United States Office of Mobile Source Air Pollution Control EPA-460/3-81 -032
Environmental Protection Emission Control Technology Division
Agency 2565 Plymouth Road
Ann Arbor, Ml 48105
Air
oEPA
Methanol
Health
Effects
-------
METHANOL HEALTH EFFECTS
with Contributions by
Bonnie L. Carson
Joy L. McCann
Harry V. Ellis III
Betty L. Herndon
Larry H. Baker
FINAL TASK 7 REPORT
December 31, 1981
Contract No. 68-03-2928
Task Specification No. 7
"Health Effects Support for the Emission Control
Technology Division"
MRI Project No. 4997-T(7)
For
Emission Control Technology Division
Office of Mobile Source Air Pollution Control
U.S. Environmental Protection Agency
2565 Plymouth Road
Ann Arbor, Michigan 48105
Attn: Robert J. Garbe
-------
PREFACE
This report on health effects of methanol was prepared by Midwest
Research Institute (MRI) on Task No. 7 under Contract No. 68-03-2928,
"Health Effects Support for the Emission Control Technology Division" for
the U.S. Environmental Protection Agency.
Health effects literature primarily related to inhalation exposures
to methanol has been collected, evaluated, tabulated, and summarized so
that this report can be used to derive a range of concern for human ex-
posure to vehicular atmospheric emissions of methanol. Because of the pos-
sible use of methanol as a fuel, a brief summary of the health effects from
ingestion and skin absorption has been included.
Task activities were coordinated by the project leader, Mrs. Bonnie L.
Carson, Senior Chemist, and task leader, Ms. Joy L. McCann, Assistant Sci-
entist. Documents were rated and summarized by senior pharmacologists,
Drs. Harry V. Ellis III, and Betty L. Herndon, of MRI, and epidemiologist,
Larry H. Baker, M.D., MRI consultant, who is Associate Professor of Com-
munity Health at the University of Kansas Medical Center. Data were tabu-
lated and the annotated bibliography prepared by Ms. McCann and Mrs. Carson.
This study was performed under the general supervision of Dr. Edward W.
Lawless, Head, Chemical Impact Assessment Section.
Mr. Robert J. Garbe was the project officer for the Emission Control
Technology Division, U.S. Environmental Protection Agency, and Ms. Colleen
DeMeyer served as Branch Technical Representative.
Approved for:
MIDWEST RESEARCH INSTITUTE
Bruce W. Macy, Directai
Center for Technoeconamic
Analysis
December 31, 1981
-------
CONTENTS
Page
Preface in
Figures vi
Tables vi
Summary 1
Goals and methods 1
Background information on methanol toxicity 2
Bioassay studies 2
Inhalation studies 3
Ingestion studies 4
Skin absorption 4
Environmental contributions to human exposure .... 4
International recommendations and standards 5
Recommended range of concern 5
I. Introduction 7
II. Bioassays 11
III. Experimental Animal Inhalation Exposures 13
IV. Experimental Human Inhalation Exposure 25
V. Occupational Exposures and Human Case Reports 33
Annotated Bibliography 39
v
-------
FIGURES
Number Page
1-1 Form for report rating 8
TABLES
Number Page
111 -1 Mice—Acute Experimental Exposure to MeOH 14
III-2 Mice—Repeated Dose Experimental Exposure to MeOH 15
111 - 3 Rats--Acute Experimental Exposure to MeOH 16
III-4 Rats--Repeated Dose Experimental Exposure to MeOH 17
111-5 Rats--Chronic Experimental Exposure to MeOH 19
III-6 Rabbits—Chronic Experimental Exposure to MeOH 20
111 - 7 Dogs--Acute Experimental Exposure to MeOH 21
III-8 Dogs--Repeated Dose Experimental Exposure to MeOH 22
III-9 Dogs--Chronic Experimental Exposure to MeOH 23
III-10 Monkeys—Acute Experimental Exposure to MeOH 24
IV-1 Humans—Acute and Repeated Dose Experimental Inhalation
Exposure to MeOH 26
V-l Studies of Occupational Exposure to MeOH 35
vi
-------
SUMMARY
GOALS AND METHODS
The purpose of this compilation of data on methanol (MeOH)* inhalation
exposures is to assist the Emissions Control Technology Division (ECTD) of
the U.S. Environmental Protection Agency (EPA) to establish the ranges of
exposure conditions that are of concern for MeOH in exhausts from vehicles
equipped with catalytic converters and to be able to advise automobile man-
ufacturers thereof. The situations of concern are during malfunctions and
during exposures in traffic jams, parking and home garages, and other situ-
ations where little dilution of the exhaust is expected before inhalation.
Most of the report is, as directed by ECTD, in the form of tables based on
the literature reviewed. Data from exposures at levels higher than those
of primary concern are included because strictly relevant information was
scarce and these related data might prove helpful in assessing health ef-
fects at lower levels.
In addition to MeOH inhalation data, literature related to oral inges-
tion and skin absorption was also retrieved and reviewed for this task.
Brief summaries of the toxicity and range of concern associated with these
two routes of exposure are included. These were included because of the
recognition by ECTD that MeOH is being proposed as an alternative fuel in
automobiles, and such usage would result in skin absorption from spills
during handling and possible ingestion from siphoning or other careless
handling.
Documents relevant to this study of health effects from exposure to
MeOH were identified from manual and computerized literature searches and
then rated in a two-step process by the project pharmacologists and epidemi-
ologist. First, the document received an A, B, C, or D rating according to
its applicability for deriving a range of concern for MeOH inhalation ex-
posure. Second, if the paper was not a low-rated, foreign language docu-
ment,'** a theoretical paper, a review, or a nontoxicology experimental paper,
it received a numerical score based on itemized features that should be
present in an ideal report. For the most part, only A- and B-rated docu-
ments were tabulated; but when data were limited as with MeOH, C- and D-
studies were also tabulated when it was felt they contributed some useful
information to the overall evaluation of health hazards. Blanks in the
tables should be construed as denoting missing information in the documents.
* Chemical formula CH30H. Also called methyl alcohol and wood alcohol.
** Most foreign language articles rated C and D were usually not translated.
Each foreign language document tentatively rated A or B from an English
language abstract or brief examination of the paper was translated in
sufficient degree to judge the experimental design and details. These
papers were numerically scored from the translation.
1
-------
BACKGROUND INFORMATION ON METHANOL TOXICITY
Methanol is a well-known poison, discussed today in most standard ref-
erence works on toxic chemicals (such as Gosselin et al., 1976). In the
past, MeOH's toxicity was debated, and, as late as 1936, doubts existed as
to the toxicity of pure MeOH. The toxicity of wood alcohol was attributed
to its impurities by some early authorities (Bennett et al., 1953). A 1904
report by Wood and Buller documented the earliest cases of MeOH poisoning;
it stated that 275 cases of blindness or death attributable to wood alcohol
were reported between 1856 (when the first scientific report of toxicity
was made) and 1904. Nevertheless, MeOH was a frequent component of lini-
ments, toilet articles, perfumes, and some patent medicines well into this
century (Wood, 1912).
Practically all the MeOH toxicity data involve its ingestion with, or
as a substitute for, ethanol (ethyl alcohol). The immediate symptom is an
inebriation, indistinguishable from that from ethanol ingestion. After 12
to 18 h, the characteristic MeOH toxicity appears, presumably caused by its
metabolites, formaldehyde and formic acid. Symptoms include headache, weak-
ness, leg cramps, and vertigo; nausea and vomiting sometimes with violent
abdominal pain; back and leg pain; vision defects; rapid, shallow breathing
from metabolic acidosis; and weak, rapid pulse with hypotension; progressing
to apathy and coma, or to excitement, mania, and convulsions. Death, if
it occurs, is usually from respiratory failure. In nonfatal cases, conva-
lescence is often protracted and complicated by debility, blindness, and
kidney problems.
Relatively few experimental studies on MeOH toxicity have been pub-
lished, and most of them involved very large doses, mechanistic studies of
the retinal toxicity, or both. Most human reports are case studies, with
little exposure data. Toxicity has occurred from ingestion, inhalation,
contact, and confounded exposure through two or all three routes (Wood and
Buller, 1904; McLean et al., 1980).
Methanol's toxicity (especially its ocular effects) is generally be-
lieved to be caused by its metabolites, although its metabolism is not
fully understood. In humans and other primates, MeOH is first oxidized to
formaldehyde by the enzyme catalase, but in lower animals this oxidation
is effected by alcohol dehydrogenase. The highly reactive formaldehyde
quickly disappears from the tissue but was formerly believed to be the
cause of toxic effects. More recently, the further metabolites, formic
acid or formate esters, have been proposed to be the toxic products.
Tephly et al. (1974; 1979) have reviewed the available information on the
metabolism of MeOH.
BIOASSAY STUDIES
The bioassay data were limited in applicability to human toxicity, but
did demonstrate that in the animal in vitro systems studied, MeOH is not
very toxic and not mutagenic. In the one respiratory tissue study, 0.4 to
2
-------
1.4 mg MeOH in aerosol at the rate of 27 mL/s inhibited ciliary activity in
the esophageal tract of the leopard frog. Another study found low concen-
trations of MeOH, ^ 0.02 mMol increased release of lung prostaglandins;
higher MeOH levels decreased rate of release.
INHALATION STUDIES
Chao (1959) exposed rats 12 h/day for 8 weeks. He found definite tox-
icity (respiratory tract irritation, liver degeneration, cortical neurop-
athy) at 50 mg/m3, but not at 1.77 mg/m3. Ubaydullayev (1968) found minor
toxicity in rats exposed continuously for 90 d to 5.31 mg/m3, but none at
0.57 mg/m3. Sayers et al. (1942) exposed dogs (including pups bred and
born during the exposure) to about 600 mg/m3 for 8 h/d, 7 d/wk for over a
year. Although blood MeOH levels were typically 7 to 15 mg/dL after a
daily exposure, no adverse effects were noted.
Human case reports (e.g., Wood and Buller, 1904; Tyson, 1912) have
shown toxicity from MeOH in lacquer thinner and similar products. Although
some skin contact would have occurred, this exposure is presumably primar-
ily from inhalation.
Several human experimental studies have determined an odor threshold
for MeOH. The highest reported value was 7,800 mg/m3 (May, 1966).
Leonardos et al. (1969) reported identification of MeOH odor at 133 mg/m3,
while Hellman and Small (1974) reported the same results at 70 mg/m3. Mini-
mum detectable thresholds include 4.3 to 11 mg/m3 (Chao, 1959); 4.5 mg/m3
(Ubaydullayev, 1968); and 5.7 mg/m3 (Hellman and Small, 1974). The discrep-
ancy may be due to the purity of the MeOH used in testing.
Two groups studied the effects of MeOH on nervous system reflexes.
Chao (1959) found that 3.3 to 3.7 mg/m3 was the threshold for degradation of
light sensitivity (dark adaptation), with 1.8 to 2.4 mg/m3 having no effect.
Ubaydullayev (1968) found EEG changes, of dubious significance at 1.17 mg/
m3, but not 1.01 mg/m3, in subjects selected for olfactory sensitivity.
The reports of studies involving occupational exposure to MeOH are not
very useful for our purposes. Several studies were confounded by the pres-
ence of other chemicals, were poorly controlled, or the reports lack neces-
sary information. Kingsley and Hirsch (1954-1955) found that office workers
complaining of recurrent headaches were exposed to ~ 22 to 500 mg MeOH/m3
from spirit duplicating machines and those workers actually operating the
machines had more severe symptoms. One study (Barmann and Angerer, 1979)
found a significant increase of formic acid (a MeOH metabolite) in the blood
and urine of print shop workers exposed to 113 to 178 mg MeOH/m3. Another
study (Dutkiewicz and Blockowicz, 1967) found that workers exposed to 45 to
1,640 mg MeOH/m3 had levels of MeOH in their urine (during the work shift
and immediately afterwards) ranging from 0.09 to 36.4 mg/L, the level vary-
ing according to level of exposure.
3
-------
INGESTION STUDIES
These usually involved overwhelming doses, since most animal studies
were prompted by fatal or near-fatal human accidents. The classic case re-
port is the Atlanta epidemic of 1951 (Bennett et al., 1953), involving 323
patients and 41 deaths from 90 gal. of contaminated moonshine whiskey. Very
notable is the extreme variability in individual sensitivity. One patient
died from ingesting 6 mL of MeOH, while another survived 200 mL. Cooper and
Kini (1962) cite contrasting reports in which one man consumed 540 mL without
irreversible toxicity, while blindness occurred with ingestion of 15 mL and
death from ingestion of 30 mL in another case.
SKIN ABSORPTION
All inhalation exposures (except mask tests) involve the possibility
of skin absorption. McCord (1931) showed that skin absorption and inhala-
tion exposures produced similar effects in animals. Yant and Schrenk (1937)
observed similar results in dogs given MeOH by inhalation, stomach tube, or
subcutaneously. Dutkiewicz et al. (1980) reported similar results in humans
given MeOH orally or on the skin. They calculated a dermal absorption rate
of 0.192 mg/cm2/min, but did not report toxicity from doses of 1.7 mL.
ENVIRONMENTAL CONTRIBUTIONS TO HUMAN EXPOSURE
Cigarette smoking is a source of MeOH exposure for humans. One gas
phase analysis of cigarette smoke found 180 |Jg MeOH/cigarette (Grob, 1965);
another study found 13 and 10 [Jg MeOH/40 mL puff of smoke from unfiltered
and filtered cigarettes, respectively (Newsome et al. 1965). Newsome and
Keith were reported to have found a range of 100 to 200 |Jg MeOH/cigarette
(Maddox and Mamenta, 1977).
Alcoholic beverages may contribute to an individual's exposure and ac-
cumulation of MeOH in the blood. Levels of 3.9 to 105.5 mg MeOH/L have
been reported in commercial alcoholic beverages (Schneck, 1979; Majchrowicz
and Mendelson, 1971; Carroll, 1970). Alcoholics with high blood ethanol
levels (> 100 mg/100 mL) tend to accumulate MeOH in their blood at levels
up to 2.7 mg/100 mL after an 11-d intoxication (flajchrowicz and Mendelson,
1971). Some of the MeOH accumulated by alcoholics is believed to be derived
from endogenous sources and accumulated due to ethanol's disruption of MeOH
oxidation and elimination. That some MeOH is endogenously produced is sup-
ported by studies finding MeOH levels of 0.06 to 0.49 |Jg/L and 0.3 to 3.4
ppm in normal human breath (Eriksen and Kulharni, 1963; Jansson and Larson,
1969). Another study of 54 healthy nonsmoking adults found only 3.6% of 387
breath samples to contain MeOH; the mean concentration when found was 0.549
mg/m3 (Krotoszynski et al., 1979).
Certain foods have been reported to contain MeOH. Brussels sprouts,
celery, onions, parsnips, potatoes, and swede (rutabaga) were vegetables
that contained "large" or "very large" levels (unquantifled) of MeOH after
boiling for 30 min. Frozen peas and corn and instant coffee contained
little or no MeOH after cooking (Self et al., 1963). Eriksen and Kulharni
(1963) found that levels of MeOH in human breath tended to increase 1 to 2 h
after eating.
4
-------
A potential contribution to human exposure would be the exhaust of ve-
hicles fueled by MeOH or MeOH/gasoline mixtures. Review of the numerous
literature data on MeOH levels in vehicular exhaust was beyond the scope of
this task.
INTERNATIONAL RECOMMENDATIONS AND STANDARDS
Several U.S. agencies and professional associations have regulations
and recommendations concerning the level of MeOH in different situations.
The Occupational Safety and Health Administration standard for MeOH exposure
in the workplace is 200 mg/m3 for a ceiling level. The American Conference
of Governmental Industrial Hygienists suggests 260 mg MeOH/m3 as the time-
weighted-average threshold limit value (TLV) and 310 mg/m3 as the short-
term-exposure limit (ACGIH, 1978). The American National Standard Institute
(ANSI) listed a ceiling concentration of 600 ppm (~ 798 mg/m3) MeOH with the
provision that the 8-h time-weighted average concentration of MeOH is at or
below 200 ppm (~ 260 mg/m3) (AIHA, 1978).
In the U.S.S.R., the Maximum Allowable Concentrations (MAC) in air for
1972 were 5 mg MeOH/m3 in the workplace, and 1 mg/m3 as the one-time limit
and 0.5 mg/m3 as the average limit in populated places (U.S.S.R., 1972).
The Czechoslovakian normal workplace MAC for 1970 was 100 mg/m3 with 500
mg/m3 as the short-term, single exposure permitted level (ILO, 1970).
RECOMMENDED RANGE OF CONCERN
MeOH is rapidly absorbed by all exposure routes, and is notorious for
the wide range of human susceptibility to it. The range of response for
oral ingestion varies from recovery after doses of 200 to 500 mL to death
and blindness after doses of only 6 to 60 mL. That a dose of 6 mL (approxi-
mately 1 teaspoon) could cause death appears surprisingly low, the report is
from Bennett et al. (1953), a relatively recent case study involving hos-
pital observation and treatment of poison victims. Dutkiewicz et al. (1980)
reported no toxicity from ingestion of 1.67 g (~ 2 mL). These data suggest
a range of concern of 0.1 to 1 mL for ingestion of MeOH while handling it
as an automotive fuel.
