United States
Environmental Protection
Agency
Office of Mobile Source Air Pollution Control
Emission Control Technology Division
2565 Plymouth Road
Ann Arbor, Ml 48105
EPA-460/3-81-026
Air
&EFK
Hydrogen Cyanide Health Effects
-------
HYDROGEN CYANIDE HEALTH EFFECTS
with Contributions by
Bonnie L. Carson Harry V. Ellis III
Betty L. Herndon Eileen M. Horn
Larry H. Baker
FINAL TASK 2 REPORT
September 11, 1981
Contract No. 68-03-2928
Task Specification No. 2
"Health Effects Support for the Emission Control
Technology Division"
MRI Project No. 4997-T(2)
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 hydrogen cyanide, was prepared by
Midwest Research Institute (MRI) as Task No.2 under Contract' No. 68-03~2928,
"Health Effects Support for the Emission Control Technology Division" for
the U. S. Environmental Protection Agency. "
The health effects literature primarily related to inhalation exposures
to hydrogen cyanide has been collected, evaluated, tabulated, and summarized
so that these results can be used to establish the ranges of human exposure
conditions that are of concern for vehicular atmospheric emissions of hydrogen
cyanide.' '
Task activities were cbordinated by the project leader, Mrs. Bonnie L.
Carson, Senior Chemist. Documents were rated and summarized by senior phar-
macologists Drs. Betty L. Herndon and Harry V. Ellis III, of MRI, and epide-
miologist LarryH. Baker, M.D., MRI consultant, who is Associate Professor
of Community Health at the University of Kansas Medical Center. Data were
tabulated by Ms. Eileen Horn, Junior Chemist, and Mrs. Carson. Ms~ Carol
Hopkin, and Ms. Carol Foret served as literature aides. The annotations
were prepared by Mrs. Carson, largely based on notes by the raters of the
documents. 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 Macy, Director,
Center for Technoeconomic
Analysis
September 11, 1981
iii
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TABLE OF CONTENTS
Summary. . . .
.. . .. .. ..
.. .. .. .. .. ..
. .. .. .. ..
.. .. .. .. ..
Goals and Methods. . . . . . .
Background Information on HCN Toxicity
and Metabolism. . . . . . . . . . . . .
Bioassays . . . . . . . . . . . . . . . . . . .
Animal Exposures. . . .. . . . . . . . . . . .
Human Exposures. .. . . . . . . . . . . .
Conclusions. . . . . . . . . . . . . . .
.. .. .. .. ..
I.
. Introduction.
.. .. .. .. .. ..
.. .. .. .. ..
.. .. .. .. ..
II.
Bioassays. . .
.. .. . .. .. ..
.. .. .. . ..
... .. .. .
.. .. .. ..
III.
Animal Exposures.
.. .. .. .. .. .. ..
..... .. .. .. .. ..
IV.
Human Exposures. . .
.. .. .. ..
.. .. .. ..
.. .. . .. ..
Bibliography. . . . . ..
.. .. .. ..
.. .. .. .. .. ..
.. .. .. .. ..
v
Page
1
1
1
3
3
4
7
11
15
17
35
47
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Number
S-1
S-2
II-I
III-l
1II-2
III-3
1II-4
1II-5
1II-6
1II-7
III-8
III-9
III-I0
III -11
1II-12
IV-l
IV-2
Number
I-I
TABLE OF CONTENTS (concluded)
List of Tables
Title
Summary of Low-Level or No Observed Effect HCN Exposure
of Animals. . . . . . . . . . . . . . . . . . . . . . . .
Generalized Data on Human Dose-Response to HCNlnhalation .
Bioassays--In Vitro Exposures to HCN. .
. . . . .
. . . . .
Species Differences in Lethal Time of Exposure to 1,000
mg HCN/Liter. . . . . . . . . . . . . . . . . . . . . . .
Highest Tolerable Concentration Barcroft (1931) (B-l1). . .
Mice--Acute Experimental Exposure to HCN. . .
. . . .
Rats--Acute Exper1mental Exposure to HCN. .
. . . . .
Guinea Pigs--Acute Experimental Exposure to HCN .
. . . . .
Rabbits--Acute Experimental Exposure to HCN .
. . . .
Rabbits--Repeated Dose Exposure to HCN. . . .
. . . . . . .
Cats--Acute Experimental Exposure to HCN. .
. . . . .
Monkeys--Acute Experimental Exposure to HCN
. . . . .
Dogs--Acute Experimental Exposure to HCN. .
. . . . .
Goats--Acute Experimental Exposure to HCN .
. . . . .
Donkeys--Acute Experimental Exposure to HCN . . .
