TOXICOLOGICAL PROFILE FOR

BROMODICHLOROMETHANE

Agency for Toxic Substances and Disease Registry

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.
iii

FOREWORD

The Superfund Amendments and Reauthorization Act of 1986 (Public

Law 99-499) extended and amended the Comprehensive Environmental Response,

Compensation, and Liability Act of 1980 (CERCLA or Superfund). This public

law (also known as SARA) directed the Agency for Toxic Substances and Disease

Registry (ATSDR) to prepare toxicological profiles for hazardous substances

which are most commonly found at facilities on the CERCLA National Priorities

List and which pose the most significant potential threat to human health, as

determined by ATSDR and the Environmental Protection Agency (EPA). The lists

of the most significant hazardous substances were published in the Federal

Register on April 17, 1987, and on October 20, 1988.

Section 110 (3) of SARA directs the Administrator of ATSDR to prepare a

toxicological profile for each substance on the list. Each profile must

include the following content:

(A) An examination, summary and interpretation of available

toxicological information and epidemiological evaluations on the

hazardous substance in order to ascertain the levels of significant

human exposure for the substance and the associated acute, subacute,

and chronic health effects,

(B) A determination of whether adequate information on the health

effects of each substance is available or in the process of

development to determine levels of exposure which present a

significant risk to human health of acute, subacute, or chronic

health effects, and

(C) Where appropriate, an identification of toxicological testing

needed to identify the types or levels of exposure that may present

significant risk of adverse health effects in humans.

This toxicological profile is prepared in accordance with guidelines

developed by ATSDR and EPA. The original guidelines were published in the

Federal Register on April 17, 1987. Each profile will be revised and

republished as necessary, but no less often than every 3 years, as required

by SARA.

The ATSDR toxicological profile is intended to characterize succinctly

the toxicological and health effects information for the hazardous substance

being described. Each profile identifies and reviews the key literature that









1

1. PUBLIC HEALTH STATEMENT

1.1 WHAT IS BROMODICHLOROMETHANE?

Bromodichloromethane (BDCM) is a colorless, heavy, nonburnable

liquid. BDCM does not usually exist as a liquid in the environment.

Rather, it usually is found evaporated in air or dissolved in water.

Most BDCM in the environment is formed as a by-product when

chlorine is added to drinking water to kill disease-causing organisms.

Small amounts of BDCM are also made in chemical plants for use in

laboratories or in making other chemicals. A very small amount (less

than 1% of the amount coming from human activities) is formed by algae

in the ocean.

BDCM evaporates quite easily, so most BDCM that escapes into the

environment from chemical facilities, waste sites, or drinking water

enters the atmosphere as a gas. BDCM is slowly broken down (about 90%

in a year) by chemical reactions in the air. Any BDCM that remains in

water or soil may also be broken down slowly by bacteria.

Further information on the properties and uses of BDCM, and how it

behaves in the environment, may be found in Chapters 3, 4, and 5.

1.2 HOW MIGHT I BE EXPOSED TO BROMODICHLOROMETHANE?

For most people, the most likely means of exposure to BDCM is by

drinking chlorinated water. Usually the levels in drinking water are

between 1 and 10 ppb (parts per billion). BDCM is also found in some

foods and beverages such as ice cream or soft-drinks that are made using

chlorinated water, but this is probably not a major source of exposure.

BDCM has been found in chlorinated swimming pools, where exposure might

occur by breathing the vapors or through the skin. Exposure to BDCM

might also occur by breathing BDCM in the air in or near a laboratory or

factory that made or used BDCM. However, BDCM is not widely used in

this country, so this is not likely for most people. Average levels of

BDCM in air are usually quite low (less than 0.2 ppb). Another place

where human exposure might occur is near a waste site where BDCM has

been allowed to leak into water or soil. In this situation, people

could be exposed by drinking the water or by getting the soil on their

skin. BDCM has been found in water and soil at some waste sites (about

1% to 10% of those tested), usually at levels of 1 to 50 ppb. Further

information on how people might be exposed to BDCM is given in

Chapter 5.
2

1. PUBLIC HEALTH STATEMENT

1.3 HOW CAN BROMODICHLOROMETHANE ENTER AND LEAVE MY BODY?

Studies in animals show that almost all BDCM swallowed in water or

food will enter the body by moving from the stomach or intestines into

the blood. It is likely that BDCM would also move from the lungs into

the blood if it were breathed in and would cross the skin if skin

contact occurred, but this has not been studied. Bromodichloromethane

leaves the body mostly by being breathed out through the lungs. Smaller

amounts leave in the urine and feces. BDCM removal is fairly rapid and

complete (about 95% in 8 hours), so it does not usually build up in the

body. Further information on how BDCM enters and leaves the body is

given in Chapter 2.

1.4 HOW CAN BROMODICHLOROMETHANE AFFECT MY HEALTH?

The effects of BDCM depend on how much is taken into the body. In

animals, the main effect of eating or drinking large amounts of BDCM is

injury to the liver and kidneys, These effects can occur within a short

time after exposure. High levels can also cause effects on the brain,

leading to incoordination and sleepiness. There is some evidence that

BDCM can be toxic to developing fetuses, but this has not been well-studied.

Studies in animals show that intake of BDCM for several years in food or

water can lead to cancer of the liver, kidney and intestines. Although

effects of BDCM have not been reported in humans, effects would probably

occur if enough BDCM were taken into the body. Further information on how

BDCM can affect the health of humans and animals is presented in Chapter 2.

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

TO BROMODICHLOROMETHANE?

Methods are available to measure low levels of BDCM in human blood,

breath, urine and fat, but not enough information is available to use

such tests to predict if any health effects might result. Because

special equipment is needed, these tests are not usually done in

doctors' offices. Because BDCM leaves the body fairly quickly, these

methods are best suited to detecting recent exposures. Further

information on how BDCM can be measured in exposed humans is presented

in Chapter 6.
3

1. PUBLIC HEALTH STATEMENT

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

Tables l-l through l-4 show the relationship between exposure to

BDCM and known health effects. Minimal Risk Levels (MRLs) are also

included in Table 1-3. These MRLs were derived from animal data for

both short-term and longer-term exposure, as described in Chapter 2 and

in Table 2-l. These MRLs provide a basis for comparison with levels

that people might encounter either in food or drinking water. If a

person is exposed to BDCM at an amount below the MRL, it is not expected

that harmful noncancer health effects will occur. Because these levels

are based only on information currently available, some uncertainty is

always associated with them. Also, because 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. Further

information on the levels of BDCM that have been observed to cause

health effects in animals is presented in Chapter 2.

1.7 WHAT RECOMMENDATIONS HAS THE FEDERAL GOVERNMENT MADE TO PROTECT HUMAN

HEALTH?

The U.S. Environmental Protection Agency (EPA) has set a Maximum

Contaminant Level in drinking water of 0.10 ppm (parts per million) for

the combination of BDCM and a group of similar compounds

(trihalomethanes). Most water samples in the U.S. have BDCM levels

lower than this. The Food and Drug Administration (FDA) has set the

same limit for bottled water, but no tolerance limits have been set for

BDCM in food. Because it has such limited use in industry, there is no

Occupational Safety and Health Administration standard for BDCM.

Further information on regulations concerning BDCM is presented in

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

BDCM. Its purpose is to present levels of significant exposure for BDCM

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 BDCM 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
10

2. HEALTH EFFECTS

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;

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 (10-4 to 10-7), 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 1980d), uncertainties are associated with the

techniques.

2.2.1 Inhalation Exposure

No studies were located regarding the following health effects in

humans or experimental animals following inhalation exposure to BDCM:

2.2.1.1 Death

2.2.1.2 Systemic Effects

2.2.1.3 Immunological Effects

2.2.1.4 Neurological Effects

2.2.1.5 Developmental Effects

2.2.1.6 Reproductive Effects

2.2.1.7 Genotoxic Effects

2.2.1.8 Cancer
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2. HEALTH EFFECTS

2.2.2 Oral Exposure

No studies were located regarding health effects in humans

associated with ingestion of BDCM. Figure 2-l and Table 2-l summarize

the health effects observed in experimental animals following oral

exposure to BDCM. These effects are discussed below.