For inhalation, the TLV is currently set at 260 mg/m3, but at that
level, a workperson inhaling 10 m3 of air over an 8-h period would have an
intake of 26 g/d or 32.5 mL/d. This is well above the upper limit of the
ingestion range of concern. Chao (1959) recommended a TLV limit of 1.5
mg/m3 after a study finding eye sensitivity unaffected by 1.8 to 2.4 mg/m3.
The data of Ubaydullayev (1968) tend to support this level; eye sensitivity
was unaffected at 3.1 mg/m3. Changes in cerebral cprtex activity were de-
tected at 1.17 and 1.47 mg/m3 but not at 1.0 mg/m3. In an isolated case,
Humperdinck (1941) reported one worker had vision problems from exposure to
1.6 to 10.9 mg/m3. For inhalation of MeOH, a range of concern of 1.0 to
3.0 mg/m3 is suggested. (An 8-h exposure would result in intake of 10 to
31 mg/d or 0.013 to 0.039 mL/d.)
5
-------
MeOH is readily absorbed through the skin, and cases have been re-
ported of death, blindness, and other injury from MeOH either spilled on
clothes or applied to the skin. A rate for skin absorption of MeOH by hu-
mans of 0.192 mg/cm2/min has been reported (Dutkiewicz et al., 1980). Im-
mersing a whole hand (~ 440 cm2) in MeOH for 2 min would result in the ab-
sorption of 170 mg (0.2 mL) of MeOH or within the range of concern for
ingestion. Long or repeated skin contact with a solution of 1% or above of
MeOH would give exposures in the range of concern and should be avoided.
Appropriate personnel protective equipment, such as rubber gloves, to pre-
vent skin contact is suggested for handling MeOH fuel.
6
-------
SECTION I
INTRODUCTION
This report on methanol (MeOH)* was compiled as the seventh task under
Contract No. 68-03-2928, "Health Effects Support for the Emission Control
Technology Division (U.S. Environmental Protection Agency, Ann Arbor,
Michigan)." The goal of the project is to evaluate health effects litera-
ture on specific compounds emitted from automobiles equipped with emission-
control devices (specifically catalytic converters), not for the purpose of
creating a criteria document but to identify a range of concern or a no-
observable-effect level for each compound to serve as guidance to automobile
manufacturers in their development of future emission-control devices. This
particular report also contains a brief review of the health effects of ex-
posure to MeOH by ingestion and skin absorption as might occur in handling
MeOH if it is adopted as an alternative automobile fuel.
The present report was meant to be largely a series of charts or tables
of pertinent data with the tests logically ordered according to exposure
levels. The narrative summary was not meant to describe again each paper in
detail. There are admittedly some disadvantages in not doing so; e.g., some
of the graduations in effect that the authors of a particular paper observed
may be diluted or lost when the details are spread throughout an exception-
ally large table, or between several tables. Papers described in a largely
narrative fashion, however, often are difficult to compare. Results that
appear within their source paper to be quite definitive may appear less so
or even anomalous when juxtaposed in tabular format with other results fron)
similar studies. Hence, the present format was designed to facilitate com-
parisons .
Literature related to health effects of MeOH exposure was collected
mainly by computer search of TOXLINE and TOXBACK and manual search through
the NIOSH criteria document on MeOH. Approximately 160 papers and other
documents were evaluated, but only about 25 contained original data suitable
for tabulation.
Experimental animal and human exposure studies were evaluated and sum-
marized by a senior Ph.D. pharmacologist. Occupational exposures were rated
by an epidemiologist with an M.D. degree. Figure 1-1 is the form used for
rating documents by the project pharmacologist and epidemiologist. Each
" Also called methyl alcohol and wood alcohol. The chemical formula is
CH30H.
7
-------
Article No. 4997-7-
CHECK WHERE APPROPRIATE:
PAPER
DEFECTIVE
0
PAPER IS
SUB-
STANDARD
1
STANDARD
QUALITY
2
SUPERIOR
PAPER
3
1. Do they state/limit the problem?
2. Adequacy of sample
3. Replicafaility
4. Controls/control procedures
5. Completeness and comprehensibility
of results
6. Validity of conclusions, inter-
pretation of data
7. Applicability to health effects of MeOH as guidance for establishing a range
of concern in automobile emissions.
(circle one)
a. Clearly, directly applies/assists in establishing a range of concern
(Chronic human studies; acute exposure of humans if minimal effects.)
b. Research requires major inferences; potentially applicable.
(Chronic animal studies; acute human, maximal effect; acute animal,
minimal effects.)
c. Useful hints or suggestions; tentatively applicable.
(Acute animal, lethal effects; studies in above categories but effects
reported not appropriate.)
d. Not directly applicable (peripheral useful information).
Figure 1-1. Form for report rating.
8
-------
document was rated in a two-step procedure according to the applicability of
its subject matter and to the quality of the experimental methodology. The
letter assigned in rating the document A, B, C, or D was derived from the
corresponding lower case letters under item 7 in Figure 1-1. Thus, a study
was rated A if it directly applies to or assists in establishing a level of
concern for exposure to MeOH. The second part of the rating is the methodol-
ogy score. The document reviewer checked off which score should be given
for each of the first six items in Figure I—1, and the total was written at
the top of the pages along with the letter that rated the paper's applica-
bility. In some cases, such as reviews, theoretical papers, and low-rated
foreign language documents, a paper may have received an applicability rat-
ing (generally C or D), but none on methodology.
Data, including the MRI-assigned rating, from the papers were tabulated
by mid-level scientists. Information for each topic heading was carefully
sought; so if blanks appear in the table, the reader can generally assume
the data were not given. Sometimes a group published several papers that
described the same tests. To avoid redundancy, all pertinent papers were
cited and the test was described as well as possible from all the papers'
descriptions.
The final written summary of the tabulated data was also performed by
a senior pharmacologist. This summary attempts to reflect objectively the
scientific community's thought as a whole and does not reflect the tabular
material by weight. The tables reflect the amount of data generated, and
the summary puts the evaluated data in perspective with the overall scien-
tific community's opinions.
The references are cited in an annotated bibliography that includes
not only each document's rating, but also a brief comment on its pertinence
(or lack of same) to the study. English titles are given for foreign lan-
guage documents. An abbreviation of the language is given in parentheses at
the end of the citation.
The report is organized into the following chapters: II - Bioassay
Tests; III - Experimental Animal Inhalation Exposures; IV - Experimental Hu-
man Inhalation Exposures; and V - Occupational Exposures and Human Case Re-
ports. The Summary precedes the entire report.
9
-------
SECTION II
BIOASSAYS
Bioassay studies involving MeOH are limited. A brief summary of the
literature is presented here rather than a tabulation of the limited data.
These in vitro studies contribute little in our understanding of the mecha-
nisms of activity or toxicity of the chemical in man that would be useful
to the task of determining a range of concern for human exposure to MeOH in
automobile exhaust.
Mazur et al. (1969) noted the gut contraction that occurred in rabbits
exposed to MeOH, defined the fraction or metabolite responsible, and mea-
sured its effects on the contraction amplitude and coronary output of the
isolated rabbit heart. Methanol (and formic acid), 0.0001 M, decreased both
rate and cardiac output while formaldehyde at that concentration had no ef-
fect .
Thomas et al. (1980) measured prostaglandin (PgE2) released from rat
isolated perfused lungs exposed to varying concentrations of aliphatic alco-
hols. MeOH in increasing concentrations, up to 0.02 mM, caused increased
PgE2 release; higher concentrations caused a decrease.
In the one bioassay study involving respiratory tissue, Tremer et al.
(1959) found that 0.4-1.4 mg MeOH in aerosols at the rate of 27 mL/s for 2 s
inhibited mucus flow of ciliated epithelium from the esophageal tract of the
leopard frog.
Gotterer (1969) showed that rat liver beta-hydroxybutyrate dehydrogenase
enzyme assay required 4,600 mM MeOH to produce 50% inhibition. For compari-
son, quinine produced 50% inhibition with 0.11 mMol.
Hohne and Patsch (1969) studied bacterial inhibition by several alco-
hols. Two percent MeOH had no effect on Staphylococcus aureus, Escherischia
coli, and Klebsiella pneumoniae were unaffected by 1% MeOH. It was less
toxic to these organisms than was isopropyl or isomeric butyl alcohols.
Khan (1969) showed that the microsomes of the common housefly produced
an epoxide with the cyclodiene aldrin, and that MeOH at high concentrations
stimulated this microsomal epoxidation.
Obe and Ristow (1977) found no sister chomatid exchange (SCE) following
7- to 8-d treatment of Chinese hamster ovary cells in culture with 0.1% (by
volume) MeOH daily.
11
-------
SECTION III
EXPERIMENTAL ANIMAL INHALATION EXPOSURES
This chapter presents the essential parameters of the studies involving
animal inhalation experiments. Relatively few studies were found in thp
literature and a number of these involve rather high-level exposures (from
55,214 to 5,320 mg/m3); effects reported range from a 6-h LD50 for mice of
54,530 mg/m3 to no illnesses when dogs inhaled MeOH at 13,300 mg/m3 for 3
min, 8 times/d for 160 d. Changes were reported in the nervous systems of
rats and rabbits, with repeated and chronic doses of 5 to 5.3 mg/m3. No
effects reported at 1.7 mg/m3 for 12 h/d for 90 d or to 0.57 mg/m3 continu-
ously for 90 d.
The primary organization of data is by species, in order of increasing
weight (mice to monkeys in this case). Within a species, studies are di-
vided by dosing duration: acute exposure (S 24 h), repeated exposure, and
chronic exposure 90 d). Within a single table, reported results are
listed in order of decreasing exposure level.
In the animal exposure tables in this section (Tables III-1 through
111-10), the column headed "Total length of experiment" includes not only
the total length of exposure to MeOH but also any recovery time observed in
the study. This recovery time was included to note the endurance or re-
versibility of the toxic effects.
13
-------
TABLE IH-1 MICE--ACUTE EXPERIMENTAL EXPOSURE TO MeOII
Compound(s) and
corn eiitration(s)
in mg/m' (ppm)
Species/ No of
Humidity/ Mode of strain/ test No oT
temp exposure age/weight animals controls
Duration and ToLal
frequency of length oT
exposure experiment
h f feel s
Kelcienie .jii(I
raling
HeOH ~ 55,214
(41,514)
2 1-L inha-
lation cham-
ber with
only head
exposed
Mice,
Swiss-
Webster
8 H
Served as 10 min
own controls
10 mm RI'so value < a I cnJ a Led from mice responses, Kane et al
RDso is defined as the concentration of (.1980)
chemical that produces a 50% decrease in C-ll
respl rat i oil i ate
MeOH ~ 54,530
(41,000)
22-25°C
28-L inha-
lation cham-
ber
Mice
6 h, once 30 h (all Calculated 6-h LC^o Livers of exposed
deaths 24 animals had a significant degree of (enLri-
h after lobular fatty metamorphosis F.yes had
exposure acute keroconiunctivitis characterized by
counted) an infiltrate of neutrophils into the
cornea and conjunctiva
Scott (1978)
B-9
-P-
-------
TABLE III-2- MICE—REPEATED DOSE EXPERIMENTAL EXPOSURE TO MeOH
Compound(s) and
concentration(s)
in mg/m3 (ppm)
Species/ No of Duration and Total
Humidity/ Mode of strain/ test No of frequency of length of
temp exposure age/weight animals controls exposure experiment
Effects
Reference and
rating
MeOH 1,329 ± 29
(999 + 22)
22-25°C
28-L inhala- Mice
tion chamber
66 H
30 M
6 h/d, 5 ~ 6 wk No abnormal behavior and no deaths Weight
d/wk, 3 wk remained steady Livers appeared normal
but were significantly lower in weight from
animals sacrificed during exposure Liver
triglyceride levels decreased significantly
during exposure but returned to control
levels during 18-d recovery period No
retinal degeneration or other histological
damage to eyes of mice examined at end of
exposure
Srott (1978)
R-9
-------
TABLF. 111-3 RATS--ACUTK EXPERIMENTAL. F.XPOSURF. TO MeOll
Compound(s) and Species/ No of Duration and Total
concenLration(s) Humidity/ Mode of strain/ test No of frequency of Length of Reference and
in mg/m3 (ppm) temp exposure age/weight animals control"; exposure experiment Fffccls rating
MeOll 6,650 250-L inha- Rats, S 6 2 6 1 h 9 li No change in carboxyhemoglobm Levels at 2 Cmchta ct
(5,000) lation cham- Sprague- or 4 h postexposure al (1979)
ber DawLey C-8
200-450 g
-------
TABLE III-4 RATS--REPEATED DOSE EXPERIMENTAL EXPOSURE TO MeOII
Compound(s) and
concentration(s)
in mg/m3 (ppm)
Species/ No. of
Humidity/ Mode of strain/ test No of
temp exposure age/weight animals controls
Duration and Total
frequency of lengLh ol
exposure experiment
Effects
Reference and
ratlng
MeOH 50
Albino
rats
10
10
12 h/d ex- £ 18 wk (1 A slight change of the ratio of the chron- Chao Chen-Tsi
cept for mo habitu- axy of the muscle antagonists was seen in (1959)
days off for ation to the 2nd wk which became more expressed in A-8 (human)
3 mo lest con- the 4th wk Starting from the 8th wk of B-8 (animal)
ditions poisoning, the values of the chronaxies of
plus 3-wk the flexors and extensors converged, buL by
recovery the end of poisoning they had diverged
period) The ratio returned to normal in the recov-
ery period
The histopathologicaI examination revealed
catarrhal-desquamative tracheitis, bronchi-
tis, hyperplasia of the tracheal submucous
glands, whose infiltrates were of a slightly
lymphoid character Changes in the trachea
were somewhat more expressed than in the
bronchi and lung tissue
Swelling, hypertrophy of the muscle layer oT
some medium- and low-caliber arteries of the
lungs, and very weakly expressed degernative
changes in the liver (nonuniform staining of
the nuclei and granularity of the protoplasm)
were sometimes observed
Dendrites of the neurons of the brain cortex
were distinctly deformed and their branches
had disappeared The top dendrites of the
pyrimidal cells were more affected
MeOH 1 77
Albino
rats
10
10
12 h/d ex-
cept for
days off for
3 mo)
i 18 wk (1
mo habitu-
ation to
test con-
di t ions
plus 3 wk
recovery
perlod)
The concentration was lower than the human
odor threshold (2 U mg/m3) or the threshold
of reflex action on light sensitivity ol
the eye
At the end of poisoning, all rats were
healthy and active and had gained weight
No classical toxic symptoms (irritation or
nervous system affection) The average
chronaxy of the muscle extensors was sig-
nificantly higher than the average chronaxy
of the flexors, a*; it. was in the control
group
Chao Chen-Tsi
(1959)
A-8 (human)
n-8 (anima1)
(< out i mini)
-------
TABLE 111-6 (con 11 nueil)
Compound(s) and
concentration(s)
in mg/m3 (ppm)
Species/ No of Duration and Total
Humidity/ Mode of strain/ test No of frequency of length of
temp exposure age/weight animals controls exposure experiment
Effects
Reference and
rati ng
No changes were observed in the internal
organs, but during staining, neurons o[ the
brain cortex of one rat showed distinct
deformations of the dendrites
The author proposed 1 5 mg/m3 as a suitable
value for the MAC
00
-------
TAIirr. ril-5 RATS'-CHRONIC FXPhRIMFNTAf. FXPOSUHP TO MeOH
Compound(s) and Species/ No of Duration and Total
concentration(s) Humidity/ Mode of strain/ Lest No of frequency of length of Reference and
in Big/m* (ppm) lemp exposure age/weipht inimnls controls exposure experiment Fffccts rating
MeOH 5 31 ± 0 62
HHCO, 0 5-0 6
MeOH, 5 0-6 0
Following intra-
tracheal intro-
duction of
resin-treated
or untreated
coal dust
MeOH 0 57 ±
0 059
Rats ,
white,
100-200 g
!¦> M
15 M
Not given
Rats
Rats,
white,
100-200 g
Cont i niioiii,
90
Nos
not
given
Rats
dosed
with 'in-
treated
coal
dust and
not ex-
posed to
HCH0 and
NeOH
15 H
Continuous9
15 M
Continuous,
90 d
90 )
6 mo
90 d plus
recovery
period
(20 d f)
Animals were k tivc, weight normal, and ap-
peared hcdlthy Significant changes in
both motor and antagonist chronaxy ratios
beginning 6th wk, returned to normal during
recovery period Drop in excretion of co-
proporphyrni in urine beginning 7th wk,
normalisation on d 20 of recovery De-
cruise in cholinesterase activity beginning
6th wk, normalization during recovery pe-
riod Change in protein fractions in blood
beginning 7th wk
This collagen content per identical lung
weight was significantly higher in the ex-
posed group that had been dosed with un-
treated coal dust (14 8 ± 0 6 versus 8 7
± 0 4 nrg %, P < 0 07 )
More severe disturbances in lung struc-
ture both in the bronchial tree and the
respiratory branch occurred in exposed
rats predosed with treated dust The
changes in the bronchi were also more se-
vere in the exposed rats than in the con-
trol s
Animals were active, weight normal, and ap-
peared healthy No effect on chronaxy in-
dex, or on blood and urine parameters
measured
Ubaydullayev
(1968)
B-8
Gadzhiev et
al (1977)
D-4
Ubaydullayev
(1968)
B-8
-------
TABLE III-6 RABBITS--CHRONIC EXPERIMENTAL FXPOSURE TO NeOII
Compounii(s) and Species/ No of Duration and Total
concentration(s) Humidity/ Mode of strain/ test No of frequency of length of Reference and
m mg/ra3 (ppm) temp exposure age/weight animals controls exposure experiment Effects rating
MeOH ~ 5 ("near
the 1968 MAC")
Rabbits,
mature
ho
o
A h/d, 6-7 6-7 mo, General nervous system changes were ob-
