
 

samples or merely higher detection limits.
 

1,2-Dichloropropane was found at concentrations of 5.6, 22, 60, 310 ppb
 

in four outfalls from the Dow Chemical of Canada plant into the St. Clair
 

River for a net loading of 11.8 kg/day (King and Sherbin 1986). This survey
 

was performed as a result of puddles of chlorinated hydrocarbons discovered
 

on the bottom of the St. Clair River. These chemicals are thought to be
 

products or byproducts of chlorinated hydrocarbon manufactured at this site.
 

Waste from this operation is now being incinerated but was historically
 

landfilled. Landfill leachate from the landfill is treated with carbon and
 

then discharged. The concentration of 1,2-dichloropropane before and after
 

treatment was 320 and 510 ppb. However, the carbon filter was reportedly
 

spent at the time of the survey.
 

Rohm and Haas in Philadelphia, PA, a manufacturer of ion exchange
 

resins, discharged weekly average amounts of 1,2-dichloropropane of 60-2250
 

lbs/day into the Northeast Philadelphia Treatment Plant during August and
 

September of 1981 (Hinnegan 1981). The daily amount of 1,2-dichloropropane
 

discharged on five days in 1979 ranged from 37.2 to 5100 lbs (Weston 1980).
 

The report covering the discharges in 1979 stated that on 4 days Rohm and
 

Haas contributed all of the 1,2-dichloropropane influent going into
 

Philadelphia's Northeast Water Pollution Control Plant (NEWPCP). On one day,
 

35% came from elsewhere. At times, all of the 1,2-dichloropropane was
 

removed in the treatment plant. Tidal excursions of the NEWPCP effluents
 

affects the intake of the Baxter Drinking Water Plant, located 2 miles
 

upstream on the Delaware River. EPA's Philadelphia Geographic Area
 

Pollutant Survey found that average 1,2-dichloropropane concentration in the
 

intake water during 1982-1983 was 1.6 ppb, indicating that 1,2­

dichloropropane was being discharged from the wastewater treatment plant
 

into the Delaware River (EPA 1986~). If the typical daily discharge from the
 

Rohm and Haas plant was 500 lbs, then the annual discharge would have been
 

182,000 lbs, a figure approaching the estimated 198,000 lbs of 1,2­

dichloropropane discharged into waterways for all production and industrial
 

use. It is not clear for what year the estimated environmental release
 

83
 

5. POTENTIAL FOR HUMAN EXPOSURE
 

figure applies and whether the releases into water include industrial
 

discharges that may undergo treatment before being discharged into a
 

waterway or only that which is discharged into a waterway. As of January,
 

1989, Rohm and Haas has discontinued use of 1,2-dichloropropane in the
 

manufacture of ion exchange resins (Rohm and Haas 1989). There are three'
 

other manufacturers of ion exchange resins in the U.S. with potentially
 

similar release patterns (HSDB 1988). 1,2-Dichloropropane was only detected
 

in one sample at 3 ppb from Eugene, OR in the National Urban Runoff Program
 

which analyzed runoff in 86 samples from 19 cities throughout the U.S. (Cole
 

et al. 1984).
 

5.2.3 Soil
 

The total estimated annual environmental release of 1,2-dichloropropane
 

by industry into land disposal sites was 176,000 lbs (EPA 1986c). This is
 

not the recommended method of disposal and this figure may have been much
 

higher in the past.
 

In the past, the major source of release of 1,2-dichloropropane into
 

soil was from its use as a soil fumigant for nematodes. For this purpose,
 

the fumigant was injected into the root zone, after which the soil was
 

compacted to enhance retention of the vapor. However, 1,2-dichloropropane is
 

no longer permitted to be used in the U.S. for agricultural purposes because
 

this use pollutes groundwater.
 

Production of 1,2-dichloropropane for use as a solvent in consumer
 

products such as paint strippers, varnishes, and furniture finish removers,
 

from which inadvertent releases to soil (i.e. spills) would be expected, has
 

been discontinued. In addition to spills, chemicals can be released into
 

soil from leaking storage tanks. A case of groundwater contamination by 1,2­

dichloropropane resulting from a leaking underground storage tank at a paint
 

factory has been documented in the literature (Botta et al. 1984).
 

Releases into the subsoil and groundwater can also result from the
 

landfilling of process residues. Four out of 11 samples of landfill leachate
 

in Minnesota and Wisconsin contained 2.0-81 ppb 1,2-dichloropropane (Sabel
 

and Clark 1984).
 

5.3 ENVIRONMENTAL FATE
 

5.3.1 Transport and Partitioning
 

The relatively high water solubility of 1,2-dichloropropane suggests
 

that washout by rain should be an important process for removing the
 

chemical from the atmosphere. The dominant removal process for 1,2­

dichloropropane from surface waters is expected to be volatilization. Based
 

on the measured relative mass transfer coefficient of 1,2-dichloropropane
 

between water and air of 0.57 (Cadena et al. 1984) and the range of
 

reaeration coefficients typical of relatively rapid and shallow streams
 
84
 

5. POTENTIAL FOR HUMAN EXPOSURE
 

found in the western U.S., 0.14 to 1.96 hr-1 (Cadena et al. 1984), the half-


life of 1,2-dichloropropane in these streams will range from 0.62 to 8.68
 

hr. The residence time in a lake or pond would be much longer. Based on
 

measured Henry's Law Constant at 24°C of 1.67x10-3 atm-m3

/mol (Chiou et al.
 