. . . . .
Human Dose-Response Data as Generalized in the
Literature. . . ... . . . . . .
. . . .
Occupational Exposure to Hydrogen Cyanide.
. . . . .
List of Figures
Title
Form for Report Rating. .
. . . . . . . . . . . . . .
vi
Page
5
9
16
19
20
21
25
26
27
28
29
30
31
32
33
36
38
Page
12
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SUMMARY
GOALS AND .METHODS
The purpose of this compilation of data on hydrogen cyanide (HCN) inhal-
ation exposures is to assist the Emission Control Technology Division (ECTD)
of the U.S. Environmental Protection Agency (EPA) to establish the ranges
of exposure conditions that are of concern for HCN in exhausts from vehicles
equipped with catalytic converters and to be able to advise automobile manu-
facturers thereof. The situations of most concern are during vehicle mal-
functions and involving exposures in traffic jams, parking and home garages,
and other situations where little dilution of the exhaust is expected be-
fore inhalation. Most. of the report is, as directed by ECTD, in the form
of tables. Since the focus is on levels where minimal effects occur, this
summary concentrates on exposures that were cited as "toterated" (in at
least some published studies) rather than higher, possibly lethal exposures.
Documents on inhalation effects of HCN identified from manual and com-
puterized literature searches were rated in a two-step process by the project
pharmacologists and epidemiologist. First, the document received an A, B,
C, or D rating according to its applicability for deriving a range of concern
for HCN in automobile emissions.' Second, if the paper was not a low-rated,
foreign language document,"''r 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 documents were tabulated; but when any C-rated studies involved low-
level HCN exposures, these were also tabulated. Blanks in the tables should
be construed as denoting missing information in the documents. .
BACKGROUND INFORMATION ON HCN TOXICITY AND METABOLISM
High levels ofHCNand the cyanide salts are recognized as highly toxic
and are controlled in the workplace and in the environment. They act on an
organism to stop aerobic metabolism after absorption of the cyanide ion.
through the respiratory tract or through the skin. The major interest for
establishirig a level of concern for HCN in autbmotive emissions lies in the
possible long-term effects of repeated exposures to very low-level HCN expos-
ure. Many studies have been made with experimental animals, but a difficulty
"k
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
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exists in extrapolating the exposure data to man. Species differences in
susceptibility to the effects of HCN are substantial, and humans and other
primates are among the least sensitive (Barcroft, 1931).
Acute poisoning at high levels of HCN produces almost immediate collapse
and cessation of respiration. Symptoms comprise giddiness, hypernea,headache,
palpitation, cyanosis, and unconsciousness. Convulsions from asphyxia may
precede death. At lower doses, early symptoms may include weakness, headache,
confusion, nausea, vomiting, and initially increased respiratory rate and
depth; breathing becomes slow and gasping in later stages (Fassett, 1963;
Swinyaid, 1975). .
. .
. .
The mechanism of toxicity at the higher levels appears to be the release
of the cyanide ion, which forms a stable coordination complex with ferric.
iron, keeping the iron in a higher oxidation state and thus reducing its
efficacy as an electron carrier in ferric-to-ferrous iron ttansitions. The
. most important result is that the almost ubiquitous cellular enzyme cytochrome
oxidase-Fe (III) is trapped with cyanide. . It thus cannot catalyze the reac-
tion of reduced cytochrome + oxygen, and the oxygen cannot be transported.
(Cyanide also form~ complexes with Fe(III) of methemoglobin, but does not
combine appreciably with the oxidized or reduced forms of hemoglobin.) This
blockage reduces or stops aerobic metabolism with a shift to the anaerobic
biochemical state. The cells become hypoxic, particularly the brain cells,
as the products of anaerobic metabolism accumulate.
. If death does not ensue, the cyanide is gradually released from the
combination with cytochrome oxidase and. is converted to thiocyanate (SCN-).
The conversion may involve thiosulfate (S2032-) (which is produced from the
metabolism of I-cysteine) according to the following reaction: .
S2032- + CN
ihodanase
)
S032- + SCN
(
Thiosulfate is used in the therapy of severe cyanide poisoning.
serious poisonings, conversion of hemoglobin to a large fraction
globin (by nitrite injection or inhalation) promotes trapping of
1963). .
In less
of methemo-
CN- (Fassett,
~-Mercaptopyruvate transsulfurase catalyzes the reaction
)SCN- + CHSCOC02-
CN
+ HSCH2COC02 <
Thiocyanate oxidase catalyzes conversion of thiocyanate to cyanide (Maehly
and Swensson,1970).