mo animals served for other animals exposed to hexa-
killed nol, heptanol, nonanol, and decanol as well
by air as methanol The reactions of the retina
embolism were of the same type after exposure to all
and eyes the alcohols at the Levels of their MACs
immedi- The structure and functional capacity of
ately enu- the retina, optic nerve, optic chiasm, op-
cleated tic tract, anterior corpora quadrigemina,
and cerebral optic lobe were damaged The
retinal changes resembled those reported
from oral dosing at MeOH--pathological
changes at the ganglionic cells and pro-
liferation of the glial elements
Irritation of the nerve fibers of the optic
nerve, optic chiasm, and optic tract was
expressed in "corkscrew" twisting of the
fine nerve fibers and protoplasm leakage
along the path of the thick fibers Pro-
liferation of the glia, hyperemia of the
vessels, and dilation of the perivascular
space also occurred The optic nerve was
least affected
Fel'dman and
VendiJ o
(1973)
C-5
Degenerative phenomena in the neurons and
proliferative phenomena in the glia were
also observed in the visual region of the
brain cortex
The histological results agree with those
of electrophysiological studies
-------
TABLE 111 - 7 DOGS--ACUTF EXPF.RIMI- NI Al, EXPOSURE 10 NeOtl
Compound(s) and
concentration(s)
in mg/m3 (ppm)
Species/ No of
Humidity/ Mode of strain/ test No of
temp exposure age/weight animals controls
Duration and Total
frequency of length of
exposure experiment
Effects
Reference and
rating
MeOH ~ 19,950
(15,000)
Dogs
22-24 h 22-24 h Blood levels of MeOH were 1,390-1,470 mg/
for two 100 g at end of exposure but dropped to
dogs, re- 335 mg/100 g 48 h later in the one dog
covery pe- LeveLs in tissue were in the 500-1,000 mg/
riod of 100 g range at end of exposure but dropped
48 h for to 200-400 mg/100 g 48 h later The dis-
one dog tribution of MeOH to tissues and fluids w.is
closely related to the amount of water in
the various body fluids and tissues
Yant and
Schrenk
(1937)
C-7
MeOH ~ 5,320
(4,000)
Dogs
12 h
12 h
Blood level of MeOH was 100 mg/100 g Lev- Yant and
els in tissue ranged from 95 mg/100 g in Schrenk
kidneys to 17 mg/100 g in adipose tissue (1937)
The distribution of MeOH to tissues and C-7
fluids was again closely related to the
amount of water in the tissue or fluid
MeOH 390-720
Inhalation
through nose
mask while
anesthetized
Dogs,
mongrel,
8-22 kg
Not re- Not re- Retention of MeOH by respiratory tract in- Egle and
ported ported creased with increased exposure concentra- Gochberg
tion hut was not affected by tidal volume (1975)
l)-l 1
MeOH 400-600
Inhalation
through
tracheotomy
while anes-
thetized
Dogs,
mongrel,
8-22 kg
g 5
Not re- Not re- Lower respiratory tract MeOH retention Egle and
ported ported rate was 64 6-68 2% with no relationship Gochberg
to ventilatory rate Upper respiratory (1975)
tract retention was 63 0-66 1% and related D-ll
to ventilatory rates, with increased reten-
tion as the ventilatory rate increased
MeOH 400-600
Inhalation
through nose
mask while
anesthetized
Dogs,
mongrel,
8-22 kg
S 5
Not re- Not re- Total respiratory tract retention of MpOII Egle and
ported reported was 81 2-88 4% over a range of ventilatory Gochberg
rates of 7-30/min There was a slatisti- (1975)
cally significant relationship between in- D-ll
creased retention and higher ventilatory
rates
-------
TABI.F. II1-8 DOGS--REPEATED DOSE EXPF.R1MEN1AL EXPOSURE 10 MhlHANOL (MeOH)
Compound(s) and
concentration(s)
in mg/m3 (ppm)
Species/ No of
Humidity/ Mode of strain/ test No of
temp exposure age/weight animals controls
Duration and Total
Frequency of length of
exposu re oxpcr\mont
Hffects
RrIcrone e and
ra 11 tig
MeOH 5,320
(4,000)
Dogs
Continuous, d for 2, Blood levels of MeOH after exposures were
5 d recovery 317-570 mg/100 g but fell to 0 in the one
period of dog 120 h later Levels in tissues were in
120 h for the 200-400 mg/100 g range at the end of
one dog exposure but 120 h later dropped to 0 The
distribution of MeOH was closely related to
the amount of water in the various body
fluids and tissues
Yant and
Schrenk
(1917)
C-7
N5
ro
-------
TABLE 111 -9 DOGS--CHRONIC EXPERIMENTAL EXPOSURE TO HcOH
Compound(s) and Species/ No of Duration and Total
concentration(s) Humidity/ Mode of strain/ test No of frequency of length of Reference and
in mg/m3 (ppm) temp exposure age/weight animals controls exposure experiment Effects rating
MeOII ~ 13,300
(~ 10,000)
288 ft3 in-
halation
chamber
Dogs
Served as ~ 3 mm, 8 ~ 160 d Regular increase in weight, no signs of Sayers et al
own control X/d for 100 discomfort, no significant changes in blood (1944)
consecutive parameters, no eye pathology other t-han C-7
d slight disk and fundi congestion on several
occasions Blood MeOH level at end of d
was avg 6 5 and 14 mg/100 ml, level dropped
to 0 by next d exposure 69% of time
HeOH ~ 599-665
(450-500)
ro
w
Inhalation Dogs 3 H, Used six 8 h/d, 7 d/ ~ 480 d No symptoms or abnormal behavior Weight
chamber, 1 F control wk, 379 d remained steady or increased, except for
288 ft3 with plus dogs; test weight changes associated with pregnancy
eight air four dogs also (Female bred to one of males during expo-
changes/h pups served as sure period, gave birth to five pups )
born own controls Pups were normal, one pup died shortly af-
dunng with 48-d ter birth, its death attributed to smother-
expo- observation ing due to crowded conditions, others grew
sure period prior and developed normally Blood chemistry
period to exposure and cell counts had no significant varia-
tions from pre-exposure levels Regular
ophthalmoscopic eye examinations were made
and found a possible slight increase in con-
gestion, but no edema, excavation, signs of
atrophy, or indications of impaired vision
Blood sampled approximately monthly had avg
MeOH levels of 7-15 mg/100 mL after 8-h ex-
posure and < 5 mg/100 ml, 16 h later before
next MeOH exposure MeOH blood levels ap-
peared to increase during the 275th to JOOth
d of exposure reaching levels of 20-50 mg/
100 mL Blood MeOH levels also increased in
some dogs when they were exercised on a
treadmill, but decreased in others No sig-
nificant pathology observed in any organs
Sayers et al
(1942)
B-10
-------
TABLE 111 -10 MONKEYS—ACUTE EXPERIMFN'I Al, EXPOSURE TO NeOH
Compound(s) and
concentration(s)
in mg/m3 (ppm)
Species/ No of
Humidity/ Mode of strain/ test No of
temp exposure age/weighl animals controls
Duration and Total
frequency of length of
exposure experiment
Effects
Reference and
rat 1ng
MeOtl 6,650
(5,000)
1,000-L in-
halation
chamber
Cynomolgus
monkeys,
2-3 kg
3-4
3-4
1 h
6 h LjtLle change in carboxyhrmoglohin levels
at 0, 2, 4, or 6 h postexposure
Ciuchta el
al ( 19 79 J
C-8
N5
-------
SECTION IV
EXPERIMENTAL HUMAN INHALATION EXPOSURE
This chapter describes acute laboratory human exposures to MeOH. A
number of the studies presented in Table IV-1 are odor threshold determina-
tions. Reported odor thresholds range from a high of 7,800 mg/m3 to a much
lower 4.3 mg/m3, with values in between of 71, 133, and 1,500 mg/m3. Vary-
ing levels of impurities in the MeOH samples tested may account for the dis-
crepancy in results, since odor thresholds of compounds of low odor are
greatly influenced by the presence of odorous impurities. Two studies mea-
sured urinary levels of MeOH during inhalation; another, cerebral cortex re-
flex activity; two investigated eye responses. Effects on eyes were found
at 3.3 to 6.5 mg/m3 levels but not at 1.8 to 2.4 mg/m3, all far below the
TLV limit of 260 mg/m3 but above the upper limit of this report's recom-
mended range of concern of 3.0 mg/m3.
25
-------
TABLF IV-1 HUMANS--ACUTE AND REPEATFD DOSE EXPFRIMFNTAL INHALATION FXPOSURE TO MeOH
Compound and No of Duration and Total
concentration Mode of test No oT frequency of length of Reference and
in mg/m3 (ppm) exposure subjects controls exposure experiment Effects rating
MeOH 11,700
Inhalation
by "sniffing"
flask of MeOH
8 M, 8 F,
ages 31-63
Tests repeated
up to 5 X/d
for an unspec-
ified number
of d for sev-
eral mo
Not gjven
Clearly perceptible odor threshold measured at 760
torr and 20°C
Hay (1966)
D-5
MeOH 7,800 Inhalation 8 M, 8 F,
by "sniffing" ages 31-63
flask of MeOH
Tests repeated
up to 5 X/d
for an unspec-
ified number
of d for sev-
eral mo
Not given
Just perceptible odor threshold measured at 760 torr
and 20°C
May (1966)
D-5
MeOH - 1,995
(1,500)
Inhalation
from air
blender
Not given
Odor threshold
Scherberger
et al (1958)
D-10
MeOH 1,430
ro
Small sealed
room, 22 9 m3
1 (G L )\
same sub-
ject also
exposed to
1,350, 732,
and 700 mg/
m3 levels
at unknown
intervals
Served as
own control
1 6 h - 1st ex-
posure, 2 9 h -
2nd exposure
~ 4 5 h Urinary MeOH level increased steadily during both Leaf and
exposures, was 2 00 mg/100 mL at end of 1st expo- Zatman (1952)
sure During 2nd exposure, level at 1 6 h was 1 88 A-7
mg/100 mL, and 2 56 mg/100 mL at 2 5 h
MeOH 1,350
Small sealed
room, 22 9 m3
1 (C L ),
same sub-
ject also
exposed to
1,430, 732,
and 700 mg/
m3 levels
at unknown
intervals
Served as
own control
3 h
3 3 h Urinary MeOH level increased steadily during expo-
sure, was 1 46 mg/100 mL** at 1 6 h and 2 06 mg/100
mL at 2 5 h
Leaf and
Zatman (1952)
A-7
* Subject's initials
** Urinary MeOH levels reported by Leaf and Zatman (1952) are corrected for the control value, the level found on entry into the exposure room prior to any
MeOH exposure
(continued)
-------
IABI.F. IV-1 (continued)
Compound and
concentrntion
in mg/m3 (ppm)
Mode of
exposure
No of
t est
sub jeel s
No of
ronl rr» I s
Uur it lon in«l
f requency of
exposu re
Totil
lrnglh of
cxpei imcnt
Fffccts
Reference and
rating
HeOH 1,230
Small sealed
room. 22 9 m3
1 (I J 7. ),
same sub-
ject also
exposed to
655 and 732
mg/m3 levels
at unknown
intervals
Served as
own control
2 5 h
- 3 h Urinary MeOll level increased steadily during expo- Leaf and
sure, was I 90 mg/100 mL at 16 h, and 2 54 mg/ Zatman (1952)
100 mL at 2 *) li A-7
MeOH 732
Small sealed
room, 22 9 m3
1 (L J Z ),
same sub-
ject also
exposed to
1,230 and
655 mg/m3
levels at
unknown
intervals
Served as
own control
4 h
4 h
Urinary MeOll level increased steadily during expo- Leaf and
sure, was 0 94 mg/100 ml. at 1 6 h, 1 32 mg/100 mL Zatman (1952)
at 2 1 h, and, at the end of the exposure, - 2 2 A-7
mg/100 mL
MeOH 732
Small sealed
room, 22 9 m3
ho
1 (G L ),
same sub-
ject also
exposed to
1,430,
1,350, and
700 mg/m3
levels at
unknown
intervals
Served as
own control
4 h
4 h
Urinary MeOll level increased steadily during expo- Leaf and
sure, was 0 77 mg/100 mL at 1 6 h, 1 05 mg/100 mL Zatman (1952)
at 2 r> h, and, at the end of exposure, ~ 1 8 mg/ A-7
100 mL
HeOH 700
Small sealed
room, 22 9 m3
1 (G L ),
same sub-
ject also
exposed to
1,430,
1,350, and
732 mg/mJ
Served as
own control
3 1 h
3 1 h Urinary MeOH level increased steadily during expo-
sure, was 0 56 mg/100 mL at I 6 h, and 0 78 mg/100
mL at 2 5 h
Leaf and
Zatman (1952)
A-7
(continued)
-------
TARI.F IV— 1 (t onLi nuetl)
Compound and
concentration
in mg/m3 (ppm)
Mode oT
exposure
No of
test
subjerts
No of
cont rols
Duration and
frequency of
exposure
Tota L
length of
experiment
Effects
Reference and
rating
HeOII 655
Small sealed
room, 22 9 m3
1 (L J 2 ) ,
same sub-
ject also
exposed to
1,230 and
732 mg/m3
levels at
unknown
intervals
Served as
own control
3 3 h
Urinary MeOH level increased steadily during expo- Leaf and
sure, was 0 76 mg/100 tnL at 1 6 h, 1 03 mg/100 mL Zatman (1952)
at 2 5 h, and, at the end of the exposure, ~ 1 4 A-7
mg/100 ml
MeOH 298-337
MeOH 300
MeOH 231-251
MeOH 205
MeOH 200
Ethanol 514
Room,
64 3 ft
Room,
64 3 rr
Room,
64 3 m3
Room,
64 3
Room,
64 3 in3
3 M, ages
31-56
4 M, ages
31-56
5 M, ages
31-56
4 M, ages
31-56
3 M, ages
31-56
17 M
14 F
17 M
14 F
8 h/d for 4
consecutive d
(urine col-
lected at 2-h
lnterva1s)
8 h, once
96 h
24 h
4 h/8 h, in
2-h periods
with exposures
chosen to cover
all possible
combinations of
early, late, and
alternate expo-
surc/nonexposure
8 h, once
8 h
24 h
No accumulation of MeOH in the body, urine levels
returned to normal before the next exposure
Lung retention independent of lung ventilation and
duration of exposure Urine MeOH level increased
from norm of ~ 0 7 mg/L to 9 5 mg/L at 8 h and re-
turned to normal 16 h after end of exposure
MeOH in urine was affected by "pauses" in exposure
level decreased Short-term urine samples did not
accurately reflect level of total exposure in this
type of intermittent exposure
Lung retention independent of lung ventilation and
duration of exposure Urine MeOH level increased
from norm of - 0 7 mg/L to 6 6 mg/L at 8 h and re-
turned to normal 16 h after end of exposure
No inhibitory effect from ethanol on level of MeOH
in urine
Sedivec et al
(1981)
A-10
Sedivec et al
(1981)
A-10
Sedivec et al
(1981)
A-10
Sedivec et al
(1981)
A-10
Sedivec et al
(1981)
A-10
(continued)
-------
TAK1! IV-1 (< nnt iniif
Compound and
concentration
in mg/m3 (ppm)
No of Dim.tI ion md Totil
Mode of tost No of f i crjirnncv c»T length of
exposure subjects iontro|<; exposure experiment
MeOII 199
Room,
64 3 n
4 M, igos
31-56, 2
1 imi ted 1 i fl-
uid intake,
2 increased
it, sub]c(ts
switched
roles 2nd wk
8 h , on( e/u It
MeOII 133 (100)
500 ft3 in-
halation
chamber
Four
trained
odor
panelists
Duration not
given, £ 20
mi n b< t ween
tests
Net g i vr n
MeOH 118
Room, 64 3 m3,
19 5-rain exer-
cise periods
on a bicycle
ergometer
4 M
8 h
ro
-------
TARI.F IV-1 fcontinued)
Compound and
concentration
in mg/m3 (ppm)
Mode of
exposure
No of
lest
subject*;
No of
controls
Duration and
frequency of
exposu re
Total
length of
experiment
Effects
Reference and
rating
MeOH - 19 95
(4 26)
Odor fountain
Trained
odor panel
with unre-
ported num-
ber of sub-
jects
20 min
20 min
Absolute odor threshold, concentration at which 50%
of the odor panel observed an odor
Hellman and
Small (1974)
A-3
HeOH 4 3-11
The author
states only
that the
method to
measure the
odor thresh-
old was that
recommended by
the "Committee
on Sanitary
Protection"
11
Not given
Not given
The range represents the minimal methanol concentra-
tions perceived by the individual subjects
Chao Chen-Tsi
(1959)
A-8 (human)
B-8 (animal)
HeOH 5 7-6 5
U>
o
Served as own
controls
15 min pure
air fol-
lowed by 5
mj n McOII-
air, "sev-
eral times"
(probably
14 or 15)
Pattern of dirk adaptation changed more strikingly
from that of the controls than seen at lower con-
centrations
Chao Chen-Tsi
(1959)
A-8 (human)
B-8 (animal)
HeOH 4 3-4 7
Not given
Served as own
contiols
15 min pure
air fol-
lowed by 5
min MeOII-
air, "sev-
eral times"
(probably
14 or 15)
Pattern of dark adaptation was markedly altered from
that of the controls
Chao Chen-Tsi
(1957)
A-8 (human)
B-8 (animal)
HeOH 4 5
25, ages
18-40
Not given
Not given Odor threshold
Ubaydullayev
(1968)
A-8
HeOH 4 11
3, ages Served as One tpst expo-
18-25 own control sure/d, 15-20
min
Not given
Eye adaptation to the dark or sensitivity to light
was determined Eye sensitivity was decreased ^
Ubaydullayev
(1968)
A-8
* Interpretation of effect uncertain because of limited information supplied by paper
-------
TABLE IV-1 (continued)
Compound and No of Duration and Total
concentration Mode of test No of frequency of length of Reference liwl
in mg/m1 (ppm) exposure subjects controls exposure experiment Effects rating
HeOH 3 3-3 7
Not given
Served as Not given
own controls
15 nun pure
air fol-
lowed by 5
min MeOH-
air, "sev-
eral times"
(probably
14 or 15)
The threshold of reflex action on light sensitivity
The pattern of dark adaptation was not greatly dif-
ferent from that of the controls
Cliao Chen-lsi
(1959)
A-8 (human)
R-R (animal)
MeOH 3 06-3 52 Not given
1, ages Served as One test ex- Not given Eye adaptation to the dark or sensitivity to light Ubaydullaycv
18-25 own control posure/d, was determined Lower concentration was no effect (1968)
15-20 min level At higher concentration sensitivity changed, A-8
first increasing, then decreasing, and finally re-
turning to near normal
MeOH 1 8-2 4 Not given
Served as Not given
own controls
15 min pure
air fol-
lowed by 5
min MeOH-
air, "sev-
eral times"
(probably
14 or 15)
No difference in the pattern of dark adaptation from
that of the controls
Chao Chen-Tsi
(1959)
A-8 (human)
B-8 (animal)
MeOH 1 46
Not given
6 (sub-
jects se-
lected for
olfactory
sensitiv-
ity)
Served as Not given Not given Significant change in a lpha-rhytlun amplitude of
own control cerebral cortex reflex activity in all sul>|ects
Ubaydullaye^
(1968)
A-8
MeOH 1 17 Not given 4 (sub- Served as Not given Not given Significant change in alpha-rhythm amplitude of UbayduIlayev
jects se- .own control cerebral cortex reflex activity in two subjects (1968)
lected for A-8
olfactory
sensiLiv-
uy)
(c on 11nurd )
-------
TABLE IV-1 (contjnueil)
Compound and No of
concentration Mode of test No of
in mg/m3 (ppm) exposure subjects controls
Duration and lota I
frequency of length of
exposure experiment
effects
Reference and
ratj ng
MeOH 1 01
6 (sub-
jects se-
lected for
olfactory
sensitiv-
ity)
Served as Not given
own control
Not given No effect on alpha-rhythm amplitude of cerebral
cortex reflex activity
Ubaydullayev
(1968)
A-8
U)
hJ
-------
SECTION V
OCCUPATIONAL EXPOSURES AND HUMAN CASE REPORTS
This chapter describes studies of occupational exposure to MeOH and
contains a brief review of the numerous human case histories reported in the
literature. The occupational studies (Table V-l) are not particularly useful
in establishing a range of concern for MeOH exposure because of poor control,
lack of health effect information, or confounded exposure. One study found
11 workers who developed vision defects from exposure to 1.6 to 10.9 mg
MeOH/m3, but this is an isolated case. Headaches were reported by office
workers exposed to 20 to 500 mg MeOH/m3, and also by two workers in another
office where the MeOH exposure was much lower (~ 3.2 to 6.5 mg/m3) but con-
founded by the presence of toluene and CO.