1980) and 2.07x10-3 atm-m3

/mol (Mackay and Yeun 1983), the volatilization
 

half-life of 1,2-dichloropropane in a model river 1 m deep flowing 1 m/sec
 

with a wind speed of 3 m/sec is estimated to be 3.7-4.6 hr, with resistance
 

in the liquid phase controlling volatilization (Lyman et al. 1982). In such
 

cases, the current will have a much greater effect on volatilization than
 

the wind speed. In wastewater treatment plants that receive volatile
 

compounds such as 1,2-dichloropropane from industrial discharges or other
 

sources, stripping will be an important mechanism for transferring the
 

chemical from the water into the air. In stripping, as opposed to ordinary
 

volatilization, the liquid and gas phases are dispersed with the result that
 

the interfacial surface area is much greater and liquid/gas mass transfer is
 

greatly enhanced. More than 99% removal of 1,2-dichloropropane from
 

wastewater plants has been attributed to this process (Kincannon et al.
 

1983).
 

The Koc of 1,2-dichloropropane is 47 in a silt loam soil (Chiou et al.
 

1979). This value is low, suggesting that 1,2-dichloropropane will not
 

adsorb appreciably to soil, sediment, and suspended solids in water. 1,2­

Dichloropropane sorbs to clay minerals in dry soil but desorbs when the soil
 

is moist (Cohen et al 1984). Where 1,2-dichloropropane has been used as a
 

soil fumigant for nematodes in California and the coastal areas of Georgia,
 

South Carolina, North Carolina, and Virginia, the soils are sandy and have a
 

low organic carbon content (Cohen et al. 1984). Adsorption to these soils
 

will be lower than to soils with a higher organic content and should not
 

reduce the mobility of 1,2-dichloropropane significantly. The leaching
 

potential of 1,2-dichloropropane is illustrated by a case study in
 

California in which a soil core was taken from an agricultural field where a
 

fumigant containing the chemical had recently been used. Residues of 1,2­

dichloropropane up to 12.2 ppb were detected throughout much of the 24-foot
 

core profile and two adjacent drinking water wells contained concentrations
 

of 1,2-dichloropropane in excess of 10 ppb (Ali et al. 1986). As much as 300
 

ppt of 1,2-dichloropropane have been detected in bank-filtered Rhine River
 

water indicating that all of the chemical was not being retained by the soil
 

(Piet and Morra 1979). The finding that highly mobile and biologically-


resistant residues of the fumigant pesticide 1,2-dibromoethane persisted in
 

topsoil for years after application, despite its mobility and volatility,
 

spurred a study of this phenomenon in other halogenated hydrocarbons
 

(Sawhney et al. 1988). Sandy loam soils treated with 10,000 ppm of 1,2­

dichloropropane for 1 day were extracted 16 times with water. The apparent
 

soil water partition coefficient, initially 0.56 (K 22), rose to 72 (K
 oc oc
 

2800); the final concentration of 1,2-dichloropropane in the soil was 1.4
 

ppm . After a 57-day period, the apparent partition coefficient was >250
 

(Koc >9700). Some of the 1,2-dichloropropane molecules were adsorbed more
 

strongly than others and these molecules became even more strongly adsorbed
 

in time. The fact that pulverization of the soil released a portion of the
 
85
 

5. POTENTIAL FOR HUMAN EXPOSURE
 

chemical, suggests that the strongly adsorbed 1,2-dichloropropane eventually
 

became occluded in the soil structure. Additionally, these observations
 

suggest that the rate at which the chemical becomes occluded, or the
 

adsorption coefficient increases, is diffusion-controlled.
 

The dissipation of 1,2-dichloropropane was determined in two clay and
 

two sandy soils in closed systems following application at normal field
 

rates (Van Dijk 1980). The mean dissipation rate was 0.013 day-1 (half-life
 

52 days), with the rate roughly twice as high in the sandy soil as in the
 

clay soil. Additionally, the rate of volatilization increased by a factor of
 

two for a 10°C increase in temperature. In another experiment in which 1,2­

dichloropropane was mixed with 3 cm of soil in an open container, covered
 

with 12 cm of soil and left outdoors, <1% of the chemical remained after 10
 

days (Roberts and Stoydin 1976). This loss was attributed to
 

volatilization.
 

A bioconcentration factor (BCF) of 19 in fish has been estimated for
 

1,2-dichloropropane using linear regression equations with an estimated log
 

Kow of 1.99 (EPA 1988b; Lyman et al. 1982). An experimental value for the
 

bioconcentration factor of <10 has also been reported (Kawasaki 1980). Only
 

for those chemical with BCF values greater than 500-1000 is bioconcentration
 

considered to be important. Therefore, 1,2-dichloropropane would not be
 

expected to bioconcentrate significantly in fish. When potatoes were grown
 

in sandy loam soil that had been treated with a mixture of 14C-labeled 1,2­

dichloropropane and 1,3-dichloropropene 5 months before sowing, only 7 ppb
 

of the radioactivity was found in the mature potatoes indicating minimal
 

uptake of either of these chemicals (Roberts and Stoydin 1976).
 

