TOXICOLOGICAL PROFILE FOR
 

METHYL MERCAPTAN
 

Agency for Toxic Substances and Disease Registry
 

U.S. Public Health Service
 

September 1992
 
ii
 

DISCLAIMER
 

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

not imply endorsement by the Agency for Toxic Substances and Disease Registry.
 










1
 

1. PUBLIC HEALTH STATEMENT
 

This Statement was prepared to give you information about methyl
 

mercaptan and to emphasize the human health effects that may result from
 

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

1,300 sites on its National Priorities List (NPL). Methyl mercaptan has been
 

found in at least 2 of these sites. However, we do not know how many of the
 

1,300 NPL sites have been evaluated for methyl mercaptan. As EPA evaluates
 

more sites, the number of sites at which methyl mercaptan is found may change.
 

This information is important for you to know because methyl mercaptan may
 

cause harmful health effects and because these sites are potential or actual
 

sources of human exposure to methyl mercaptan.
 

When a chemical is released from a source, such as an industrial plant,
 

or from a container, such as a drum or bottle, it enters the environment as a
 

chemical emission. This emission, which is also called a release, does not
 

always lead to exposure. You can be exposed to a chemical only when you come
 

into contact with the chemical. You may be exposed to it in the environment
 

by breathing, eating, or drinking substances containing the chemical or from
 

skin contact with it.
 

If you are exposed to a hazardous chemical such as methyl mercaptan,
 

several factors will determine whether harmful health effects will occur and
 

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

include the dose (how much), the duration (how long), the route or pathway by
 

which you are exposed (breathing, eating, drinking, or skin contact), the
 

other chemicals to which you are exposed, and your individual characteristics
 

such as age, sex, nutritional status, family traits, life style, and state of
 

health.
 

1.1 WHAT IS METHYL MERCAPTAN?
 

Methyl mercaptan, also known as methanethiol, is a colorless gas with a
 

smell like rotten cabbage. It is a natural substance found in the blood,
 

brain, and other tissues of humans and other animals, and it is released from
 

animal feces. It occurs naturally in certain foods such as some nuts
 

(filberts) and cheese (Beaufort).
 

Methyl mercaptan is released from decaying organic matter in marshes and
 

is present in the natural gas of certain regions of the United States, in coal
 

tar, and in some crude oils. Methyl mercaptan is manufactured for use in
 

pesticides, as a jet fuel additive, in the plastics industry, and in making
 

methionine, a nutrient that is added to poultry feed. Methyl mercaptan is
 

also released as a decay product of wood in pulp mills.
 

We know very little about what happens to methyl mercaptan after it is
 

released to the environment. Because it is a gas, most of it probably goes
 

into the air. Sunlight can break it down into other substances. If methyl
 

mercaptan is released to soil, it probably then goes into the air or is
 
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1. PUBLIC HEALTH STATEMENT
 

carried through the soil by rain or any other water that contacts it. More
 

information on the properties and uses of methyl mercaptan and how it behaves
 

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

1.2 HOW MIGHT I BE EXPOSED TO METHYL MERCAPTAN?
 

Methyl mercaptan is always present in your body and in your urine and
 

feces. It can also be present in the breath of persons with liver damage.
 

You can be exposed to methyl mercaptan in the air if you live near a natural
 

source of this gas, such as a marsh, an underground gas pocket, or a dump site
 

that releases it. We have no information on the levels of methyl mercaptan that
 

come from these sources.
 

Methyl mercaptan has not been found in drinking water, so you would
 

probably not be exposed to it in this way. Methyl mercaptan is a natural part
 

of certain foods, such as nuts and cheeses. It has also been approved for use
 

as a food additive. Because of its unpleasant smell, very little can be added
 

to food. You could be exposed to small amounts of methyl mercaptan by eating
 

foods that contain it. However, we have no information on the levels of
 

methyl mercaptan in food.
 

You can be exposed to methyl mercaptan if you work at a wood-pulp mill
 

or sewage treatment plant or if you work in a factory that uses it to make
 

other products such as jet fuel, pesticides, or poultry feed. Measurements of
 

methyl mercaptan in the air inside these mills were lower than 4 ppm (4 parts
 

of methyl mercaptan per million parts of air). Methyl mercaptan has been
 

found in the environmental air at 4 ppb (4 parts of methyl mercaptan per
 

billion parts of air).
 

Levels of methyl mercaptan in soil are probably very low. Even at
 

hazardous waste sites, the levels were about 83 ppb. More information on how
 

you might be exposed to methyl mercaptan is given in Chapter 5.
 

1.3 HOW CAN METHYL MERCAPTAN ENTER AND LEAVE MY BODY?
 

Methyl mercaptan can enter your body when you breathe in air or eat food
 

that contains this chemical. We do not know if methyl mercaptan can enter your
 

body through the skin or what happens to it after it enters your body. Studies
 

in rats suggested it leaves the body quickly. After methyl mercaptan reaches
 

the blood, it is either breathed out unchanged or is broken down to other
 

substances (within one hour). These substances may be breathed out from the
 

lungs or leave the body with the urine within a few hours.
 

More information on how methyl mercaptan enters and leaves the body is
 

given in Chapter 2.
 
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1. PUBLIC HEALTH STATEMENT
 

1.4 HOW CAN METHYL MERCAPTAN AFFECT MY HEALTH?
 

We have very little information on the health effects of exposure to
 

methyl mercaptan. A worker exposed to very high levels (exact amount unknown)
 

of this compound for several days when he opened and emptied tanks of methyl
 

mercaptan went into a coma (became unconscious), developed anemia (a blood
 

disorder) and internal bleeding. He died within a month after this incident.
 

We do not know whether long-term exposure of humans to low levels of
 

methyl mercaptan can result in harmful health effects such as cancer, birth
 

defects, or problems with reproduction.
 

Methyl mercaptan can be smelled and recognized in air when it is there
 

at a level of about 1.6 ppb (1.6 parts of methyl mercaptan per billion parts
 

of air). It can be smelled when it is present in water at a level far lower
 

than 1 ppb.
 

More information on the health effects of methyl mercaptan in humans and
 

animals can be found in Chapter 2.
 

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

EXPOSED TO METHYL MERCAPTAN?
 

Methyl mercaptan is always present in your body. There is a test that
 

can be used to find out if it is present in your blood at levels that are
 

higher than normal, which may happen if you are exposed to high levels of this
 

substance. This test requires special equipment and is not usually available in
 

a doctor's office. It can be done in a special laboratory. However, this test
 

cannot be used to find out how much methyl mercaptan you were exposed to or to
 

predict whether harmful health effects will occur.
 

More information on how methyl mercaptan can be measured in exposed
 

humans is given in Chapters 2 and 6.
 

1.6 WHAT RECOMMENDATIONS HAS THE FEDERAL GOVERNMENT MADE TO
 

PROTECT HUMAN HEALTH?
 

The federal government has set certain regulations and guidelines to
 

help protect people from the possible harmful health effects of methyl
 

mercaptan in the environment. When more than 100 pounds of methyl mercaptan
 

is released to the environment (such as during an industrial accident or
 

spill), the EPA National Response Center must be notified. The Food and Drug
 

Administration (FDA) allows methyl mercaptan to be used as a food additive but
 

does not set specific limits on the levels that can be used. The Occupational
 

Safety and Health Administration (OSHA) has set an average limit of 0.5 ppm for
 

exposure to this chemical in workplace air. The American Conference of
 
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1. PUBLIC HEALTH STATEMENT
 

Governmental Industrial Hygienists (ACGIH) has recommended that the average
 

concentration of airborne methyl mercaptan should not be more than 0.5 ppm for
 

each 8-hour exposure (time-weighted average) in a 40-hour work week.
 

More information on governmental rules for methyl mercaptan can be found
 

in Chapter 7.
 

1.7 WHERE CAN I GET MORE INFORMATION?
 

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

contact your state health or environmental department or:
 

Agency for Toxic Substances and Disease Registry
 

Division of Toxicology
 

1600 Clifton Road, E-29
 

Atlanta, Georgia 30333
 

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

nearest occupational and environmental health clinic. Such clinics specialize
 

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

hazardous substances.
 
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2. HEALTH EFFECTS
 

2.1 INTRODUCTION
 

The primary purpose of this chapter is to provide public health
 

officials, physicians, toxicologists, and other interested individuals and
 

groups with an overall perspective of the toxicology of methyl mercaptan and a
 

depiction of significant exposure levels associated with various adverse
 

health effects. It contains descriptions and evaluations of studies and
 

presents levels of significant exposure for methyl mercaptan based on
 

toxicological studies and epidemiological investigations.
 

2.2 DISCUSSION OF HEALTH EFFECTS BY ROUTE OF EXPOSURE
 

To help public health professionals address the needs of persons living
 

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

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

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

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

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

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

Levels of significant exposure for each route and duration are presented
 

in tables and illustrated in figures. The points in the figures showing noobserved-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. They should
 

also help to determine whether or not the effects vary with dose and/or
 

duration, and place into perspective the possible significance of these effects
 

to human health.
 

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

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

concerned with the interpretation of clinical findings in exposed persons may
 

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

health officials and project managers concerned with appropriate actions to
 

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

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

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

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

interest to health professionals and citizens alike.
 

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

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

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

variability from laboratory animal data to humans.
 
 

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2. HEALTH EFFECTS
 

Although methods have been established to derive these levels (Barnes
 

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

Furthermore, ATSDR acknowledges additional uncertainties inherent in the
 

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

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

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

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

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

significant human exposure improve, these MRLs will be revised.
 

2.2.1 Inhalation Exposure
 

Very little information is available on the health effects in humans or
 

experimental animals after inhalation exposure to methyl mercaptan. Most
 

studies of occupational exposure to methyl mercaptan in the pulp industry also
 

involve exposure to other sulfur-containing compounds such as hydrogen sulfide,
 

dimethyl sulfide, and sulfur dioxide as well as to methyl mercaptan (Kangas et
 

al. 1984).
 

2.2.1.1 Death
 

A single case of death resulting from occupational exposure to methyl
 

mercaptan has been located. A 53-year-old Black male laborer worked for about
 

1 week emptying tanks containing methyl mercaptan. No details of exposure
 

level were available; however, it is assumed that both inhalation and dermal
 

exposure were probably involved. The man was hospitalized in a coma,
 

developed hemolytic anemia and methemoglobinemia, and died 28 days after
 

admission (Shults et al. 1970). The immediate cause of death was determined
 

to be a massive embolus that occluded both main pulmonary arteries.
 

An LC50 of 675 ppm was reported for male and female rats exposed to 

methyl mercaptan for 4 hours (Tansy et al. 1981). However, no deaths (O/10) 

occurred in rats exposed to 400 ppm for 4 hours, and there was 100% mortality 

at 700 ppm and above. These authors also reported that no mortality was 

observed in male rats exposed to methyl mercaptan at doses up to 57 ppm for 

3 months. 

The highest NOAEL values and an LC50 for rats in each duration category 

are recorded in Table 2-l and plotted in Figure 2-1. 

2.2.1.2 Systemic Effects
 

Based on the available information, effects on body weight are the only
 

systemic effects that can be clearly associated with inhalation exposure to
 

methyl mercaptan. No studies were located regarding musculoskeletal effects in
 

humans or animals after inhalation exposure to methyl mercaptan.
 


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2. HEALTH EFFECTS
 

A NOAEL and a reliable LOAEL for systemic effects in rats in the
 

intermediate-duration category are recorded in Table 2-1 and plotted in
 

Figure 2-l.
 

Respiratory Effects. No studies have been located that would be useful
 

in assessing the potential effects on the respiratory system in humans
 

breathing methyl mercaptan. Irritation of mucous membranes of the nose and
 

respiratory tract have been reported by workers exposed to mercaptans in
 

general (Key et al. 1977).
 

No compound-related histopathological changes were observed in the lungs
 

of male rats exposed to methyl mercaptan at doses up to 57 ppm, 7 hours/day, 5
 

days/week, for 3 months (Tansy et al. 1981).
 

Cardiovascular Effects. Increased pulse rate and blood pressure were
 

reported by Shults et al. (1970) in a 53-year-old comatose patient who had
 

been working with tanks of methyl mercaptan. Exposure level data were not
 

available.
 

No histopathological changes were found in the hearts of male rats
 

exposed to methyl mercaptan at levels up to 57 ppm, 7 hours/day, 5 days/week,
 

for 3 months (Tansy et al. 1981).
 

Gastrointestinal Effects. No studies were located regarding
 

gastrointestinal effects in humans after inhalation exposure to methyl
 

mercaptan.
 

No evidence of histopathological changes was found in the small
 

intestines of male rats exposed to methyl mercaptan at levels up to 57 ppm,
 

7 hours/day, 5 days/week, for 3 months (Tansy et al. 1981). Intestinal
 

transit performance, as measured by the amount of small intestine traversed in
 

30 minutes, was not found to be affected by exposure in this study. There
 

was, however, a statistically significant dose-related decrease in the length
 

of the small intestines at 17 ppm and above. However, the clinical
 

significance of this observation is not clear, and it is not viewed as a
 

serious adverse effect.
 