2.2.2.1 Death

Most estimates of acute oral LD50 values for BDCM in rodents range

between 400 and 1000 mg/kg (Aida et al. 1987; Chu et al. 1980; Bowman

at al. 1978). Typical pathological changes observed in acutely poisoned

animals include fatty infiltration of liver and hemorrhagic lesions in

kidney, adrenals, lung and brain (Bowman et al. 1978). In a 14-day

repeated-dose study in mice, all animals dosed with 150 mg/kg/day died

(NTP 1987). This dose has been converted to an equivalent concentration

of 1,200 ppm in food for presentation in Table l-4. Males appear to be

slightly more susceptible to the lethal effects of BDCM than females,

both in rats (Aida et al. 1987; Chu et al. 1980, 1982a; NTP 1987), and

in mice (Bowman et al. 1978; NTP 1987).

The highest NOAEL values and all reliable LOAEL values for death in

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

in Figure 2-l.

2.2.2.2 Systemic Effects

No studies were located regarding effects on the respiratory,

cardiovascular, gastrointestinal, musculoskeletal, or dermal systems in

humans or animals following oral exposure to BDCM.

Hematological Effects. Hemoglobin and hematocrit were

significantly reduced in male rats following a single dose of 390 mg/kg

of BDCM (Chu et al. 1982a). The basis of this effect was not

investigated. Exposure in drinking water for 90 days to a dose of

213 mg/kg/day caused no effect on lymphocyte levels in either males or

females (Chu et al. 1982b). A slight reduction in lymphocyte count was

noted in females 90 days after exposure ceased, which the authors felt

might be related to endogenous release of steroids. Rats fed BDCM in

their diets at intake levels of 130 mg/kg/day for 24 months exhibited no

hematological changes compared to controls (Tobe et al. 1982).






18

2. HEALTH EFFECTS

Hepatic Effects. A number of studies in animals indicate that the

liver is susceptible to injury by BDCM. Typical signs include increased

liver weight, pale discoloration, increased levels of hepatic tissue

enzymes in serum, decreased levels of secreted hepatic proteins

(fibrinogen) in blood, and focal areas of inflammation or degeneration.

In acute (single dose) studies, these effects have been noted at doses

of around 1,250 mg/kg or higher (NTP 1987). It should be noted that

this dose level causes death within two weeks (NTP 1987).

In subchronic studies (10 to 14 days) in mice and rats, mild

effects on liver have been noted at doses as low as 37 mg/kg/day (Condie

et al. 1983) and 50 mg/kg/day (Ruddick et al. 1983). Effects included

slightly increased liver weights (Ruddick et al. 1983) and microscopic

changes that were rated as "minimal" (Condie et al. 1983). The effects

become more pronounced at doses of 125 to 300 mg/kg/day (Condie et al.

1983; Munson et al. 1982). The dose of 37 mg/kg/day has been converted

to an equivalent concentration of 280 ppm in food for presentation in

Table 1-4.

Although hepatic effects at doses of 40 to 50 mg/kg/day are

minimal, it appears that this is the approximate threshold for the

appearance of more marked effects at higher doses, so the dose of

37 mg/kg/day (Condie et al. 1983) has been used to derive the acute MRL

for BDCM. Based on this value, an acute oral MRL of 0.037 mg/kg/day was

calculated, as described in the footnote in Table 2-1. This MRL has

been converted to an equivalent concentration in food (1.3 ppm) for

presentation in Table 1-3.

Most longer-term studies report signs of liver injury in rats or

mice at doses of 50 to 200 mg/kg/day (Dunnick et al. 1987; NTP 1987;

Tobe et al. 1982). These doses are not significantly different from

those observed to cause hepatic injury in acute and short-term studies,

suggesting that there is a relatively low tendency toward cumulative

injury to liver.

An exception is the study of Chu et al. (1982b), where

statistically significant effects on liver were noted in rats exposed to

doses as low as 7 mg/kg/day for 90 days. However, these effects were

minimal (the authors assigned a severity score of 2 on a scale of 1 to

10) and showed essentially no dose-response tendency. Because this

observation is of uncertain significance and is inconsistent with NOAEL
19

2. HEALTH EFFECTS

estimates from other intermediate and chronic studies, it has not been

selected for calculation of a longer-term MRL. The chronic dose level

of 50 mg/kg/day (NTP 1987) has been converted to an equivalent

concentration of 380 ppm in food for presentation in Table l-4.

The highest NOAEL values and all reliable LOAEL values for hepatic

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

and plotted in Figure 2-l.

Renal Effects. Studies in animals reveal that the kidney is also

susceptible to injury by BDCM, typically at dose levels similar to those

that effect the liver. For example, in 14-day studies, Munson et al.

(1982) observed increases in blood urea nitrogen (BUN) in mice dosed

with 250 mg/kg/day, and Condie et al. (1983) reported decreased uptake

of p-aminohippurate (PAH) into kidney slices from mice dosed with 74 to

148 mg/kg/day. Similarly, Ruddick et al. (1983)observed increased

renal weight in rats dosed with 200 mg/kg/day for 10 days. The dose of

74 mg/kg/day has been converted to an equivalent concentration of

570 ppm in food for presentation in Table l-4.

In longer-term studies, areas of focal necrosis were observed in

the proximal tubular epithelium in male mice exposed for 13 weeks to

doses of 100 mg/kg/day, and cytomegaly was noted following chronic

exposure to 25 mg/kg/day (Dunnick et al. 1987; NTP 1987). Female mice

were somewhat less susceptible than males. In rats, cytomegaly and

nephrosis were observed in both males and females at chronic exposure

levels of 50 to 100 mg/kg/day (NTP 1987). The dose of 25 mg/kg/day has

been converted to an equivalent concentration of 190 ppm in food for

presentation in Table l-4. This dose has also been selected as the most

appropriate value for calculation of the chronic MRL for BDCM. Based on

this value, a chronic oral MRL of 0.018 mg/kg/day was calculated, as

described in the footnote in Table 2-l. This MRL has been converted to

an equivalent concentration in food (0.6 ppm) for presentation in

Table l-3.

The highest NOAEL values and all reliable LOAEL values for renal

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

and plotted in Figure 2-l.

2.2.2.3 Immunological Effects

The effects of BDCM on the immune system have not been thoroughly

studied. Munson et al. (1982) administered BDCM to mice for 14 days,

and observed a decrease in female mice in the number of antibody forming
20

2. HEALTH EFFECTS

cells in spleen and a decrease in the hemagglutination titer at doses of

125 to 250 mg/kg/day. The authors felt that the humoral immune system

may have potential to serve as an early indicator of halomethane

toxicity.

2.2.2.4 Neurological Effects

No studies were located regarding histological or

electrophysiological effects of BDCM on the nervous system. Rats and

mice administered oral doses of 150 to 600 mg/kg often display acute

signs of CNS depression, including lethargy, labored breathing, sedation

and flaccid muscle tone (NTP 1987; Aida et al. 1987; Balster and

Borzelleca 1982; Chu et al. 1980). These effects tend to reverse after

a period of several hours.

To determine whether BDCM exposure resulted in any longer-lasting .

changes in behavior, Balster and Borzelleca (1982) performed a series of

tests in mice 24 hours or more after the last of a series of doses of

BDCM. Exposure to doses of 1.2 to 11.6 mg/kg/day for 14 to 90 days had

no effect on tests of coordination, strength, endurance or exploratory

activity, and 90 days exposure to 100 mg/kg/day did not effect

passiveavoidance

learning. Exposure to 100 or 400 mg/kg/day for go-days did

result in an acute effect on operant behavior (decreased pressing of a

lever that presented food), but this change tended to diminish over the

exposure period, suggesting there was no progressive effect and that

partial tolerance developed.