5.3.2 Transformation and Degradation
 

5.3.2.1 Air
 

The primary mode of degradation in air is through reaction with
 

photochemically-produced hydroxyl radicals by H-atom abstraction (Singh et
 

al. 1982). Experimental determinations of the reaction rate yield a halflife
 

of >23 days (Atkinson 1985), whereas theoretical estimates result in a
 

half-life of 16 days (Atkinson 1985). Lacking a chromophore that absorbs
 

radiation >290 nm, direct vapor phase photolysis would not be expected.
 

Accordingly, no photolysis occurred when 1,2-dichloropropane was exposed to
 

simulated sunlight for prolonged periods of time (Cohen et al. 1984).
 

5.3.2.2 Water
 

1,2-Dichloropropane is resistant to hydrolysis, with an estimated
 

hydrolysis half-life of 25-200 wk (Cohen et al. 1984). Most studies
 

indicated that 1,.2-dichloropropane is also resistant to biotransformation.
 

There was no degradation in a semicontinuous activated sludge process in ten
 

weeks even when the retention time was as long as 25 hr (Shell 1984). There
 

is also no degradation in standard 4-week tests that simulate
 
86
 

5. POTENTIAL FOR HUMAN EXPOSURE
 

biodegradability in environmental waters (Kawasaki 1980; Anonymous 1983).
 

While >99% of 1,2-dichloropropane was lost in a wastewater treatment
 

facility, the loss was attributed to stripping, rather than biodegradation
 

(Kincannon et al. 1983).
 

5.3.2.3 Soil
 

Little or no degradation of 1,2-dichloropropane has been reported in
 

soil. When 71 ppm of radiolabeled 1,2-dichloropropane was applied to a sandy
 

loam and medium loam soil in closed glass containers and incubated for 20
 

weeks, <0.2% of the applied radioactivity was found in degradation products
 

(Roberts and Stoydin 1976).
 

5.4 LEVELS MONITORED OR ESTIMATED IN THE ENVIRONMENT
 

5.4.1 Air
 

No levels of 1,2-dichloropropane in rural or remote areas of the U.S.
 

have been reported in the literature. Samples collected in 397
 

urban/suburban areas of the country had a median concentration of 57 parts
 

per trillion (ppt) and a range of 22 to 110 ppt (Brodzinsky and Singh 1982).
 

Round-the-clock sampling for periods of 1-2 weeks in seven U.S. cities
 

ranged from 21-78 ppt (Singh et al. 1982). Levels of some of the chemicals
 

measured were highest at night or in the early morning, and lowest in the
 

afternoon, although no mention of this fact was specifically directed to
 

1,2-dichloropropane. Only 2% of the 1,2-dichloropropane levels monitored at
 

four sites by the California Air Monitoring Program were above the
 

quantitation limit of 0.2 ppt, although one value recorded in Riverside was
 

1100 ppt (Shikiya et al. 1984). During rain events in Portland, Oregon, gas
 

phase concentrations of 1,2-dichloropropane ranged from 4.4-8.4 ppt (Ligocki
 

et al. 1985). Levels of 1,2-dichloropropane in industrial or source-related
 

areas of the U.S. ranged (39 sites) from 0-130 ppt with 120 ppt median
 

(Brodzinsky and Singh 1982). The average concentration during a 3-month
 

survey of ten source-related sites in Philadelphia, PA, was 259 ppt
 

(Sullivan et al. 1985). In EPA's Philadelphia Geographic Area Multimedia
 

Pollutant Survey, average ambient 1,2-dichloropropane levels ranged from 40­

740 ppt in various sections of the city and 7700-120,000 ppt downwind of the
 

Northeast Water Pollution Control Plant (EPA 1986c). This plant had
 

received discharges from the Rohm and Haas plant which produced ion exchange
 

resins using 1,2-dichloropropane as a solvent. The data compiled by
 

Brodzinsky and Singh (1982) has been reviewed and most of it is of good
 

quality. More data has now been added to this National Ambient Volatile
 

Organic Compounds Database bringing the number of monitoring data points to
 

714 (Shah and Heyerdahl 1988). With the addition of the new data, the
 

overall median concentration of 1,2-dichloropropane is 22 ppt and the lower
 

and upper quartile concentrations are 11 and 65 ppt. The median
 

concentration of the suburban, urban, and source-dominated sites were 42
 

ppt, 11 ppt, and 1 ppt, respectively. The fact that the 1,2­

dichloropropane concentrations are higher at the 'cleaner' sites may
 
87
 

5. POTENTIAL FOR HUMAN EXPOSURE
 

indicate that the degradation rate is lower at these sites rather than that
 

there are more 1,2-dichloropropane emissions at these sites. The
 

concentration of hydroxyl radicals that are responsible for the
 

photooxidation of 1,2-dichloropropane are generally lower in cleaner
 

atmospheres than dirty ones (Winer et al. 1984). The fact that the addition
 

of more recent data to the National Ambient Volatile Organic Compounds
 

Database has lowered the median 1,2-dichloropropane concentration from 57
 

ppt to 22 ppt (Brodzinsky and Singh 1982; Shah and Heyerdahl 1988) suggests
 

that the reduction in 1,2-dichloropropane use has had an effect on ambient
 

air concentrations.
 