Hematological Effects. The only information on hematologic effects
 

resulting from human inhalation and presumably dermal exposure to methyl
 

mercaptan is a case report by Shults et al. (1970). A Black 53-year-old
 

worker who had been handling and emptying tanks of methyl mercaptan for about
 

1 week became comatose and developed methemoglobinemia and hemolytic anemia
 

before his death. After transfusions, these conditions were reversed. The
 

authors postulated that the hemolysis may have been due to the oxidant effect
 

of methyl mercaptan on erythrocytes in a person who was deficient in
 

glucose-6-phosphate dehydrogenase (G-6-PD). An inherited deficiency of this
 
10
 

2. HEALTH EFFECTS
 

enzyme may be common in American Blacks (Calabrese 1986; Goldstein et al.
 

1974; Shannon and Buchanan 1982). This worker was found to have some degree
 

of G-6-PD deficiency (Shults et al. 1970).
 

No studies were located regarding hematological effects in animals after
 

inhalation exposure to methyl mercaptan.
 

Hepatic Effects. No studies were located regarding hepatic effects in
 

humans after inhalation exposure to methyl mercaptan.
 

In male rats exposed to methyl mercaptan at levels up to 57 ppm,
 

7 hours/day, 5 days/week, for 3 months, no compound-related histopathologic
 

changes of the liver were noted (Tansy et al. 1981). The authors stated that
 

results of blood chemistry studies (i.e., increased total protein with
 

decreased serum albumin) were suggestive of liver damage, but that dehydration
 

could not be ruled out as the cause.
 

Renal Effects. No studies were located regarding renal effects in
 

humans after inhalation exposure to methyl mercaptan. Shults et al. (1970)
 

reported that bilateral polycystic kidneys were found during the autopsy of a
 

53-year-old man who died after working with tanks of methyl mercaptan.
 

However, it is possible that this was a pre-existing condition.
 

No compound-related histopathologic changes in the kidneys of male rats
 

exposed to methyl mercaptan at levels up to 57 ppm, 7 hours/day, 5 days/week,
 

for 3 months (Tansy et al. 1981).
 

Dermal/Ocular Effects. Irritation of the skin and eyes have been
 

reported by workers occupationally exposed to mercaptans in general (Key
 

et al. 1977). However, there is no available information that is specifically
 

related to methyl mercaptan.
 

No studies were located regarding dermal or ocular effects in animals
 

after inhalation exposure to methyl mercaptan.
 

Other Systemic Effects. No studies were located regarding other
 

systemic effects in humans after inhalation exposure to methyl mercaptan.
 

Male rats exposed to methyl mercaptan at 57 ppm for 7 hours/day, 5 days/week,
 

for 3 months had significantly decreased body weights (Tansy et al. 1981).
 

This effect was not observed in rats exposed to 17 ppm and below. Decreased
 

levels of food consumption were not observed in rats in the 57-ppm dose group.
 

2.2.1.3 Immunological Effects
 

No studies were located regarding immunological effects in humans or
 

animals after inhalation exposure to methyl mercaptan.
 
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2. HEALTH EFFECTS
 

2.2.1.4 Neurological Effects
 

The only available information on neurological effects in humans exposed
 

to methyl mercaptan via inhalation is from a case study by Shults et al.
 

(1970). A 53-year-old man went into an irreversible coma after emptying tanks
 

of methyl mercaptan for about 1 week. Levels of exposure were not estimated.The
 

authors also noted minimal movement in response to painful stimuli,
 

hypoactivity of all deep tendon reflexes, and seizure activity. The patient
 

died about one month after the onset of this coma.
 

Fifteen-minute exposures to methyl mercaptan at 1,400 ppm have been
 

found to result in lethargy or coma in rats (Zieve et al. 1974). Exposures to
 

1,200 ppm and below did not result in either of these conditions. A methyl
 

mercaptan concentration of 0.5 nmol/mL in the blood was identified as the
 

level associated with coma. This study also demonstrated that the doses of
 

intraperitoneally injected ammonium acetate or sodium octanoate needed to
 

induce hepatic coma (coma following acute necrosis of the liver) were greatly
 

reduced when animals were exposed to methyl mercaptan at 1,200 ppm within
 

1 minute after injection. (However, hepatic effects were not actually
 

demonstrated in this study.) The authors suggested that methyl mercaptan
 

exposure may intensify the toxic effects of ammonia and fatty acids in human
 

hepatic failure.
 

These values are recorded in Table 2-l and plotted in Figure 2-l.
 

No studies were located regarding the following health effects in humans
 

or animals after inhalation exposure to methyl mercaptan:
 

2.2.1.5 Developmental Effects
 

2.2.1.6 Reproductive Effects
 

2.2.1.7 Genotoxic Effects
 

2.2.1.8 Cancer
 

2.2.2 Oral Exposure
 

No studies were located regarding the following health effects in humans
 

or animals after oral exposure to methyl mercaptan:
 

2.2.2.1 Death
 

2.2.2.2 Systemic Effects
 

2.2.2.3 Immunological Effects
 

2.2.2.4 Neurological Effects
 

2.2.2.5 Developmental Effects
 

2.2.2.6 Reproductive Effects
 

2.2.2.7 Genotoxic Effects
 

2.2.2.8 Cancer
 
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2. HEALTH EFFECTS
 

2.2.3 Dermal Exposure
 

Occupational exposure as reported in the case study by Shults et al.
 

(1970) may have involved dermal exposure since the victim's wife noted a
 

repugnant odor on his clothes; however, there is not enough information to
 

assess this possibility.
 

No studies were located regarding the following health effects in humans
 

or animals after dermal exposure to methyl mercaptan:
 

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
 

2.2.4 Other Routes of Exposure
 

Because the available data on the toxicity of methyl mercaptan via
 

inhalation, oral, or dermal exposure are extremely limited, studies conducted
 

via intraperitoneal exposure have also been considered. These studies are
 

also limited in number and scope, and serve only to provide additional
 

evidence that coma is associated with exposure to this chemical.
 

2.2.4.1 Death
 

No information is available on the levels of methyl mercaptan
 

administered to animals via intraperitoneal injection that would result in
 

death. Studies described in Section 2.2.4.4 have resulted in coma in the test
 

animals; however, recovery and/or death in response to these injections were
 

not among the topics of investigation.
 

2.2.4.2 Systemic Effects
 

No studies were located regarding respiratory, cardiovascular,
 

gastrointestinal, hematological, musculoskeletal, hepatic, renal, or
 

dermal/ocular effects in humans or animals after intraperitoneal exposure to
 

methyl mercaptan.
 

2.2.4.3 Immunological Effects
 

No studies were located regarding immunological effects in humans or
 

animals after intraperitoneal exposure to methyl mercaptan.
 
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2. HEALTH EFFECTS
 

2.2.4.4 Neurological Effects
 

Two studies that investigated the neurological effects of
 

intraperitoneal administration of methyl mercaptan have been located. An
 

injection equivalent to 4.8 mg/kg was sufficient to induce coma in 100% of
 

treated rats in 2-4 minutes (Zieve et al. 1984). In germ-free rats
 

administered methyl mercaptan at 9.6-28.8 mg/kg, 200 nmol/mL was the minimum
 

blood concentration associated with coma (Al Mardini et al. 1984). It is
 

interesting to note that this level was much higher than the blood level of
 

0.5 nmol/mL in comatose rats reported by Zieve et al. (1974) in inhalation
 

studies.
 

In addition, an important observation was made by Al Mardini et al.
 

(1984) who reported that blood methyl mercaptan concentrations were
 

significantly higher in patients with hepatic encephalopathy (coma) than in
 

normal subjects or patients with liver disease without encephalopathy.
 

(Methyl mercaptan was not administered to any of these persons, but presumably
 

resulted from the endogenous breakdown of methionine.) Methyl mercaptan
 

concentrations were also higher (but not significantly) in the blood of liver
 

disease patients without encephalopathy than in normal subjects. These
 

findings, combined with the observations of Zieve et al. (1974) in rats with
 

liver damage from ammonium ion or octanoate (Section 2.2.1.4), suggest that
 

persons with existing liver damage may already have elevated blood levels
 

ofmethyl mercaptan and thus may be at greater risk for the neurological effects
 

of exposure to exogenous methyl mercaptan than would be persons with normal
 

livers.
 

No studies were located regarding the following health effects in humans
 

or animals after intraperitoneal exposure to methyl mercaptan:
 

2.2.4.5 Developmental Effects
 

2.2.4.6 Reproductive Effects
 

2.2.4.7 Genotoxic Effects
 

2.2.4.8 Cancer
 

2.3 TOXICOKINETICS
 

The only studies located on the toxicokinetics of methyl mercaptan have
 

been conducted via the intraperitoneal route. There is indirect evidence of
 

absorption of methyl mercaptan by humans in a human case study and by rats in
 

a toxicity study.
 

2.3.1 Absorption
 

2.3.1.1 Inhalation Exposure
 

Based on adverse effects (hemolysis, methemoglobinemia, coma, and
 

death)reported in a 53-year-old worker exposed to methyl mercaptan via
 

inhalation
 
14
 

2. HEALTH EFFECTS
 

(Shults et al. 1970) and on the induction of coma in rats exposed to 1,400 ppm
 

(Zieve et al. 1974), it can be inferred that absorption occurs via this route
 

of exposure. No other data are available.
 

2.3.1.2 Oral Exposure
 

No studies were located regarding absorption in humans or animals after
 

oral exposure to methyl mercaptan.
 

2.3.1.3 Dermal Exposure
 

No studies were located regarding absorption in humans or animals after
 

dermal exposure to methyl mercaptan.
 

2.3.2 Distribution
 

No studies were located regarding distribution in humans or animals
 

after exposure to methyl mercaptan via the following routes:
 

2.3.2.1 Inhalation Exposure
 

2.3.2.2 Oral Exposure
 

2.3.2.3 Dermal Exposure
 

2.3.2.4 Other Routes of Exposure
 

After injection of 14C- or 35S-labeled methyl mercaptan into rats,
 

distribution of the radioactivity that remained in the body (from either the
 

14C or 35S label) after 6 hours was: 22.7% in plasma proteins, 17.8% in the
 

liver, 16.7% in the intestinal mucosa, 11.5% in the lungs, 11.4% in the
 

kidneys, 9.8% in the spleen, 8.5% in the testes, and 0% in the erythrocytes
 

(Canellakis and Tarver 1953). No other information on the distribution of
 

methyl mercaptan was located.
 

2.3.3 Metabolism
 

Information on the metabolism of methyl mercaptan is available only in
 

studies in rodents using intraperitoneal administration. Susman et al. (1978)
 

injected methyl mercaptan into one mouse and found the unchanged compound and
 

dimethyl sulfide in the expired breath.
 

In rats, intraperitoneal administration of methyl mercaptan resulted in
 

the excretion of CO2 and volatile sulfur-containing compounds in the expired
 

breath (Canellakis and Tarver 1953). The 35S from labeled methyl mercaptan
 

in injected rats could be found mostly (94%) as 35S04 in urine (Derr and
 

Draves 1983, 1984).
 

1
 
15
 

2. HEALTH EFFECTS
 

Methyl mercaptan is an intermediate in the catabolism of the amino acid
 

methionine (Blom et al. 1988, 1989). These in vitro studies were conducted
 

with the blood of methionine-loaded patients and with human and rat
 

hepatocytes. Blom and Tangerman (1988) found that, in whole blood, methyl
 

mercaptan is oxidized by the erythrocytes, the carbon-sulfur bond is split,
 

and the resulting products are formic acid, sulfite ion, and sulfate ion.
 

2.3.4 Excretion
 

No studies were located regarding excretion by humans or animals after
 

exposure to methyl mercaptan via the following routes:
 

2.3.4.1 Inhalation Exposure
 

2.3.4.2 Oral Exposure
 

2.3.4.3 Dermal Exposure
 

2.3.4.4 Other Routes of Exposure
 

The only information available on the excretion of methyl mercaptan or 

its metabolites is found in studies in rats conducted via intraperitoneal 

administration. Within 6 hours after administration of 14C-methyl mercaptan, 

more than 40% of the administered 14C was recovered as CO2 (presumed to result 

solely from pulmonary excretion) (Canellakis and Tarver 1953). Another 6.4% was 

excreted in 1 hour in volatile sulfur compounds (route not stated), and 2.3% 

was excreted in the urine within 6 hours. Within 8 hours after 

administration of 35S-methyl mercaptan, 32% of the administered 35S was 

recovered in sulfur compounds (mostly sulfates) in the urine. Derr and Draves 

(1983), however, found that within 21 hours, 94% of the 35S-label of 35S-methyl 

mercaptan intraperitoneally administered to rats was excreted in the urine. No 

data on fecal excretion have been located. 

2.4 RELEVANCE TO PUBLIC HEALTH
 

As discussed in Section 2.2, estimates of levels of exposure to methyl
 

mercaptan posing minimal risk to humans (MRLs) were to have been made, where
 

data were believed reliable, for the most sensitive noncancer effect for each
 

route and exposure duration. However, no MRLs could be derived for methyl
 

mercaptan. Available data on effects of acute-duration inhalation exposure to
 

methyl mercaptan in humans or animals suggests that neurological effects may
 

be the most sensitive indicator of toxicity, but this information does not
 

reliably identify the threshold for this effect. Available data on effects of
 

intermediate-duration inhalation exposure to methyl mercaptan in animals does
 

not identify the most sensitive effect or the threshold for adverse effects.
 