Thiocyanate conversion reduces the acute hazard of cyanide, and SCN
is excreted re~dily !n the urine (Fassett, 1963). Hardy et al. (1950) pointed
out_that because SCN excretion is irregular, one ca~not correlate the urinary
SCN concentration with the degree of exposure to CN. This was confirmed
by Maehly arid Swensson(1970). .
2
-------
-,- --
Hardy et al. (1950) suggested that if thiocyanate excretion is inade-
quate during c~ronic exposure, symptoms of thiocyanate toxicity (known fro~
the use of SCN to treat hypertension) and goiter may occur. (Excess SCN
is known to compete with iodide ion for uptake by the thyroid gland.) Fassett
(1963) discounted one of the two cases of goiter described by Hardy et a1.
in persons occupationally exposed to HCN plus dusts of cyanide salts because
the patient was from an endemic goiter region. The occupational study by
El Ghawabi et al. (1975) does seem to confirm this effect of thiocyanate--56%
of the electroplating workers exposed to cyanide salts and HCN vapors showed
a mild thyroid enlargement. On the other hand, survivors of rats fed a diet
containing~ 100 or 300 ppm HCN for 2 y showed no histologic abnormality of
the thyroids. All pathology was related to old age (Hanzel and Howard, 1955).
Workers constantly exposed to cyanide (as HCN) consistently excrete
low levels of thiocyanate. Averages range from 6 to 13 mg SCN /L urine
(Hardy et a1., 1950). By comparison, concentrations of thiocyanate to be
expected in the urine of nonsmoking, nonoccupationally exposed persons might
be ~ 0.3 to 4 mg/L (Maehly and Swensson, 1970). Smokers also are exposed
to HCN; e.g., Gori and Lynch (1978) found 9 to 141 ~g HCN/cigarette in mod-
ern American brands. In the Levine and Radford study, nonoccupationally
exposed young men who were heavy smokers had 0.653'mg SCN-/L urine. Values-
reported in the literature for nonexposed smokers are generally < 14 mg SCN /L
urine (Maehly andSwensson, 1970).
Another confounding cause of thiocyanate in. the urine besides occupa-
tional or smoking:-tobacco exposure to cyanide is a diet rich in high sulfur-
containing vegetables, notably Brassica spp.: broccoli, brussel sprouts,
cabbage, cauliflower, kale, kohlrabi, mustard, and turnips (Hardy et a1.,
1950). . . .'
BIOASSAYS
. The three in vitro studies using hamster lung and hen and rabbit trachea
cultures described in Chapter II are aimed at correlating the respiratory
effects due to smoking with the various smoke components such as NO, HCN,
and acrolein, which are among the most harmful. The levels of HCN studied
are not especially relevant to expected levels of HCN in automobile exhaust.
For example, eight puffs of 250mg HCN/m3 air.inhibited ciliary activity of
hen trachea in vitro to 50% that of the ~ontrols (Battista and Kensler, 1970).
--
ANIMAL EXPOSURES
The guinea pig is used as a standard model of bronchiolar sensitivity,
having one of the most sensitive upper respiratory tract responses to toxi-
cants. It is therefore striking that Barcroft (1931) found that the guinea
pig was considerably more resistant to lethal HCN levels than several other
. laboratory mammals. Dudley et al. (1942) indicated that most mammals showed
about the same toxicity to acrylonitrile as they do to a stoichiometrically
equivalent level of HCN. Although guinea pigs and rabbits were tolerant of
~ 100 to 200 ppm of either, kidney lesions were more evident in these species
3
-------
exposed to acrylonitrile. (Experimental details were not given for HCN tests
and it is likely that the authors were summarizing earlier literature.)
The authors speculated that this migh~ be due to differences in species meta-
bolism or more active excretion of CN .
The tabulated data from animal exposures (several acute, a few repeated-
dose for rabbits, and no chronic studies) are very sparse in Chapter III.
Table S-l summarizes the data from the lower level tests or from the lowest
level studies in Tables 111-3 to 111-12. Aside from showing large species
differences in resistance to HCN, the tests described at ~ 35 mg HCN/m3 are
not especially useful for the goals of this task. Noxious effects were seen
in mice at levels as low as 3 ppm for 6 h (with HCN alone).
HUMAN EXPOSURES
Diet and cigarettes .
Humans are exposed to cyanide in their diets via residue from HCN fumi-
gation and in foods such as cherries, almonds, sorghum, cassava, and lima
beans, which release HCN after hydrolysis of their cyanogenic glycosides
(Towill et a1., 1978). As mentioned above, the common measure of cyanide
exposure is the concentration of the cyanide metabolite thiocyanate in urine
or blood. But this measure can be misleading if the diet contains these
foods or foods (commonly Brassica spp.) containing glucosinolates (thiogluco-
sides) that release thiocyanate or isocyanate in the body (Towill et al.,
1978). .