Traces of 1,2-dichloropropane were detected outside 2 of 9 homes at the
 

Old Love Canal in Niagara Falls, N.Y. (Barkley et al. 1980), while 0.29 ppb
 

was found in the ambient air in a household basement (Pellizzarri 1982).
 

The same authors did not find any 1,2-dichloropropane at the Kin-But waste
 

disposal site near Edison, N.J. Traces to 0.46 ppb of 1,2-dichloropropane
 

were found in Iberville Parish, LA, where many organic chemical and
 

producer, user, and storage facilities are located along the Mississippi
 

River (Pellizzarri 1982).
 

While one of 1,2-dichloropropane's major uses was once as a soil
 

fumigant, no air monitoring data could be located in the available
 

literature for agricultural areas in which it was used.
 

5.4.2 Water
 

1,2-Dichloropropane has been identified in 1.6% of samples from 11
 

water utilities along the Ohio River at a level of 0.1 ppb (Ohio River
 

Valley Sanitation Commission 1979). In a U.S. Groundwater Supply survey in
 

which 945 water supplies derived from groundwater sources were tested, 13
 

supplies were positive for 1,2-dichloropropane, with a median and maximum
 

concentrations of 0.9 and 21 ppb, respectively (Westrick et al. 1984). In an
 

ongoing study of 575 community water systems using groundwater sources and
 

approximately 19,000 non-community and private wells in Suffolk County, NY,
 

0.9% of the community water systems and 5.5% of the other wells contained
 

1,2-dichloropropane making it the 5th most common contaminant found there
 

(Suffolk County 1983b; Zaki 1986). In 1982 the California State Water
 

Resources Control Board started investigating the presence of 1,2­

dichloropropane in wells (Cohen et al. 1986; Ali et al. 1986) because of its
 

high mobility in soil and possible carcinogenicity and mutagenicity. They
 

found the chemical in 75 wells in nine counties ranging up to 1200 ppb; 12
 

wells exceeded the State's action level of 10 ppb (Ali et al. 1986). It is
 

worth noting that 3 contaminated wells in residential and
 

residential/commercial areas of Suffolk County, NY with 1,2-dichloropropane
 

levels of 13-550 ppb were in areas where agricultural use was claimed not to
 

be a source of contamination (Suffolk County 1983a). 1,2-Dichloropropane
 

was found in at least 7 shallow wells in western Washington associated with
 

soil injection in strawberry fields (Cohen et al. 1986). Nine out of 20
 

samples of groundwater underlying landfills in Minnesota contained 0.5-43
 
88
 

5. POTENTIAL FOR HUMAN EXPOSURE
 

ppb of 1,2-dichloropropane (Sabel and Clark 1984). In a separate Minnesota
 

landfill study, 1.5-7.6 ppb of 1,2-dichloropropane was found in the
 

groundwater underlying a landfill in a sand plain that was known to have
 

received industrial waste, but was absent from the boring taken directly
 

above the contaminated groundwater; while 1.1 ppb of 1,2-dichloropropane was
 

found in the groundwater from a clay landfill in southwestern Minnesota
 

(Sabel and Clark 1984).
 

1,2-Dichloropropane has been found in major rivers of the United
 

States; up to 20% of the samples from monitoring studies contained from
 

trace quantities to >l0 ppb of the chemical (Kaiser et al. 1983; Ohio River
 

Valley Water Sanitation Commission 1980; Ohio River Valley Water Sanitation
 

Commission 1982). Of the 95 stations monitored in Lake Ontario, 4 had
 

concentrations ranging from 210-440 ppt and 15 others had trace quantities,
 

while in 16 stations in the Lower Niagara River, 4 stations had
 

concentrations ranging from 7-55 ppt, while 5 other stations had trace
 

quantities (Kaiser et al. 1983). Of the 4972 samples at 11 stations on the
 

Ohio River monitored in 1980-81, 8.8% were positive, with 28 samples between
 

l-10 ppb and 1 sample contained >10 ppb (Ohio River Valley Water Sanitation
 

Commission 1982). Between 1980 and 1988, 29,320 samples of surface water in
 

EPA's STORET database were analyzed for 1,2-dichloropropane (STORET 1988).
 

Ten percent of the samples were 0.40 parts per billion (ppb) or higher with
 

a maximum level of 300 ppb. In addition, of the 859 sediment analyzed, 10%
 

contained 1,2-dichloropropane above 44 ppb. Of the 22,457 samples of
 

groundwater in the database, 10% were above 3 ppb and the maximum was 1500
 

ppb.
 

5.4.3 Soil
 

1,2-Dichloropropane was present in concentrations up to 12.2 ppb in
 

soil cores underlying a recently fumigated field in California (Ali et al.
 

1986). In another California study, it was found at 0.2-2.2 ppb in soil
 

cores up to 7 meters below the surface (Cohen et al. 1984). Some unspecified
 

samples of soil, water, or sediment from the Love Canal contained
 

unspecified amounts of 1,2-dichloropropane (Hauser and Bromberg 1982). 1,2­

Dichloropropane was found at nine of the 951 hazardous waste sites listed on
 

the National Priority List (NPL) of highest priority sites for possible
 

remedial action (ATSDR 1988). Runoff and soil and groundwater contamination
 

with 1,2-dichloropropane was reported at these sites. Additionally, it was
 

found in 5 sites in the Contract Laboratory Statistical Database at median
 

concentrations ranging from 6.5 to 23,000 ppb (Viar and Company 1987).
 