No data were located on effects of chronic-duration inhalation exposure to
 

methyl mercaptan in humans or animals. Therefore, no inhalation MRLs were
 

derived. No data were located on effects of acute-duration, intermediate
 

duration, or chronic-duration oral exposure to methyl mercaptan in humans or
 
16
 

2. HEALTH EFFECTS
 

animals, Therefore, no oral MRLs were derived. Acute-duration, intermediate
 

duration, and chronic-duration dermal MRLs were not derived for methyl
 

mercaptan due to the lack of an appropriate methodology for the development of
 

dermal MRLs.
 

The observations in a single human case study, combined with the results
 

of studies in animals, suggest that the principal health risk associated with
 

short-term exposure to high levels of methyl mercaptan is coma. Hematological
 

effects such as hemolytic anemia and methemoglobinemia may also result, but
 

there is less information on this topic. In total, the available database on
 

this chemical is so limited that the relevance of methyl mercaptan exposure to
 

public health cannot be determined.
 

Death. The accidental death of a 53-year-old worker who had been
 

handling tanks of methyl mercaptan for 1 week was reported by Shults et al.
 

(1970). After a month in a coma and despite aggressive medical intervention,
 

the patient died from a massive embolus that occluded both main pulmonary
 

arteries. The exposure level was not known or estimated. An LC50 of 675 ppm
 

was determined for a 4-hour exposure in rats (Tansy et al. 1981). However, no
 

deaths (O/10) occurred at 400 ppm. Exposure to 57 ppm for 3 months also
 

resulted in no deaths in rats. The available data indicate that high level
 

exposure to this substance, at least by inhalation, can be lethal to exposed
 

humans and animals.
 

Systemic Effects.
 

Hematological Effects. The major systemic effects reported in the case
 

study of the 53-year-old Black worker who died after acute inhalation exposure
 

to methyl mercaptan were methemoglobinemia and hemolytic anemia (Shults et al.
 

1970). The authors stated that the observed hemolysis may have been due to
 

oxidant stress to erythrocyte membranes with glucose-6-phosphate dehydrogenase
 

deficiency. In an analysis of hospital data on 14 Black children (aged 3 weeks
 

to 11 years) with hemolytic anemia, 7 of these patients were found to be
 

deficient in glucose-6-phosphate dehydrogenase in an initial screening test
 

(Shannon and Buchanan 1982). Similarly, methemoglobinemia susceptibility has
 

been attributed to this enzyme deficiency (Goldstein et al. 1974). It is
 

obviously not possible to draw firm conclusions from the single case study
 

presented by Shults et al. (1970) with no other studies in humans or animals to
 

provide evidence. However, that study does provide consistent preliminary
 

evidence for the potential for hematological effects resulting from inhalation
 

exposure to methyl mercaptan by an individual who may also be deficient in
 

erythrocytic glucose-6-phosphate dehydrogenase.
 

Other Systemic effects. The only systemic effect clearly associated with
 

methyl mercaptan in an animal study was a significant decrease in body weight
 

in rats exposed to methyl mercaptan by inhalation at 57 ppm for 3 months (Tansy
 

et al. 1981). This suggests that effects on body weight may be of concern for
 

humans exposed to methyl mercaptan.
 
17
 

2. HEALTH EFFECTS
 

Immunological Effects. There is currently no information in humans or
 

animals to suggest that exposure to methyl mercaptan is associated with
 

immunological effects.
 

Neurological Effects. The main neurotoxic effect reported in a human
 

exposed to methyl mercaptan at high levels is coma. Shults et al. (1970)
 

reported that a 53-year-old worker who had been working with tanks of methyl
 

mercaptan for about a week went into an irreversible coma accompanied by
 

convulsions and died about 1 month later. Rats exposed via inhalation to
 

methyl mercaptan at 1,400 ppm, but not 1,200 ppm or below, for 15 minutes
 

became lethargic or comatose (Zieve et al. 1974). Intraperitoneal injections
 

of methyl mercaptan in rats can also induce coma (Al Mardini et al. 1984;
 

Zieve et al. 1984). Although this route of administration is not relevant to
 

potential human exposure to this compound, these studies serve to provide
 

additional evidence that neurological effects are a major risk when methyl
 

mercaptan is absorbed by humans.
 

Developmental Effects. There is currently no information in humans or
 

animals to suggest that exposure to methyl mercaptan is associated with
 

developmental effects, therefore the relevance to human health is not known.
 

Reproductive Effects. There is currently no information in humans or
 

animals to suggest that exposure to methyl mercaptan is associated with
 

reproductive effects, therefore the relevance to human health is not known.
 

Genotoxic Effects. There is currently no information in humans or
 

animals to suggest that exposure to methyl mercaptan is associated with
 

genotoxic effects, therefore the relevance to human health is not known.
 

Cancer. There is currently no information in humans or animals to
 

suggest that exposure to methyl mercaptan is associated with cancer effects,
 

therefore the relevance to human health is not known.
 

2.5 BIOMAREERS OF EXPOSURE AND EFFECT
 

Biomarkers are broadly defined as indicators signaling events in
 

biologic systems or samples. They have been classified as markers of
 

exposure, markers of effect, and markers of susceptibility (NAS/NRC 1989).
 

A biomarker of exposure is a xenobiotic substance or its metabolite(s)
 

or the product of an interaction between a xenobiotic agent and some target
 

molecule(s) or cell(s) that is measured within a compartment of an organism
 

(NAS/NRC 1989). The preferred biomarkers of exposure are generally the
 

substance itself or substance-specific metabolites in readily obtainable body
 

fluid(s) or excreta. However, several factors can confound the use and
 

interpretation of biomarkers of exposure. The body burden of a substance may
 

be the result of exposures from more than one source. The substance being
 

measured may be a metabolite of another xenobiotic substance (e.g., high
 
18
 

2. HEALTH EFFECTS
 

urinary levels of phenol can result from exposure to several different
 

aromatic compounds). Depending on the properties of the substance (e.g.,
 

biologic half-life) and environmental conditions (e.g., duration and route of
 

exposure), the substance and all of its metabolites may have left the body by
 

the time biologic samples can be taken. It may be difficult to identify
 

individuals exposed to hazardous substances that are commonly found in body
 

tissues and fluids (e.g., essential mineral nutrients such as copper, zinc,
 

and selenium). Biomarkers of exposure to methyl mercaptan are discussed in
 

Section 2.5.1.
 

Biomarkers of effect are defined as any measurable biochemical,
 

physiologic, or other alteration within an organism that, depending on
 

magnitude, can be recognized as an established or potential health impairment
 

or disease (NAS/NRC 1989). This definition encompasses biochemical or
 

cellular signals of tissue dysfunction (e.g., increased liver enzyme activity
 

or pathologic changes in female genital epithelial cells), as well physiologic
 

signs of dysfunction such as increased blood pressure or decreased lung
 

capacity. Note that these markers are often not substance specific. They also
 

may not be directly adverse, but can indicate potential health impairment
 

(e.g., DNA adducts). Biomarkers of effects caused by methyl mercaptan are
 

discussed in Section 2.5.2.
 

A biomarker of susceptibility is an indicator of an inherent or acquired
 

limitation of an organism's ability to respond to the challenge of exposure to
 

a specific xenobiotic substance. It can be an intrinsic genetic or other
 

characteristic or a preexisting disease that results in an increase in absorbed
 

dose, biologically effective dose, or target tissue response. If
 

biomarkers of susceptibility exist, they are discussed in Section 2.7,
 

"POPULATIONS THAT ARE UNUSUALLY SUSCEPTIBLE."
 

2.5.1 Biomarkers Used to Identify and/or Quantify Exposure to
 

Methyl Mercaptan
 

Methyl mercaptan itself and its metabolites, carbon dioxide and sulfate,
 

can be measured in human tissues, fluid, and excreta. However, these
 

compounds are always present in these media regardless of exposure to methyl
 

mercaptan. Elevated blood levels of methyl mercaptan may be detected in
 

persons who have recently been exposed to it, or in nonexposed persons with
 

liver disease or in hepatic coma (Al Mardini et al. 1984; Challenger and
 

Walshe 1955; Zieve 1981). In cases of liver damage, these elevated levels may
 

be the result, rather than the cause, of liver problems.
 

The best indication of exposure to methyl mercaptan would probably be a
 

combination of elevated levels of the substance itself in the breath and blood
 

along with evidence or suspicion of exposure from environmental sources. There
 

are currently no subtle or sensitive biomarkers of effects associated with
 

exposure to methyl mercaptan.
 
19
 

2. HEALTH EFFECTS
 

2.5.2 Biomarkers Used to Characterize Effects Caused by Methyl Mercaptan
 

As stated previously, no subtle or sensitive biomarkers of effects
 

associated with exposure to methyl mercaptan have been identified.
 

2.6 INTERACTIONS WITH OTHER CHEMICALS
 

Interactions between mercaptans, including methyl mercaptan, and
 

Ammonium acetate or sodium octanoate in the induction of coma in rats has been
 

reported (Zieve et al. 1974). The dose of intraperitoneally injected ammonium
 

acetate required to induce coma in 50% of the rats was 1.45 mmols without
 

methyl mercaptan exposure but only 0.46 mmols when the animals were exposed to
 

methyl mercaptan via inhalation at 1,200 ppm within 1 minute after the
 

injection. Similarly, the dose of sodium octanoate decreased from 0.48 to
 

0.16 mmols to induce coma using the same procedures.
 

The condition induced in these rats was referred to as "hepatic coma"
 

(Zieve et al. 1974) because it was demonstrated in a previous study that
 

injection of an ammonium salt or fatty acid into rats resulted in coma
 

accompanied by massive hepatic necrosis. In the current study of synergism,
 

Zieve et al. (1974), hepatic damage was assumed but not demonstrated, and it
 

is not clear if methyl mercaptan exposure resulted in increased hepatic damage
 

in these rats. These results suggest, however, that human exposure to methyl
 

mercaptan in conjunction with hepatotoxins may result in exacerbated liver
 

damage and/or neurotoxicity. There is a possibility of these multiple
 

exposures in the workplace and in the vicinity of hazardous waste sites.
 

2.7 POPULATIONS THAT ARE UNUSUALLY SUSCEPTIBLE
 

A hemolytic response to methyl mercaptan exposure, as reported in the
 

case study by Shults et al. (1970), may be enhanced by the presence of
 

inherited erythrocytic glucose-6-phosphate dehydrogenase (G-6-PD) deficiency.
 

Although hemolysis may occur in any person who is exposed to a sufficiently
 

high dose of methyl mercaptan, this enzyme deficiency may cause some persons
 

to be unusually sensitive, since it results in an inability to maintain
 

reduced glutathione which is needed for the integrity of the erythrocyte
 

membrane (Goldstein et al. 1974). The incidence of the deficiency among
 

Caucasians of European origin is relatively low, whereas there is a higher
 

incidence among certain groups of Asians and Mediterranean (Italians,
 

Sardinians, Greeks), and Middle Eastern populations (Shannon and Buchanan
 

1982). A study of hemolytic anemia in American Black children with G-6-PD
 

deficiency by Shannon and Buchanan (1982) suggests that this is another
 

population that may be susceptible to the hemolytic effects of methyl
 

mercaptan exposure. Calabrese (1986) estimated that 16% of Black males are
 

G-6-PD-deficient; Berkow et al. (1982) estimated that 10% of American Black
 
20
 

2. HEALTH EFFECTS
 

males and fewer Black females have this deficiency. According to Shannon and
 

Buchanan (1982), a syndrome of acute severe hemolysis following exposure to
 

oxidative stress is associated with the Mediterranean variant of the
 

deficiency, whereas the hemolytic anemia seen in American Blacks is generally
 

mild.
 

The pattern of inheritance for G-6-PD deficiency is that of an
 

autonomous sex-linked defect (Berkow et al. 1982; Goldstein et al. 1974).
 

This is an X-linked disorder and is thus fully expressed in males who carry it
 

on their single X chromosome and in females who carry it on both X
 

chromosomes. Female heterozygotes (who have one normal and one defective gene
 

for this trait) have a wide variety of values for the enzyme which suggests
 

that other factors influence the degree to which this trait is influenced in
 

identical genotypes (Goldstein et al. 1974).
 

Studies by Zieve et al. (1974) and Al Mardini et al. (1984) suggest that
 

the major neurological effects of methyl mercaptan exposure (i.e., coma) may
 

occur at lower levels of this compound in persons with liver disease. Methyl
 

mercaptan levels may already be higher than normal in these persons and
 

additional exposure may bring their blood concentrations of this compound to a
 

more dangerous level.
 

2.8 MITIGATION OF EFFECTS
 

This section will describe clinical practice and research concerning methods
 

for reducing toxic effects of exposure to methyl mercaptan. However, because
 

some of the treatments discussed may be experimental and unproven, this
 

section should not be used as a guide for treatment of exposures to methyl
 

mercaptan. When specific exposures have occurred, poison control centers and
 

medical toxicologists should be consulted for medical advice.
 