The highest NOAEL values and all reliable LOAEL values for

neurological effects in each species and duration category are recorded

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

2.2.2.5 Developmental Effects

Ruddick et al. (1983) reported an increased incidence of sternebral

anomalies in fetuses from rats that had been exposed to BDCM at doses of

50 to 200 mg/kg/day on days 6 to 15 of gestation (the critical period

for organogenesis). No other dose-related visceral or skeletal

anomalies were observed. The authors interpreted the sternebral

anomalies to be evidence of a fetotoxic (rather than a teratogenic)

effect. These doses also resulted in significant maternal toxicity, as

evidenced by a 40% reduction in body weight gain. The dose of 50

mg/kg/day has been converted to an equivalent concentration of 1,000 ppm

in food for presentation in Table l-4.
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2. HEALTH EFFECTS

2.2.2.6 Reproductive Effects

No studies were located regarding reproductive effects in humans or

animals following oral exposure to BDCM.

2.2.2.7 Genotoxic Effects

An increased frequency of sister chromatic exchange (SCE) in mice

exposed to BDCM was reported by Morimoto and Koizumi (1983).

Statistically significant increases in SCEs in bone marrow cells were

observed in animals dosed with 50 or 100 mg/kg/day for 4 days. Mice

given the highest dose tested, 200 mg/kg/day for 4 days, died and could

not be evaluated for SCEs in bone marrow cells.

2.2.2.8 Cancer

No studies were located regarding carcinogenic effects in humans

following chronic oral exposure to BDCM per se. There are several

epidemiological studies that indicate there may be an association

between ingestion of chlorinated drinking water (which typically

contains BDCM) and increased risk of cancer in humans (Gottlieb et al.

1981; Kanarek and Young 1982; Marienfeld et al. 1986), but such studies

cannot provide information on whether any effects observed are due to

BDCM or to one or more of the hundreds of other byproducts that are also

present in chlorinated water.

However, chronic oral studies in animals provide convincing

evidence that BDCM is carcinogenic. In rats, increased frequency of

liver tumors was observed in females exposed to 150 mg/kg/day for

180 weeks (Tumasonis et al. 1985), and kidney tumors were observed in

both males and females exposed to 100 mg/kg/day (NTP 1987; Dunnick

et al. 1987). Incidences of renal tumors were 13/50 and 15/50 in males

and females, respectively. Tumors of the large intestine were also

observed in rats, at incidences of 13/50 and 45/50 in males exposed to

50 and 100 mg/kg/day, and at an incidence of 12/47 in females dosed at

100 mg/kg/day. In mice, renal tumors were observed in males dosed with

50 mg/kg/day, and hepatic tumors were observed in females dosed with 75

or 150 mg/kg/day. Increased intestinal tumors were not observed in mice

(Dunnick et al. 1987; NTP 1987).

2.2.3 Dermal Exposure

No studies were located regarding the following toxic effects in

humans or animals following dermal exposure to BDCM:
22

2. HEALTH EFFECTS

2.2.3.1 Death

2.2.3.2 Systemic Effects

2.2.3.3 Immunological Effects

2.2.3.4 Neurological Effects

2.2.3.5 Developmental Effects

2.2.3.6 Reproductive Effects

2.2.3.7 Genotoxic Effects

2.2.3.8 Cancer

2.3 RELEVANCE TO PUBLIC HEALTH

Oral exposure studies in animals identify the central nervous

system, the liver, the kidney and the intestine as the principal target

tissues of BDCM. Effects on the central nervous system (lethargy,

sedation) are observed mostly following large doses, and are likely the

result of a direct narcotic or anaesthetic effect similar to other

related chemicals (e.g., chloroform, carbon tetrachloride).

Effects on the liver and kidney include increased organ weight,

focal areas of inflammation or degeneration, and decreased function.

These effects tend to appear in both tissues at roughly similar doses,

usually between 25 and 100 mg/kg/day. This indicates that both tissues

are approximately equally susceptible to BDCM. The doses which lead to

renal and hepatic injury following intermediate or chronic exposure are

generally similar to those causing acute effects (e.g., see Figure 2-l),

suggesting that there is a relatively low tendency toward cumulative

injury for these noncarcinogenic endpoints. This is probably because

both the liver and the kidney are able to repair damaged cells or

replace dead cells within a short period after exposure.

BDCM exposure has also been observed to result in developmental

toxicity (Ruddick et al. 1983). However, data are available only for

doses that cause significant maternal toxicity, so it is not possible to

judge whether-developmental effects are likely to occur in animals or

humans exposed at lower dose levels.
23

2. HEALTH EFFECTS

The greatest reason for concern with BDCM exposure is evidence from

animal studies that BDCM is carcinogenic. Compared with other

trihalomethanes (THMs), BDCM causes the widest spectrum of neoplasms in

rats and mice, and is the only THM observed to cause intestinal tumors

(Dunnick et al. 1987). In addition, BDCM has been found to be mutagenic

in some (but not all) in vitro gene mutation and sister chromatid

exchange assays (summarized in Table 2-2). BDCM has also been reported

to cause increased sister chromatid exchange in bone marrow cells of

mice exposed in vivo (Morimoto and Koizumi 1983). These positive

carcinogenicity and genotoxicity studies indicate that exposure to BDCM

in chlorinated water or near waste sites might contribute to increased

risk of cancer in humans.

Several studies indicate that there are differences in

susceptibility to BDCM between species and between sexes. With regard

to lethality, for example, male mice are more susceptible than female

mice, and both male and female mice are more susceptible than rats.

Male mice are also more susceptible to the renal effects of BDCM than

females, while in rats, males respond to BDCM with renal cytomegaly and

females develop nephrosis. Intestinal tumors are observed in both male

and female rats, but not in mice. The basis of these differences is not

known, but may possibly be attributed to differences in disposition and

metabolism of BDCM between sexes and species. That significant

differences exist have been demonstrated by Mink et al, (1986) and Smith

et al. (1985), as discussed below in Section 2.6.

Because of the differences in dose susceptibility and tissue

specificity observed between sexes and species in animal studies, it is

difficult to extrapolate the observations in animals to humans. Until

an improved understanding of the mechanistic or toxicokinetic basis of

these variables is achieved, it is prudent to assume that the same

effects observed in animals will be observed in humans ingesting

comparable dose levels.

2.4 LEVELS IN HUMAN TISSUES AND FLUIDS ASSOCIATED WITH HEALTH EFFECTS

BDCM was not detected in samples of human fat studied in the

National Human Adipose Tissue Survey (NHATS) (EPA 1986c), and was not

detected in the blood of 250 patients studied by Antoine et al. (1986).

25

2. HEALTH EFFECTS

A BDCM concentration of 14 ng/ml was found in a blood sample from one

resident living near a waste site in New York (Barkley et al. 1980), but

the significance of this isolated observation is difficult to judge. No

other studies were located regarding levels of BDCM in human tissues and

fluids.

2.5 LEVELS IN THE ENVIRONMENT ASSOCIATED WITH LEVELS IN HUMAN TISSUES AND/OR

HEALTH EFFECTS

No studies were located regarding the relationship between

environmental levels of BDCM and levels of BDCM in human tissues or

fluids or the occurrence of any adverse health effects. Epidemiological

studies which indicate there may be an association between consumption

of chlorinated water (which contains BDCM) and increased risk of cancer

are consistent with, but do not establish, the hypothesis that BDCM

increases cancer risk in humans, since chlorinated water contains

hundreds'of other chemicals as well.

2.6 TOXICOKINETICS

No studies were located regarding BDCM toxicokinetics in humans,

but there are limited data from studies in animals. These data are

summarized below,

2.6.1 Absorption

2.6.1.1 Inhalation Exposure

No studies were located regarding absorption following inhalation

exposure to BDCM. By analogy with other similar chemicals, it seems

likely that BDCM would be well absorbed across the lung in both humans

and animals.

2.6.1.2 Oral Exposure

Female monkeys, dosed with radioactive BDCM by gavage, excreted 2%

of the administered radioactivity in feces, indicating that

gastrointestinal'absorption was essentially complete (Smith et al.

1985). In mice, absorption was also rapid and extensive (Mink et al.