Thus, occupational exposure studies, which frequently recognize the
contribution of HCN in cigarette tobacco smoke and stratify the population
according to smokers and nonsmokers, seldom mention the possibility of die-
tary contributions to cyanide or thiocyanate in the urine. Another problem
with occupational cyanide exposure studies of workers who are heavy smokers
is that their increased exposure to cyanide may be due not only to inhaling
HCN in cigarette smoke but also to hand-to-mouth transfer while smoking at
work.
. Some estimates of cyanide exposure from the diet and cigarettes are
derived in parts 1a and Ib, respectively, to place the occupational studies
described in part 2 in better perspective.
Dietary Contribution--
Cabbage, kale, and kohlrabi contain the equivalent of 1 to 7 ppm thio-
cyanate or isocyanate (Towill et al., 1978). An improbable diet consisting
solely of such vegetables (based on ~ 2 kg food intake per day) would con-
tribute 2 to 14 mg/d to the thiocyanate content of the body and excreta.
Actual data on cyanide residues on food after fumigation have not been
sought, but the Food and Agriculture Association/World Health Organization
has set an acceptable daily intake (ADl) of cyanide from food at 0.05 mg/kg
body weight (Vettorazzi, 1977), which would be about 3.5 mg/d for a 70-kg
adult male (commonly called Reference Man).
4
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TABLE S-l.
SUMMARY OF LOW-LEVEL OR NO OBSERVED
EFFECT HCN EXPOSURE OF ANIMALS
Level of HCN,
mgfm3 (ppm) .
275 in each
70-ml puff
delivered at
the rate of
6 puffs/min
240
125
33-44
35
11 (10)
(3-10) .
5.5 plus CO,
C02' lOOoF
1. 1 plus CO ,
C02' 100°F
0.55 alone or
plus NO and/
or CO
Exposure
'" 0.5 h
Indefinite
?
12 min
4-5 h
Acute
2 h
6 h
4 h
4 h
1-4 wk
Species
Donkeys
Goats
Rabbit
Monkeys
Cats
Dogs
Mice
Mice
Mice
Mice
Rabbit
Details and
References in
Table. . .
III-12
III-ll
III-6
111-9
111-8
III-10
II I -3 .
III-3
1II-3
111-3
111-7
5
Effects
Immediate arrest of
bronchial clearance.
Recovered within 20
min after the start
of exposure.
Tolerable, yet 360
mg/m3 for 24 min was
100% lethal for four
goats.
No marked toxic effect.
Toxic symptoms.
No effect. But 55
mg/m3 caused severe
effects after 1.5 h.
Tolerable, but '125
mgfm3 was lethal.
Mobility hindrance,
labored respiration,
reduced food intake.
Wt. loss of 3.4-4.0 g
2 wk after exposure.
Controls had gained
1.0 g.
Lethal to 2 of 10.
All 10 survived.
No lung morphology
changes. Changes
found in the intimal
layer of certain blood
vessels were not sig-
nificantly different
from those seen in the
controls.
-------
Contribution from Cigarettes--
A two-pack-per-day smoking habit might contribute as much as 22 mg HCN
to the daily intake (calculated from the data of Brunnemann et al., 1977).
This is not a trivial amount compared to occupational exposure. For example,
a worker constantly exposed to the TLV (11 mg HCN/m3) for 8 h could inhale
as much as 110 mg HCN per work day. Thus, a worker who is a heavy smoker
might derive 17% of his daily cyanide intake from cigarettes and even more
if his occupational exposure is regularly less than the TLV. The actual
lung contents while smoking may also contain HCN at levels higher than the
TLV. For example, we have estimated from the data of Mattina (1972) that
after each puff containing 35 ~g HCN from a nonfilter cigarette, the lung
will momentarily hold air containing HCN at a concentration of ~ 50 mg/m3
(35 ~g/0.7 L tidal lung volume).
Rickert et al. (1980) reported the level of HCN in 102 brands of Canadian
cigarettes varied from 4 to 269 ~g/cigarette, and that the average Canadian
smoker is exposed to 400 ppm (440 mg/m3) HCN during puffing. Rickert and
Robinson (1981) continued the study and calculated that a person smoking <
10 cigarettes/d is exposed to ~ 1.4 mg HCN/d; 17.5-22.5 cigarettes, 3.2
mg/ HCN/d; and> 37.5 cigarettes resulted in exposure to ~ 8.4 mg HCN/d.