Inhalation is the primary route of human exposure to methyl mercaptan,
 

although dermal absorption or ingestion of small amounts in food or water may
 

occur (see Chapter 5). General procedures following acute, high-level
 

exposure to methyl mercaptan consist of measures to reduce or eliminate
 

further absorption. Following inhalation exposure, these measures include
 

removal of the victim and administration of high-flow, humidified oxygen
 

(Bronstein and Currance 1988; Stutz and Janus2 1988). Following dermal and
 

ocular exposure, contaminated clothing is removed and the skin and eyes
 

thoroughly washed with water (Bronstein and Currance 1988; Stutz and Janusz
 

1988). Procedures used following acute, high-level oral exposure include
 

emptying the stomach, using care to avoid pulmonary aspiration of the gastric
 

contents, particularly in victims with severe nervous system depression or
 

seizures. Stomach emptying is followed by administration of activated
 

charcoal to bind the methyl mercaptan and a cathartic which may stimulate
 

fecal excretion (Stutz and Janusz 1988).
 
21
 

2. HEALTH EFFECTS
 

Supportive measures for symptoms induced by acute, high-level exposure to
 

methyl mercaptan include administration of anticonvulsant drugs to control
 

seizures (Stutz and Janusz 1988) and blood transfusion or alkaline diuresis to
 

alleviate effects of hemolysis (Shannon and Buchanan 1982; Shults et al.
 

1970). Supportive treatment for noncardiogenic pulmonary edema, central
 

nervous system depression, and hypertension with tachycardia may be required.
 

In patients with methemoglobinemia of approximately 30% or greater methylene
 

blue is administered to reduce methemoglobin levels (Ellenhorn and Barceloux
 

1988; Goldfrank et al. 1990). However, treatment of G-6-PD deficient
 

individuals with methylene blue may be contraindicated.
 

Limited information is available regarding the retention in the body or
 

metabolism of methyl mercaptan. Studies in animals demonstrate that carbon
 

dioxide and sulfate are the final metabolites found in the expired breath
 

and/or urine and that methyl mercaptan is cleared from the body within several
 

hours (Canellkis and Traver 1953; Derr and Draves 1983, 1984; Susman et al.
 

1978). Studies with human blood indicated that methyl mercaptan is oxidized in
 

erythrocytes yielding formic acid and sulfate ion as metabolites in urine (Blom
 

et al. 1988, 1989; Blom and Tangerman 1988). No method is commonly used to
 

enhance the elimination of the absorbed dose of methyl mercaptan.
 

Acute intoxication with methyl mercaptan may cause methemoglobinemia,
 

hemolytic anemia and neurological effects leading to lethargy, seizures, coma,
 

and death (see Section 2.2). However, because of the lack of information
 

regarding the mechanism of toxicity of methyl mercaptan, no specific method for
 

reducing its toxic effects is available.
 

2.9 ADEQUACY OF THE DATABASE
 

Section 104(i)(5) of CERCLA, as amended, directs the Administrator of
 

ATSDR (in consultation with the Administrator of EPA and agencies and programs
 

of the Public Health Service) to assess whether adequate information on the
 

health effects of methyl mercaptan is available. Where adequate information is
 

not available, ATSDR, in conjunction with the National Toxicology Program
 

(NTP), is required to assure the initiation of a program of research designed
 

to determine the health effects (and techniques for developing methods to
 

determine such health. effects) of methyl mercaptan.
 

The following categories of possible data needs have been identified by
 

a joint team of scientists from ATSDR, NTP, and EPA. They are defined as
 

substance-specific informational needs that, if met, would reduce or eliminate
 

the uncertainties of human health assessment. In the future, the identified
 

data needs will be evaluated and prioritized, and a substance-specific research
 

agenda will be proposed.
 
22
 

2. HEALTH EFFECTS
 

2.9.1 Existing Information on Health Effects of Methyl Mercaptan
 

The existing data on health effects of inhalation, oral, and dermal
 

exposure of humans and animals to methyl mercaptan are summarized in
 

Figure 2-2. The purpose of this figure is to illustrate the existing
 

information concerning the health effects of methyl mercaptan. Each dot in
 

the figure indicates that one or more studies provide information associated
 

with that particular effect. The dot does not imply anything about the
 

quality of the study or studies. Gaps in this figure should not be
 

interpreted as "data needs" information (i.e., data gaps that must necessarily
 

be filled).
 

Figure 2-2 graphically depicts the information that currently exists on
 

the health effects that have been observed or studied in humans and animals
 

following inhalation, oral, or dermal exposure to methyl mercaptan. There is
 

little information available on this chemical, and, therefore, almost any
 

additional information would probably be useful. This section, however, will
 

attempt to focus on those areas of investigation that would appear to be the
 

most useful for a chemical about which almost nothing is known.
 

2.9.2 Data Needs
 

Acute-Duration Exposure. The available information in humans and
 

animals suggests that the nervous system is the major target organ following
 

acute inhalation exposure (Shults et al. 1970; Zieve et al. 1974). However,
 

quantitative data were available in only one study in rats (Zieve et al.
 

1974)and this was not considered sufficient to calculate an MRL via this route,
 

and no studies conducted via the oral and dermal routes were available.
 

Although any new data for this exposure duration would be useful, estimates of
 

a lethaldose via inhalation would be most helpful, because a human death has
 

been reported as a result of occupational exposure. Currently, LC,, data are
 

available only for the rat (Tansy et al. 1981). Because there are no data on
 

absorption via the oral and dermal route, it is not known if toxicity studies
 

using these routes would be useful.
 

Intermediate-Duration Exposure. There are no data on humans exposed
 

tomethyl mercaptan for this duration period. A 3-month study in rats exposed to
 

methyl mercaptan via inhalation (Tansy et al. 1981) comprises virtually the
 

entire useful database for this compound and indicates that decreased body
 

weight is the only compound-related effect that was observed. Data were not
 

considered sufficient to calculate an inhalation MEL for this exposure
 

duration due to an inadequate database. There are no animal studies using the
 

oral route, and, therefore, an intermediate oral MRL has not been calculated.
 

Any further studies using either of these routes should use doses high enough
 

to elicit clinically evident neurological effects and should focus on
 

hematological effects such as hemolytic anemia and methemoglobinemia. The use
 

of an animal model that is susceptible to these hematological effects may be
 

24
 

2. HEALTH EFFECTS
 

the best choice for these tests. Dose-response information for these effects
 

would be useful in assessing the risks of persons exposed to methyl mercaptan
 

in the vicinity of hazardous waste sites and in the workplace. Studies via
 

the dermal route would also be useful if pharmacologic studies have
 

demonstrated that methyl mercaptan can be absorbed through the skin.
 

Chronic-Duration Exposure and Cancer. No chronic inhalation, oral, or
 

dermal studies in any species were located for methyl mercaptan. This appears
 

to be the most important category of duration for future study of this compound
 

because low level chronic exposure is likely to occur via the
 

inhalation route in occupational settings and in the vicinity of hazardous
 

waste sites. Although the entire population is exposed via the oral route
 

since methyl mercaptan is naturally present at low levels in certain foods,
 

this compound has not been reported in drinking water. Since the potential
 

for dermal exposure is not known, it is not clear if these studies would be
 

useful.
 

Evaluations of its carcinogenic potential via the oral and inhalation
 

routes would, therefore, also be useful. Studies using the dermal route would
 

be useful if dermal exposure were first demonstrated to occur in populations
 

living or working in the vicinity of methyl mercaptan emissions.
 

Genotoxicity. There are currently no genotoxicity data available in
 

humans or animals for methyl mercaptan. A battery of in vitro genotoxicity
 

tests would be useful as a preliminary step in determining its mutagenic
 

potential and the need for further testing.
 

Reproductive Toxicity. There are no available data on the reproductive
 

toxicity of methyl mercaptan in humans or animals via any route. Available data
 

indicate that when intraperitoneally injected into rats, some methyl mercaptan
 

is distributed to the testes (Canellakis and Tarver 1953). Based on this
 

observation, potential effects on reproductive organs and sperm count should be
 

considered in any future intermediate (go-day) or chronic durationstudies
 

conducted via any route. Studies via inhalation would probably be the most
 

relevant to assessing the potential effects on the fertility of men exposed in
 

the vicinity of hazardous waste sites or in occupational settings. This
 

information would probably also be useful in the development of MRLs for these
 

durations.
 

Developmental Toxicity. There are currently no available data on this end
 

point in humans or animals. A study in animals exposed via inhalation would be
 

useful in assessing the potential developmental effects on fetuses carried by
 

women exposed to methyl mercaptan in the vicinity of hazardous waste sites and
 

in occupational settings, since this is expected to be themain route of human
 

exposure.
 

Immunotoxicity. No studies related to the immunological effects of
 

methyl mercaptan in humans or animals have been located. Immunologic
 
25
 

2. HEALTH EFFECTS
 

assessments such as effects on peripheral white blood cell counts would
 

provide useful preliminary information on this end point, especially as a part
 

of intermediate or chronic duration exposure studies using the inhalation route
 

since this is the most likely route of exposure of persons in the vicinity of
 

hazardous waste sites and in occupational settings.
 

Neurotoxicity. The available information in humans and animals
 

indicates that high level exposure to methyl mercaptan via inhalation or
 

intraperitoneal injection can result in irreversible coma (Al Mardini et al.
 

1984; Shults et al. 1970; Tansy et al. 1981; Zieve et al. 1984). Animal
 

studies that describe neurological effects and assess morphological damage to
 

the brain associated with intermediate or chronic duration inhalation exposure
 

to methyl mercaptan at levels similar to those in the vicinity of hazardous
 

waste sites or in occupational settings would be extremely useful, since
 

inhalation is expected to be the main route of human exposure in those
 

settings.
 

Epidemiological and Human Dosimetry Studies. Occupational exposure to
 

methyl mercaptan, such as occurs in pulp mills, also involves exposure to other
 

sulfur-containing compounds such as hydrogen sulfide, sulfur dioxide, and
 

dimethyl sulfide. Epidemiological studies of such populations may not provide
 

useful data since observed effects may not clearly be attributable to methyl
 

mercaptan. Human dosimetry studies would be useful, however, because
 

measurement of levels of exposure to methyl mercaptan would help to indicate
 

whether humans were at risk for methyl mercaptan-induced effects associated
 

with those levels (assuming that this toxicity information would eventually
 

become available).
 

Biomarkers of Exposure and Effect. There are no sensitive biomarkers of
 

methyl mercaptan exposure. This would be useful information, especially for the
 

levels of this compound present in the vicinity of hazardous waste sites and in
 

occupational settings. However, because methyl mercaptan is always present in
 

the human body and blood levels can become elevated as a result of liver damage
 

(without exogenous exposure), progress in this area may not be forthcoming.
 

Currently, the only effect clearly associated with methyl mercaptan
 

toxicity is coma (Shults et al. 1970). The identification of more subtle
 

effects that might result from chronic low-level exposure would be useful.
 

Absorption, Distribution, Metabolism, and Excretion. There are no
 

toxicokinetic studies for methyl mercaptan via the inhalation, oral, or dermal
 

routes. These studies would be valuable for tracing its metabolic fate
 

following each route of exposure. Studies of absorption via the oral and
 

dermal routes may be useful in helping to determine if toxicity studies using
 

these routes are warranted.
 
26
 

2. HEALTH EFFECTS
 

Comparative Toxicokinetics. There is no available information on the
 

comparative toxicokinetics of methyl mercaptan. Although species differences
 

in response to methyl mercaptan exposure may exist, these studies may not be
 

useful until several other aspects of this chemical's toxicity are first
 

investigated. These comparisons would then serve as an aid in putting the
 

results of animal toxicity data into perspective in relation to its relevance
 

to potential human health effects.
 

Mitigation of effects. Recommended methods for the mitigation of acute
 

effects of methyl mercaptan poisoning include administration of oxygen if
 

exposure is by inhalation, or thorough washing of the skin and flushing the
 

eyes with water if exposure is to these organs (Bronstein and Currance 1988;
 

Stutz and Janusz 1988). Drugs may also be administered to control seizures and
 

transfusions to alleviate anemia. No information was located concerning
 

mitigation of effects of lower-level or longer-term exposure to methyl
 

mercaptan. Further information on techniques to mitigate such effects wouldbe
 

useful in determining the safety and effectiveness of possible methods for
 

treating methyl mercaptan-exposed populations surrounding hazardous waste
 

sites.
 

2.9.3 On-going Studies
 

No studies on toxicity, toxicokinetics, epidemiology, or other topics
 

discussed in Section 2.8.2, above are known to be in progress.
 
27
 

3. CHEMICAL AND PHYSICAL INFORMATION
 

3.1 CHEMICAL IDENTITY
 

Common synonyms, trade names, and other pertinent identification
 

information for methyl mercaptan are listed in Table 3-1.
 

3.2 PHYSICAL AND CHEMICAL PROPERTIES 

Important physical and chemical properties of methyl mercaptan are
 

listed in Table 3-2.
 



31
 

4. PRODUCTION, IMPORT, USE, AND DISPOSAL
 

4.1 PRODUCTION
 

Methyl mercaptan is produced commercially by the reaction of hydrogen
 

sulfide with methanol (Santodonato et al. 1985; Windholz 1983). Methyl
 

mercaptan is manufactured by the Organic Chemical Division of Pennwalt
 

Corporation in Beaumont and Houston, Texas. Production volumes for these
 

facilities were not located (SRI 1987, 1988, 1989).
 

4.2 IMPORT/EXPORT
 

No data were located regarding the import or export of methyl mercaptan.
 