1986). Within eight hours of administration, 90% of the administered

radioactivity was excreted in urine or expired air, indicating that
26

2. HEALTH EFFECTS

absorption was at least 90% complete. In rats, BDCM was not absorbed as

readily as in mice and monkeys with only about 60% of the orally

administered dose appearing in the expired air and urine (Mink et al.

1986).

2.6.1.3 Dermal Exposure

No studies were located regarding absorption following dermal

exposure to BDCM. By analogy with other similar chemicals, it seems

likely that BDCM will be absorbed across the skin.

2.6.2 Distribution

2.6.2.1 Inhalation Exposure

No studies were located regarding distribution in humans or animals

following inhalation exposure to BDCM.

2.6.2.2 Oral Exposure

When BDCM was administered to rats by gavage, the compound was slow

to leave the stomach (Smith et al. 1985). Three hours after

administration, 21.5% of the dose was still in the stomach. Fat,

muscle, and liver each contained from 1.8 to 2.8% of the dose, with

lower levels in other tissues.

2.6.2.3 Dermal Exposure

No studies were located regarding distribution in humans or animals

following dermal exposure to BDCM.

2.6.3 Metabolism

Pathways of BDCM metabolism have not been characterized. Studies

in mice indicate that carbon dioxide is a major endproduct in that

species, accounting for 81% of the administered dose (Mink et al. 1986).

In rats, only 14% of the administered dose was expired as carbon

dioxide, and 42% as the parent compound (Mink et al. 1986). As

discussed previously, toxicology studies in rats and mice showed that

BDCM was more toxic to mice than to rats, and it is possible that these

toxicokinetic differences in metabolism may contribute to these

differences.
27

2. HEALTH EFFECTS

2.6.4 Excretion

2.6.4.1 Inhalation Exposure

No studies were located regarding excretion in humans or animals

following inhalation exposure to BDCM.

2.6.4.2 Oral Exposure

The major route of excretion of BDCM in rats, mice, and monkeys is

expiration through the lung, either as parent BDCM, or as volatile

metabolites such as CO2 (Mink et al. 1986; Smith et al, 1977; Smith

et al. 1985). Excretion via the urine accounts for only a minor

fraction of the administered dose (1.4% in rats, 2.2% in mice, and 2% to

6% in monkeys) (Mink et al. 1986; Smith et al. 1985).

Fecal excretion in monkeys accounted for less than 2% of the

administered dose 72 hours after dosing (Smith et al. 1985). In rats,

Smith et al. (1985) found no detectable amounts of radiolabelled BDCM or

metabolites in the feces, but the feces were evaluated only up to

6 hours after administration of BDCM. The shortness of the time

interval does not give an accurate assessment of the feces as a route of

excretion for BDCM, since 37% of the administered dose in the rats was

accounted for in the gastrointestinal tract. No data were available on

fecal excretion in mice.

The half-life of BDCM in rats and mice was estimated to be 1.5 and

2 hours, respectively (Mink et al. 1986), and the half-life in monkeys

was 4 to 6 hours (Smith et al. 1977). This indicates that BDCM is

effectively excreted and that tissue accumulation of BDCM is unlikely.

2.6.4.3 Dermal Exposure

No studies were located regarding excretion in humans or animals

following dermal exposure to BDCM.

2.7 INTERACTIONS WITH OTHER CHEMICALS

Hewitt et al. (1983) reported that pretreatment of rats with an

oral dose of acetone dramatically increased the hepatic and renal

toxicity of an oral dose of BDCM given 18 hours later. This is very

similar to the well-documented potentiation of CCl4 by a variety of

alcohols, ketones and other chemicals, suggesting that BDCM and CCl4 may
28 

2. HEALTH EFFECTS

exert their toxicity through common mechanisms. Because of the

widespread use of alcohols and ketones in industry and in consumer

products, this sort of potentiation could be quite important. 

A study in rats by Wester et al. (1985) evaluated the effects of

ingestion of a mixture of 11 halogenated hydrocarbon contaminants of

drinking water, including BDCM. No effects were observed after 25

months of exposure, but the doses employed were so low (0.003 to 0.28

mg/kg/day for BDCM) that this observation does not constitute strong

evidence that BDCM does not interact with other chemicals. 

2.8 POPULATIONS THAT ARE UNUSUALLY SUSCEPTIBLE 

No studies were located regarding human populations that are

unusually susceptible to BDCM. Because BDCM is known to cause liver

injury in animals, humans with preexisting liver diseases (e.g. ,

hepatitis, cirrhosis) may be particularly susceptible to the

hepatotoxic effects of BDCM. Likewise, humans with preexisting kidney

diseases may be susceptible to BDCM. By analogy with CCl4, persons who

are heavy drinkers and/or take certain drugs that affect the liver may

also be particularly susceptible to the effects of BDCM.

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 BDCM 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. 
29

2. HEALTH EFFECTS

2.9.1 Existing Information on Health Effects of BDCM

As summarized in Figure 2-2, there are no data on the health

effects of BDCM in humans. In animals, there are a number of studies of

health effects following oral exposure, and information exists for most

endpoints except reproduction. However, no animal toxicity data exist

for inhalation or dermal exposure to BDCM.

2.9.2 Data Needs

Single Dose Exposure. There are a number of single dose studies in

animals by the oral route, and the range of intake doses leading to

lethal and most sublethal effects is reasonably well defined. However,

the mechanism of toxicity has not been studied. Such studies would be

useful in revealing why there are significant differences in

susceptibility between males and females, and whether this is pertinent

to the evaluation of human health risk from BDCM. Studies by the oral

route are likely to be most relevant, but studies of acute inhalation

and dermal toxicity would also be useful, since humans may be exposed by

these pathways while bathing or swimming.

Repeated Dose Exposure. Existing studies of health effects in

animals administered repeated oral doses of BDCM indicate that there is

a relatively low tendency toward cumulative toxicity and that chronic

noncarcinogenic effects resemble short-term effects. However, the

threshold dose for noncarcinogenic effects is not known with certainty.

For example, the study by Chu et al. (1982b) identified minimal effects

on the liver at doses of 7 mg/kg/day or higher, while other studies (NTP

1987; Tobe et al. 1982) did not detect effects at doses 6- to 20-times

higher. Thus, additional studies to define long-term no-effect levels

with greater certainty would help improve risk assessments for BDCM.

Chronic Exposure and Carcinogenicity. Several studies have

indicated that chronic oral exposure to BDCM increases cancer risk in

animals. Tumors were observed in both liver and kidney tissues (known

to be target tissues from subchronic studies of this chemical), and

tumors were also observed in the large intestines in rats. This is an

unusual tumorigenic response in rats, and the basis for the

susceptibility of the large intestine is not known. Further studies

would be valuable to reveal the basis for this tissue selectivity, and

to obtain improved dose-response data to allow reliable quantitative

cancer risk assessment.

31

2. HEALTH EFFECTS

Genotoxicity. An in vivo mutagenicity study in mice indicated that

BDCM has potential to cause genetic damage, and in vitro studies also

suggest that BDCM has genotoxic potential. Additional in vitro and in

vivo studies to evaluate the genotoxicity of BDCM and to identify the

mechanism of genotoxic damage in intact mammalian cells would be

valuable.

Reproductive Toxicity. No studies were located regarding effects

of BDCM on reproduction. Multigeneration studies in animals to evaluate

effects of BDCM on reproduction would be valuable.

Developmental Toxicity. One study in rats (Ruddick et al. 1983)

indicates that BDCM is fetotoxic at doses that cause maternal toxicity,

but effects at lower doses were not evaluated. Additional developmental

studies at lower doses and in several other species would be helpful in

evaluating more fully the potential of BDCM to cause effects on the

developing organism.

Immunotoxicity. Limited data from subchronic oral studies in mice

indicate that BDCM adversely affects the immune system. However, the

data do not define the threshold for the effect with certainty, nor do

the data reveal whether the function of the immune system is

significantly impaired. Further studies on the immunotoxicity of BDCM

in animals would be valuable in establishing the no-effect level and the

relevance to human health.