Occupational exposures
Human complaints following long-term HCN exposure involve evanescent,
general, and nonspecific symptoms, many of which involve parasympathetic
nervous system-related symptoms. Since some of the effects occur in some
experimental animal species as well as in man, the. symptoms involved have
been studied in some depth. Colle (1972) and several more recent workers
have suggested that low-level exposure appears to cause no symptoms; but
when repeated regularly over a long period, HCN exposure leads to the para-
sympathetic symptoms often described by workers.
It is of interest to the current task whether the halt of aerobic meta-
bolism which occurs with HCN at acute high-level exposures also acts after
long-term, low-level exposure of a frequent or infrequent nature. It is
also of interest to determine if any short-term, low-level HCN exposure may
produce an effect that occurs after cessation of the acute exposure.
The studies of Levine and Radford (1978) may be relevant in this regard.
Levine and Radford's population consisted of firefighters who had acute,
high-level exposure to HCN in a fire. Over a fourth of them had thiocyanate
in their urine, and the cigarette smokers among them had more thiocyanate
than the nonsmokers; e.g., the clearance of thiocyanate was not inducible,
in that smokers did not clear the additional thiocyanates resulting from
the fire exposure any faster than nonsmokers. An increase in urinaryexcre-
tion of thiocyanate upon exposure to cyanide has been reported in man by
several investigators (see the recent review by Chandra et al., 1980), and
sensitivity to the thiocyanates and an inability to excrete them rapidly
has been suggested to be a mechanism of chronic toxicity to CN-exposed humans
(Hardy et al., 1950).
6
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The finding by Levine and Radford (1978) of 6.53 ~g SCN-/mL urine* of.
heavy smokers otherwise unexposed to HCN versus 3.75 ~g SCN-/mL urine of
nonsmokers who were exposed to HCN in a major fire shows that heavy smoking
can be as important as occupational exposure to the urinary excretion of
thiocyanate. .
Radojicic (1973), reporting on a group of 43 Yugoslav workers who had
been chronically exposed to cyanides at 7 to 14 mg/m3 in the annealing and
electroplating departments of the electronics industry, were not able to
classify the symptoms by a disease syndrome or any specific complaint. A
central nervous system component is apparent in some of the complaints.
Workers who smoked cigarettes had higher urinary thiocyanate levels than
did nonsmoker~. Radojicic appears to have overlook~d the possibility that
. the smokers I work-related complaints may have been due to their hand-to-
mouth transfer of additional cyanide while smoking. Chandra et al. (1980)
found similar results, complaints ascribed to cyanide inhalation exposure
and increased thiocyanate, especially in smokers, in a group of 23 Indian
electroplaters and casehardeners. This study was careful to request that
workers abstain from eating foods that would add to their CN-/SCN- exposure
for a few days before the concentrations of these anions were measured in .
their blood and urine.
Other occupational studies have not considered the contributions of
diet or smoking to cyanide exposure. Ju'zwiak et al. (1979) found no signi-
ficant HCN-related disease in a recent industrial study. In 74 employees
in 12 galvanizing shops, HCN-exposed females had cardiovascular symptoms
less frequently than controls, and exposed males differed from control males
in having greatly decreased . central nervous system symptoms ("neurosis").
Kiryakov et al. (1978) reported more upper respiratory infections and
15% more time missed from work due to illness in farm workers expos~d to
HCN, H2S, and phenol compared to a control population of farm workers exposed
to lower concentrations of these air contaminants.
The study of Dinca et al. (1972) found subtle depression of the oxygen-
carrying abilities of the blood in HCN-exposed workers. . This report is one
of the few that describe very long-term,low-level exposure (2.4 mg/m3 cal-
culated) for an average length of occupation of 5.4 y. ..
. El Ghawabi et a!. (1975) reported thyroid changes and effects on sense
re~eptors (taste and odor perception) in workers exposed to mean HCN concen-
trations in the breathing zones of ~ 7 to 11 mg/m3. Other symptoms of a
general nature occurred more often in the control population than in the
exposed. . .
CONCLUSIONS
The bioassay, animal, and occupational studies tabulated are not espe-
cially helpful in identifying the entire range of concern for HCN in auto-
mobile exhaust (especially for long-term, low-level exposure) except that
if,
This would represent an output of ~ 13 mg SCN-/d if ~ 2 L urine were
voided per day.
7
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'-
one may conclude that the upper boundary of the long-term exposure range
should be no higher than the TLV, since workers do register complaints at
these levels. .