4.3 USE
 

Methyl mercaptan is used as a chemical intermediate in the production of
 

jet fuel, certain pesticides, and plastics and in the synthesis of the amino
 

acid methionine (ACGIH 1986; HSDB 1989; Santodonato et al. 1985). Methyl
 

mercaptan is also used to add odor to certain odorless hazardous gases. Methyl
 

mercaptan is not one of the chemicals considered acceptable for use as an
 

odorant in natural gas (AGA 1983; HSDB 1989; Reid 1958; Santodonato et al.
 

1985; Windholz 1983).
 

4.4 DISPOSAL
 

Since methyl mercaptan is listed as a hazardous substance, disposal of
 

wastes containing methyl mercaptan is controlled by a number of federal
 

regulations (see Chapter 7). Land disposal restrictions for methyl mercaptan
 

are among those scheduled for promulgation in 1990 (40 CPR 268.12). Methyl
 

mercaptan may be disposed of by controlled incineration, and it is a potential
 

candidate for fluidized bed and rotary.kiln incineration (HSDB 1989). No
 

quantitative data were located on the amount of methyl mercaptan disposed of in
 

waste sites.
 

33
 

5. POTENTIAL FOR HUMAN EXPOSURE
 

5.1 OVERVIEW
 

Methyl mercaptan is a naturally occurring gaseous compound produced as a
 

result of microbial degradation and present in trace amounts in natural gas.
 

It is likely to volatilize from soil and water and be photooxidized in the
 

atmosphere. Methyl mercaptan is probably mobile in soils, and it is not
 

likely to bioaccumulate.
 

Human exposure to trace amounts of methyl mercaptan probably occurs from
 

all environmental media. However, since this compound has an extremely
 

unpleasant odor and the odor threshold is quite low, it is unlikely that
 

significant human exposure to methyl mercaptan will occur, except possibly in
 

the vicinity of sewage treatment plants or industrial facilities or in the
 

workplace.
 

The EPA has identified 1,177 NPL sites. Methyl mercaptan has been
 

found at 2 of the sites evaluated for the presence of this chemical. However,
 

we do not know how many of the 1,177 NPL sites have been evaluated for this
 

chemical. As more sites are evaluated by the EPA, the number may change (View
 

1989). The frequency of occurrence at these sites within the United States
 

can be seen in Figure 5-l.
 

5.2 RELEASES TO THE ENVIRONMENT
 

Releases of methyl mercaptan may occur from industrial sources.
 

However, manufacturers, users, and processors of methyl mercaptan are not
 

required to report quantities of this substance released to environmental
 

media, since methyl mercaptan is not on the SARA Section 313 Toxic Chemical
 

List. Therefore, releases of methyl mercaptan during normal operations are
 

not reported in the Toxics Release Inventory (TRI 1989).
 

5.2.1 Air
 

Methyl mercaptan is released to the atmosphere from both natural and 

anthropogenic sources. Natural sources-include vegetation, animal wastes, 

microbial degradation, and natural gas (Adams et al. 1979; Farwell et al. 

1979; Graedel 1978; Reid 1958). Estimation of average methyl mercaptan 

emission from a saline marsh in North Carolina was 6.56 g sulfur/m2

/year 

(Adams et al. 1979). No other quantitative data regarding emissions from 

natural sources were located. 

Potential industrial emission sources include wood pulp, oil shale, and
 

petroleum-processing plants and sewage treatment plants (EPA 1987b; Graedel
 

1978; Reid 1958; Sklarew et al. 1984). Releases may also occur from .
 

hydrolysis or combustion of wool (Junk and Ford 1980; Reid 1958). A survey of
 

about 2,950 industrial facilities in North Carolina reported fugitive and
 

stack emissions of methyl mercaptan totalling 239,594 pounds/year (McCune
 

1990).
 

35
 

5. POTENTIAL FOR HUMAN EXPOSURE
 

5.2.2 Water
 

No data were located regarding the amount of methyl mercaptan released
 

to water. However, this compound was identified in both the influent and the
 

effluent of a wastewater treatment plant. It is likely that methyl mercaptan
 

is formed in the water by chemical reaction or microbiological fermentation,
 

rather than being released from industrial or municipal sources (Reid 1958;
 

Van Langenhove et al. 1985). Data from the Contract Laboratory Program (CLP)
 

Statistical Database indicate that methyl mercaptan was not detected in
 

surface water or groundwater at about 400 hazardous waste sites (CLPSD 1986).
 

5.2.3 Soil
 

Methyl mercaptan occurs naturally in many soils and may be adsorbed to
 

the soil from the atmosphere (Smith et al. 1973). No data were located
 

regarding land releases of methyl mercaptan from industrial sources. Land
 

disposal.restrictions have been proposed for methyl mercaptan (EPA 1989c).
 

Methyl mercaptan was detected in two soil samples at a geometric mean 

concentration in positive samples of 83 μg/kg, at 1 of 455 hazardous waste 

sites (CLPSD 1986). It is important to note that the CLP Statistical Database 

includes data from both NPL and non-NPL sites. Since methyl mercaptan may 

occur naturally in soils, occurrence at a hazardous waste site does not 

necessarily indicate a release to the environment from the site. 

5.3 ENVIRONMENTAL FATE
 

5.3.1 Transport and Partitioning
 

Methyl mercaptan is a gas with a vapor pressure of 1.97 atm at 25°C (EPA 

1983). A small fraction of atmospheric methyl mercaptan may dissolve intowater 

vapor (such as clouds and rain drops). A Henry's law constant (H) 

estimates the tendency of a chemical to partition between its gas phase and 

water. A value for H has not been experimentally measured, but it may be 

estimated by dividing the vapor pressure of methyl mercaptan by its water 

solubility at the same temperature (Mabey et al. 1982). In this case, an 

estimated value for H is 3.85x10-3 atm-m3

/mole (EPA 1983). The magnitude of 

this value suggests that only a small fraction of gaseous methyl mercaptan 

would dissolve in water and that most would remain in the air. 

Gaseous methyl mercaptan may also partition to soils. Sorption 

capacities of six-air-dry soil samples ranged from 2.4 to 32.1 mg CH3,SH per g 

of soil (Smith et al. 1973). The range for most soils was 2.2-21.4 mg/g of 

soil. These authors concluded that soil may be a sink for gaseous 

organosulfur compounds. No information was located on the fate of sorbed 

methyl mercaptan. 
36
 

5. POTENTIAL FOR HUMAN EXPOSURE
 

Methyl mercaptan is very soluble in water. Its solubility at 20°C is
 

approximately 23.3 g/L (EPA 1983). The magnitude of the estimated Henry's law
 

constant (3.85x10-3atm-m3

/mole) indicates that a large fraction of the
 

dissolved methyl mercaptan will volatilize from solution, depending on
 

temperature, relative humidity, air currents, and the extent of mixing of the
 

solution.
 

Methyl mercaptan may not be bioconcentrated significantly in water; 

however, no information was located on this topic. An octanol/water partition 

coefficient (Kow) estimates the partitioning of a chemical between octanol and 

water. Octanol is believed to best imitate the fatty structures in plants and 

living animal tissues. Based on its solubility in water (Hassett et al. 

1983), the Kow of methyl mercaptan can be calculated as approximately 19. 

This low value suggests that methyl mercaptan will not partition to fat 

tissues significantly. A bioconcentration factor (BCF) relates the 

concentration of chemical in aquatic plants or animals to the concentration of 

the chemical in the medium in which they live. Based on the empirical 

regressions of Kenaga (1980) using soil sorption parameters, an estimated BCF 

for methyl mercaptan is about l-2. This low BCF indicates that 

bioconcentration is not a significant fate mechanism for volatile methyl 

mercaptan released into the environment. However, no experimentally-measured 

BCFs for methyl mercaptan were located to corroborate these predicted values. 

Methyl mercaptan in water may have very little tendency to be adsorbed
 

by soils and sediments. The extent of adsorption of sparingly water-soluble
 

compounds is often highly correlated with the organic-carbon content of the
 

adsorbent (Hassett et al. 1983). When adsorption is expressed as a function
 

of organic-carbon content, an organic carbon/water partition coefficient (Koc) 

is generated, and may be used to rank the relative mobility of the chemical in 

soil-water systems. Based on its solubility in water, an estimated Koc for 

methyl mercaptan can be calculated as 17, using the empirical regression of 

Hassett et al. (1983). This low value indicates that methyl mercaptan is very 

highly mobile in soil as compared with other compounds listed by Roy and 

Griffin (1985). However, methyl mercaptan is not a sparingly soluble chemical 

in water. Methyl mercaptan is also a weak acid that dissociates in water, 

yielding an anion. The adsorption of ionic chemicals cannot be predicted by 

Koc concepts. The dissociation constants (pKa) of mercaptans in general are 

on the order of 11.4 (Reid 1958; Yabroff 1940). Consequently, the relative 

proportion of methyl mercaptan as an ion is probably insignificant in 

environmentally-relevant waters where the pH is less than 9. Therefore, the 

estimated Koc value of 17 may be a reasonable indicator of how this chemical 

partitions between water and soil. No corroborative information was located. 
37
 

5. POTENTIAL FOR HUMAN EXPOSURE
 

5.3.2 Transformation and Degradation
 

5.3.2.1 Air
 

The major fate of atmospheric methyl mercaptan is photooxidation. 

Methyl mercaptan may be transformed by photon-photolytic oxidation, yielding 

hydrogen, sulfur dioxide, dimethyl disulfide, and other polysulfides (Haines 

et al. 1956; Sheraton and Murray 1981). Methyl mercaptan may also be oxidized 

by tropospheric oxygen radicals, yielding dimethyl disulfide and other sulfide 

compounds (Nip et al. 1981). The rate constant for this reaction at ambient 

temperatures (about 25°C) has been measured to be approximately 1.77-1.90x10-12

cm 3/molecule-set (Nip et al. 1981; Slagle et al. 1976). If the mean 

concentration of ground-state oxygen radicals is about 5x10-4 molecules/cm3 

(Cupitt 1980), then the atmospheric half-life of methyl mercaptan is on the 

order of 4 months. 

Methyl mercaptan may be more rapidly transformed by interacting with 

atmospheric hydroxyl radicals. The measured rate constant for this reaction 

at ambient temperatures ranges from 2.1 to 9.04x10-11 cm3/molecule-see 

(Atkinson et al. 1977; Cox and Sheppard 1980; Hynes and Wine 1987; Mac Leod 

et al. 1984; Wine et al. 1984). Given that the concentration of tropospheric 

hydroxyl radicals varies from 3x105

 to about 1x107 molecules/cm3 (Mac Leod et 

al. 1984), it follows that the atmospheric half-life of methyl mercaptan is on 

the order of 0.2-30 hours. Consequently, it appears that gaseous methyl 

mercaptan is labile in the troposphere. Transformation products include 

sulfur dioxide, methylsulfenic acid (CH3SOH), and methyl sulfide radicals 

(Hatakeyama and Akimoto 1983). Several other reaction products have been 

predicted but not confirmed. 

Experimental data have also demonstrated that methyl mercaptan is labile
 

in polluted air where nitrogen oxide (NOx) concentrations are higher (Balla and
 

Heicklen 1985; Sickles and Wright 1979). Nitrogen oxides catalyze the
 

photooxidative transformations of methyl mercaptan. Reaction products
 

underthese conditions include sulfur dioxide, nitric acid, formaldehyde,
 

methylnitrate, methanesulfonic acid, inorganic sulfate (Grosjean 1984),
 

dimethyldisulfide, and nitric oxide (Balla and Heicklen 1985).
 

Reaction with the nitrate radical (NO3) may be the dominant atmospheric 

loss process for methyl mercaptan under certain conditions (Dlugokencky and 

Howard 1988; Mac Leod et al. 1986). The rate constant for the reaction of 

atmospheric methyl mercaptan with NO3 was recently determined (Dlugokencky and 

Howard 1988; Mac Leod et al. 1986). Based on a rate constant of about 

1x1O-l2 cm3/molecule-set and a NO3 concentration of 2.4x108

 molecule/cm3, 

Mac Leod et al. (1986) calculated an atmospheric lifetime of 1.2 hours for 

methyl mercaptan, less than the estimated atmospheric lifetime (8.4 hours) 

based on reaction with the OH radical. 
38
 

5. POTENTIAL FOR HUMAN EXPOSURE
 

5.3.2.2 Water
 

Very little is known about nonbiologically-mediated transformations of
 

methyl mercaptan in water. It seems likely that methyl mercaptan will
 

photooxidize and oxidize in water, but no information was located.
 

5.3.2.3 soil
 

Methyl mercaptan may be degraded by methanogenic bacteria in soil, but
 

there is little information available. Methyl mercaptan in solution was
 

metabolized to methane and carbon dioxide when in contact with anaerobic
 

freshwater sediments and sewage sludge (Zinder and Brock 1978). No other
 

information on transformation or degradation in soil was located.
 

5.4 LEVELS MONITORED OR ESTIMATED IN THE ENVIRONMENT
 

5.4.1 Air
 

Methyl mercaptan was detected in ambient air at 4 ppb (8.2 μg/m3

> and in 

a primary school in Japan at 2.8 ppb (5.7 μg/m3) (Okita 1970). No other 

studies were located regarding atmospheric concentrations of methyl mercaptan. 

5.4.2 Water
 

Groundwater and surface water monitoring studies do not generally
 

include methyl mercaptan. This compound was not detected in a screen of about
 

1,800 community and private wells in Wisconsin (Krill and Sonzogni 1986). No
 

other studies regarding water concentrations of methyl mercaptan were located.
 