Neurotoxicity. High doses of BDCM affect the CNS like other

halocarbons, causing depressed function and anesthesia. Limited data

indicate that repeated exposures may lead to transient effects on

behavior, but this has not been investigated in detail. Further

neurobehavioral,studies using more sensitive operant measures would help

define the exposure levels that lead to these effects, and whether any

permanent neurological changes occur.

Epidemiological and Human Dosimetry Studies. No epidemiological

studies were located regarding human health effects from exposure to

BDCM per se. Epidemiological studies of cancer frequency in populations

consuming chlorinated drinking water have been performed, but since BDCM

levels tend to vary in concert with the levels of other trihalomethanes

and numerous other byproducts of disinfection, it is unlikely that

studies of this sort will be able to provide information on the risks

contributed specifically by BDCM.
32

2. HEALTH EFFECTS

Biomarkers of Disease. Since no cases of human disease due to BDCM

exposure have been reported, it is not possible to identify biomarkers

of disease in humans. Assuming that hepatic and renal injury similar to

that observed in animals might occur in exposed humans, early signs of

these effects could be detected by standard clinical methods such as

serum enzyme levels, PAH clearance, and so on. These tests would not be

specific for BDCM, however, and would only detect effects after injury

to the tissues has occurred. Efforts to identify a sensitive and

specific biomarker of BDCM-induced disease would be helpful.

Disease Registries. No disease registry exists for BDCM-induced

diseases in humans. Since the effects observed in animals (hepatic and

renal injury, cancer of liver, kidney and intestines) are common

diseases in humans, it is likely that a registry of individuals with

these diseases would contain only a small number of cases that might be

attributable solely to BDCM exposure.

Bioavailability from Environmental Media. No studies were located

on the relative bioavailability of BDCM in different environmental

media. Based on the physical properties of BDCM, it is not expected

that bioavailability would vary widely between water, soil, food, and

other media. Studies to investigate this would, nevertheless, be

helpful.

Food Chain Bioaccumulation. BDCM is biosynthesized by a variety of

marine macroalgae, but whether BDCM from this source or other sources

enters the food chain has not been studied. While the relatively rapid

metabolism and excretion of BDCM in laboratory animals suggest that

marked bioaccumulations is not likely, information on BDCM uptake and

retention by fish, plants, and other food sources would be helpful.

Absorption, Distribution, Metabolism, and Excretion. Currently

there are no toxicokinetic studies on BDCM following inhalation

exposure. Consequently, it would be helpful to determine the fraction

of BDCM that is absorbed via inhalation and to investigate whether any

significant differences in metabolism or retention exist between

inhalation and oral exposures. Similarly, there are no toxicokinetic

data regarding dermal exposure to BDCM. Although direct dermal contact

with concentrated BDCM is unlikely, dermal contact with water containing

BDCM is very common. Consequently, information on dermal absorption

rates from aqueous solutions would be helpful.

Most toxicokinetic studies were conducted prior to the findings of

cancer in the large intestine of male and female rats following chronic
33

2. HEALTH EFFECTS

ingestion of BDCM. Since tumors in the gastrointestinal tract are

uncommon in rats, additional toxicokinetic studies focusing on BDCM

metabolism and distribution in this tissue would be valuable in

understanding the metabolic pathways for BDCM and how the metabolism may

be related to the mechanism of toxicity and carcinogenicity of BDCM.

Detailed studies of the enzymic pathways of BDCM metabolism and of

the intermediates formed would also be valuable. Metabolic activation

to yield highly toxic intermediates is known to be a critical step in

the toxicity of some similar compounds (e.g., CCl4). Investigations to

determine whether similar pathways are involved in BDCM toxicity might

help resolve many of the special aspects of the toxicity of this

compound.

Comparative Toxicokinetics. Since BDCM toxicity appears to differ

significantly between sexes and species, additional toxicokinetic

studies in several species would be valuable. Such studies would aid in

understanding the differences in toxicity between species, and could

help identify the most appropriate animal species for use as a model for

humans.

2.9.3 On-going Studies

Dr. James Mathews (Research Triangle Institute) is currently

performing studies of the dose-dependency of absorption, metabolism and

clearance of BDCM following oral exposure of rodents. This research is

sponsored by the National Toxicology Program.

35

3. CHEMICAL AND PHYSICAL INFORMATION

3.1 CHEMICAL IDENTITY

Table 3-l lists common synonyms, trade names and other pertinent

identification information for BDCM.

3.2 PHYSICAL AND CHEMICAL PROPERTIES

Table 3-2 lists important physical and chemical properties of BDCM.



39

4. PRODUCTION, IMPORT, USE, AND DISPOSAL

4.1 PRODUCTION

BDCM is produced commercially by the reaction of dichloromethane

with aluminum bromide. Small quantities of BDCM are currently produced

in the United States, but quantitative production volumes are not

available.

4.2 IMPORT

No data on imports or exports of BDCM were located. Little, if

any, of either is expected.

4.3 USE

In the past, BDCM has been used as a solvent for fats, waxes, and

resins, as a flame retardant, as a heavy liquid for mineral and salt

separations, and as a fire extinguisher fluid ingredient (Sax 1984). At

present, the principal use of BDCM is as a chemical intermediate for

organic synthesis and as a laboratory reagent (Sittig 1985; Verschueren

1983). BDCM is not listed as a current ingredient in fire

extinguishers, solvents or other commercial products (Gosselein et al.

1984).

4.4 DISPOSAL

Bromodichloromethane is categorized as a hazardous waste

constituent (40 CFR 261 App. VIII) and, therefore, must be disposed of

in accordance with RCRA regulations. Acceptable disposal methods

include incineration using liquid injection, rotary kiln or fluidized

bed techniques. At the present time, land disposal of BDCM is also

permitted, although trihalomethanes are being evaluated for land

disposal prohibition.

BDCM has been detected in the raw and treated wastewater of

numerous industries (EPA 1983), but no quantitative data on amounts of

BDCM disposed of to the environment were located. BDCM has been

detected at 7% of chemical waste sites investigated under Superfund

(CLPSD 1988).
40

4. PRODUCTION, IMPORT, USE AND DISPOSAL

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 Public Health Service) to assess whether adequate information on the

health effects of BDCM 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, Use, Release and Disposal. The minimal commercial use

of BDCM is reflected in the absence of available production data. Data

on current uses and disposal practices would be valuable in determining

whether industrial activities pose an important source of human exposure

to BDCM.

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.
41

5. POTENTIAL FOR HUMAN EXPOSURE

5.1 OVERVIEW

The major source of BDCM in the environment is formation as a byproduct

during chlorination of water, and many people are exposed to low

levels of BDCM in their drinking water. Industrial use of BDCM is

sufficiently limited that exposures to industrial emissions outside the

workplace are not expected to be of general concern. BDCM has been

detected in water and soil at some chemical waste sites, and human

exposure may potentially occur in such cases.

BDCM is a volatile chemical, so most of the BDCM that is formed in

water or released by industry tends to evaporate into air. BDCM does

not adsorb strongly to soils or sediments, nor does it tend to

bioaccumulate in fish or other animals.

In the atmosphere, BDCM is thought to undergo slow destruction

through oxidative pathways, with a half-life of about two to three

months. BDCM remaining in soil or water may undergo microbial

degradation. However, these fate processes have not been studied in

detail.

5.2 RELEASES TO THE ENVIRONMENT

5.2.1 Air

No studies were located regarding industrial release of BDCM into

air. Because of the low volume of BDCM currently in use, it is expected

that releases from industrial activities are probably small.

5.2.2 Water

The principal source of BDCM in the environment is from

chlorination of water. EPA (1980a) estimated that over 800 kkg (1 kkg =

1 metric ton) are produced annually in this way. It is presumed that

essentially all of this is ultimately released into the environment,

mainly through volatilization. This may occur either indoors (e.g.,

while showering, washing, cooking, etc.) or outdoors after discharge of

the water to the surface.
42

5. POTENTIAL FOR HUMAN EXPOSURE

Class et al. (1986) observed trace levels (<l parts per trillion

(ppt)) of BDCM and other brominated methanes in seawater and in the air

above the ocean at several locations in the Atlantic. The presence of

BDCM can be attributed to biosynthesis and release of BDCM by macroalgae

(Class et al. 1986; Gschwend et al. 1985). BDCM from this source

accounts for less than 1% of the anthropogenic burden of bromomethanes

in the atmosphere (Class et al. 1986).