Almost all of the case histories are early publications that give lim-
ited information, especially as to level of exposure. Because of the lim-
ited data, these cases are difficult to tabulate and contribute little to-
ward quantifying a range of concern, but are of interest in that they
definitely establish the toxicity of MeOH to humans through all routes of
exposure.
Some of the earliest inhalation cases involved occupational exposure
of workmen shellacking the interiors of beer vats. Wood and Buller (1904),
Wood (1912), Carhart (1908), Herbert (1902), Jelliffe (1905), Tyson (1912),
and Hamilton (1925) all report cases of workmen entering poorly ventilated
beer vats and using varnish made with MeOH. These reports indicate that a
number of workmen collapsed and either died or were left partially or to-
tally blind as a result. These papers--as well as ones by De Schweinity
(1901), Strieker (1908), and Hawes (1905) that reported other cases of
painters and varnishers harmed by MeOH exposure—established the toxicity
of MeOH by inhalation years ago. Descriptions of cases are limited; but,
in general, the initial signs of toxicity were delayed until 1 day or more
after the initial exposure when the workmen experienced various symptoms
such as headaches, nausea, and failing vision.
Tyson (1912) reports the cases of two women who worked polishing lead
pencils using varnish made with MeOH. Both had failing vision and other
symptoms that cleared somewhat when leaving the workplace and getting fresh
air.
The hat stiffeners were another early occupation in which workers suf-
fered from MeOH exposure. Baskerville (1913) reported the cases of 15 such
workers who had various health effects and diminished vision from MeOH ex-
posure while working from 6 months to 32 years with MeOH. The testimony of
33
-------
Danburg, Connecticut, hatters before Congress that 75 of their number had
suffered health effects and/or impairment of sight contributed to the pass-
age of a measure that made revenue-free denatured grain alcohol available
for industrial use.
Another case of loxic occupational exposure to MeOH involved workers
manufacturing artificial flowers. Twenty women were reported to have con-
junctivitis and skin inflammation from their use of dyes dissolved in MeOH.
Other occupational cases involved a man using a liquid shoe dye (Robinson,
1918), a worker in a nitrocellulose plant, and a chemical-pharmaceutical
factory worker (NIOSH, 1976).
A few case histories clearly involving skin absorption have been re-
ported, although some inhalation may have occurred in each case. One in-
volved a painter who spilled a gallon of MeOH down his leg soaking his
clothes and shoe. He let them dry on him and within a few days blindness
developed (Hamilton, 1925). Wood and Buller (1904) report the case of a
woman who bathed her head and face daily with MeOH for weeks. Her vision
diminished until the MeOH applications were discontinued. Other cases in-
volved 21 children who had cloths soaked in MeOH applied to their abdomens
and held in place by rubber pants. Signs of intoxication developed in 1 to
13 h; 12 died, the others recovered without any permanent damage (NIOSH,
1976).
Literally hundreds of cases of poisoning by ingesting MeOH have been
reported. By 1913, Baskerville had listed a series of 720 reported cases
of which ~ 50% were fatal and ~ 25% resulted in permanent impairment of
vision or blindness. Most of these cases involved drinking bootleg or
cheap alcoholic beverages that had been adulterated with the cheap, readily
available wood alcohol. Dose information is limited, but Baskerville re-
ports a case where total blindness resulted from drinking 0.5 fluid ounce
wood alcohol (~ 15 mL) and another case of death from 0.75 ounce (~ 22 mL).
These case histories also indicate that extreme variability of individual
sensitivity to MeOH exists as other cases were reported of individuals con-
suming four or more ounces of MeOH and recovering completely (Baskerville,
1913).
Cooper and Kini (1962) report that during the prohibition period in
the United States there were 400 fatalities due to MeOH ingestion in
7 months. They also quote a 1950 report by Zohl that estimates 6% of all
blindness in the Armed Forces during World War II was caused by MeOH inges-
tion. Other papers that detail later case histories but with limited dose
information are Menne (1938), Closs and Solberg (1970), McLean et al.
(1980), and McMartin et al. (1980).
Several major outbreaks of MeOH poisoning have been reported. Kane
et al. (1968) reported on 18 cases in Kentucky. Cooper et al. (1952),
Benton and Calhoun (1953), and Bennett et al. (1953) reported on the
Atlantic epidemic of 323 cases with 41 deaths. Individuals had consumed
illicit whiskey of 30 to 40% MeOH. Onset of symptoms varied from 40 min to
72 h and included visual disturbances, headache, and gastrointestinal dis-
turbances. Again, great individual variable was evidenced—one individual
died from ingesting 15 mL, another individual survived 500 mL.
34
-------
TABLE V-l STUDIES OF OCCUPATIONAL EXPOSURE TO MeOII
Compound(s) and
Concentration(s)
in mg/m3 (ppm)
Description
Population Group
Exposed
Controls
Effects
Rema rks
Reference and
Ra 11 rig
leOH 754-1,640
'hand unloading
ind crushing of
rholesterol, 1 h
?ach shift)
Workers in a plant
manufacturing emul-
gents from choles-
terol
None
Urine sampled during work shift and 8 h
afterwards at 2-h intervals
MeOH in urine during work shift ranged
from 14 4-36 4 mg/L, with 1st level of
one worker at only 4 8 mg/L After work,
levels ranged from 0 36 to 3 96 mg/L
with highest levels 6 and 8 h after work
shift
No health effects measured Useful, Dutkiewicz
however, for correlation of environ- and
mental exposures to physiologic mea- Blochowicz
surements in exposed persons In- (1967)
adequate numbers to be convincing C-6
and no real controLs are present
Ui
MeOH 45-894
(short-term ex-
posures for 0 25-
5 h during cer-
tain processes in
production cycle)
Urine MeOH levels during work shift
ranged from 0 83 to 22 5 mg/L After
work levels ranged from 0 046-1 37 mg/L
No health effects measured Useful, Dutkiewicz
however, for correlation of environ- and
mental exposures to physiologic mea- Blochowicz
surements in exposed persons In- (1967)
adequate numbers to be convincing C-6
and no real controls are present
HeOH 59-270
(longer-term ex-
posures during
regular produc-
tion for most of
8 h shift)
Urine MeOH levels during work shift
ranged from 0 09-12 3 mg/L with most
< 4 mg/L; after work levels ranged from
0 07-1.37 mg/L with most < 1 mg/L
No health effects measured Useful, Dutkiewicz
however, for correlation of environ- and
mental exposures to physiologic mea- Blochowic7
surements in exposed persons In- (1967)
adequate numbers to be convincing C-6
and no real controls are present
MeOH ~ 20-499
(15-375)
Office workers
Not given None
Workers reported frequent, recurrent,
persistent headaches, especially in
cooler weather when windows were closed
Workers closer to the spirit duplicating
machines and those actually operating
them had most severe symptoms
No quantification of health effects Kingsley and
nor numbers of persons affected Hirsch
Air measurements taken are not re- (1954-1955)
lated to any measure of physiologic D-3
parameters It ratps as an anecdotal
case report
(cont inued)
-------
TABLE V-l (continued)
Compound(s) and
Concentration^)
in mg/m3 (ppm)
Description
Population Group
Exposed
Controls
Effects
Rema rks
Reference and
Ra ting
MeOH - 113-178
(85-134)
Mean of air con-
centration in
three locations
in shop, range
over 16 5-h sam-
pling period was
< 10 to 650 ppm
Workers in printing 20
shop
15-36 Blood and urine levels of formic acid
were compared between workers and con-
trols
In blood, mean value of controls in the
morning was 5 6 14 5 mg/L, and, in the
afternoon, 4 9 1 4 2 mg/L In the work-
ers, the mean value in the morning was
3 2 12 4 mg/L, and, in the afternoon,
7 9 13 4 mg/L The controls had either
lower or slightly higher (0 6 mg/L) af-
ternoon values compared to morning val-
ues, whereas all the workers had higher
afternoon values Both the increased
level in the afternoon and the differ-
ences between the control and workers'
afternoon values are significant
In urine, the mean value of controls in
the morning was 11 9 16 4 mg/L, and, in
the afternoon, 11 7 15 6 mg/L In the
workers, the mean morning value was 13 1
13 9 mg/L, and, in the afternoon, 20 2
17 0 mg/L Same significant increase
as with blood in workers' afternoon val-
ues over morning or control values
Analysis of MeOH content of alveolar air
of exposed worker showed slightly signifi-
cant increase between morning and after-
noon levels
Cross-sectional study of measured
air exposure to MeOH and effect as
measured by blood and urine formic
acid leveL No health effects were
measured Controls revealed wide
variability of formic acid concentra-
tions in blood (0 to 20 mL) and
urine Unfortunately, information
was not obtained on factors which in-
fluence formic acid levels (i e ,
diet, cigarette smoking status,
etc ) Stratification on these pa-
rameters may have permitted a better
understanding of the use of these
measures in epidemiological or occu-
pational studies Useful since, al-
though no correlation was present be-
tween air exposure levels, there was
a significant difference over time
(i e , beginning at end of shift) as
compared to controls
Baumann and
Angerer
(1979),
Angerer and
Lehnert
(1977),
Angerer
et al
(1977)
B-9
Angerer et aJ (1977) compared air levels
of MeOH in the three locations to mean
workers' formic acid levels in urine and
MeOH in alveolar air and found no dose
relationship to measured levels
(continued)
-------
Compound(«;) and
ConcentratLon(s)
in mg/m3 (ppm)
Population Group
Description Exposed
HCHO 5-78 Workers in the for- 99 F, 25- 84 F in
HeOH 2 1-7 5 malm department of 40-y-old, other
EtOH 47 5-110 a sheepskin dyeing worked for shops,
factory 5-20 y free ol
HCHO vapors
MeOH ~ 3 2-6 5 Workers in a husi- 2 Hone
(2 4-4 9) ness office
Toluene (0 6-1 0)
CO (< 5 0)
MeOH and toluene
were generated by
even limited use
of the copying
machine
TAHIF V-l (continued)
F f f ccts
Remarks
Reference and
Rating
Complaints of persistent headiche, ver-
tigo, irritability, and tendency to
weep Skin tempei .iture was measured <">n
the forehead, chest, arid forearm, ind
the variations between the left jnd right
sides of the body reported The mci-
denie of physiological thermal asymmetry
(a differen
-------
TABLE V-1 (continued)
Compound(s) and
Concentration(s) Population Group Reference and
in mg/m3 (ppm) Description Exposed Controls Effects Remarks Rating
During injec
tion, at the
pump
IICI10 0
(MAC =
MeOH 2
(MAC =
4-0 5
0 5)
6-10 3
5 0)
During cleanup
work
HCHO 0 2-0 13
MeOH, 0 14-0 8
UJ
00
Workers in coal
mines whose air con-
tent of dust and
methane was con-
trolled by injecting
a urea-HCHO resin
into the coal-bearing
strata.
Donetes Coal Basin,
1973-1975
(The major effect
of the treatment was
the lowering of the
dustiness by 32%,
but the particles
2 5-5 Mm in size
still comprised 70-
75% of the total
dust particles )
Not Workers in Workers examined in the course of 1-3 mo
given untreated after the treatment and 4 mo later did
mines not show any differences from the norms
or from the control group in the follow-
ing indexes arterial pressure, pulse
rate, C02 content in air exhaled at rest,
vital capacity of the lungs, muscular
work capacity, rate of processing infor-
mation, and blood analysis values
The exposure is confounded The Gadzhiev et
number of persons and symptoms are al (1977)
not quantified D-4
MeOH 1 6-10 9
Workers handling
material wet with
35-40% MeOH in a
nitrocellulose
manufacturing
plant
23; 16 had
0 5-3 y ex-
posure ,
seven had
'3 5-6 y
exposure
None
One worker who had worked in the area
exposed to MeOH for 4 y developed symp-
toms of pleura irritation and vision de-
fects These cleared during a 6-wk
leave After 2 vk back at work, vision
failed again, but was restored within
15 mo None of the other workers had
any symptoms of MeOH toxicity
Uncontrolled descriptive study of
workers in a nitrocellulose manufac-
turing plant Essentially a case re-
port Exposure times and levels were
taken, but are not well correlated to
health effects
Humperdmck
(1941)
C-6
-------
ANNOTATED BIBLIOGRAPHY
39
-------
7-106 ACGIH, American Conference of Governmental Industrial Hygienists.