5.4.3 Soil
 

Although methyl mercaptan is produced by microbial degradation in soils,
 

is adsorbed from the atmosphere by soil, and is volatilized from soil (Adams et
 

al. 1 979; Farwell et al. 1979; Reid 1958; Smith et al. 1973), no
 

quantitative data on the concentration of methyl mercaptan in ambient soils
 

were located.
 

5.4.4 Other Environmental Media
 

Methyl mercaptan has been identified as a volatile component of roasted
 

filberts and Beaufort cheese (Dumont and Adda 1978; Kinlin et al. 1972).
 

Trace amounts are present in the roots and leaves of some plants, in natural
 

gas and, as a result of digestive and metabolic processes, in urine and feces
 

(Reid 1958). Methyl mercaptan is also found in commercially extractable
 

quantities in the "sour gas" of west Texas (Reid 1958).
 
39
 

5. POTENTIAL FOR HUMAN EXPOSURE
 

5.5 GENERAL POPULATION AND OCCUPATIONAL EXPOSURE
 

Since methyl mercaptan is a naturally occurring substance present in
 

foods and sometimes formed during digestive and metabolic processes, the
 

general population will most likely be exposed to trace amounts of this
 

compound. However, the available data are inadequate to estimate the extent
 

of exposure of the general population to either natural or anthropogenic
 

sources of methyl mercaptan.
 

Inhalation exposure in occupational settings is probably the most
 

significant human exposure scenario for methyl mercaptan. Santodonato et al.
 

(1985) estimated that about 19,000 workers were potentially exposed to methyl
 

mercaptan in the 1970s. The estimate of workers potentially exposed to methyl
 

mercaptan increased from 357 in the early 1970s to about 6,200 in the early
 

1980s (NOES 1989; NOHS 1989). Neither the NOHS nor the NOES databases contain
 

information on the frequency, concentration, or duration of exposure of
 

workers to any of the chemicals listed therein. These surveys provide only
 

estimates of the number of workers potentially exposed to chemicals in the
 

workplace. Most occupational exposures are likely to occur in sewage
 

treatment plants and pulp mills, rather than in methyl mercaptan production or
 

consumptive use facilities. Mean methyl mercaptan concentrations in workplace
 

air ranged from 0.070 to 0.263 ppm in sewage plants and from 0.021 to 3.70 ppm
 

in pulp mills in Finland (Kangas and Ryosa 1988; Kangas et al. 1984) and from
 

0.55 to 1.06 ppm at a lockgate on a Japanese river (Okita 1970). No other data
 

on workplace air concentrations were located.
 

Since methyl mercaptan has a penetrating and extremely unpleasant odor
 

and the odor threshold in air is quite low (1.6 ppb) (Amoore and Hautala
 

1983), it is unlikely that humans would willingly tolerate exposure to
 

concentrations much above the odor threshold for any substantial time period.
 

However, humans in occupational settings may rapidly succumb to extremely high
 

levels of methyl mercaptan, as in the case of the worker who died after
 

emptying tanks of methyl mercaptan (see Chapter 2).
 

5.6 POPULATIONS WITH POTENTIALLY HIGH EXPOSURES
 

Workers in sewage treatment plants, pulp mills, chemical plants, and
 

other industrial or agricultural settings where chemical or microbiological
 

formation of methyl mercaptan is significant would have potentially high
 

exposure to this compound. People living in the immediate vicinity of these
 

facilities as well as in the vicinity of hazardous waste sites also have
 

higher exposure potential than does the general population.
 

5.7 ADEQUACY OF THE DATABASE
 

Section 104(i)(5) of CERCLA, as amended, directs the Administrator of
 

ATSDR (in consultation with the Administrator of EPA and agencies and programs
 

of the Public Health Service) to assess whether adequate information on the
 
40
 

5. POTENTIAL FOR HUMAN EXPOSURE
 

health effects of methyl mercaptan is available. Where adequate information
 

is not available, ATSDR, in conjunction with the NTP, is required to assure
 

the initiation of a program of research designed to determine the health
 

effects (and techniques for developing methods to determine such health
 

effects) of methyl mercaptan.
 

The following categories of possible data needs have been identified by
 

a joint team of scientists from ATSDR, NTP, and EPA. They are defined as
 

substance-specific informational needs that, if met, would reduce or eliminate
 

the uncertainties of human health assessment. In the future, the identified
 

data needs will be evaluated and prioritized, and a substance-specific research
 

agenda will be proposed.
 

5.7.1 Data Needs
 

Physical and Chemical Properties. The dissociation constant of methyl
 

mercaptan in water is not known precisely (Reid et al. 1958; Yabroff 1940) and
 

this measurement would be useful in predicting the environmental fate and
 

transport of this compound. A laboratory verification of the estimated
 

Henry's law constant for methyl mercaptan (Hassett et al. 1983) would provide
 

a more accurate measurement of air-water partitioning.
 

Production, Import/Export, Use, and Disposal. No data were located with
 

regard to past or present production, use, release, or disposal of methyl
 

mercaptan. Since most human exposure to methyl mercaptan is not associated with
 

production, use, or disposal, but rather with sewage treatment, wood pulping,
 

or oil processing facilities (EPA 1987b; Graedel 1978; Reid 1958; Sklarew et
 

al. 1984), additional data on its production and use will probably not
 

significantly affect estimates of human exposure to this compound. However,
 

data on methyl mercaptan releases from those facilities where the chemical is
 

produced inadvertently (sewage treatment, wood pulping, etc.) would be useful
 

in evaluating the potential for human exposures.
 

Environmental Fate. Small amounts of methyl mercaptan may partition
 

from air to water or soil (EPA 1983; Smith et al. 1973). Based on measured
 

physical properties, methyl mercaptan is likely to volatilize from water to
 

air (EPA 1983), but has little tendency to adsorb to soils (Hassett et al.
 

1983). Methyl mercaptan is likely to be mobile in environmental media
 

(Hassett et al. 1983). Additional research on the soil sorption of gaseous
 

methyl mercaptan may be helpful in describing the transport of the gas phase
 

in the vadose zone. The reaction mechanisms of methyl mercaptan
 

transformations in the atmosphere are fairly-well understood (Atkinson et al.
 

1977; Balla and Heickler 1985; Cox and Sheppard 1980; Dlugokencky and Howard
 

1988; Haines et al. 1956; Hynes and Wine 1987; Mac Leod et al. 1986; Nip
 

et al. 1981; Sheraton and Murray 1981; Slagle et al. 1976), but the
 

environmental fates of some of the transformation products are not well known.
 

Very little is known about the fate of methyl mercaptan in water. It would be
 

helpful to collect data on oxidation, hydrolysis, photodegradation, and
 
41
 

5. POTENTIAL FOR HUMAN EXPOSURE
 

biodegradation in surface water and groundwater. Research on the
 

biodegradation and abiotic transformation of methyl mercaptan in soils would
 

also be useful.
 

Bioavailability from Environmental Media. Methyl mercaptan is soluble in
 

water and may have very little tendency to be adsorbed to soils or
 

sediments (EPA 1983; Hassett et al. 1983). Therefore, it will be bioavailable
 

from natural waters. However, there are no data on the potential absorption
 

of methyl mercaptan via the oral or dermal routes. These data would be useful
 

in assessing the potential effects of recreational use of natural waters
 

contaminated with methyl mercaptan. Information on the absorption of inhaled
 

methyl mercaptan released to air would also be useful in assessing its
 

bioavailability from that medium.
 

Food Chain Bioaccumulation. There are no data on the bioconcentration of
 

methyl mercaptan by aquatic organisms, or data on the bioaccumulation of methyl
 

mercaptan in the food chain. However, this lack of data may not be amajor
 

limitation, because the food chain bioaccumulation of methyl mercaptan is
 

unlikely owing to its high volatility and water solubility (EPA 1983; Hassett
 

et al. 1983).
 

Exposure Levels in Environmental Media. There are few studies measuring
 

concentrations of methyl mercaptan in any environmental media (Krill
 

andSonzogni 1986; Okitu 1970). Since levels in ambient air, water, and soil are
 

unknown, monitoring studies would confirm the presence or absence of this
 

compound in these media. Data on ambient air levels at hazardous waste sitesand
 

estimates of human intake would be particularly useful.
 

Exposure Levels in Humans. Exposures of humans to natural sources of
 

methyl mercaptan are difficult to estimate. Measurements of methyl mercaptan
 

in workplace air would be useful in estimating occupational exposures.
 

Because methyl mercaptan is always present in human tissue independent of
 

exposure, these levels cannot be used as a measure or indication of exposure
 

without confirmatory data on exogenous levels of methyl mercaptan.
 

Exposure Registries. No exposure registries for methyl mercaptan were
 

located. This compound is not currently one of the compounds for which a
 

subregistry has been established in the National Exposure Registry. The
 

compound will be considered in the future when chemical selection is made for
 

subregistries to be established. The information that is amassed in the
 

National Exposure Registry facilitates the epidemiological research needed to
 

assess adverse health outcomes that may be related to the exposure to this
 

compound.
 
42
 

5. POTENTIAL FOR HUMAN EXPOSURE
 

5.7.2 On-going Studies
 

Remedial investigations and feasibility studies conducted at the 2 NPL
 

sites known to be contaminated with methyl mercaptan will add more information
 

to the available database on exposure levels in environmental media and
 

exposure levels in humans. No other information was located on any on-going
 

studies on the fate, transport, or potential for human exposure to methyl
 

mercaptan.
 
43
 

6. ANALYTICAL METHODS
 

The purpose of this chapter is to describe the analytical methods that
 

are available for detecting and/or measuring and monitoring methyl mercaptan
 

in'environmental media and in biological samples. The intent is not to
 

provide an exhaustive list of analytical methods that could be used to detect
 

and quantify methyl mercaptan. Rather, the intention is to identify
 

well established methods that are used as the standard methods of analysis. Many
 

of the analytical methods used to detect methyl mercaptan in
 

environmental samples are the methods approved by federal agencies such as EPA
 

and the National Institute for Occupational Safety and Health (NIOSH). Other
 

methods presented in this chapter are those that are approved by groups such as
 

the Association of Official Analytical Chemists (AOAC) and the American Public
 

Health Association (APHA). Additionally, analytical methods are included that
 

refine previously used methods to obtain lower detection limits, and/or to
 

improve accuracy and precision.
 

As a volatile material boiling at only 5.95°C (Windholz 1983), methyl 

mercaptan, CH3SH, also called methanethiol, is readily determined by gas 

chromatographic analysis. The sensitivity and selectivity of detection are 

increased by the use of sulfur-selective detectors; in one study, substitution 

of a sulfur-selective flame photometric detector for a flame ionization 

detector reduced the detection limit from 20 to 2 μg/unit sample (Knarr 

andRappaport 1980). Hydrogen sulfide (H2S), dimethyl sulfide ([CH3]2S), and 

dimethyl disulfide ([CH3]2S2) are other reduced sulfur compounds that may occur 

along with methyl mercaptan and are commonly determined along with it. 

Normally, methyl mercaptan is collected from the gas phase or from vapor 

evolved from the sample matrix on a column of solid sorbent, such as Tenax@. 

Collection on molecular sieve is also possible (Kangas and Ryosa 1988), 

although problems are encountered from incomplete desorption of methyl 

mercaptan from molecular sieve. Cryogenic (low temperature) collection may also 

be possible and is less likely to lead to alterations of the analyte in the 

collection apparatus (Brettell and Grob 1985). The presence of water can result 

in reduced sorption capacity for methyl mercaptan as well as decomposition 

during thermal desorption. Sorption efficiency is improved markedly by removal 

of water from the air stream with calcium chloride (Tangerman 1986). Purgeand-trap techniques are used to collect methyl mercaptan from water (Badings et 

al. 1985). Headspace vapor in equilibrium with the sample in a closed container 

may also be subjected to gas chromatography. 

6.1 BIOLOGICAL MATERIALS
 

Methods for detection of methyl mercaptan in biological materials are
 

summarized in Table 6-l.
 

Methyl mercaptan has been determined in a variety of biological
 

materials as shown in Table 6-l. Normally,'for determination in biological
 

samples, methyl mercaptan is released from the sample matrix and collected on
 

a column of solid sorbent, cryogenically or as headspace gas. As a result of
 

45
 

6. ANALYTICAL METHODS
 

Phase II metabolic reactions in biological systems (Manahan 1989), methyl
 

mercaptan may be bound as conjugates from which it must be released prior to
 

analysis. Two such bound fractions of methyl mercaptan have been identified
 

in human serum (Tangerman et al. 1985). In one fraction, from which the
 

methyl mercaptan is released by acid, the methyl mercaptan is thought to be
 

bound as methyl-beta-D-thioglucuronide. In another fraction methyl mercaptan
 

is covalently bound to proteins in a disulfide linkage and is released by
 

reaction with dithiothreitol.
 

6.2 ENVIRONMENTAL SAMPLES
 

For the determination of methyl mercaptan in air, the analyte is usually 

trapped and concentrated from a large volume of air on a solid sorbent such as 

Tenax, activated carbon, or molecular sieve from which it is released 

thermally for subsequent measurement. It is advisable to dry the air sample 

with calcium chloride prior to collection of methyl mercaptan to preventanalyte 

decomposition on the collection medium (Kangas and Ryosa 1988; 

Tangerman 1986). For aqueous and solid waste samples, methyl mercaptan is 

purged with an inert gas and collected on a solid such as Tenax, or 

cryogenically, followed by thermal desorption and measurement. Gas 

chromatography using sensitive and highly specific mass spectrometry (MS) or 

highly sensitive flame photometric detection (FPD) for detection is the 

analytical method of choice for the determination of methyl mercaptan in 

environmental samples. 