5.4.4 Other Media
 

No documentation of 1,2-dichloropropane in flora or fauna in the U.S.
 

was located.
 
89
 

5. POTENTIAL FOR HUMAN EXPOSURE
 

5.5 GENERAL POPULATION AND OCCUPATIONAL EXPOSURE
 

A National Occupational Exposure Survey (NOES) conducted by NIOSH from
 

1981 to 1983 estimated that 2119 workers including 949 women were
 

potentially exposed to 1,2-dichloropropane in the United States (NIOSH
 

1988). The distribution of these estimated exposed workers by standard
 

industrial category (SIC) was: 408 in business services, 831 in machinery,
 

except electrical, 161 in fabricated metal products, 672 in the chemical and
 

allied products, and 47 in textile mill products. The estimate was
 

provisional as all of the data for trade name products which may contain
 

1,2-dichloropropane has not been analyzed. The NOES was based on field
 

surveys of 4490 facilities and was designed as a nationwide survey based on
 

a statistical sample of virtually all workplace environments in the United
 

States where eight or more persons were employed in all SIC codes except
 

mining and agriculture. The use pattern of 1,2-dichloropropane has changed
 

radically since the survey was made, as it has been eliminated from
 

agricultural fumigants, photographic film manufacture, and paint strippers.
 

The results of the NOES, even though it excludes agricultural workers, are
 

expected to be high. Another category of worker that may be exposed to 1,2­

dichloropropane are workers at wastewater treatment facilities that handle
 

effluent containing this chemical. Volatilization would be expected during
 

treatment operations. According to Dow Chemical Company, the major
 

manufacturer of 1,2-dichloropropane, all processes involving the production,
 

conversion, and disposal of 1,2-dichloropropane are closed process (Dow
 

Chem. Co. 1983). By their estimates, 45 and 123 workers are routinely and
 

potentially exposed, respectively, to the chemical (Dow Chem. Co. 1983).
 

The levels of exposure they report are <2 ppm for toluene diisocyanate
 

(TDI) production, <l ppm in ion exchange resin manufacture, and <25 ppm in
 

paper coating (Dow Chem. Co. 1983).
 

According to drinking water surveys (Ali et al. 1986; Cohen et al. 

1986; Ohio River Valley Sanitation Commission 1979; Westrick et al. 1984; 

Zaki 1986), a significant number of drinking water supplies contained 1,2­

dichloropropane and people drinking this water would have been exposed to 

this chemical. In the most broadly-based groundwater survey, 1.4% of these 

supplies contained median water concentrations of 0.9 parts per billion 

(ppb) (Westrick et al. 1984). People drinking this water would ingest 1.8 

c(g of 1,2-dichloropropane per day. While most of the drinking supplies 

tested for 1,2-dichloropropane were taken from groundwater sources, in 

cities such as Philadelphia, PA which obtains its water from a river that 

received sizeable amounts of 1,2-dichloropropane-containing effluent, the 

concentration of 1,2-dichloropropane in the drinking water from the Baxter 

Drinking Water Plant averaged 1.5 ppb (EPA 1986). People consuming this 

water would have ingested 3.0 μg of 1,2-dichloropropane daily. 

The general population is exposed to 1,2-dichloropropane in ambient 

air, which contains median 1,2-dichloropropane levels of 22 ppt which 

translates into a daily intake of 2.1 μg. Residents of Philadelphia, 

according to EPA's Philadelphia Geographic Area Multimedia Pollutant Survey, 
90
 

5. POTENTIAL FOR HUMAN EXPOSURE
 

would have been exposed to much higher inhalation doses, 98-660 μg/day
 

because a large user of 1,2-dichloropropane was located there (EPA 1986c).
 

People living in the vicinity of landfills containing 1,2-dichloropropane
 

may be exposed to 1,2-dichloropropane present in landfill gases.
 

Not enough information is available to estimate what the level of
 

exposure from this source might be. Subsurface and surface emissions of
 

volatile organic compounds (VOCs) have been found from RCRA Subtitle D
 

disposal sites which reportedly received only non-hazardous waste. However,
 

hazardous waste from small quantity generators or household hazardous waste
 

may be disposed of at these landfills. For landfills that are similar in
 

design and content, emissions are estimated to be a factor of 2.6 greater in
 

a wet climate than in a dry one (Vogt et al. 1987)
 

5.6 POPULATIONS WITH POTENTIALLY HIGH EXPOSURE
 

Those people consuming contaminated drinking water will have the
 

greatest potential for exposure to significant levels of 1,2­

dichloropropane. Since the odor threshold for 1,2-dichloropropane is 10
 

ppb (Amoore and Hautala 1983), people consuming water with this level of
 

1,2-dichloropropane may have a warning that their water is contaminated.
 

In general, drinking water supplies that are most apt to be contaminated are
 

those taken from groundwater sources. Contaminated drinking water wells are
 

most likely to be found in agricultural areas with sandy soil where the
 

chemical was used as a fumigant. However, there are special situations,
 

such as in Philadelphia, where drinking water derived from surface water
 

sources may be contaminated with 1,2-dichloropropane-containing effluent.
 