1971. Documentation of the Threshold Limit Values for Substances
in Workroom Air, 3rd ed. ACGIH, Cincinnati, Ohio. pp. 155-156.
C--. Brief review of MeOH toxicity data.
ACGIH, American Conference of Governmental Industrial Hygienists.
1980. TLVs. Threshold Limit Values for Chemical Substances and
Physical Agents in the Workroom Air Adopted by ACGIH for 1980.
Publications Office, ACGIH, Cincinnati, Ohio. p. 22.
A--. Recommends time-weighted TLV of 260 mg MeOH/m3 and short-
term exposure limit of 310 mg/m3.
7-145 ACT, Advisory Center on Toxicology. 1960. ACT Report No. 35;
Report on Methanol. In: Toxicity Evaluation of Potentially
Toxic Materials Part III. National Academy of Sciences-National
Research Council, Washington, D.C. 22 pp.
D—. Brief review of MeOH toxicity with recommended limits for
persons exposed to MeOH from spirit duplicating machine, for 1
h exposure every 24 h, a limit of 500 ppm; 200 ppm limit for
2 h exposure every 24 h.
7-143 AIHA, American Industrial Hygiene Association. 1978. Hygienic
Guide Series; Methyl Alcohol. American Industrial Hygiene Asso-
ciation, Akron, Ohio.
D--. Summary of various exposure standards such as TLV's, toxic-
ity data, recommended industrial and medical treatment.
7-001 Angerer, J., and G. Lehnert. 1977. Occupational Exposure to
Methanol. Acta. Pharmacol. Toxicol. Suppl. 41(2):551-556.
B-9. Some of same data presented in Baumann and Angerer (1977)
[7-005], same study of print shop workers exposed to MeOH. Pre-
sents the data on formic acid levels in urine and expired air of
workers compared to controls.
7-002 Angerer, J., A. Manz, G. Lehnert, and D. Szadkowski. 1977. Formic
Acid in the Urine and Methanol Concentration in the Alveolar Air
in Low Pressure Workers Exposed to Methanol. Med. Monatsschr.
31(1):36-39 (Ger).
40
-------
B--. Same study as Angerer and Lehnert (1977) [7-001] and Baumann
and Angerer (1979) [7-005] on workers exposed to MeOH in a print
shop. Presents data on formic acid level in urine and MeOH in
alveolar air broken down by work area with average exposure to
MeOH reported for each area.
7-004 Baskerville, C. 1913. Second Report of the Factory Investigating
Commission on the Chemistry, Technology and Pharmacology of the
Legislation Pertaining to Methyl Alcohol., Volume 2. J. B. Lyon
Company, New York, New York. pp. 921-1042.
C--. Summary of production, uses and toxicity of MeOH. Brief
case histories of 15 persons affected by MeOH while working in
stiffening departments of hat factories are presented as well as
listing of ~ 75 others injuried by the same type of exposure.
Eye inflammation and loss of vision were reported in majority of
cases.
7-005 Baumann, K., and J. Angerer. 1979. Occupational Chronic Exposure
to Organic Solvents. VI. Formic Acid Concentration in Blood and
Urine as an Indicator of Methanol Exposure. Int. Arch. Occup.
Environ. Health 42(3-4):241-249.
B-9. Study of workers in printing shop exposed to MeOH at levels
of ~ 10 to 650 ppm (mean for 3 locations 85-134 ppm). Formic acid
levels in blood and urine were measured in the morning and again
in the afternoon to see if there was an increase during exposure
to MeOH. Formic acid levels did significantly increase during ex-
posure both compared to morning levels in the workers and in com-
parison to levels in control persons. Authors concluded urine and
especially blood levels of formic acid can be checked for indica-
tion of exposure to MeOH but is not accurate enough to monitor oc-
cupational exposure because of individual variability.
7-081 Bennett, I. L., F. H. Cary, G. L. Mitchell, Jr., and M. N. Cooper.
1953. Acute Methyl Alcohol Poisoning--A Review Based on Experi-
ences in an Outbreak of Cases. Medicine 32:431-463.
C--. Review of toxicity of MeOH to humans through ingestion.
Description of medical cases of individuals involved in the 1951
Atlanta incident involving bootleg whiskey adulterated with MeOH.
In-depth clinical discussion of the cases as well as review of
related literature.
7-159 Benton, C. D., Jr., and F. P. Calhoun. 1953. The Ocular Effects
of Methyl Alcohol Poisoning: Report of a Catastrophe Involving
320 Persons. Am. J. Ophthalmol. 36:1677-1685.
B-8. In depth report on eye damage resulting from the Atlanta
poisoning incident involving 323 persons poisoned by bootleg
whiskey adulterated with MeOH. Majority experienced visual dis-
turbance ranging from seeing spots to complete blindness. Most
of survivors (41 died) regained partial or complete visual acuity
41
-------
7-126
Bertarelli, E. 1934. Routine Hazards of Methyl Alcohol. Ann.
Igiene. 44:729-731 (Ital).
D--. Brief review of the uses, and just a mention that MeOH is
toxic via several routes. Mentions one accident when hundreds
were temporarily "afflicted" (no symptoms), but only ~ 10 died.
7-127 Birch-Hirschfeld, A. 1901. Experimental Studies of the Patho-
genesis of Methyl Alcohol Amblyopia. [Albrect von Graefe's] Arch.
Ophthalmol. 52:358-383 (Ger).
D--. Optic changes were described after rabbits and hens were
dosed orally with 50% aqueous solutions containing a total of
^ 287.5 mL over S 25 d.
7-102 Browning, E. 1965. Toxicity and Metabolism of Organic Solvents.
Elsevier Publishing Co., Amsterdam, The Netherlands, pp. 311-323
and 401-411.
D--. General review of MeOH and its toxicity to animals and hu-
mans, effects on different organs, symptoms of poisoning, and
treatment.
7-121 Carhart, W. M. 1908. Toxic Amblyopia from Wood Alcohol. Am.
Med. 14:176-177.
B-5. Report of one human case involving a worker exposed to
unknown concentration MeOH while shellacking a beer vat for 3
wk. Blindness developed within 2 d and only limited vision was
regained.
7-162 Carroll, R. B. 1970. Analysis of Alcoholic Beverages by Gas-
Liquid Chromatography. Quart. J. Studies Ale. Suppl. No. 5:6-19.
D--. Study identified MeOH in a number of beverage alcohols, at
levels from 0.26 to 105.5 g/100 L.
7-007 Chao, Chen-Tsi. 1959. Materials on the Hygienic Standardization
of the Maximally Permissible Concentration of Methanol Vapors in
the Atmosphere. Gig. Sanit. 24(10):7-12 (Russ).
A-7, Human, B-7, Animal Tests. The odor threshold ranged from 4.3
to 11 mg MeOH/m3 for 13 human subjects. With 3 human subjects,
changes in light sensitivity were noted at 3.3-3.7 mg Me0H/m3.
Rats exposed to 50 mg/m3 for 12 h/d for 3 mo showed changes in
chronaxies of the flexors and extensors, changes in the trachea
somewhat more expressed than those of the bronchi and lungs, and
deformation of the brain cortical neurons. The only abnormalities
seen from 10 rats exposed similarly to only 1.77 mg MeOH/m3 was
deformation of the dendrites in one rat brain.
42
-------
7-009 Ciuchta, H. P., G. M Savell, and R. C. Spiker, Jr. 1979. The
Effect of Alcohols and Toluene upon Methylene Chloride-Induced
Carboxyhemoglobin in the Rat and Monkey. Toxicol. Appl. Pharmacol.
49(2):347-354.
C-8. Exposure of rats and monkeys to 5,000 ppm MeOH for 1 h
caused little or no effect on carboxyhemoglobin levels.
7-083 Clay, K. L., R. C. Murphy, and W. D. Watkins. 1975. Experimental
Methanol Toxicity in the Primate--Analysis of Metabolite Acidosis.
Toxicol. Appl. Pharmacol. 34(l):49-6l.
D--. Pigtail monkeys (Macaca nemestrina) are a suitable model for
human methanol toxicity with 4 g MeOH/kg (~ LD5q) producing marked
acidosis, which could be accounted for primarily by formate.
7-165 Closs, K., and C. 0. Solberg. 1970. Methanol Poisoning. J. Am.
Med. Assoc. 211(3):497-A99.
C--. Case history of man hospitalized in coma with indications
of MeOH poisoning from adulterated alcohol ingested 18 h earlier.
After treatment full recovery was made.
7-084 Cook, W. A. 1945. Maximum Allowable Concentrations of Industrial
Atmospheric Contaminants. Ind. Med. 14(11): 936-9A6.
D--. Early listing of MAC's from 8 state and federal agencies.
The allowable concentration for MeOH ranged from 100-200 ppm.
7-085 Cooper, J. A., and M. M. Kini. 1962. Biochemical Aspects of
Methanol Poisoning (editorial). Biochem. Pharmacol. 11:405-416.
D--. Review of toxicity of MeOH, metabolism, and mechanism of
effect.
7-086 Cooper, J. R., and P. Felig. 1961. The Biochemistry of Methanol
Poisoning II. Metabolic Acidosis in the Monkey. Toxicol. Appl.
Pharmacol. 3(2):202-209.
C-9. Monkeys were given oral doses of 0.48-9.0 g MeOH/kg of body
wt. LD50 was 7.9 g/kg. No obvious effects at < 5 g/kg. Ataxia,
weakness, lethargy, and transient coma occurred at higher doses.
Those that survived recovered within 24 h, for others, coma con-
tinued to death. Only moderate increase in excretion of organic
acids in urine measured.
7-155 Cooper, M. N. , G. L. Mitchell, I. L. Bennett, and F. H. Cary.
1952. Methyl Alcohol Poisoning: An Account of the 1951 Atlanta
Epidemic. J. Med. Assoc. Ga. 41:48-51.
43
-------
C--. Brief description of cases of MeOH poisoning from adulter-
ated bootleg whiskey, description of hospital emergency care and
treatment, symptoms of patients, and response to treatment. Situ-
ation involved 323 patients with 41 deaths.
7-011 De Schweinitz, G. E. 1901. A Case of Methyl-Alcohol Amaurosis,
the Pathway of Entrance of the Poison Being the Lungs and the
Cutaneous Surface. Ophthalmic. Rec. 10:289-296.
C--. Case history of man exposed daily for 3 mo and intermit-
tently over a 2-y period to MeOH-based varnish. After a sudden
illness without typical signs of MeOH toxicity other than, blurred
vision, he suffered total loss of vision.
7-087 Dutkiewicz, T., and A. Blockowicz. 1967. Evaluation of Exposure
to Methanol in View of Field Studies. Med. Pr. 18:132-141 (Pol).
C-6. Workers in an emulgent manufacturing plant were exposed to
MeOH at 3 different levels and time frames. Exposure was compared
to MeOH levels measured in urine during work shift and 8 h later.
Exposures were to 754-1640 mg/m3 for 1 hr, 45-894 mg/m3 for 0.25-
5 h, 59-270 mg/m3 for 8 h. Urine MeOH levels increased directly
with increased exposure.
7-146 Dutkiewicz, B., J. Konczalik, and W. Karwacki. 1980. Skin Ab-
sorption and Per 0s Administration of Methanol in Men! Int. Arch.
Occup. Environ. Health 47(1):81—88.
B—11. Rate of absorption of MeOH by human skin was 0.131-0.291 mg
Me0H/cm2/min.
7-013 Egle, J. L., Jr., and B. J. Gochberg. 1975. Retention of Inhaled
Isoprene and Methanol m the Dog. Am. Ind. Hyg. Assoc. J. 36(5):
369-373.
D-ll. Exposure of dogs to ~ 400-700 mg/m3 MeOH for unknown period
of time. Relationship found between increased retention of MeOH
by respiratory tract and increased exposure concentration, also
increased retention at higher ventilatory rates.
7-129 Eisenberg, A. A. 1917. Visceral Changes in Wood Alcohol Poison-
ing by Inhalation. Am. J. Publ. Health 7 (9):765-771.
C-7. Rabbits were exposed in a ~ 0.1 m3 chamber to air saturated
with 0.5 and 1.0 ounce of MeOH for 15 min, 3 x/d. At the 1.0-ounce
level, 3 of 6 animals died, others (9) were examined after 2-10 mo
exposure and found to have lesions of brain, optic nerve, liver,
kidney, muscles, and especially cardiac muscles.
44
-------
7-157
Enksen, S. P., and A. B. Kulkarm. 1963. Methanol in Normal
Human Breath. Science 141(3581):639-640.
D—. MeOH levels in normal human'breath ranged from 0.06 to 0.49
M8/L-
7-014 Ermolenko, A. E., V. B. Pankova, N. G. Popova, and S. N. Khmara.
1975. Some Problems of Occupational Hygiene and the Health Status
of Core-Molders Working in a Foundry of a Modern Motor Car Manu-
facturing Plant. Gig. Tr. Prof. Zabol. No. 8:11-14 (Russ);
English translation available from John Crerar Library, Chicago,
Illinois. Order No. 76-12470-06J.
D-6. Study of foundry workers where furan bonding agents are
utilized exposing the workers to a mixture of 0.6 to 10.0 mg
HCHO/m3, 1.3 to 30.0 mg MeOH/m3, 0.01 to 0.5 mg furfural/m3, 0.2
to 15.0 mg NH3/m3, 0 to 22.5 mg furyl alcohol/m3, trace to 12.5
mg CO/m3, and 0.03 to 0.2 mg P^io/m3. Workers were questioned
concerning health and 68% reported frequent angina; 20.4%, dryness
of throat, nose and hoarseness; and 25%, nasal obstruction. Work-
ers when examined and compared to control group had increased fre-
quency of respiration; 40-54% had decreased maximal velocity of air
flow exhalation; 26-51%, chronic rhinitis; 46%, chronic tonsilli-
tis; and 32%, elevated olfactory threshold.
7-163 Fannick, N. 1980. Health Hazard Evaluation Determination Report
HE-78-81-658. PB80-169832. National Technical Information Ser-
vice, Springfield, Virginia. 10 pp.
C-5. Study of office where workers complained of illness from
operation of copying machine. Air contained 2.1-4.9 ppm MeOH,
0.6-1.0 ppm toluene, and < 5.0 ppm CO. Workers reported head-
aches and dry or sore throats with the periods of illness corre-
lating with the operation of the copying machine. Study found
that even limited use of copier generated MeOH and toluene.
7-015 Fel'dman, N. G. , and M. V. Vendilo. 1973. Effect of Aliphatic
Alcohols on the Visual Analyzer. Neurohistological Study. Gig.
Tr. Prof. Zabol. No. 3:55-56 (Russ).
C-5. Rabbits exposed for 4 h/d for 6-7 mo to the MAC's of methanol
(5 mg/m3), hexanol, heptanol, nonanol, or decanol showed similar
damage of structure and functional capacity of the retina, optic
nerve, optic chiasma, optic tract, anterior corpora quadrigemma,
and cerebral optic lobe.
7-109 Flury, F., and 0. Klimmer. 1943 (German version 1938). Alcohols,
Esters, Aldehydes, Ketones, Ethers, Plasticizers. In: Toxicology
and Hygiene of Industrial Solvents. K. B. Lehman and F. Flury,
Eds. Translated from German by E. King and H. F. Smith, Jr. The
Williams and Wilkins Company, Baltimore, Maryland, pp. 198-325.
,45
-------
C--. General discussion of MeOH use, human and animal toxicity,
human poisoning and treatment.
7-016 Funes-Cravioto, F., C. Zapata-Gayon, B. Kolmodin-Hedman, B.
Lambert, J. Lindsten, E. Norberg, M. Nordenskjoeld, R. Oliri, and
A. Swensson. 1977. Chromosome Aberrations and Sister-Chromatid
Exchange in Workers in Chemical Laboratories and a Rotoprinting
Factory and in Children of Women Laboratory Workers. Lancet
2(8033):322-325.
D-9. Workers were exposed to a variety of organic solvents, such
that any possible abberations caused by MeOH are confounded by the
other chemicals. Laboratory technicans were exposed to toluene
and chloroform in addition to MeOH in each case as well as up to
4 other solvents. Possible exposure to MeOH occurred in 24 of the
73 workers studied. These MeOH exposed workers showed the same
significant increase in chromosome aberrations and sister-chromatid
exchange as the whole group of 73 workers studied. Authors conclude
some environmental factor was causing the increased frequency of
chromosome breaks but that the causative agent could not be deter-
mined .
7-051 Gadzhiev, G. P., V. G. Deinega, V. V. Sukhanov, I. M. Levshina,
N. I. Yarym-Agaeva, and G. A. Petrenko. 1977. Hygienic Evalua-
tion of a New Technology of Methane and Dust Control in Coal
Mines. Gig. Sanit. No. 7:24-26 (Russ).
D-4. The physical condition of miners in mines treated with urea-
HCHO resin did not differ after several months from that of miners
in untreated mines. In treated mines, the air contained 0.02-0.13
mg HCHO/m3 and 0.14-0.8 mg MeOH/m3 during cleaning operations.