Methods for the determination of methyl mercaptan in environmental
 

samples are summarized in Table 6-2.
 

6.3 ADEQUACY OF THE DATABASE
 

Section 104(i)(5) of CERCLA, as amended, directs the Administrator of
 

ATSDR (in consultation with the Administrator of EPA and agencies and programs
 

of the Public Health Service) to assess whether adequate information on the
 

health effects of methyl mercaptan is available. Where adequate informationis
 

not available, ATSDR, in conjunction with the NTP, is required to assurethe
 

initiation of a program of research designed to determine the health effects
 

(and techniques for developing methods to determine such health effects) of
 

methyl mercaptan.
 

The following categories of possible data needs have been identified by
 

a joint team of scientists from ATSDR, NTP, and EPA. They are defined as
 

substance-specific informational needs that, if met, would reduce or eliminate
 

the uncertainties of human health assessment. In the future, the identified
 

data needs will be evaluated and prioritized, and a substance-specific ­

research agenda will be proposed.
 

47
 

6. ANALYTICAL METHODS
 

6.3.1 Data Needs
 

Methods for Determining Biomarkers of Exposure and Effect. Sensitive
 

and selective methods are available for the qualitative and quantitative
 

measurement of methyl mercaptan in biological materials, after it is separated
 

from its sample matrix (Al Mardini et al. 1984; Hayward et al. 1977; Johnsonand
 

Tonzetich 1985; Rimbault et al. 1986; Tangerman et al. 1983, 1985). However,
 

there are currently no methods available to qualitatively or
 

quantitatively correlate exposure to methyl mercaptan with biomarkers in
 

tissue or fluid. As discussed previously (Section 2.5), tissue and fluid
 

levels of methyl mercaptan can be independent of exogenous exposure to that
 

compound.
 

In the analysis of methyl mercaptan in biological materials, capillary
 

gas chromatography, also commonly known as high-resolution gas chromatography
 

(HRGC), has greatly facilitated the analysis of compounds such as methyl
 

mercaptan that can be measured by gas chromatography and has resulted in vast
 

improvements in resolution and sensitivity. The instrumental capability to
 

separate volatile analytes by HRGC is, for the most part, no longer the
 

limiting factor in their analysis.
 

It would be useful to have the means to transfer analytes that have been
 

isolated from a biological matrix, quantitatively and in a narrow band, to the
 

HRGC, and to identify and accurately measure the quantity of compounds in the
 

HRGC peaks. Mass spectrometric detection and Fourier transform infrared
 

spectroscopy (FTIR) may prove to be the most useful methods for these
 

functions.
 

There is a lack of standard methods for the measurement of metabolites of
 

methyl mercaptan in biological materials and development of these methods would
 

facilitate their determination in routine practice.
 

Specific methods for biomarkers that correlate levels of methyl
 

mercaptan or its metabolites with toxic effects in exposed populations are not
 

available. These methods would be helpful in defining the potential health
 

risks of certain tissue or fluid levels of these compounds, independent of
 

their source.
 

Methods for Determining Parent Compounds and Degradation Products in
 

Environmental Media. Methods for determining the parent compound, methyl
 

mercaptan, in water, air and waste samples with excellent selectivity and
 

sensitivity are well developed (ASTM 1987, 1988; Badings et al. 1985; De Souza
 

1987; EPA 1986; Kang as and Ryosa 1988; Knarr and Rappaport 1980; Tangerman
 

1986; Van Langenhove et al. 1985), so the database in this area is good
 

andundergoing constant improvement. For example, research is on-going to
 

develop a "Master Analytical Scheme" for organic compounds in water (Michael et
 

al. 1988), which includes methyl mercaptan as an analyte. The overall goal is
 

to detect and quantitatively measure organic compounds at 0.1 μg/L in drinking 
48
 

6. ANALYTICAL METHODS
 

water, 1 ug/L in surface waters, and 10 μg/L in effluent waters. Analytes are 

to include numerous nonvolatile compounds and some compounds that are only 

"semi-soluble" in water, as well as volatile compounds (bp<l50"C). 

Improved methods are needed for the determination of methyl mercaptan in
 

solid environmental samples, including soil and sediments. The standard EPA
 

Method 8240 for gas chromatography/mass spectrometry of volatile organics in
 

wastes, soils, and sediments (EPA 1986) could be tested thoroughly for methyl
 

mercaptan analysis and optimized for this application.
 

Sampling methodologies for compounds such as methyl mercaptan continue
 

to pose problems such as nonrepresentative samples, insufficient sample
 

volumes, contamination, and labor-intensive, tedious extraction and
 

purification procedures (Green and Le Pape 1987). It is desirable to have
 

means to measure organic compounds such as methyl mercaptan in situ in water
 

and other environmental media without the need for sampling and extraction
 

procedures to isolate the analyte prior to analysis.
 

Degradation products of methyl mercaptan in environmental media are
 

difficult to determine because these products may come from a number of
 

sources other than methyl mercaptan.
 

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 methyl mercaptan and other volatile
 

organic compounds in blood. These methods use high resolution gas
 

chromatography and magnetic sector mass spectrometry which gives detection
 

limits in the low parts per trillion range.
 

Examination of the literature suggests that other studies are underway
 

to improve means for determining methyl mercaptan and other reduced sulfur
 

compounds in biological samples and environmental media. Improvements
 

continue to be made in chromatographic separation and detection, including
 

supercritical fluid extraction and supercritical fluid chromatography (Smith
 

1988). Fourier transform infrared flow cell detectors are sensitive and
 

selective for the detection of compounds such as methyl mercaptan that have
 

been separated by fluid chromatography (Wieboldt et al. 1988). Immunoassay
 

methods of analysis are very promising for the determination of various
 

organic pollutants and toxicants, and it is reasonable to assume that methyl
 

mercaptan, and particularly its metabolites such as methyl-beta-


Dthioglucuronide are candidates for this type of analysis.
 
49
 

7. REGULATIONS AND ADVISORIES
 

Because of its potential to cause adverse health effects in exposed
 

people, a number of regulations and guidelines have been established for
 

methyl mercaptan by various national and state agencies. These values are
 

summarized in Table 7-1.
 

51


 8. REFERENCES
 

* ACGIH. 1986. Documentation of the threshold limit values and biological


 exposure indices. 5th ed. American Conference of Governmental Industrial


 Hygienists. Cincinnati, OH.
 

Ackerman DG, Haro MT, Richard G, et al. 1980. Health impacts, emissions, and
 

emission factors for noncriteria pollutants subject to de minimis guidelines
 

and emitted from stationary conventional combustion processes. Report to U.S.
 

Environmental Protection Agency, Research Triangle Park, NC, by TRW, Redondo
 

Beach, CA, and Battelle, Columbus, OH. EPA-450/2-80-074. NTIS No. PB80­

221237.
 

* Adams DF, Farwell SO, Pack MR, et al. 1979. Preliminary measurements of


 biogenic sulfur-containing gas emissions from soils. J Air Pollut Control


 Assoc 29:380-382.
 

* AGA. 1983. Odorization manual. Arlington, VA: American Gas Association,


 1, 14, 15. Catalog No. X00683.


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63
 

9. GLOSSARY
 

Acute Exposure -- Exposure to a chemical for a duration of 14 days or less, as
 

specified in the Toxicological Profiles.
 

Adsorption Coefficient (Koc) -- The ratio of the amount of a chemical adsorbed 

per unit weight of organic carbon in the soil or sediment to the concentration 

of the chemical in solution at equilibrium. 

Adsorption Ratio (Kd) -- The amount of a chemical adsorbed by a sediment or 

soil (i.e., the solid phase) divided by the amount of chemical in the solution 

phase, which is in equilibrium with the solid phase, at a fixed solid/solution 

ratio. It is generally expressed in micrograms of chemical sorbed per gram of 

soil or sediment. 

Bioconcentration Factor (BCF) -- The quotient of the concentration of a
 

chemical in aquatic organisms at a specific time or during a discrete time
 

period of exposure divided by the concentration in the surrounding water at
 

the same time or during the same period.
 

Cancer Effect Level (CEL) -- The lowest dose of chemical in a study, or group
 

of studies, that produces significant increases in the incidence of cancer (or
 

tumors) between the exposed population and its appropriate control.
 

Carcinogen -- A chemical capable of inducing cancer.
 

Ceiling Value -- A concentration of a substance that should not be exceeded,
 

even instantaneously.
 

Chronic Exposure -- Exposure to a chemical for 365 days or more, as specified
 

in the Toxicological Profiles.
 

Developmental Toxicity -- The occurrence of adverse effects on the developing
 

organism that may result from exposure to a chemical prior to conception
 

(either parent), during prenatal development, or postnatally to the time of
 

sexual maturation. Adverse developmental effects may be detected at any point
 

in the life span of the organism.
 

Embryotoxicity and Fetotoxicity -- Any toxic effect on the conceptus as a
 

result of prenatal exposure to a chemical; the distinguishing feature between
 

the two terms is the stage of development during which the insult occurred.
 

The terms, as used here, include malformations and variations, altered growth,
 

and in utero death.
 

EPA Health Advisory -- An estimate of acceptable drinking water levels for a
 

chemical substance based on health effects information. A health advisory is
 

not a legally enforceable federal standard, but serves as technical guidance to
 

assist federal, state, and local officials.
 
64
 

9. GLOSSARY
 

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

concentration of a contaminant from which one could escape within 30 min 

without any escape-impairing symptoms or irreversible health effects.

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

as specified in the Toxicological Profiles.
 

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

that may result from exposure to environmental agents such as chemicals.
 

In Vitro -- Isolated from the living organism and artificially maintained, as
 

in a test tube.
 

In Vivo -- Occurring within the living organism.
 

Lethal Concentration(Lo)(LCLo) -- The lowest concentration of a chemical in air 

which has been reported to have caused death in humans or animals.

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

air to which exposure for a specific length of time is expected to cause death 

in 50% of a defined experimental animal population. 

Lethal Dose(Loj (LDLo) -- The lowest dose of a chemical introduced by a route
 

other than inhalation that is expected to have caused death in humans or
 

animals.
 

Lethal Dose(50) (LD50) -- The dose of a chemical which has been calculated to 

cause death in 50% of a defined experimental animal population. 

Lethal Time(50) (LT50) -- A calculated period of time within which a specific
 

concentration of a chemical is expected to cause death in 50% of a defined
 

experimental animal population.
 

Lowest-Observed-Adverse-Effect Level (LOAEL) -- The lowest dose of chemical in
 

a study or group of studies, that produces statistically or biologically
 

significant increases in frequency or severity of adverse effects between the
 

exposed population and its appropriate control.
 

Malformations -- Permanent structural changes that may adversely affect
 

survival, development, or function.
 

Minimal Risk Level -- An estimate of daily human exposure to a chemical that is
 

likely to be without an appreciable risk of deleterious effects
 

(noncancerous) over a specified duration of exposure.
 

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.
 
65
 

9. GLOSSARY
 

Neurotoxicity -- The occurrence of adverse effects on the nervous system
 

following exposure to chemical.
 

No-Observed-Adverse-Effect Level (NOAEL) -- The dose of chemical at which there
 

were no statistically or biologically significant increases in frequency or
 

severity of adverse effects seen between the exposed population and its
 

appropriate control. Effects may be produced at this dose, but they are not
 

considered to be adverse.
 

Octanol-Water Partition Coefficient (Kow) -- The equilibrium ratio of the 

concentrations of a chemical in n-octanol and water, in dilute solution. 

Permissible Exposure Limit (PEL) -- An allowable exposure level in workplace 

air averaged over an 8-hour shift. 

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

curve -as determined by the multistage procedure. The 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-hour period.
 

Reproductive Toxicity -- The occurrence of adverse effects on the reproductive
 

system that may result from exposure to a chemical. The toxicity may be
 

directed to the reproductive organs and/or the related endocrine system. The
 

manifestation of such toxicity may be noted as alterations in sexual behavior,
 

fertility, pregnancy outcomes, or modifications in other functions that are
 

dependent on the integrity of this system.
 

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.
 
66
 

9. GLOSSARY
 

Target Organ Toxicity -- This term covers a broad range of adverse effects on
 

target organs or physiological systems (e.g., renal, cardiovascular) extending
 

from those arising through a single limited exposure to those assumed over a
 

lifetime of exposure to a chemical.

Teratogen -- A chemical that causes structural defects that affect the
 

development of an organism.
 

Threshold Limit Value (TLV) -- A concentration of a substance to which most
 

workers can be exposed without adverse effect. The TLV may be expressed as a
 

TWA, as a STEL, or as a CL.
 

Time-weighted Average (TWA) -- An allowable exposure concentration averaged
 

over a normal 8-hour workday or 40-hour workweek.
 

Toxic Dose (TD50) -- A calculated dose of a chemical, introduced by a route 

other than inhalation, which is expected to cause a specific toxic effect in 

50% of a defined experimental animal population. 