A range of human acute dose-response data, as usually generalized in
the literature without original source attribution, has been gathered in
Table IV-I. A condensed version is given here in Table S-2. From these
generalizations, it appears that the range of concern upon acute inhalation
exposure to HCN should be from some value below 0.2 to 5.5 mg/m3 (the odor
threshold) to 11 mg/m3 (the threshold limit value), or to 5to < 20 mg/m3
(levels where headache and vertigo may be the only symptoms). In view of
the very steep dose-response curve seen in many animal experiments (wherein
twice the no-obServed-effect level can be lethal) the upper boundary value
should perhaps be decreased bY a reasonable safety factor. In this regard,
it is interesting.. to note that the average MAC for HCN is ambient air of
populated places is 0.01 mgHCNjm3 (the workplace MAC of 0.3 mg/m3 is much
lower than the u.s. limit) (USSR, 1972).
When assessing the range of concern for HCN in auto exhaust, the addi-
tional contribution of HCN from tobacco should be considered. However, smokers
as a class, do not include those individuals who are more susceptible to
the noxious effects of the smokestream constituents and are, in fact, rela-
tively inured to these effects. Human experiments are required with subjects
who do not smoke and are not occupationally exposed to cyanide to determine
a lower limit of the range of concern for HCN in auto exhaust.
8
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TABLE S-2.
GENERALIZED DATA ON HUMAN DOSE-RESPONSE TO HCN INHALATION
Dose of HCN
mg/m3 ppm
110 100
50-60 45-54
20-50 18-45
20-40 18-36
5-20 4.5-18
11 10
0.2-5.5 0.2-5.0
O. 11':'0.99 0.1-0.9
Response
Fatal in 1 h.
Tolerated for 0.5 to 1 h without
immediate or late effects. .
Headache, nausea, vomiting, and tachy-
. cardia after several hours.
Slight symptoms (headache) after
several hours.
Headache and vertigo.
Threshold limit value.
Odor threshold.
No effect.
9
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SECTION I
INTRODUCTION
This report was compiled as the second of several tasks 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 literature on specific
.compounds emitted from automobiles equipped with emission-control devices
(specifically catalytic converters), not for the purpose of creating a cri-
teria document but to identify a level 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.
Literature related to health effects of inhaled HCNwas collected mainly
by cQmputer search of TOXLINE and TOXBACK and manual search through the NIOSH
criteria document on HCN and cyanides. Approximately 170 papers and other
documents were obtained, but few contained original data suitable for tabula-
tion. . .
Experimental animal exposure studies were evaluated and summarized by
senior Ph.D. pharmacologists. There were no studies related to HCN exposures
by the general public. Occupational exposure studies were rated by an epi-
demiologist with an M.D. degree and a senior pharmacologist. Figure I-I is
the form used for rating documents by the project pharmacologists and epidemi-
ologist. Each 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
I-I. Thus, a study was rated A if it directly applies to or assists in estab-
lishing a level of concern for exposure to HCN. The second part of the rat-
ing is the methodology score.. The document reviewer checked off which score
should be given for each of the first six items in Figure I-I, and the total
was written at the top of the page along with the letter that rated the paper's
applicability. In some cases, such as reviews, theoretical papers, and low-
rated foreign-language documents, a paper may have received an applicability
rating but none on methodology. .
Data, including the MRI-assigned rating, from the A-, B-, and only if
near the range of concern, C-rated papers were tabulated by mid-level and
junior-level scientists. Information for each topic heading was carefully
sought; so if blanks appear in the summary, the reader can generally assume
the data were not given.
11
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Article No. 4997-1-_-
PAPER :\ PAPER IS I STANDARD SUPERIOR
CHECK WHERE APPROPRIATE: DEFECTIVE. SUB- QUALITY PAPER
STANDARD
0 I 2 3
1. Do they state/limit the problem?
2. Adequacy of sample
3. Replicability
4. Controls/control procedures
5. Completeness and comprehensibility
of results
6. Validity of conclusions, inter-
pretation of data
. --~--- - -
7.
Applicability to health effects of HCN as guidance
range of concern in automobile emissions.
(circ Ie one)
for establishing a
a.
Clearly, directly applies/assists in establishing --a range of concern
(Chronic human studies; acute exposure of humans if minimal effects.)
b.
Research
(Chronic
minimal
requires major inferences; potentially applicable.
animal studies; acute human, maximal effect; acute
effects.) .
animal,
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 I-I - Form for Report Rating
12
-------
The .final summary of the tabulated data was also'performed by
pharmacologists. This summary attempts to reflect objectively the
findings related to HCN effects in the literature reviewed.
the senior
important
The references are cited in an annotated bibli6graphy
not only each document's rating but also a brief comment on
(or lack of same) to the study. .
that includes
its pertinence
The report is organized into the following chapters: II Bioassay
III Experimental Animal Inhalation Exposures, and IV Human Exposures.