Rats given an intratracheal dose of treated or untreated dust
showed more severe bronchial changes if the dust was followed by a
6-mo exposure to 0.5-0.6 mg HCHO/m3 and 5.0-6.0 mg MeOH/m3.
7-089 Goss, A. E., and G. H. Vance. 1948. Methanol Vapors from Dupli-
cating Machines may be Health Hazard. Ind. Hyg. Newsletter.
8(9):15.
D—. Study of spirit duplicating machine using solvent ranging
from 40-100% MeOH found air concentration during operation to
range from 40-635 ppm and depended on % MeOH in solvent and amount
of solvent used during operation.
7-149 Gosselm, R. E. , H. C. Hodge, R. P. Smith, and M. N. Gleason.
1976 Clinical Toxicology of Commercial Products; Acute Poisoning,
4th ed. The Williams and Wilkins Co., Baltimore, Maryland, pp.
229-233.
D--. Review of MeOH toxicity, symptoms and treatment.
46
-------
7-150
Gotterer, G. S. 1969. Rat Liver D-p-Hydroxybutyrate Dehydrogenase.
III. Inhibition by Topical Anesthetics. Biochem. 8(2):641-645.
D--. High concentration of MeOH, 4,600 mMol of MeOH, required for
50% inhibition of rat liver beta hydroxybutyrate dehydrogenase
enzyme.
7-017 Green, L. A. 1977. Methanol: A Selective Cross-Discipl inary
Bibliography. National Technical Information Service, Springfield,
Virginia. 31 pp.
D--. This bibliography of the literature on MeOH, covering the pe-
riod 1965 to 1977, contains over 500 references.
7-161 Grob, K. 1965. Gas chromatography of Cigarette Smoke. Part III.
Separation of the Overlap Region of Gas and Particulate Phase by
Capillary Columns. 3(2):52-56.
D--. Analysis of gas phase portion of cigarette smoke found 180
|Jg MeOH/cigarette and 45 |Jg acrolein/cigarette.
7-122 Hale, A. B. 1901. Statement made during discussion following
H. Moulton's paper: A Case of Blindness from Drinking Bay Rum,
Compared with the Reported Cases Due to Methyl Alcohol and to
Essence of Jamaica Ginger, Etc. [pp. 1447-1449]. J. Am. Med.
Assoc. 37:1450.
D--. Report of two ingestion cases, review of other cases in
literature and discussion of various aspects of MeOH poisoning.
7-113 Hamilton, A. 1925. Industrial Poisons in the United States.
MacMillan Company. New York, New York. pp. 418-428
C--. Review of the toxicity of MeOH and of many of the early re-
ported cases of poisoning from industrial exposure.
7-020 Hawes, A. T. 1905. Amblyopia from the Fumes of Wood Alcohol.
Boston Med. Sur. J. 153(19):525.
B-4. Case history of painter exposed to MeOH fumes in a closed
room. He developed typical smyptoms of MeOH poisoning including
loss of vision.
7-078 Hellman, T. M., and F. H. Small. 1974. Characterization of the
Odor Properties of 101 Petrochemicals Using Sensory Methods. J.
Air Pollut. Control Assoc. 24(10):979-982.
A-3. Determination of odor thresholds using a trained odor panel.
Absolute threshold or minimum for 50% of panel was 4.26 ppm; odor
recognition threshold for 100% of panel was 53.3 ppm.
47
-------
2-014 Henderson, Y., and H. Haggard. 1943. In: Noxious Gases and the
Principles of Respiration Influencing Their Action, 2nd ed., No.
35, ACS Monograph Series. Reinhold Publishing Corporation, New
York, New York. pp. 216-220.
C--. Review of MeOH toxicity information. Contains recommenda-
tion that maximum prolonged exposure be below 145-500 mg/m3.
7-103 Henson, E. V. 1960. The Toxicology of Some Aliphatic Alcohols -
Part II. J. Occup. Med. 2(10):497-502.
D--. This brief review of MeOH toxicity includes a discussion
of the acidosis and visual effects seen only in primates. Henson
stated that the formic acid produced from 100% MeOH conversion
is not sufficient to cause the acidosis and proposed that the ox-
idation of other acids is blocked by the metabolites due to secon-
dary enzyme inhibitions.
7-123 Herbert, J. F. 1902. Blindness from Inhalation of Methyl Alcohol
and Charcoal Fumes: Complete Recovery. Am. Med. 3:300.
B-4. Report of case involving a worker who while cleaning and re-
varnishing a beer vat was exposed to both charcoal stove fumes and
MeOH. After 4 d, he because nauseous and dizzy. He slept for 3 d
and awoke blind. After treatment, unlike other cases, he recovered
his sight.
7-151 Hohne, C., and R. Patsch. 1969. Tolerance Limit of Various Spe-
cies of Bacteria to Univalent Aliphatic Alcohols. Arch. Hyg.
Bakteriol. 153(2):162-167 (Ger).
D--. Bacterial growth of Staphylococcus aureus unaffected by 2%
MeOH and Escheriscia coli and Klebsiella pneumoniae by 1% MeOH.
7-022 Holmberg, P. C. 1974. Central-Nervous-System Defects in Children
Born to Mothers Exposed to Organic Solvents During Pregnancy.
Lancet 2(8135):177-179.
D-9. Study of mothers of children with congenital central-nervous-
system defects and their exposure to noxious influences during
pregnancy. Significant increase in defects in children of women
exposed to organic solvents during 1st trimester of pregnancy.
Cases involving MeOH were confounded by exposure to other sol-
vents; also there were no specific exposure measurements.
7-023 Humperdinck, K. 1941. On the Problem of Chronic Intoxication
with Methanol Vapors. Arch. Gewerbepathol. Gewerbehyg. 10:569-
574 (Ger).
C-6. Study of workers in nitrocellulose plant exposed to MeOH
concentrations of 1600-10,900 mg/m3. Out of 23 workers exposed
for 0.5-6 y, one (4 y) developed symptoms of MeOH toxicity--pn-
marily loss of vision, which cleared when exposure was stopped.
48
-------
1-0172 ILO. 1970. Permissible Levels of Toxic Substances in the Working
Environment. Occupational Safety and Health Series 20, Interna-
tional Labour Office, Geneva, pp. 194-198.
C--. Maximum Acceptable Concentrations in Czechosolvakia
Normal MAC (mg/m3) Short, single exposure MAC (mg/m3)
Acrolein 0.5 1.0
NH3 40 80
HCHO 2 5
HCN 3 15
MeOH 100 500
H2S 30
7-090 Jansson, B. 0. and B. T. Larsson. 1969. Analysis of Organic Com-
pounds in Human Breath by Gas Chromatography-Mass Spectrometry.
J. Lab. Clin. Med. 74(6):961-966.
D--. No information is given about the human subjects or their
number except that the samples were collected by respiratory mask.
The concentrations of organic compounds in ppm determined by GC/MS
analysis were methanol, 0.3-3.4; ethanol, 0.05-0.36; acetone, 0.2-
0.8; isoprene, 0.09-0.45; and methane, 0-30.
3-133 Jedrychowski, W. , K. Prochowska, J. Garlmska, and J. Bruzgielewicz.
1979. Occurrence of Chronic Nonspecific Diseases of the Respira-
tory Tract in Workers of a Vinyl Resin Plant. Przegl. Lek. 36(9):
679-682 (Pol).
D-7. 456 workers examined, in different departments with different
atmospheres including acetaldehyde, MeOH, and NH3. One group may
have been more exposed to NH3 (0.42-13.39 mg/m3), along with other
compounds and had significantly higher incidence of chronic bron-
chitis and lower FEVi values.
7-024 Jelliffe, S. E. 1905. Multiple Neuritis in Wood Alcohol Poison-
ing. Med. News 86:387-390.
B-4. Discussion of health hazards from MeOH. Report of two cases
of varnishers who developed symptoms of peripheral neuritis, 1 e.,
numbing, prickling, and shooting pain in hands and forearms, pain
from pressing nerve trunks, as well as motor weakness. No infor-
mation on duration of illness or consequences.
5-143 Kamchatnov, V. P., and S. S. Gayazova. 1971. Temperature Asym-
metry in Workers Exposed to Formaldehyde Vapor. Hyg. Sanit.
86(1):286-287.
C-8. Exposure to 2.1-7.5 mg MeOH/m3, 5-78 mg HCHO/m3, and 47.5-
110 mg EtOH/m3 for 5-20 y caused a pathological skin thermal asym-
metry (0.6 to 2.2°C) which existed before a workday began in
48.4% of the workers and increased to 60% by the end of the work-
day. The authors consider this evidence of adverse CNS effects.
Headache, vertigo, and irritability were also reported.
49
-------
7-025 Kane, L. E., R. Dombroske, and Y. Alarie. 1980. Evaluation of
Sensory Irritation from Some Common Industrial Solvents. 41(6):
451-455.
C-8. Mice were exposed to 7,000 to 60,000 ppm of MeOH for 10 mm.
Calculated RD50 value was 41,514 ppm. RD50 1S level that causes
average respiration rate decrease of 50%.
7-156 Kane, R. L., W. Talbert, J. Harlan,.G. Sizemore, and S. Cataland.
1968. A Methanol Poisoning Outbreak in Kentucky: A Clinical,
Epidemiological Study. Arch. Environ. Health 17(1):119-129.
C—. Incident of MeOH poisoning in 18 people who consumed a drink
made from shellac thinner. Discussion of doses and treatments in-
cluding possible protective effect of ethanol.
5-367 Kettner, H. 1978. Indoor Contamination by Chemical Substances
of Daily Use and Their Hygienic Significance. In: Org. Verunreig.
Umwelt: Erkennen, Bewerten, Vermidern, K. Aurand, V. Haesselbarth,
E. Lahmann, G. Muller, and W. Niemitz, eds. Erich Schmidt Verlag,
Berlin, Germany, pp. 448-453 (Ger).
C—. Maximum allowable indoor air in the USSR:
Acrolein 0.1 mg/m3
NH3 0.2
HCN 0.002
HCHO 0.01
MeOH 0.5
7-148 Khan, M. A. Q. (1969). Some Biochemical Characteristics of the
Microsomal Cyclodiene Epoxidase System and Its Inheritance in the
House Fly. J. Econ. Entom. 62(2):388-392.
D—. MeOH stimulated microsomal epoxidation of aldrin by house
flies.
7-026 Kimura, E. T., D. M. Ebert, and P. W. Dodge. 1971. Acute Toxic-
ity and Limits of Solvent Residue for Sixteen Organic Solvents.
Toxicol. Appl. Pharmacol. 19(4):669-704.
C-12. Toxicity study of newborn rats, young adults, and older
adults found LD5o's of 7.4, 13.0, 8.8 mL/kg, respectively. Based
on rat response, authors recommend a maximum permissible single
oral dose limit of 0.001 mL/kg.
7-027 Kingsley, W. H. and F. G. Hirsch. 1954-1955. Toxicologic Consid-
erations in Direct Process Spirit Duplicating Machines. Compen.
Med. 40:7-8.
50
-------
D-3. Air concentration of MeOH during operation of spirit dupli-
cating machines using solvents of 5-98% MeOH ranged from 15 to
375 ppm in poorly ventilated areas. Employees using these ma-
chines reported frequent recurrent and persistent headaches, es-
pecially in cooler weather when windows were closed.
7-132 Koelsch, F. 1921. Industrial-Medical Judgement of Wood Spirit or
Methyl Alcohol. Zentr. Gewerbehyg. 9:198-203 (Ger).
C--. A review of early reports of methanol intoxication (case
histories) and a discussion of methanol's metabolism.
7-028 Koivusalo, M. 1970. Methanol. Int. Encycl. Pharmacol. Ther. 20
(Ale. Deriv., v2):465-505.
D--. Review of the absorption, distribution, elimination and
metabolism of MeOH.
7-142 Krotoszynski, B. K. , G. M. Bruneau, and H. J. O'Neill. 1979.
Measurement of Chemical Inhalation Exposure in Urban Population in
the Presence of Endogenous Effluents. J. Anal. Toxicol. 3(6):
255-234.
C--. The expired air from 54 normal, healthy, nonsmoking urban
adults (18-60 y old) contained MeOH in 3.6% of the 387 samples.
The geometric mean concentration, when found, was 0.549 mg/m3
(range 0.151-1.99 mg/m3).
7-029 Leaf, G. and L. J. Zatman. 1952. A Study of Conditions under
Which Methanol May Exert a Toxic Hazard in Industry. Br. J. Ind.
Med. 9:19-31.
A-7. Exposure of 2 subjects to levels of 655-1430 mg MeOH/m3.
No effects reported other than level of urinary MeOH, which stead-
ily increased during exposure. Subjects (5 males) ingested 29-84
mg MeOH/kg body wt. Constant ratio of 1.3 for concentration of
MeOH in urine to concentration in blood from time of ingestion un-
til most excreted 13-16 h later. Study of exposure of workers in
ammonia synthesis plant. From these studies it was calculated
that exposure to ~ 3,000 ppm would result in gradual accumulation
of MeOH in the body.
3-059 Leonardos, G. , D. Kendall, and N. Barnard. 1969. Odor Threshold
Determinations of 53 Odorant Chemcials. J Air Pollut. Control
Assoc. 19(2):91—95.
A-ll. Definitive paper. The odor thresholds for various compounds
were:
NH3 46.8 ppm
H2S 0.00047 ppm
H2(from Na2S) 0.0047 ppm
HCHO 1.0 ppm
Acrolein 0.21 ppm
Methanol 100 ppm
51
-------
7-031
Maddox, W. L., and G. Mamantov. 1977. Analysis of Cigarette
Smoke by Fourier Transform Infrared Spectrometry. Anal. Chem.
49(2):331-336.
D--. Analysis method for cigarette smoke. Reports findings of
100-200 |jg MeOH/cigarette.
7-030 Machyulite, N. I. 1978. Hygienic Characterization of Working
Conditions in the Production of Levomycetin. Gig. Tr. Prof.
Zabol. No. 12:8-12 (Russ).
D--. Although concentrations of various chemicals present in
the air for different kinds of jobs is given, the health effects
observed are not related to the jobs of the workers. The air of
the work zone was polluted by styrene, MeOH, dichoroethane, Br2,
:L-PrOH, levomycetin, etc., in concentrations often exceeding the
MAC's.
7-164 Magnnat, G., J. P. Dolan, R. L. Biddy, L. D. Miller, and B. Korol.
1973. Ethanol and Methanol Metabolites in Alcohol Withdrawal.
Nature 244(5413):234-235.
D--. Alcoholics with high blood-ethanol levels had much higher
MeOH blood levels compared to low blood-ethanol subjects. The
buildup of MeOH may be due to MeOH impurity in the liquor and to
endogenous MeOH, whose enzymatic breakdown competes with that of
ethanol.
7-093 Majchrowicz, E., and J. H. Mendelson. 1971. Blood Methanol Con-
centrations During Experimentally Induced Ethanol Intoxication in
Alcoholics. J. Pharm. Exp. Ther. 179:293-300.
C--. Alcoholics with high blood-ethanol levels accumulated up to
27 mg MeOH/100 mL in their blood after a 11-day intoxication.
7-112 Martynova, A. P. 1965. Problems of Industrial Hygiene in the
Production of the Synthetic Fiber "Lavsan." Gig. Tr. Prof.
Zabol. 9(9):13-18 (Russ).
D--. Gases emitted, including MeOH, during specific operations
in the production of Lavsan (polyethylene terephthalate) fibers
are enumerated, but worker health effects are not evaluated.
7-104 Massachusetts Department of Labor and Industries. 1937. Occupa-
tional Health Hazards in Massachusetts Industries IV. Wood Heel
Covering. The Commonwealth of Massachusetts Department of Labor
and Industries, Division of Occupational Hygiene, Boston,
Massachusetts. 7 pp.
D-5. Study of the wood heel covering industry. MeOH was used as
a solvent in the cement and in a softener of the celluloid heel
covers. Workplace air concentration of MeOH ranged from 110 to
880 ppm. No health effects of inhalation were mentioned.
52
-------
7-032
May, J. 1966. Odor Thresholds of Solvents for Evaluating Solvent
Odors in Air. Staub-Reinhalt Luft. English Translation. 26(9):
385-389.
D-5. Odor thresholds determined for a number of solvents. For
MeOH the just perceptible threshold was 7,800 mg/m3 and the clearly
perceptible threshold was 11,700 mg/m3.
7-073 Mazur, M. , S. Dzialek, J. Lembke, and W. Dologicz. 1969. Effect
of Methanol and Its Metabolites on the Contraction Amplitude and
Coronary Output of the Isolated Rabbit Heart. Agressologie
10(4):317-324 (Fre).
D-7. MeOH caused a rapid and sharp increase in contraction ampli-
tude of an isolated rabbit heart but a decrease in heart rate and
cardiac output.
7-094 McAllister, R. G. 1954. Exposure to Methanol from Spirit Dupli-
cating Machines. Am. Ind. Hyg. Assoc. Q.' 15(l):26-28.