In Philadelphia, 1,2-dichloropropane-containing effluent from an industrial
 

plant was driven upstream to the influent of a drinking water plant by tidal
 

action. This plant recently discontinued using 1,2-dichloropropane. People
 

residing in the vicinity of industrial sources may be exposed to 1,2­

dichloropropane in the ambient air, either from direct emissions or
 

volatilization of the chemical from wastewater.
 

5.7 ADEQUAGY OF THE DATABASE
 

Section 104 (i) (5) of CERCLA, 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-dichloropropane is available. Where adequate information is
 

not available, ATSDR, in cooperation with the National Toxicology Program
 

(NTP), is required to assure the initiation of a program of research
 

designed to determine these health effects (and techniques for developing
 

methods to determine such health effects). The following discussion
 

highlights the availability, or absence, of exposure and toxicity
 

information applicable to human health assessment. A statement of the
 

relevance of identified data needs is also included. In a separate effort,
 

ATSDR, in collaboration with NTP and EPA, will prioritize data needs across
 

chemicals that have been profiled.
 
91
 

5. POTENTIAL FOR HUMAN EXPOSURE
 

5.7.1 Data Needs
 

Physical and Chemical Properties. The physical and chemical properties
 

of 1,2-dichloropropane have been adequately characterized (see table 3.2).
 

Environmental Fate. Sufficient data exists to show that chemical
 

hydrolysis and aerobic biodegradation of 1,2-dichloropropane are very slow
 

and are not significant in determining the half-life in surface water or
 

soil. No experimental studies of anaerobic biotransformation are available;
 

these could be useful in estimating the half-life of 1,2-dichloropropane in
 

soil and groundwater. Experimental hydrolysis data at pH 5-9 would be
 

helpful for predicting the half-life of 1,2-dichloropropane in groundwater
 

where volatilization is not significant.
 

Exposure Levels in Environmental Media. Since 1,2-dichloropropane was
 

phased out as a fumigant and its use in solvents has declined, recent
 

monitoring data are needed for air, groundwater, and surface water. This is
 

particularly important with respect to groundwater, where it is especially
 

long-lived and may be present in significant concentrations. Field
 

monitoring studies of 1,2-dichloropropane would also be useful. This may be
 

the only feasible way of determining the half-life of 1,2-dichloropropane in
 

groundwater. Air monitoring and surface water studies would show the effects
 

of changing 1,2-dichloropropane use patterns. While EPA's Storet database
 

contains considerable water.monitoring data, there are problems with the
 

database that limit its usefulness. The detection limit is apparently
 

recorded when no chemical is detected, so that it is impossible to say
 

whether the 90 percentile figures for surface water and groundwater quoted
 

in Section 5.4.2 represent positive determinations or merely detection
 

limits. It would be helpful if this monitoring data would indicate whether
 

1,2-dichloropropane was actually detected in the samples.
 

Exposure Levels in Humans. The use pattern of 1,2-dichloropropane has
 

changed radically since NIOSH's National Occupational Exposure Survey
 

(NOES). Since the elimination of 1,2-dichloropropane from agricultural
 

fumigants, photographic film manufacture, and paint strippers, fewer workers
 

are exposed. While agricultural workers were not included in the survey,
 

those engaged in the manufacture of agricultural chemicals were included.
 

As a chemical in paint strippers, 1,2-dichloropropane would have a
 

particularly high potential for exposing large numbers of people at high
 

levels of exposure, since such applications are labor intensive and
 

performed in the open. Therefore the results of the NOES will have to be
 

reanalyzed in light of current use patterns in order to reflect current
 

occupational exposures.
 

Exposure Registries. Other than the NIOSH survey, no exposure
 

registries for 1,2-dichloropropane were located. The development of a
 

registry of exposed persons would provide a useful reference tool in
 

assessing exposure levels and frequency. In addition, a registry would
 
92
 

5. POTENTIAL FOR HUMAN EXPOSURE
 

allow an assessment of the variations in exposure concentrations by, for
 

example, geography, season, regulatory actions, presence of hazardous waste
 

landfills, or manufacturing or use facility. These assessments, in turn,
 

would provide a better understanding of the needs for some types of research
 

or data acquisition based on the current exposure concentrations.
 

Additionally, such a database of exposures may be useful for linking
 

exposure to 1,2-dichloropropane with specific toxic effects or diseases.
 

5.7.2 On-going Studies
 

No on-going monitoring studies or studies relating to the environmental
 

fate of 1,2-dichloropropane were located in the available literature.
 

According to Emergency Planning and Community Right to Know Act of 1986
 

(EPCRTKA), (§313), (Pub. L. 99-499, Title III, §313), industries are
 

required to submit release information to the EPA. The Toxic Release
 

Inventory (TRI), which contains release information for 1987, became
 

available in May of 1989. This database can be updated yearly and should
 

provide a more reliable estimate of industrial production and emissions,
 

which will be useful for determining potential human exposure.
 

NIOSH is continuing to revise its estimates of occupational exposures
 

in its National Occupational Exposure Survey (NOES) through the inclusion of
 

trade name compounds. 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 Conrol, will be analyzing human blood samples for 1,2­

dichloropropane and other volatile organic compounds. These data will give
 

an indication of the frequency of occurrence and background levels of these
 

compounds in the general population.
 