BDCM has been detected in wastewater from a number of industrial

discharges and municipal wastewater treatment facilities, usually at

concentrations between 1 and 100 μg/L (Staples et al. 1985; Perry et al.

1979; Dunovant et al. 1986). These levels of BDCM are similar to those

found in many chlorinated drinking water supplies (see Section 5.4.2,

below), and probably most discharges of this sort do not represent a

major source of BDCM release to the environment.

5.2.3 Soil

No studies were located regarding release of BDCM to soil.

5.3 ENVIRONMENTAL FATE

5.3.1 Transport and Partitioning

Because of the relatively high vapor pressure of BDCM (50 mm Hg at

20°C), the principal transport process in the environment is

volatilization (Class et al. 1986; Gschwend et al. 1985). Over 99% of

all BDCM in the environment is estimated to exist in air (EPA 1980a).

Volatilization from surface waters depends on factors such as

turbulence and temperature. The volatilization half-life from rivers

and streams has been estimated to range from 33 minutes to 12 days, with

a typical half-life of 35 hours (Kaczmar et al. 1984). Volatilization

rates from surface soils have not been studied in detail, but Wilson

et al. (1981) found that about 50% of BDCM applied to a soil column in

the laboratory escaped by volatilization.

BDCM may be removed from air by washout in rainfall (Class et al.

1986), but the average rate of this transport process has not been

estimated. It is expected that BDCM removed from air in this way would

be largely returned to air through volatilization.
43

5. POTENTIAL FOR HUMAN EXPOSURE

BDCM is moderately soluble in water (4,500 mg/L), and significant

transport of BDCM can occur in water, especially in groundwater where

volatilization is restricted. This transport pathway may be important

at waste sites or other locations where BDCM spills lead to groundwater

contamination.

In soil, the relatively low log octanol-water partition coefficient

(Kow) indicates that adsorption is not likely to be a dominant factor,

and that BDCM spilled into soil will be relatively mobile and may

migrate into groundwater (EPA 1985a; Piet et al. 1981). In support of

this, Wilson et al. (1981) found that BDCM was not significantly

retarded during percolation through a column of sandy soil.

The moderate solubility and low log Kow indicate that

bioaccumulation of BDCM by fish or other aquatic species is likely to be

minor, but no estimate of a bioaccumulation factor in aquatic species

was located.

5.3.2 Transformation and Degradation

5.3.2.1 Air

Pathways responsible for BDCM destruction in the atmosphere are not

well studied, but probably involve oxidative reaction with hydroxyl

radicals or singlet oxygen (EPA 1980a; Mabey et al. 1982). Direct

photochemical decomposition is not likely to be significant (EPA 1980a).

The typical atmospheric lifetime of BDCM has been estimated to be two to

three months (EPA 1980a). This relatively persistent tropospheric halflife

of BDCM suggests that a small percentage of the BDCM present in air

will eventually diffuse into the stratosphere where it will be destroyed

by photolysis. In addition, long-range global transport is possible.

5.3.2.2 Water

Hydrolysis of BDCM in aqueous media is very slow, with an estimated

rate constant at neutral pH of 5.76 x 10-8 hr-1 (Mabey et al. 1982).

This corresponds to a half-life of more than 1,000 years.

Biodegradation in aqueous media may be significant in some cases.

For example, Tabak et al. (1981) reported 35% transformation after seven

days incubation in a medium inoculated with sewage. Repeated culturing

lead to increased losses, indicating gradual adaptation of the degradative

microbes.
44

5. POTENTIAL FOR HUMAN EXPOSURE

Under aquatic conditions where volatilization cannot occur,

biodegradation may be the predominant mechanism for degradation of BDCM.

Bouwer et al. (1981) and Bouwer and McCarty (1983a) studied the

degradation of BDCM under aerobic and anaerobic conditions in both

static and continuous flow systems inoculated with mixed methanogenic

bacterial cultures from sewage. Degradation was found to be very

limited under aerobic conditions, but essentially complete within 2 days

under anaerobic conditions. Slow degradation (50% to 70% in 16 weeks)

occurred in sterile media, indicating that a chemical mechanism

(hypothesized to be reductive dehalogenation) was operative in addition

to the rapid microbial degradation. Microbial degradation was also

observed under anaerobic conditions in media inoculated with

denitrifying bacteria (Bouwer and McCarty 1983b).

5.3.2.3 Soil

Biodegradation of BDCM in soil has not been studied, but studies in

aqueous media indicate that biodegradation might occur under anaerobic

conditions (Bouwer et al. 1981; Bouwer and McCarty 1983a, 1983b; Tabak

et al. 1981). This suggests that, in regions of soil where

volatilization is restricted, biodegradation could be a major removal

process.

5.4 LEVELS MONITORED OR ESTIMATED IN THE ENVIRONMENT

5.4.1 Air

Ambient air monitoring data compiled by Brodzinsky and Singh (1983)

identified BDCM at four of six sites investigated. Concentrations

ranged from 0.76 to 180 ppt, with a mean value of 1.1 ppt. BDCM levels

from four sites monitored in California were reported to range from 20

to 100 ppt (Shikiya et al. 1984). BDCM was not detected in a survey of

bromine-containing gasses in the atmosphere at the South Pole (Rasmussen

and Khalil 1984), although trace levels (1 ppt) were detected in air at

several locations in the Atlantic Ocean (Class et al. 1986). This was

judged by the authors to be due to releases from macroalgae.

5.4.2 Water

BDCM occurs in water primarily as a by-product of chlorination.

Surveys of BDCM levels in chlorinated public drinking water systems

across the United States have revealed that BDCM is present in most
45

5. POTENTIAL FOR HUMAN EXPOSURE

systems at concentrations averaging around 1 to 20 μg/L, but ranging up

to 125 μg/L in some cases (Coleman et al. 1975; EPA 1979; Furlong and

D'itri 1986; Symons et al. 1975).

The concentration of BDCM in chlorinated water depends on reaction

conditions during the chlorination process. Important parameters

include temperature, pH, bromide ion concentration in the source water,

fulvic and humic substance concentration in the water, and the

chlorination treatment practices (EPA 1985b). The amount of BDCM tends

to increase as a function of increasing organic content and bromide ion

in the source water (Bellar et al. 1974; Argue110 et al. 1979). Studies

by Brett and Calverly (1979) and Argue110 et al. (1979) indicate that

BDCM levels increased by 30 to 100% in water system distribution pipes,

presumably because formation continues as long as a chlorine residual

and organic precursors remain.

BDCM is also formed in chlorinated swimming pools. Beech et al.

(1980) measured THM levels in several swimming pools in Miami, and found

total THM concentrations averaged from 120 to 660 μg/L. In freshwater

pools, most of the total THM was chloroform, with BDCM levels ranging

from 13 to 34 μg/L. In saltwater pools, bromoform was the principal THM

present, and BDCM concentrations were roughly the same as in freshwater

pools.

Monitoring studies of groundwater and surface water at chemical

waste sites indicate that BDCM is a relatively infrequent contaminant.

BDCM was detected at only 4 of 818 sites on the National Priority List

(NPL) , and at 7% of a number of other sites being investigated under

Superfund (CLPSD 1988). The average concentration of BDCM in

groundwater at these sites was 30 μg/L. Quantitative data for surface

water were not available.