D--. The solvent for spirit duplicating machines contains 40 to
100% methanol with ethanol and Cellosolve. During use of the ma-
chines in small rooms, a probably common practice in schools and
business offices, the methanol concentration can attain as high as
635 ppm in the air. No human health effects are mentioned.
7-033 McCord, C. P. 1931. Toxicity of Methyl Alcohol (Methanol) Fol-
lowing Absorption and Inhalation--A Progress Report. Ind. Eng.
Chem. 23:931-936.
C-8. Exposure of rats, rabbits, and monkeys to MeOH by inhalation
and skin absorption. Inhalation of concentrations of 1,000 to
40,000 ppm caused death, but with marked variation in individual
susceptibility. Skin exposure to a concentration of 0.5 cm3/kg of
body wt. applied 4x/d caused illness and death of monkeys. MeOH
was detected in organs of animals exposed either by inhalation or
skin absorption, but formaldehyde was not present except occasional
traces.
7-034 McLean, D, R., H. Jacobs, and B. W. Mielke. 1980. Methanol Poi-
soning: A Clinical and Pathological Study. Ann. Neurol. 8(2):
161-167.
B-7. Two case histories of alcoholic persons who survived severe
MeOH poisoning but developed a Parkinson-like extrapyramidal syn-
drome. One was blind, the other regained some peripheral vision.
7-075 McMartin, K. E. , J. J. Ambre, and T. R. Tephly. 1980. Methanol
Poisoning in Human Subjects: Role for Formic Acid Accumulation
in the Metabolic Acidosis. Am. J. Med. 68(3):4l4-4l8.
53
-------
B-7. Case histories of 2 men hospilized in a comatose state from
MeOH poisoning, only 1 survived. Accumulation of formic acid and
its role in acidosis was studied.
7-105 McNally, W. D. 1937. Toxicology. Industrial Medicine, Chicago,
Illinois, pp. 613-631.
D--. Review of toxicity of MeOH, of some medical cases involving
MeOH poisoning, and of methods of diagnosis and treatment.
7-035 McQueen, E. G. 1978. Toxicology of Methanol/Petrol Blends. In:
Alcohol Fuels, Sebel Town House, Sydney,1 Australia. August 9-11,
1978. R. G. H. Prince, Chairman. J. Chem. Eng. NSW Group.
Sidney, Australia, pp. 6/1-6/4.
D-8. Exposure of mice to petrol/15% MeOH mixture for 1 h resulted
in 21% mortality compared to 27% for exposure to petrol alone
(levels of exposure not reported). Repeated 1-h exposure (2-5x)
resulted in 61 and 53% mortality, respectively.
7-160 Menne, F. R. 1938. Acute Methyl Alcohol Poisoning: A Report of
22 Instances with Postmortem Examinations. Arch. Pathol. 26(1):
77-92.
D--. Case histories of 22 alcoholic men who died from drinking
MeOH adulterated alcohol. All were in last stages of poisoning
when first treated.
7-037 Moriarity, A. J. 1978. Toxicological Aspects of Alcohol Fuel
Utilization. Paper 8-1. In: Proc. Int. Symp. Alcohol Fuel
Technol. Methanol, Ethanol, Wolfsburg, Federal Republic of
Germany. Nov. 21-23, 1977. CONF-771175, National Technical
Information Service, Springfield, Virginia. 5 pp.
C—. Review of toxic properties of MeOH and hazards associated
with its possible widespread use as a fuel.
6-124 Newsome, J. R., V. Norman, and V. L. Parotzian. 1965. Vapor
Phase Analysis of Cigarette Smoke. Tob. Sci. 9:102-110; or
Tobacco 161(4):24-32.
D—. Levels in tobacco smoke (|J g/40 mL puff):
unfiltered filtered
MeOH 13 10
HCHO 4.1 3.6
acrolein 8.2 7.9
HCN 32 29
H2S 3.4 3.1
NH3 12 13
54
-------
7-003 New York Department of Labor. 1917. Dangers in the Manufacture
and Industrial Uses of Wood Alcohol. Special Bulletin No. 86.
State of New York Department of Labor, Division of Industrial
Hygiene, Albany, New York. 17 pp.
D-7. Discussion of conditions in various industries producing
or using MeOH with suggestions for improving conditions. A
number of cases of death, blindness, or other injury are reported
from the inhalation of MeOH but no concentrations are given.
7-038 Nikul'tseva, A. A. 1976. Immunological Reaction of Workers in
the Synthetic Rubber Industry. Immunopatol. Prof. Porazhenn.
137-147 (Russ).
D--. Workers exposed to 2-9 times the MAC's of HCHO and dimethyl-
dioxane and to 1.7-2.2 times the MAC of isoprene as well as to
MeOH and isobutylene vapors showed changes in their immunological
reactivity.
7-039 NIOSH, National Institute for Occupational Safety and Health.
1976. Criteria for a Recommended Standard; Occupational Exposure
to Methyl Alcohol. HEW Publication No. (NIOSH) 76-148, Superin-
tendent of Documents, U.S. Government Printing Office, Washington,
DC. 136 pp.
C--. Broad review of animal and human toxicity data and human
case exposures. Recommended occupational exposure limit of 200
ppm as time-weighted average exposure for a 10 h workday, 40 h
workweek with a 15 min ceiling of 800 ppm.
7-153 Obe, G. , and H. Ristow. 1977. Acetaldehyde, but not Ethanol,
Induces Sister Chromatid Exchanges in Chinese Hamster Cells In
Vitro. Mutat. Res. 56:211-213.
D--. Treatment of cell culture for 7-8 d with 0.1% v/v MeOH daily
caused no sister chromatid exchanges.
7-040 Orusev, T., S. Bauer, K. Nikolova, and P. Popovski. 1975.
Hygienic Evaluation of Working Conditions in Laboratories of the
Organic Chemical Industry. God. Zb. Med. Fak. Skopje. 21:111-116
(Macedon).
D--. Laboratory workers were exposed to 822 ppm benzene, 960 ppm
xylene, 202 ppm MeOH, and 764 ppm ethyl ether. Female workers
showed difference in psuedocholmesterase activity and increased
levels of phenols in urine.
7-041 Pavlenko, S. M. 1972. Certain Common Features of the Effects of
Industrial Nonelectrolyte Poisons Entering the Body Simultaneously
with Water and Air. Gig. Sanit, 37(1):40-45 (Russ); English
Translation available from John Crerar Library, Chicago, Illinois.
Order No. 77-13531-06J.
55
-------
B-7. Rats were exposed by inhalation for 4 h/d for 6 mo to EtOH,
MeOH, cyclohexane, and benzene at 1.6, 0.022, 0.066, and 0.018
mg/L, respectively. The same chemicals were simultaneously ad-
ministered orally at 250, 0.75, 0.05, and 0.25 mg/kg daily, re-
spectively. Increase in the latent period of the conditioned re-
flexes to positive stimuli and decrease of the strength of the
reflexes, especially to weak stimuli, was reported.
5-260 Pavlenko, S. M. and V. A. Guseva. 1973a. Dynamics of the Devel-
opment of Adaptive Reactions Under the Long-Term Effect of Indus-
trial Poisons Entering an Organism by Different Means. Itogi
Nauki Tekh. Farmakol., Khimioter. Sredstva, Toksikol., Probl.
Toksikol. 5:110-119 (Russ).
D--. The elaborate set of tests performed on rats exposed to
low levels of HCHO, C2H50H, CH30H, CC14, or cyclohexanone given
by inhalation and/or by mouth does not distinguish the effects
caused by each poison; i.e., they each elicit the same responses
at nearly the same times.
7-042 Pavlenko, S. M. and V. A. Guseva. 1973b. Development of Adaptive
Shifts After Complex Administrations of Nonelectrolyte Poisons.
Gig. Sanit. No. 1:15-20 (Russ).
D--. This is a slightly different version of Pavlenko and Guseva
(1973a) [5-260].
7-043 Perel, S. S. 1979. Occupational Hygiene in the Manufacture of
Some Organosilicon Liquids. Gig. Tr. Prof. Zabol. No. 8:21-25
(Russ).
/
D--. Workers were exposed to MeOH, benzene, toluene, HC1, organo-
chlorosilanes, hexamethyldisiloxane, and methylphenyldimethoxy-
silane in the manufacture of organosilicon liquids. Concentra-
tions of the gases were related to jobs but not to the health
effects observed.
7-166 Pieper, W. A. and M. J. Skeen. 1973. Changes in Blood Methanol
Concentrations in Chimpanzees During Periods of Chronic Ethanol
Ingestion. Biochem. Pharmacol. 22:163-173.
D--. Chimpanzees accumulated MeOH in increasing concentration
for first 4-5 d of chronic ethanol ingestion. Blood MeOH levels
remained at the level through 6-14 wk period until ethanol level
declined, then MeOH in blood declined at a rate positively corre-
lated with the rate of elimination of blood ethanol.
7-044 Pigolev, S. A. 1971. Physiological Shifts in Workers from the
Isoprene Rubber Industry. Gig. Tr. Prof. Zabol. 15(2):49-50
(Russ).
56
-------
D--. The isoprene rubber industry workers were exposed to toluene,
MeOH, and isopentane at levels within their MAC's but the isoprene
concentration was as high as 73 mg/m3 (18% of the samples exceeded
the MAC). Changes in nervous and cardiovascular systems were
found.
7-045 Posner, H. S. 1975. Biohazards of Methanol in Proposed New Uses.
J. Toxicol. Environ. Health 1(1):153-171.
C--. Discussion of hazards from ingestion, inhalation, or skin
absorption of MeOH during its production, handling, and use as
a fuel. Reviews of numerous cases of humans poisoned by these
types of exposure.
7-144 Potts, A., J. Praglin, I. Farkas, L. Orbison, and D. Chickering.
1955. Studies on the Visual Toxicity of Methanol. Am. J.
Ophthalmol. 40(5 Part II):76-82.
D--. Monkeys dosed with 6.0 mg MeOH/kg showed damage to the basal
ganglia and retina not seen when other monkeys were given l.v.
lethal doses of HCHO or 188 mM Na formate/kg.
7-046 Pryor, G. T. , L. R. Bingham, and R. A. Howd. 1978. Behavioral
Toxicology in Rats of a Mixture of Solvents Containing Substances
Subject to Inhalation Abuse by Humans. Toxicol. Appl. Pharmacol.
45(1):252.
D-7. Exposure of rats to a mixture of methylene chloride, MeOH,
heptane, and toluene at 60-226 mg/L for 10 mm caused concentra-
tion related behavior changes, ataxia, paralysis, and unconscious-
ness. Cumulative effects were seen from intermittent exposures.
MeOH as 10% of mixture was probably not the limiting toxicity.
7-096 Ritchie, J. M. 1970. The Aliphatic Alcohols. In: The Pharma-
cological Basis of Therapeutics, 4th ed., L. S. Goodman and A.
Gilman, Eds. The MacMillan Co., New York, New York. pp. 135-150.
D—. Short review of MeOH toxicity, metabolism, and treatment of
poisoning.
7-141 Robinson, J. M. 1918. Blindness from Industrial Use of a 4 Per
Cent Admixture of Wood Alcohol. J. Am. Med. Assoc. 70(3):148-149.
C—. Discussion of the dangers of exposure to MeOH. Report on the
case of a man who worked dyeing hats for 2-3 h/d. He used a dye
containing 4% MeOH which evidently was both inhaled and absorbed
through his hands as they were reportedly often stained black.
His vision began failing after ~ 3 mo and total blindness followed.
7-133 Roche, L., J. Champeix, L. Echegut, A. Nicolas, and A. Marin
1957. A Study of the Pathology of Collective Accidents Observed
in an Industrial Establishment. Ann. Med. Leg. 37:43-51 (Fre.)
57
-------
D--. Case studies (6 in detail) of 52 workers making electrical
apparatus with a range of medical complaints: narcosis, convul-
sions, nausea, vomiting, prickling in the extremities, violent
headaches, dryness of mouth and pharynx, constriction of the
thorax, coma, and syncope. The cause was believed to be vapori-
zation of trichloroethylene and another unknown solvent, probably
methanol. Experiments were done on guinea pigs exposed to each of
these, alone and together (levels unknown), to confirm the belief.
After removal of the solvent vats from the work area, only com-
plaints of slight, benign symptoms were received, the authors at-
tributing them to psychological causes.
7-047 Rodionov, I. S. 1973. Effect of Chemical Factors in the Manufac-
ture of Synthetic Lavsan Fibers on the Health Status of Workers.
Gig. Tr. Prof. Zabol. 17(2):1-4 (Russ).
D--. Lavsan fiber workers were exposed to several other compounds
(dimethyl terephthalate, ethylene glycol, dinyl, and/or polyethyl-
ene terephthalate thermal decomposition products (terephthalic
acid and acetaldehyde besides 1.6-25.5 mg MeOH/m3.
7-048 Rodriguez, R. , M. Lorenzana-Jimenez, A. Manjarrez, and H. Gomez-
Ruiz. 1978. Behavioral Effects from the Acute and Chronic Inha-
lation of Thinner in Rats of Various Ages. In: Voluntary Inhala-
tion Ind. Solvents. ADM-79-779, National Institute on Drug Abuse,
Alcohol, and Mental Health Administration, U.S. Public Health Ser-
vice, Department of Health, Education, and Welfare, Rockville,
Maryland.
D-6. Rats were exposed to thinner containing 25% MeOH plus tolu-
ene, hetone, and other solvent constituents. LD50 decreased sig-
nificantly with increased age, and young rats in general seemed
more resistant than adults to effect of solvent, but chronic ex-
posure did retard body development in young rats. Exposure was
too confounded to relate any toxicity to MeOH.
7-097 Roe, 0. 1955. The Metabolism and Toxicity of Methanol. Pharmacol.
Rev. 7(3):399-412.
D--. Review of MeOH toxicity, metabolism, and treatment of poi-
soning.
7-049 Sayers, R. R. , W. P. Yant, H. H. Schrenk, J. Chronyak, S. J.
Pearce, F. A. Patty, and J. G. Linn. 1942. Methanol Poisoning.
I. Exposure of Dogs to 450-500 P.P.M. Methanol Vapor in Air.
Report of Investigations No. 3617, Bureau of Mines, U. S. Depart-
ment of the Interior. 10 pp.
58
-------
B-10. Chronic exposure of 4 adult dogs and 4 pups born during ex-
posure period to 450-500 ppm MeOH for 8 h/d for 379 d. No signif-
icant variations in blood chemistry or cell counts, in eyes or ma-
jor organs. Pups were born normal. Blood MeOH levels averaged
7-15 mg/100 ml after 8 h exposure but dropped to < 5 mg/100 mL
16 h later.
7-116 Sayers, R. R., W. P. Yant, H. H. Schrenk, J. Chornyak, S. J.
Pearce, F. A. Patty, and J. G. Linn. 1944. Methanol Poisoning
II. Exposure of Dogs for Brief Periods Eight Times Daily to High
Concentrations of Methanol Vapor in Air. J. Ind. Hyg. 26(8):255-
259.
C-7. Exposure of 2 dogs to ~ 10,000 ppm for ~ 3 min, 8 x/d for
100 d. No effect on weight, blood, or eyes. Blood MeOH levels
increased during 8 h exposure, decreased frequently to 0 before
next day's exposure.
7-050 Scherberger, R. F. , G. P. Happ, F. A. Miller, and D. W. Fassett.
1958. A Dynamic Apparatus for Preparing Air-Vapor Mixtures of
Known Concentrations. Am. Ind. Hyg. Assoc. J. 19:494-498.
D-10. Determination of odor thresholds using an air blender,
which is described in detail. Odor threshold for MeOH was re-
ported as 1,500 ppm, which is very high compared to other reported
odor thresholds.
7-051 Schneck, S. A. 1979. Methyl Alcohol. In: Handbook of Clinical
Neurology, Vol. 36, Intoxications of the Nervous System, Part 1.
P. J. Vinken, and C. W. Bruyn, Eds. Elsevier/North-Holland, Inc.,
New York, New York. pp. 351-360.
D--. A good review of methanol poisoning and the presumed role
of HCHO.
7-052 Scott, J. B. 1978. Exposure of Mice to Methylene Chloride and
Methanol Alone and in Combination. UR-3490-1413. National Tech-
nical Information Service, U.S. Department of Commerce,
Springfield, Virginia.
B-9. Mouse LC50 for MeOH determined as 41,000 ppm. Mice were ex-
posed to 1,000 ppm MeOH 6 h/d, 5 d/wk for 3 wk. No deaths, ab-
normal behavior, wt. changes, or eye damage; some lowering of
liver triglycerides. Eye damage did occur during the 6 h exposure
at LC50 level.
7-135 Scott, E., M. K. Helz, and C. P. McCord. 1933. The Histopathol-
ogy of Methyl Alcohol Poisoning. Am. J. Clin. Path. 3:311-319.