93

6. ANALYTICAL METHODS
 

6.1 BIOLOGICAL MATERIALS
 

The analytical methods for the determination of 1,2-dichloropropane in
 

biological matrices are given in Table 6-l. The purge and trap method used
 

for environmental samples is also commonly used for biological samples. The
 

discussion about the methods that may be most sensitive for the
 

determination of 1,2-dichloropropane levels in environmental samples, the
 

advantages and disadvantages of the commonly used methods, and the
 

precautions required to avoid evaporation losses as given in Subsection 6.2
 

is also applicable for biological samples.
 

6.2 ENVIRONMENTAL SAMPLES
 

As with all extremely volatile chemicals, it is essential to take
 

precautions during sampling, storage, and analysis to avoid loss of 1,2­

dichloropropane. Analytical methods for determining 1,2-dichloropropane in
 

environmental samples are presented in Table 6-2. The two common methods
 

that are used for the preconcentration of 1,2-dichloropropane for the
 

determination of its levels in air are adsorption on a sorbent column or
 

collection in a cryogenically-cooled trap, although the use of oxygen-doped
 

electron capture detection may eliminate the need for preconcentration
 

(Rasmussen et al. 1980). The disadvantages of cryogenic cooling are that
 

the method is cumbersome and that condensation of moisture in air may block
 

the passage of further air flow through the trap. The disadvantages of the
 

sorption tubes are that the sorption and desorption efficiencies may not be
 

100% and that the background impurities in the sorbent tubes may limit the
 

detection limit for samples at low concentrations (Cox 1983).
 

The most common method for the determination of 1,2-dichloropropane
 

levels in water, sediment, soil and aquatic species is the purging of the
 

vapor from the sample or its suspension in water with an inert gas and
 

trapping the desorbed vapors in a sorbent trap. Subsequent thermal
 

desorption is used for the quantification of its concentration.
 

The two methods that provide the lowest detection limits are halide-


specific detectors (e.g., Hall electrolytic conductivity detector) and mass
 

spectrometer. The advantage of halide specific detectors are they are not
 

only very sensitive but are also specific for halide compounds. The mass
 

spectrometer, on the other hand, provides an additional confirmation of the
 

presence of a compound through the ionization patterns and is desirable when
 

a variety of compounds are required to be quantified. The disadvantage of
 

halide-specific detectors for their inability to detect and quantify nonhalogen
 

compounds can be greatly overcome by using other detectors (e.g.,
 

photoionization detector) in series (Lopez-Avila et al. 1987; Driscoll et
 

al. 1987). High-resolution gas chromatography with capillary columns is a
 

better method for volatile compounds than packed columns because they
 

provide better resolution of closely eluting compounds and increase the
 



97
 

6. ANALYTICAL METHODS
 

sensitivity of detection. In addition, purge and whole column cryotrapping
 

eliminates the need for the conventional purge and trap unit and reduces the
 

time of analysis (Pankow and Rosen 1988). The plugging of the trap by the
 

condensation of moisture during cryotrapping may be avoided by the use of
 

very wide bore capillary column, although the chromatographic resolution of
 

such a column is inferior to narrow bore capillary columns (Pankow and Rosen
 

1988; Mosesman et al. 1987).
 

6.3 ADEQUACY OF THE DATABASE
 

Section 104 (i) (5) of CERCLA, 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-dichloropropane is available. Where adequate information is
 

not available, ATSDR, in cooperation with the National Toxicology Program
 

(NTP), is required to assure the initiation of a program of research
 

designed to determine these health effects (and techniques for developing
 

methods to determine such health effects). The following discussion
 

highlights the availability, or absence, of exposure and toxicity
 

information applicable to human health assessment. A statement of the
 

relevance of identified data needs is also included. In a separate effort,
 

ATSDR, in collaboration with NTP and EPA, will prioritize data needs across
 

chemicals that have been profiled.
 

6.3.1 Data Needs
 

Methods for Determining Parent Compounds and Metabolites in Biological
 

Materials. The analytical methods for determining volatile chlorinated
 

hydrocarbon levels in biological matrices are quite general. However,
 

there is a paucity of data specific to 1,2-dichloropropane. The limited
 

number of publications that discuss the methods for the determination of
 

this compound in biological matrices do not report either the recovery or
 

the detection limit of the compound in different biological matrices. The
 

study of the levels of the parent compound in human blood, urine or other
 

biological matrices can be useful in deriving a correlation between the
 

level of this compound found in the environment and those found in the body.
 

One study (Ghittori et al. 1987) reported that a correlation exists between
 

the urinary level and the TWA level of 1,2-dichloropropane measured at the
 

breathing zone. No metabolite of 1,2-dichloropropane from human exposure to
 

this compound has yet been identified, although specific metabolites have
 

been identified in the urine of rats (see Subsection 2.6.3). The changes in
 

metabolite concentrations with time in human blood, urine, or other
 

appropriate biological medium may be useful in estimating its rate of
 

metabolism in humans. In some instances, metabolite levels may be useful in
 

correlating exposed doses to human body burdens. Such studies on the levels
 

of metabolites in human biological matrices are not available for this
 

compound.
 
98
 

6. ANALYTICAL METHODS
 

Methods for Biomarkers of Exposure. No biomarker of exposure to 1,2­

dichloropropane has been identified (see Subsection 2.9.2). If a biomarker
 

for this compound in a human biological tissue or fluid were available and 'a
 

correlation were found to exist between the level of biomarker and a certain
 

health effect, it could be used as an indication of a health effect caused
 

by the exposure to this chemical.
 