Uncertainty Factor (UF) -- A factor used in operationally deriving the RfD
 

from experimental data. UFs are intended to account for (1) the variation in
 

sensitivity among the members of the human population, (2) the uncertainty in
 

extrapolating animal data to the case of human, (3) the uncertainty in
 

extrapolating from data obtained in a study that is of less than lifetime
 

exposure, and (4) the uncertainty in using LOAEL data rather than NOAEL data.
 

Usually each of these factors is set equal to 10.
 
A-l
 

APPENDIX A
 

USER'S GUIDE
 

Chapter 1
 

Public Health Statement
 

This chapter of the profile is a health effects summary written in nontechnical
 

language. Its intended audience is the general public especially people living
 

in the vicinity of a hazardous waste site or substance release. If the Public
 

Health Statement were removed from the rest of the document, it would still
 

communicate to the lay public essential information about the substance.
 

The major headings in the Public Health Statement are useful to find specific
 

topics of concern. The topics are written in a question and answer format. The
 

answer to each question includes a sentence that will direct the reader to
 

chapters in the profile that will provide more information on the given topic.
 

Chapter 2
 

Tables and Figures for Levels of Significant Exposure (LSE)
 

Tables (2-1, 2-2, and 2-3) and figures (2-l and 2-2) are used to summarize
 

health effects by duration of exposure and endpoint and to illustrate
 

graphically levels of exposure associated with those effects. All entries in
 

these tables andfigures represent studies that provide reliable, quantitative
 

estimates of No-Observed-Adverse-Effect Levels (NOAELS), Lowest-ObservedAdverse-Effect Levels (LOAELs) for Less Serious and Serious health effects, or
 

Cancer Effect Levels (CELs). In addition, these tables and figures illustrate
 

differences in response by species, Minimal Risk Levels (MRLs) to humans for
 

noncancer end points, and EPA'S estimated range associated with an upper-bound
 

individual lifetime cancer risk of 1 in 10,000 to 1 in 10,000,000. The LSE
 

tables and figures can be used for a quick review of the health effects and to
 

locate data for a specific exposure scenario. The LSE tables and figures should
 

always be used in conjunction with the text.
 

The legends presented below demonstrate the application of these tables and
 

figures. A representative example of LSE Table 2-l and Figure 2-1 are shown.
 

The numbers in the left column of the legends correspond to the numbers in the
 

example table and figure.
 

LEGEND
 

See LSE Table 2-1
 

(1) Route of Exposure One of the first considerations when reviewing the


 toxicity of a substance using these tables and figures should be the


 relevant and appropriate route of exposure. When sufficient data exist,
 
A-2
 

APPENDIX A
 

three LSE tables and two LSE figures are presented in the document. The
 

three LSE tables present data on the three principal routes of exposure,
 

i.e., inhalation, oral, and dermal (LSE Table 2-1, 2-2, and 2-3,
 

respectively). LSE figures are limited to the inhalation (LSE Figure 2­

l)and oral (LSE Figure 2-2) routes.
 

(2)	 Exposure Duration Three exposure periods: acute (14 days or less);
 

intermediate (15 to 364 days); and chronic (365 days or more) are
 

presented within each route of exposure. In this example, an inhalation
 

study of intermediate duration exposure is reported.
 

(3)	 Health Effect The major categories of health effects included in
 

LSE tables and figures are death, systemic, immunological,
 

neurological, developmental, reproductive, and cancer. NOAELs and
 

LOAELs can be reported in the tables and figures for all effects but
 

cancer. Systemic effects are further defined in the "System" column
 

of the LSE table.
 

(4)	 Kev to Figure Each key number in the LSE table links study information to
 

one or more data points using the same key number in the corresponding
 

LSE figure. In this example, the study represented by key number 18 has
 

been used to define a NOAEL and a Less Serious LOAEL (also see the two
 

"18r" data points in Figure 2-l).
 

(5)	 Species The test species, whether animal or human, are identified in this
 

column.
 

(6)	 Exposure Frequencv/Duration The duration of the study and the weekly and
 

daily exposure regimen are provided in this column. This permits
 

comparison of NOAELs and LOAELs from different studies. In this case (key
 

number 18), rats were exposed to [substance x] via inhalation for 13
 

weeks, 5 days per week, for 6 hours per day.
 

(7) 	 System This column further defines the systemic effects. These systems
 

include: respiratory, cardiovascular, gastrointestinal, hematological,
 

musculoskeletal, hepatic, renal, anddermal/ocular. "Other" refers to any
 

systemic effect (e.g., a decrease in body weight) not covered in these
 

systems. In the example of key number 18, one systemic effect
 

respiratory) was investigated in this study.
 

(8)	 NOAEL A No-Observed-Adverse-Effect Level (NOAEL) is the highest exposure
 

level at which no harmful effects were seen in the organ system studied.
 

Key number 18 reports a NOAEL of 3 ppm for the respiratory system which
 

was used to derive an intermediate exposure, inhalation MRL of 0.00s ppm
 

(see footnote "c").
 

(9)	 LOAEL A Lowest-Observed-Adverse-Effect Level (LOAEL) is the lowest
 

exposure level used in the study that caused a harmful health effect.
 

LOAELs have been classified into "Less Serious" and "Serious" effects.
 

These distinctions help readers identify the levels of exposure at which
 

adverse health effects first appear and the gradation of effects with
 

increasing dose. A brief description of the specific end point used to
 
A-3
 

APPENDIX A
 

quantify the adverse effect accompanies the LOAEL. The "Less Serious"
 

respiratory effect reported in key number 18 (hyperplasia) occurred at a
 

LOAEL of 10 ppm.
 

(10)	 Reference The complete reference citation is given in Chapter 8 of the
 

profile.
 

(11)	 CEL A Cancer Effect Level (CEL) is the lowest exposure level associated
 

with the onset of carcinogenesis in experimental or epidemiological
 

studies. CELs are always considered serious effects. The LSE tables and
 

figures do not contain NOAELs for cancer, but the text may report doses
 

which did not cause a measurable increase in cancer.
 

(12)	 Footnotes Explanations of abbreviations or reference notes for data in
 

the LSE tables are found in the footnotes. Footnote "c" indicates the
 

NOAEL of 3 ppm in key number 18 was used to derive an MRL of 0.005 ppm.
 

LEGEND
 

See LSE Figure 2-l
 

LSE figures graphically illustrate the data presented in the corresponding LSE
 

tables. Figures help the reader quickly compare health effects according to
 

exposure levels for particular exposure duration.
 

(13)	 Exposure Duration The same exposure periods appear as in the LSE table.
 

In this example, health effects observed within the intermediate and
 

chronic exposure periods are illustrated.
 

(14)	 Health Effects These are the categories of health effects for which
 

reliable quantitative data exist. The same health effects appear in the
 

LSE table.
 

(15)	 Levels of Exposure Exposure levels for each health effect in the LSE
 

tables are graphically displayed in the LSE figures. Exposure levels are
 

reported on the log scale "y" axis. Inhalation exposure is reported in
 

mg/m3 or ppm and oral exposure is reported in mg/kg/day.
 

(16)	 NOAEL In this example, 18r NOAEL is the critical end point for which an
 

intermediate inhalation exposure MRL is based. As you can see from the
 

LSE figure key, the open-circle symbol indicates a NOAEL for the test
 

species (rat). The key number 18 corresponds to the entry in the LSE
 

table. The dashed descending arrow indicates the extrapolation from the
 

exposure level of 3 ppm (see entry 18 in the Table) to the MRL of 0.005
 

ppm (see footnote "b" in the LSE table).
 

(17)	 CEL Key number 38r is one of three studies for which Cancer Effect Levels
 

(CELs) were derived. The diamond symbol refers to a CEL for the test
 

species (rat). The number 38 corresponds to the entry in the LSE table.
 
A-4
 

APPENDIX A
 

(18). Estimated Upper-Bound Human Cancer Risk Levels This is the range
 

associated with the upper-bound for lifetime cancer risk of 1 in 10,000
 

to 1 in 10,000,000. These risk levels are derived from EPA's Human Health
 

Assessment Group's upper-bound estimates of the slope of the cancer dose
 

response curve at low dose levels (q1*).
 

(19). Key to LSE Figure The Key explains the abbreviations and symbols used in
 

the figure.
 


A-7
 

APPENDIX A
 

Chapter 2 (Section 2.4)
 

Relevance to Public Health
 

The Relevance to Public Health section provides a health effects summary based
 

on evaluations of existing toxicological, epidemiological, and toxicokinetic
 

information. This summary is designed to present interpretive,
 

weight-of-evidence discussions for human health end points by addressing the
 

following questions.
 

1. What effects are known to occur in humans?
 

2. What effects observed in animals are likely to be of concern to
 

humans?
 

3. What exposure conditions are likely to be of concern to humans,
 

especially around hazardous waste sites?
 

The section discusses health effects by end point. Human data are presented
 

first, then animal data. Both are organized by route of exposure (inhalation,
 

oral, and dermal) and by duration (acute, intermediate, and chronic). In vitro
 

data and data from parenteral routes (intramuscular, intravenous, subcutaneous,
 

etc.) are also considered in this section. If data are located in the
 

scientific literature, a table of genotoxicity information is included.
 

The carcinogenic potential of the profiled substance is qualitatively
 

evaluated, when appropriate, using existing toxicokinetic, genotoxic, and
 

carcinogenic data. ATSDR does not currently assess cancer potency or perform
 

cancer risk assessments. MRLs for noncancer end points if derived, and the end
 

points from which they were derived are indicated and discussed in the
 

appropriate section(s).
 

Limitations to existing scientific literature that prevent a satisfactory
 

evaluation of the relevance to public health are identified in the
 

Identification of Data Needs section.
 

Interpretation of Minimal Risk Levels
 

Where sufficient toxicologic information was available, MRLs were derived. MRLs
 

are specific for route (inhalation or oral) and duration (acute, intermediate,
 

or chronic) of exposure. Ideally, MRLs can be derived from all six exposure
 

scenarios (e.g., Inhalation - acute, -intermediate, -chronic; Oral - acute, ­

intermediate, - chronic). These MRLs are not meant to support regulatory
 

action, but to acquaint health professionals with exposure levels at which
 

adverse health effects are not expected to occur in humans. They should help
 

physicians and public health officials determine the safety of a community
 

living near a substance emission, given the concentration of a contaminant in
 

air or the estimated daily dose received via food or water. MRLs are based
 

largely on toxicological studies in animals and on reports of human
 

occupational exposure.
 
A-8
 

APPENDIX A
 

MRL users should be familiar with the toxicological information on which the
 

number is based. Section 2.4, "Relevance to Public Health," contains basic
 

informationknown about the substance. Other sections such as 2.6, "Interactions
 

with Other Chemicals" and 2.7, "Populations that are Unusually Susceptible"
 

provide important supplemental information.
 

MRL users should also understand the MRL derivation methodology. MRLs are
 

derived using a modified version of the risk assessment methodology used by the
 

Environmental Protection Agency (EPA) (Barnes and Dourson, 1988; EPA 1989a) to
 

derive reference doses (RfDs) for lifetime exposure.
 

To derive an MRL, ATSDR generally selects the end point which, in its best
 

judgement, represents the most sensitive humanhealth effect for a given
 

exposure route and duration. ATSDR cannot make this judgement or derive an MRL
 

unless information (quantitative or qualitative) is available for all potential
 

effects (e.g., systemic, neurological, and developmental). In order to compare
 

NOAELs and LOAELs for specific end points, all inhalation exposure levels are
 

adjusted for 24hr exposures and all intermittent exposures for inhalation and
 

oral routes of intermediate and chronic duration are adjusted for continous
 

exposure (i.e., 7 days/week). If the information and reliable quantitative data
 

on the chosen end point are available, ATSDR derives an MRL using the most
 

sensitive species (when information from multiple species is available) with
 

the highest NOAEL that does not exceed any adverse effect levels. The NOAEL is
 

the most suitable end point for deriving an MRL. When a NOAEL is not available,
 

a Less Serious LOAEL can be used to derive an MRL, and an uncertainty factor
 

(UF) of 10 is employed. MRLs are not derived from Serious LOAELs. Additional
 

uncertainty factors of 10 each are used for human variability to protect
 

sensitive subpopulations (people who are most susceptible to the health effects
 

caused by the substance) and for interspecies variability (extrapolation from
 

animals to humans). In deriving an MRL, these individual uncertainty factors
 

are multiplied together. The product is then divided into the adjusted
 

inhalation concentration or oral dosage selected from the study. Uncertainty
 

factors used in developing a substance-specific MRL are provided in the
 

footnotes of the LSE Tables.
 





APPENDIX C
 

PEER REVIEW
 

A peer review panel was assembled for methyl mercaptan. The panel
 

consisted of the following members: Dr. Sharon Johnson, Visiting Scientist,
 

Department of Biology, Johns Hopkins University; Dr. Derek Hodgson, Chairman,
 

Department of Chemistry, University of Wyoming; Dr. Shane Que Hee, Associate
 

Professor, School of Public Health, University of California. These experts
 

collectively have knowledge of methyl mercaptan'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 Section
 

104(i)(13) of the Comprehensive Environmental Response, Compensation, and
 

Liability, as amended.
 

A joint panel of scientists from the Agency for Toxic Substances and
 

Disease Registry (ATSDR) and the Environmental Protection Agency 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
 

its approval of the profile's final content. The responsibility for the
 

content of this profile lies with the ATSDR.