59
-------
C—. Study involving exposure of 31 rhesus monkeys, 58 rabbits,
and 176 albino rats to unspecified levels of MeOH by either inha-
lation, skin absorption, or ingestion. Threshold of danger re-
ported to be < 1,000 ppm for inhalation and 0.5 cm3 MeOH/kg of
body wt, 4 x/d by skin absorption. In-depth discussions of patho-
logical findings, these included changes in liver, spleen, kid-
neys, heart, lungs, vascular and nervous systems including optic
nerve degeneration.
7-166 Sedivec, V. , M. Mraz, and-J. Flek. 1981. Biological Monitoring
of Persons Exposed to Methanol Vapors. Int. Arch. Occup. Environ.
Health 48(3):257-271.
A-10. Study of relationship between level of MeOH exposure and
MeOH urine levels in humans. A correlation was found between
level of exposure and level of MeOH excreted in urine when mea-
sured in mg/L or mmol/L.
7-158 Self, R., J. C. Casey, and T. Swain. 1963. The Low-Boiling Vola-
tiles of Cooked Foods. Chem. Ind. No. 21:863-864.
D--. MeOH was detected in a number of cooked foods after boiling
for 30 min. Levels were not quantified; but brussel sprouts,
cauliflower, onion, parsnip, potato, and swede were described as
having "large" or "very large" levels of MeOH.
7-054 Sova, B. 1979. Harmful Chemicals in the Air of the Working Envi-
ronment from the Standpoint of New Regulations. Kozarstvi.
29(6):153-155 (Czech).
C--. Maximum permissible concentration of MeOH in workplace air
is 100 mg/m3.
7-125 Strieker, L. 1908. The Toxic Amblyopias. Lancet-Clinic 99(18):
481-499.
C--. Discussion of human cases involving blindness due to expo-
sure to MeOH of unknown concentration. Two cases of inhalation
discussed, one a review of a previously published case in Wood and
Buller (1904) and a new one concerning a man overcome while shel-
lacking the interior of a hot beer vat. This short exposure of
< 0.5 d resulted in total blindness.
7-077 Takeda, I. 1972. Metabolism of Alcohol, with Reference to that
of Ethanol and Methanol in the Rabbit. Nichidai Igaku Zasshi.
l(6):518-526 (Japan).
C--. MeOH administered orally to rabbits was excreted in 40 h
compared to 7 h for EtOH. The MeOH was not appreciably metabo-
lized, which may account for its lower toxicity in rabbits com-
pared to other mammals.
60
-------
7-055 Tephly, T. R. 1977. Factors in Responses to the Environment.
Organismal Response to the Environment. Introduction. Fed.
Proc., Fed. Am. Soc. Exp. Biol. 36(5):1627-1628.
C--. Review of metabolism and toxicity of MeOH in humans and
monkeys. Comparison is made with rats, which are much less sensi-
tive to MeOH, and differences are discussed.
7-056 Tephly, T. R., W. D. Watkins, and J. I. Goodman. 1974. The Bio-
Chemical Toxicology of Methanol. In: Essays in Toxicology, Vol.
5, W. J. Hays, Jr., Ed. Academic Press, New York, New York. pp.
149-177.
D--. Review of the metabolism of MeOH, HCHO, and formic acid. It
is proposed that HCHO is likely the cause of MeOH toxicity but
that its presence is rarely verified in tissues because of its
high reactivity.
7-057 Tephly, T. R., A. B. Maker, K. E. McMartin, S. S. Hayreh, and G.
Martm-Amat. 1979. Methanol. Its Metabolism and Toxicity. Bio-
chem. Pharmacol. Ethanol.; Vol. 1, E. Majchrowicz and E. P. Noble,
Eds. Plenum Press, New York, New York pp. 145-164.
D--. Review of metabolism of MeOH, HCHO and formate, review of
information on metabolic acidosis and ocular toxicity and dis-
cussion of MeOH poisoning treatment.
7-059 Thomas, M., A. L. A. Boura, and R. Vijayakumar. 1980. Prosta-
glandin Release by Aliphatic Alcohols from the Rat Isolated Lung.
Clin. Exp. Pharmacol. Physiol. 7(4):373-381.
D-8. An evaluation of the ability of MeOH to release prostaglan-
dins from rat isolated perfused lung. Increasing concentrations,
up to 0.02 mM MeOH, caused increased prostaglandin release, higher
concentrations caused a decrease.
7-060 Timourian, H. and F. Milanovich. 1979. Methanol as a Transporta-
tion Fuel: Assessment of Environmental and Health Research.
UCRL-52697, National Technical Information Service, U.S. Depart-
ment of Commerce, Springfield, Virginia. 97 pp.
D--. Review of health and environmental impacts of the use of
MeOH as a fuel. In depth analysis of available knowledge for gaps
that need filling in order for the full impact of MeOH fuel use to
be assessed. Areas needing further research are pointed out and
recommended research outlined.
5-402 Tremer, H. M. , H. L. Falk, and P. Kotin. 1959. Effect of Air
Pollutants on Ciliated Mucous-Secreting Epithelium. J. Nat
Cancer Inst. 23(5):979-997.
61
-------
D-8. Methods developments for measuring effect of various atmo-
spheric contaminants on respiratory epithelium in vitro. Sections
of the ciliated epithelium of the esophageal tract of the leopard
frog were exposed to 1.1-3.3 mg HCHO or 0.4-1.4 mg MeOH in aero-
sols at the rate of 27 mL/s for 2 s. Mucous flow was inhibited by
HCHO and accelerated by MeOH.
7-061 Tyson, H. H. 0. 1912. Amblyopia from Inhalation of Methyl Alco-
hol. Arch Ophthalmol. 16:459-471.
B-5. Case studies of 3 individuals exposed by inhalation and pos-
sibly skin absorption to MeOH while working. Typical symptoms of
MeOH toxicity including damage to vision. Two cases were chronic
exposure where the severity of symptoms decreased when exposure
was reduced by proper ventilation. One case was acute exposure
and permanent damage to vision occurred from the 2 d exposure to
MeOH. Levels of MeOH involved in exposures were not reported.
7-117 Tyson, H. H. and M. J. Schoenberg. 1914. Experimental Researches
in Methyl Alcohol Inhalation. J. Am. Med. Assoc. 63(11):915-922.
C-8. Early exposure study using rabbits, dogs, and monkeys but
with poor information on quantity of MeOH used in exposures. Ef-
fects included death at higher concentrations, acidosis, hemor-
rhages and congestion of internal organs, eye damage, and blind-
ness .
7-062 Ubaydullayev, R. 1968. A Study of Hygienic Properties of Methanol
as an Atmospheric Air Pollutant. In: U.S.S.R. Literature on Air
Pollution and Related Occupational Diseases; Volume 17; A Survey,
B.S. Levme (translator) PB 180522, National Technical Information
Service, U.S. Department of Commerce, Springfield, Virginia, pp.
39-45.
A-8, Human, B-8, Animal Tests. Odor threshold determined as 4.5
mg/m3, concentration causing change in human eye sensitivity, 3.5-
4.1 mg/m3, in electrical brain reflexes, 15 mg/m3. Rats exposed
continuously to 5.3 mg/m3 for 90 d had changes in chonaxy indexes,
and in blood and urine biochemistry. No effect on rats exposed to
0.5 mg/m3.
3-094 U.S.S.R. State Committee of the Council of Ministers for Construc-
tion. 1972. Sanitary Norms for Industrial Enterprise Design.
Izdatel'stvo Literatury po Stroitel1stvu [Publishing House of Lit-
erature on Construction]. Moscow. 96 pp.
C--. In the USSR, the MAC for MeOH in workplaces was 5 mg/m3, and
1 mg/m3 as the one-time limit and 0.5 mg/m3 as the average limit in
populated places.
62
-------
Van Gemert, L. J. and A. H Nettenbreijer. 1977. Compilation of
Odour Threshold Values in Air and Water. National Institute Lor
Water Supply. Leidschendam, The Netherlands, and Central Insti-
tute for Nutrition and Food Research, TNO, Zeist, The Netherlands.
A--. Compilation of odor threshold values reported by different
researchers, for many compounds, including:
NH3 0.03-37 mg/m3
HCN < 1.1-6
H2S 0.001-2
HCH0 0.033-2.2
MeOH 4.3-19,300
Acrolein 0.05-4.1
Varela Rodelo, F. 1978. Biochemistry of Methanol Intoxication.
Rev. Inst. Nac. Med. Leg. Colomb. 3(1):79-91 (Spa).
D--. Review of the toxicity and metabolism of MeOH.
Vilisov, B. A., N. S. Irger, L. M. Kremko, Z. N. Pavlyutina, I. G.
Tseluiko, Y. S. Danishevich, and S. S. Khudnitskn. 1980. Hy-
gienic Evaluation of Some Synthetic Resins and Their Effect on the
Health of Molding Department Workers. Zdravookhr. Beloruss. No.
1:31-34 (Russ).
D-7. Foundry core makers using phenol-formaldehyde copolymer,
urea-formaldehyde, and furan resins suffered a higher rate of dis-
orders of the skin, liver, kidney, and respiratory organs compared
to workers involved in machine building. Metal casting workers
using these resins were ill about half as often and half as long
as the core makers. Amounts of substances released in g/ton dur-
ing mixing and hardening of the resins (and during heating of the
molds up to 800°C) were as follows: HCHO, 0.4-34.6 (not detected
to 10.4); phenol, N. D. (not detected) to 1.7 (N.D.-8.5); MeOH,
1.6-124.9 (N.D.-4.2); furfurol, N.D.-2.9 (N.D.-1.6); furyl alco-
hol, N.D.-142.7 (N.D.); NH3, 0.3-16.7 (1.2-1875.5); CO, N.D.-61.5
(12.7-4014.7); and HCN, N.D.-0.6 (N.D.-376.3). Thus, the more
frequently ill core makers were exposed to more HCHO, MeOH, and
furyl alcohol than the casters; and the casters were exposed to
more phenol, NH3, CO, and HCN than the core makers.
Von Oettingen, W. F. 1943. The Aliphatic Alcohols--Their Toxic-
ity and Potential Dangers in Relation to their Chemical Constitu-
tion and Their Fate in Metabolism. Public Health Service Bull.
281 253 pp.
D--. In-depth review of the toxicity of MeOH to both animals and
humans and of pathology resulting from various types of exposure.
Von Oettingen, W. F. 1958. Poisoning; A Guide to Clinical Diag-
nosis and Treatment. 2nd ed , W. B. Saunders Co., Philadelphia,
Pennsylvania, pp. 425-427.
63
-------
D--. In-depth description of MeOH poisoning symptoms and suggested
treatment.
7-064 Wmek, C. L., W. D. Collom, and E. R. Davis. 1973. Accidental
Solvent Fatality. Clin. Toxicol. 6(1):23-27.
D-6. Case history of man overcome while removing paint from wall
in church. He was using a product containing benzene, MeOH, and
acetone. He died after < 3 h exposure. Autopsy finding were
6-27% benzene, 1-6% MeOH, and 3-8% acetone in the tissues sampled.
7-119 Witte, R. 1934. Methylalkohol. In: Flury, F., and W. Wirth.
Toxicology of Solvents. Arch. Gewerbepath Gewerbehyg. 5:58-63
(Ger).
C—. A review largely devoted to describing the results of Loewy
and Von der Heide (1914) [7-114].
7-065 Wood, C. A. 1912. Death and Blindness from Methyl or Wood-
Alcohol Poisoning with Means of Prevention. J. Am. Med. Assoc.
59 (22):1962-1966.
C-5. Discussion of the dangers of MeOH, illness and death caused
by its improper use. Legal remedies and means of prevention are
discussed. Three more cases of workers poisoned by MeOH while
shellacking the interior of beer vats are presented. One ap-
peared to recover without serious effects, one was blinded, and
the other one died.
7-066 Wood, C. A. and F. Buller. 1904. Poisoning by Wood Alcohol.
Cases of Death and Blindness from Columbian Spirits and other
Methylated Preparations. J. Am. Med. Assoc. 43:972-977,1058-
1062, 1117-1123, 1213-1221, and 1289-1296.
C--. Summary of health hazards of MeOH. Contains a number of
reports of individual cases, both ingestion and inhalation. Most
report typical MeOH poisoning symptoms, especially blindness.
7-120 Yant, W. P. and H. H. Schrenk. 1937. Distribution of Methanol
in Dogs after Inhalation and Administration by Stomach Tube and
Subcutaneously. J. Ind. Hyg. 19(7):337-345.
C-7. Inhalation by dogs of 4000 ppm MeOH for 12 h resulted in
blood MeOH levels of 100 mg/100 g; a 5 d exposure resulted in lev-
els of 317-570 mg/100 g, that dropped to 0 after 120 h. Similar
levels resulted from ingestion and subcutaneous exposure to 2.5-
5.0 g MeOH/kg body wt. Inhalation of 15,000 ppm for 24 h resulted
in blood MeOH levels of 1390-1470 mg/100 g, falling to 335 mg/100 g
48 h later. The distribution of MeOH in tissues and fluids closely
followed the amount of water in various tissues and fluids.
64
-------
7-138 Yant, W. P., H. H. Schrenk, and R. R. Sayers. 1931. Methanol
Antifreeze and Methanol Poisoning. Ind. Eng. Chem. 23(5):551-555.
D-4. General information on study of health effects of inhalation
or skin absorption of MeOH antifreeze. Inhalation and dermal
studies on animal described with no results reported. Occupa-
tional study of worker in MeOH production plants and truck drivers
who were users of the antifreeze. No harmful health effects noted
in exposed persons but no details of study reported.
7-067 Zhigunov, N. F. 1976. Effect of Industrial Factors on Certain
Indexes of Cellular Immunity in Workers Manufacturing Synthetic
Fibers. Aktual. Vopr. Okhr. Tr. Khim. Prom-sti. pp. 57-59 (Russ).
D--. Workers spinning Lavsan fibers were exposed to terephthalic
acid, acetaldehyde, dimethyl terephthalate, ethylene glycol, MeOH,
CO, and crotonaldehyde below their MAC's. The chemical department
workers were exposed to terephthalate esters and MeOH above their
MAC's and to ethylene glycol and dinyl below the MAC's. The
changes in phagocytosis in the workers of both departments of
Lavsan production were usually in the form of inhibition, which
was more distinct and more stable after a year of work.
7-068 Ziegler, S. L. 1921. The Ocular Menace of Wood Alcohol Poisoning.
J. Am. Med. Assoc. 77(15):1160-1166.
B-7. Discussion of the hazards of MeOH and the reporting of sev-
eral human cases, two involving toxicity from inhalation of un-
known concentrations. One was an acute 3 d exposure, the other
a chronic exposure of 1 h/d for some period of time. Both subject
showed typical MeOH toxicity symptoms, especially eye damage.
65
-------
TECHNICAL REPORT DATA
(Please read Inurucnons on the reverse before completing)
1 REPORT NO
EPA 460/3-81-032
2
3 RECIPIENT'S ACCESSIOf+NO
4 TITLE AND SUBTITLE
Methanol Health Effects
5 REPORT DATE
September 1981
6 PERFORMING ORGANIZATION CODE
7 AUTHOR(S)
Bonnie L. Carson, Joy L. McCann, Harry V. Ellis III,
Betty L. Herndon, and Larry H. Baker
8 PERFORMING ORGANIZATION REPORT NO
9 PERFORMING ORGANIZATION NAME AND ADORESS
Midwest Research Institute
10 PROGRAM ELEMENT NO
425 Volker Boulevard
Kansas City, Missouri 64110
11 CONTRACT/GRANT NO
68-03-2928
12 SPONSORING AGENCY NAME AND ADDRESS
Environmental Protection Agency
13. TYPE OF REPORT AND PERIOD COVERED
Final Report
Office of Mobile Source Air Pollution Control
Emission Control Technology Division
2565 Plymouth Road, Ann Arbor, Michigan 48102
14 SPONSORING AGENCY CODE
15 SUPPLEMENTARY NOTES
16 ABSTRACT
Health effects literature primarily related to inhalation exposure to methanol
was collected, evaluated, tabulated, and summarized- Approximately 160 documents were
collected from computerized and manual literature searches covering the period 1901-
1980. Pharmacologists and an M.D. epidemiologist rated the documents according to
their applicability to the study and their methodology. The approximately 25 documents
considered useful for deriving a range of concern for human exposure to methanol from
automotive emissions were tabulated. The pages of tables detail the results of acute,
repeated dose, and chronic testing of mice, rats, rabbits, dogs, monkeys and humans
as well as human occupational studies. A brief summary of oral and skin absorption
toxicity is included. Most of the documents evaluated are described in an annotated
bibliography.
17
KEY WORDS AND DOCUMENT ANALYSIS
a DESCRIPTORS
b IDENTIFIERS/OPEN ENDED TERMS
c cosati Field/Group
Toxicity Bibliographies
Methanol Toxic Tolerances
Acyclic Alcohols Occupational Diseases
Mammals Respiratory System
Inhalation Health Effects
06T
13 DISTRIBUTION STATEMENT
19 SECURITY CLASS /This Report)
Unclassified
21 NO OF PAGES
69
Release Unlimited
20 SECURITY CLASS (This page)
Unclassified
22 PRICE
EPA Form 2220-1 (9-73)
67
------- |