Methods for Determining Parent Compounds and Degradation Products in
 

Environmental Media. Analytical methods are available for the
 

quantification of 1,2-dichloropropane in environmental samples. The levels
 

of this compound in different environmental media can be used to indicate
 

exposure of 1,2-dichloropropane to humans through the inhalation of air and
 

ingestion of drinking water and foods containing 1,2-dichloropropane. If a
 

correlation with human tissue or body fluid levels was found to exist, the
 

intake levels from different environmental sources could be used to estimate
 

the body burden of the chemical in humans. Although the products resulting
 

from the biotic or abiotic degredation of 1,2-dichloropropane in the
 

environment can be inferred, there has been no systematic study of the
 

concentrations of these reaction products in the environment. In instances
 

where the product(s) of an environmental reaction is more toxic than the
 

parent compound, it is important that the level of the degradation products
 

in the environment be known. No such reaction products have been identified
 

for 1,2-dichloropropane. Analytical methods are available for the
 

quantification of the known reaction products of 1,2-dichloropropane in the
 

environment.
 

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-dichloropropane and other
 

volatile organic compounds in blood. These methods use purge and trap
 

methodology and magnetic mass spectrometry which gives detection limits in
 

the low parts per trillion range.
 
99
 

7 . REGULATIONS AND ADVISORY STANDARDS
 

National and state regulations and guidelines pertinent to human
 

exposure to 1,2-dichloropropane are summarized in Table 7-l.
 

The Clean Water Effluent Guidelines regulate 1,2-dichloropropane for
 

the following industrial point sources: electroplating, organic chemicals,
 

steam electric, asbestos, timber products processing, metal finishing,
 

paving and roofing, paint formulating, ink formulating, gum and wood, and
 

carbon black (EPA 1988).
 

_________________________ 

101
 

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*Rubin DF. 1988. Occupational health implications of a toxic spill of
 

propylene dichloride. West J Med 148:78-79.
 

*Sahel GV, Clark TP. 1984. Volatile organic compounds as indicators of
 

municipal solid waste leachate contamination. Waste Manag Res 2:119-130.
 

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*Sawhney BL, Pignatello JJ, Steinberg SM. 1988. Determination of 1,2­

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*Secchi GC, Alessio L. 1968. On the appearance of the mitochondrial
 

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8. REFERENCES
 

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percutaneous toxicity, skin and eye irritancy and skin sensitizing potential
 

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115
 

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 time period.
 

Cancer Effect Level (CEL) -- The lowest dose of chemical in a study or group
 

of studies which produces significant increases in incidence of cancer (or
 

tumors) between the exposed populaton and its appropriate control.
 

Carcinogen -- A chemical capable of inducing cancer.
 

Ceiling Value (CL) -- 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.
 
116
 

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 (LC ) -- (LO) LO
 The lowest concentration of a chemical in


air which has been reported to have caused death in humans or animals.
 

Lethal Concentration (LC ) -- (50) 50
 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 (LD (L0) LO
) -- 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 (LD ) (50) 50
 -- The dose of a chemical which has been calculated


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 which produces statistically or biologically
 

significant increases in frequency or severity of adverse effects between
 

the exposed population and its appropriate control.
 

LT50 (lethal time) -- 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.
 

Malformations -- Permanent structural changes that may adversely affect
 

survival, development, or function.
 

Minimal Risk Level (MRL) -- 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.
 
117
 

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 a chemical.
 

No-Observed-Adverse-Effect Level (NOAEL) -- That dose of chemical at which
 

there are 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-h shift.
 

q1* -- The upper-bound estimate of the low-dose slope of the dose-response
 

curve as determined by the multistage procedure. The ql* can be used to
 

calculate an estimate of carcinogenic potency, the incremental excess cancer
 

risk per unit of exposure (usually g/L for water, mg/kg/day for food, and
 

g/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-h 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.
 
118
 

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.
 

TD50 (toxic dose) -- 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.
 

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-h workday or 40-h workweek.
 

Uncertainty Factor (UF) -- A factor used in operationally deriving the RfD
 

from experimental data. UFs are intended to account for (1) the variation il
 

sensitivity among the members of the human population, (2) the uncertainty
 

in extrapolating animal data to the case of humans, (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.
 
119

APPENDIX: PEER REVIEW
 

A peer review panel was assembled for 1,2-dichloropropane. The panel
 

consisted of the following members: Dr. William Lappenbusch, Toxicologist,
 

Lappenbusch Environmental Health, Inc.; Dr. Hugh Farber, Private Consultant,
 

Farber Associates; Dr. Carson Conaway, Research Scientist, Naylor Dana
 

Institute; and Dr. Richard Carchman, Associate Professor, Toxicology and
 

Pharmacology, Medical College of Virginia. These experts collectively have
 

knowledge of 1,2-dichloropropane'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
 

Superfund Amendments and Reauthorization Act of 1986, Section 110.
 

A joint panel of scientists from ATSDR and EPA has 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
 

their approval of the profile's final content. The responsibility for the
 

content of this profile lies with the Agency for Toxic Substances and
 

Disease Registry.
 

U.S. GOVERNMENT PRINTING OFFICE 1999 – 535 – 152/