Summary precedes the entire report.
Tests,
The
7
13
-------
SECTION II
BIOASSAYS
The in vitro studies described in Table 11-1 are aimed at correlating
the respiratory effects due to smoking cigarette tobacco with smoke compo-
nents such as HCN and acrolein. The levels studied are not particularly
relevant to expected HCN levels in automobile exhaust.
15
-------
TABLE II-I.
BIOASSAYS--IN VITRO EXPOSURES TO HCN
HCN Concentration
Temperature
Mode of
Exposure
Preparation
Exposed
Description of
Tests and Duration
Results
Reference
and Rating
HCN in
cigarette
smoke
35-77 IJg
. (per 4 puffs)
153 IJg/4 puffs
extreme value
HCN 200 mg/m3 (180 ppm)
I-'
0'1
38°C
CSM12
Smoking
Machine
9-10°
inclined
mounting
of trachea
in chamber
pH
Hamster lung
cultures
Rabbit
trachea
12 different experiments with
> 7,000 lung cultures including
nonexposed control cultures ex-
posed to 4 puffs daily (25 ml
at intervals of 58 s). Fresh
smoke from 8 different types
of cigarettes on 3 consecu-
tive days/wk for a period of
1 wk-6 mo.
GC or chemically analyzed and
SH reactivity determined.
In vivo assay of ciliary
activity quantitated by
particulate movement.
Exposed for 18 s.
Leuchtenberger
et a!.
(1976)
C-14
Malignant transformations were
seen in cultures exposed to
cigarette puffs containing 40-
153 IJg HCN and riot seen in cul-
tures exposed to puffs contain-
ing 35-77 IJg HCN. Of the vapor-
phase constituents studied, the.
NO content, however, was best
correlated with the frequency of
malignant transformations. High
SH reactivity was alsG positively
correlated with malignant trans-
formation.
50% inhibitory concentration of
ciliary activity. Similar re-
sults were described for in
vitro experiments with hen-
trachea by Battista and Kensler
(1970) (rating C-9).
Eight puffs of 250 mg HCN/m3
inhibited ciliary activity to
50% that of the controls.
Kensler and
Battista
(1966 )
B-9
-------
SECTION III
ANIMAL EXPOSURES
Most studies looking only at the lethality of HCN in various animal
species have not been considered for tabulation. However, it is interesting
to note the variability in resistance of species to lethal and "tolerable"
levels of HCN. Table 111-1 shows that, at the same HCN level (1,000 mg/m3);
the monkey(s) lived four times longer than the dog(s). Table 111-2 shows
some reordering of the species; but the dog is still the most sensitive,
tolerating 100 mg HCN/m3 air; the monkey, 180 mg/m3; and the guinea pig,
400 mg/m3. Barcroft (1931), however, did not use many animals and without
much effort we have found other studies disagreeing with his results (see
footnotes of Table 111-2). Other discrepancies can also be seen in the fol-
lowing tables when Barcroft's tests are included.
The animal tests were grouped into tables by species and by length of
exposure. The tables are arranged in this chapter by increasing approxi-
mate weight of the test animals. Thus, Table 111-3 includes data from ac-
utely exposed mice. Mice exposed to the threshold limit value set by the
American Conference of Governmental Industrial Hygienists (ACGIH, 1981) of
10 mg HCN/m3 air (10 ppm) for 2 h showed mobility hindrance and generally
labored respiration and after 6 h, greatly reduced food intake. Five mice
exposed t03 to 10 ppm for 6 h showed a body weight 105s of 3.4 to 4.0 g
over the next 2 wk compared to a 1.0 g weight gain by th'e controls (Sato et
al., 1955). When combined with combustion products (C02 and CO) at 100°F,
even 11 mgHCN/m3 (10 ppm) was lethal to 2 of 10 mice after 4 h(Pryor et
al., 1975).
Very little experimental detail was found for the acute rat exposures
mentioned in Table III-4. . Several more lethality studies were identified,
but no studies were found for low-level acute exposures. The situation was
similar for acute exposures of guinea pigs (230 to 1,000 mg HCN/m3) (Table
III~5). . .
Dudley et al. (1942) stated that rabbits showed no marked toxic symp-
toms when exposed for 125 mg HCN/m3 (see Table 111-6). [Dudley et al. (1942)
apparently did not perform the HCN tests they cited to compare with their
exposures of various animals to acrylonitrile. Not having identified the
original source, we include these values with little experimental detail.]
In repeated dose studies (Table 111-7), Hugod (1979) found no significant
difference in lung morphology or in the vascular. intima (aortic arch, thor-
acic artery, pulmonary artery) from the controls when rabbits were exposed
for 1 to 4 wk to 0.55 mg HCN/m3 alone or plus CO or plus CO and NO.