5.4.3 Soil

No studies were located on BDCM levels in ambient soil. Because of

its volatility, it is likely that BDCM would be present only at low

levels in most soils. BDCM was detected in 2% of soil samples taken

near chemical waste sites being investigated under Superfund (CLPSD

1988), but quantitative estimates of soil concentration are not

available.
46

5. POTENTIAL FOR HUMAN EXPOSURE

5.4.4 Other Media

BDCM is not a common contaminant of food, occurring only in trace

quantities in some samples. A market basket study of 39 food items

detected BDCM in one dairy composite at 1.2 ppb and in butter at 7 ppb

(Entz et al. 1982). A study of BDCM in food processing water and

processed foods revealed no detectable levels except in ice cream at one

processing plant (0.6 to 2.3 ppt) (Uhler and Diachenko 1987). Soft

drinks have been found to contain BDCM (Abdel-Rahman 1982; Entz et al.

1982), but usually at concentrations (0.1 to 6 μg/L) below those found

in municipal water supplies. Cooking foods in water containing BDCM is

unlikely to lead to contamination, since BDCM would rapidly volatilize

(Kool et al. 1981).

BDCM is biosynthesized by marine macroalgae, and has been measured

in these organisms at 7-22 ng/g dry weight (Gschwend et al. 1985).

Whether BDCM enters and accumulates in the food chain from this source

appears to be unlikely, but has not been studied.

5.5 GENERAL POPULATION AND OCCUPATIONAL EXPOSURE

The estimated exposure of the general human population to BDCM from

drinking water, assuming a median BDCM concentration of 0.014 mg/L and a

water intake for an adult of 2.18 L/day, would be 0.03 mg/day (EPA

1980a). Low levels of exposure might also occur by inhalation of BDCM

volatilized from chlorinated water (e.g., while showering, cooking, or

swimming), or by dermal contact with such water. Based on a chemical

structure analogy to chloroform, an estimated dermal exposure to BDCM in

a child swimming two hours/day in a saline pool would typically be

0.003 mg/day, with a maximum of 0.04 mg/day (Beech 1980). Higher

exposure levels might occur through ingestion of water contaminated with

BDCM near a waste site, but available data suggest that this is not a

common occurrence.

No studies were located on human exposure levels in the workplace.

5.6 POPULATIONS WITH POTENTIALLY HIGH EXPOSURES

The environmental medium most likely to be contaminated with BDCM

is chlorinated water, so any person with above-average contact with such

water could have above-average exposures. This includes individuals-who

drink very large quantities of water, such as diabetics, workers in hot

climates, and so on. It may also include persons with swimming pools or

saunas, where exposure could occur by inhalation (especially if the pool
47

5. POTENTIAL FOR HUMAN EXPOSURE

or sauna is indoors) or by dermal contact. Since BDCM levels depend on

the organic content of the source water before chlorination, persons

whose water source is high in organics are likely to have finished water

with higher-than-average BDCM levels.

People working in chemical plants or laboratories where BDCM is

made or used would also have potentially high exposures to the chemical,

most likely by inhalation exposure. Persons living near waste sites may

have potentially high exposure to BDCM, but this can only be evaluated

on a case-by-case basis.

5.7 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 BDCM 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.

5.7.1 Data Needs

Physical and Chemical Properties. The physical and chemical

properties of BDCM have been determined (see Table 3-2), and further

studies on these parameters do not appear to be essential.

Environmental Fate. There are very few quantitative data on the

environmental fate and transport of BDCM, and most evaluations are

based, entirely or in part, on extrapolations from studies of other

similar compounds such as chloroform. Consequently, studies to obtain

reliable quantitative rate values for the key fate processes of BDCM

would be valuable. Of particular importance would be studies on the

volatilization of BDCM from chlorinated drinking water, and on the

atmospheric reactions of BDCM. Studies of chemical and biological

transformation and degradation rates in soil and water under conditions

comparable to those around waste sites would also be helpful.
48

5. POTENTIAL FOR HUMAN EXPOSURE

Exposure Levels in Environmental Media. Data are available on BDCM

levels in drinking water and on how these levels depend on water organic

content and treatment conditions. Nevertheless, continued monitoring

will be valuable in revealing whether changes in drinking water

treatment and disinfection procedures are effective in reducing levels

of BDCM and other contaminants.

Studies of BDCM levels in air (especially indoor air) in the

vicinity of open bodies of chlorinated water would also be helpful.

This would include water treatment plants, swimming pools, and perhaps

even home bathtubs or showers. In view of the ready volatilization of

BDCM from water, airborne levels in such locations might be significant.

Further monitoring of groundwater, soil and ambient air in the

vicinity of chemical waste sites is also needed to determine whether

emissions of BDCM from such sites adds significantly to total BDCM

exposure.

Exposure Levels in Humans. Current data on BDCM levels in air are

not adequate to estimate inhalation exposure in ambient air or the

workplace. Collection of such information would be helpful in

evaluating the relative contribution of this exposure pathway to the

total intake of BDCM. Similar data would be useful for airborne levels

of BDCM around swimming pools (especially indoor pools). Data on the

presence of BDCM in drinking water appears to be adequate for estimating

exposure from consumption of water immediately after taking it from the

tap. However, it would be helpful to know how rapidly the BDCM would

volatilize from a glass of water or from a bathtub full of water, and

what concentration would then be in the breathing zone of occupants of

the house.

Exposure Registries. No registry exists for humans known to have

been exposed to BDCM. Although exposure to BDCM through drinking water

is common, a registry of humans exposed in this way is not likely to

help identify BDCM-related diseases in humans, since exposure to BDCM in

water are usually low and typically involve exposure to other

trihalomethanes and many other byproducts of disinfection as well. A

registry of individuals exposed to BDCM during manufacture or use of

this chemical might be helpful in identifying possible health effects in

humans, although the size of the exposed population is believed to be

small.
49

5. POTENTIAL FOR HUMAN EXPOSURE

5.7.2 On-going Studies

No information was located on any on-going studies on the potential

for human exposure to BDCM.

As part of the Third National Health and Nutrition Evaluation

Survey (NHANES III), the Environmental Health Laboratory Sciences

Division of the Center for Environmental Health and Injury Control,

Centers for Disease Control, will be analyzing human blood samples for

BDCM 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.

51

6. ANALYTICAL METHODS

6.1 BIOLOGICAL MATERIALS

As a volatile organohalide, BDCM may be measured with good

sensitivity and specificity using gas-chromatographic methods employing

halide-specific or election-capture detection. Methods available for

separation of BDCM from biological samples prior to analysis include

headspace analysis, purge-and-trap collection, solvent extraction, and

direct collection on resins.

Headspace analysis offers speed, simplicity, and good

reproducibility for a particular type of sample. However, partitioning

of the analyte between the headspace and the sample matrix is dependent

upon the nature of the matrix and must be determined separately for

different kinds of matrices (Walters 1986).

Purge-and-trap collection is well suited to biological samples that

are soluble in water (Peoples et al. 1979), and is readily adapted from

techniques that have been developed for the analysis of BDCM and other

VOCs in water and wastewater. This method consists of bubbling inert

gas through a small volume of the sample and collecting the vapor in a

trap packed with sorbent. The analytes are then removed from the trap

by heating it and backflushing the analytes onto a gas chromatographic

column (Pankow et al. 1988). The two materials most widely used for

adsorption and thermal desorption of volatile organic compounds

collected by the purge-and-trap technique are Carbotrap, consisting of

graphitized carbon black, and Tenax,a porous polymer of 2,6-diphenyl-pphenylene oxide (Fabbri et al. 1987).

Solvent extraction of volatile components from biological fluids is

usually performed using dimethyl ether (Zlatkis and Kim 1976).

Homogenization of tissue with the extractant and lysing of cells

improves extraction efficiency. When, as is often the case, multiple

analytes are being determined using solvent extraction, selective

extraction and loss of low-boiling compounds can cause errors.

Supercritical fluid extraction using pure carbon dioxide or carbon

dioxide with additives offers some exciting potential for the extraction

of organic analytes such as BDCM from biological samples (Hawthorne

1988).

Analytical methods for the determination of BDCM in biological

samples are given in Table 6-1.

53

6. ANALYTICAL METHODS

6.2 ENVIRONMENTAL SAMPLES

BDCM may be isolated from environmental samples using the same

methods and principles used for biological samples, followed by gas

chromatographic analysis. The most convenient procedure for most liquid

and solid samples is the purge-and-trap method. A similar procedure is

used for air, involving passing the air through an adsorbent canister,

followed by thermal desorption.

Analytical methods for the determination of BDCM in environmental

samples are given in Table 6-2.

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 BDCM 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. Methods are available for the determination of

BDCM in biological samples, but there is a need for development of

validated standard methods of analysis with well-defined limits of

detection, such as those that exist for water and wastewater (EPA 1982a,

EPA 1982b) and for solid wastes (EPA 1986a, EPA 1986b).

Animal studies show that BDCM is excreted via the lungs as parent

compound or carbon dioxide. Small amounts of carbon monoxide have also

been measured in animals after administration of BDCM (Anders et al.

1978). Other metabolites of BDCM have not been identified. Since

carbon dioxide and carbon monoxide are not specific to BDCM, measurement

of these metabolites is not likely to provide a good index of BDCM

exposure.

55

6. ANALYTICAL METHODS

Methods for Biomarkers of Exposure. No biomarkers of exposure to

BDCM are currently known. By analogy with CCl4, it is possible that

BDCM may be metabolized to reactive intermediates that form covalent

adducts with cellular macromolecules. If so, immunoassays and 32 P-post

labeling assays might be capable of identifying and quantifying these

adducts, although levels would likely be very low. Efforts to identify

such adducts and to develop appropriate measurement techniques would be

valuable for determining exposure.

Methods for Determining Parent Compounds and Degradation Products

in Environmental Media. BDCM can be analyzed in water, air, and waste

samples with good selectivity and sensitivity. However, since BDCM may

be carcinogenic in humans, very low levels in water, air or other media

may be of concern, so improvements in sensitivity would be valuable.

6.3.2 On-going Studies

The development of supercritical fluid (SCF) extraction holds great

promise for analysis of nonpolar organic analytes such as BDCM. Current

research in this area has been summarized by Hawthorne (1988).

Research is ongoing to develop a "Master Analytical Scheme" for

organic compounds in water (Michael et al. 1988), which includes BDCM as

an analyte. The overall goal is to detect and quantify organic

compounds at 0.1 μg/L (1 ppb)in drinking water, 1 μg /L in surface

waters, and 10 μg/L in effluent waters. A comprehensive review of the

literature leading up to these efforts has been published (Pellizzari

et al. 1985).

The introduction of capillary column chromatography has markedly

improved both sensitivity and resolution of gas chromatographic

analysis, but because of the very small quantities of sample required,

has made sample delivery more difficult. One of the more promising

approaches to sample introduction using capillary columns with purgeandtrap collection is the use of cryofocusing. Basically, this

procedure consists of collecting purged analyte on a short section of

the capillary column cooled to a low temperature (e.g., -l00°C),

followed by heating and backflushing of the sample onto the analytical

column. Several compounds closely related to BDCM have been determined

in water by this method (Washall and Wampler 1988), including mefhylene

chloride, chloroform, chlorobromomethane and bromoform.
56

6. ANALYTICAL METHODS

Methods are also being developed for in situ measurement of

organohalide levels in water. This has been demonstrated for

chloroform-contaminated well water using remote fiber fluorimetry (RFF)

and fiber optic chemical sensors (FOGS) (Milanovich 1986). With this

approach, fluorescence of basic pyridine in the presence of organohalide

(the Fujiwara reaction) is measured from a chemical sensor immersed in

the water at the end of an optical fiber. If conditions can be found

under which BDCM undergoes a Fujiwara reaction, its determination might

be amendable to this approach.

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 BDCM 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.
57

7. REGULATIONS AND ADVISORIES

Because of its potential to cause adverse effects in exposed

people, a number of regulations and advisory values have been

established for BDCM by various national and state agencies. These

values are summarized in Table 7-1. No international values were

located.

59

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Tomasi A, Albano E, Biasi F, Slater TF, Vannini V, Dianzani MU. 1985.

Activation of chloroform and related trihalomethanes to free radical

intermediates in isolated hepatocytes and in the rat in vivo as

detected by the ESR-SPIN. Chem Biol Interact 55:303-316.

* Tumasonis CF, McMartin DN, Bush B. 1985. Lifetime toxicity of

chloroform and bromodichloromethane when administered over a lifetime

in rats. Ecotoxicol Environ Safety 9:233-240.

* Uhler AD, Diachenko GW. 1987. Volatile halocarbon compounds in process

water and processed foods. Bull Environ Contam Toxicol 39:601-607.
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8. REFERENCES

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systems. J Environ Syst 14:115-125.

* Verschueren K. 1977. Handbook of environmental data on organic

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* Verschueren K. 1983. Handbook of environmental data on organic

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* Walters SM. 1986. Cleanup of samples. In Zweig G, Sherman J, eds.

Analytical methods for pesticides and plant growth regulators, Vol 15.

Academic Press, New York, NY: 67-110.

* Washall JW, Wampler TP. 1988. Purge and trap analysis of aqueous

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* Weast RC, ed. 1985. CRC handbook of chemistry and physics. 66th ed.

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Carcinogenicity study in rats with a mixture of eleven volatile

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Williams DT, Nestmann ER, LeBel BL, et al. 1982. Determination of

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* Wilson JT, Enfield CG, Dunlap WJ, Cosby RL, Foster DA, Baskin LB. 1981.

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71

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 population 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.
72

9. GLOSSARY

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.

Immediately Dangerous to Life or Health (IDLH) -- The maximum

environmental concentration of a contaminant from which one could escape

within 30 min without any escape-impairing symptoms or irreversible

health effects.

Intermediate Exposure -- Exposure to a chemical for a duration of 15-364

days, as specified in the Toxicological Profiles.

Immunologic Toxicity -- The occurrence of adverse effects on the immune

system that may result from exposure to environmental agents such as

chemicals.

In vitro -- Isolated from the living organism and artificially

maintained, as in a test tube.

In vivo -- Occurring within the living organism.

Lethal Concentration (LO) (LCLO) -- The lowest concentration of a

chemical in air which has been reported to have caused death in humans

or animals.

Lethal Concentration (50) (LC50) -- A calculated concentration of a

chemical in air to which exposure for a specific length of time is

expected to cause death in 50% of a defined experimental animal

population.

Lethal Dose(LO) (LDLO) -- The lowest dose of a chemical introduced by a

route other than inhalation that is expected to have caused death in

humans or animals.
73

9. GLOSSARY

Lethal Dose (50) (LD50) -- 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 -- 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.

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,
74

9. GLOSSARY

q1* -- The upper-bound estimate of the low-dose slope of the doseresponse

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 μg/L for

water, mg/kg/day for food, and μg/m3

 for air).

Reference Dose (RfD) -- An estimate (with uncertainty spanning perhaps

an order of magnitude) of the daily exposure of the human population to

a potential hazard that is likely to be without risk of deleterious

effects during a lifetime. The RfD is operationally derived from the

NOAEL (from animal and human studies) by a consistent application of

uncertainty factors that reflect various types of data used to estimate

RfDs and an additional modifying factor, which is based on a

professional judgment of the entire database on the chemical. The RfDs

are not applicable to nonthreshold effects such as cancer.

Reportable Quantity (RQ) -- The quantity of a hazardous substance that

is considered reportable under CERCLA. Reportable quantities are: (1) 1

lb or greater or (2) for selected substances, an amount established by

regulation either under CERCLA or under Sect. 311 of the Clean Water

Act. Quantities are measured over a 24-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.

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.
75

9. GLOSSARY

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 in 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.

77

APPENDIX: PEER REVIEW

A peer review panel was assembled for BDCM. The panel consisted of

the following members: Dr. Sheldon Murphy, Professor of Environmental

Health, University of Washington; Dr. Joseph Gould, Research Scientist,

Georgia Institute of Technology; Dr. Nancy Reiches, Director of

Research, Riverside Methodist Hospital, Columbus, Ohio; and

Dr. Sanford Bigelow, President, MultiSciences, Inc. These experts

collectively have knowledge of BDCM'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 1991 –535-152/