17
-------
The lowest dose acutely tested with cats was 33 to 44 mg/m3, where no
effect was seen after 4 to 5 h. However, at 55 mg/m3 severe pathological
symptoms were seen after 1.5 h (Lehmann, 1903). The latter results are very
different from those of Barcroft (1931), who reported that the cat could
tolerate 180 mg HCN/m3 "indefinitely." These results are in Table III-8.
Monkeys acutely exposed to 125 mg HCN/m3 for 12 min showed toxic symp-
toms (Dudley et al., 1942). The other two tests in Table 111-9 are at higher
concentrations. .
The lowest level used in acute experiments with dogs (Table 111-10)
was 35 mg HCN/m3, which is described as a tolerable level by the same authors
(Dudley et al., 1942) who reported 125 mg/m3 to be lethal.
The lowest HCN concentration to which Barcroft (1931), the only author
represented in Table III-II, acutely exposed goats was 240 mg/m3. This level
could be breathed indefinitely, yet 360 mg/m3 killed all four goats exposed
within 24 min.
Table 111-12 is also very limited. Two donkeys showed bronchial clear-
ance arrest at the onset of "" 0.5-h exposure to 200 70-ml puffs of smoke at
275 or 1,350 mg HCN/m3 per puff. Clearance recovered within 20 min of the
. exposure for the lower level but required 25 min post exposure at the higher
level. No effects were seen if clearance studies were performed by initiat-
ing exposure to radioactive particles after exposure rather than before as
in the tests just described (Albert et ~ 1974).
Chronic inhalation studies were not found for any species.
Table 8-1 in the summary is a composite of the more interesting tests
from Tables 111-3 to 111-12.
18
-------
TABLE III-I.
SPECIES DIFFERENCES IN LETHAL TIME OF EXPOSURE TO
1,000 mg HCN/LITER
BARCROFT (1931) (B-ll)
Animal
Time
(min)
Dog
Mouse
Cat
Rabbit
Rat
Guinea Pig
Goat
Monkey
0.8
1.0
1.0
1.0
2.0
2.0
3.0
3.5
19
-------
TABLE III-2.
HIGHEST TOLERABLE CONCENTRATION
BARCROFT. (1931) (B-ll)
HCN Concentration,
. mgfm3
Animal
Effect
100
100;'c
140
180**
Dog
Rat
Mouse
Rabbit
Monkey
Cat
Goat
Guinea Pig
Highest approximate concentration
which can be breathed "indefinitely."
Last experimental values recorded
are at 60 min.
180
180
240
400
The 1-h LCso for male rats was reported to be 484 ppm HCN by
Vernot et al.(1977). A review of four other lethal rat
studies by Hilado and Cumming (1978) shows a dose-response
curve for 250-g rats wherein the LCso falls from ~ 500 ppm
at ~ 5. min e~posure to ~ 140 ppm at 1 h.
i,
**
Nishimaru et al. (1973) reported that ~ 150 ppm HCN killed
all the exposed rabbits within 3-5 min.
20
-------
TABLE III-3. MICE--ACUTE EXPERIMENTAL EXPOSURE TO HCN
Compound(s) and Duration and Total
Concentration(s), Humidity/ Mode of Species/Strain/ No. of No. of Frequency of Length of Reference
mg/m3 (ppm) Temperature Exposure Age/Weight Test Animals Controls Exposure Experiment Effects and Rating
HCN 1,000 Mouse 1 min, once Lethal Barcroft (1931)
B-11
HCN 165 (150) 850F Exposure Swiss 10 0 4 h, once No survivors Pryor et al.
Chamber albino, (1975)
Webster B-13
strain
random-
bred
mice
young male
and female
HCN 140 Mouse Indefinite Highest "tolerable concentra- Barcroft
tration." Last experimental (1931)
values recorded by Barcroft B-11
(1931) are at 60 min.
HCN 110 (100) 850F Exposure Swiss 10 0 12 h, once No survivors .Pryor et al.
N Chamber albino, (1975)
I-'
Webster B-13
strain
random-
bred
mice
young male
and female
HCN 110 (100) 850F Exposure Swiss 10 0 4 h, once 10 d 9 survivors. .(10'; mortality) Pryor et al.
Chamber albino, (1975)
Webster B-13
strain
random-
bred
mice
young male
and female
(continued)
-------
TABLE III-3. (continued)
Compound(s) and Duration and Total
Concentration(s)~ Humidity/ Hode of Species/Strain/ No. of No. of Frequency of Length of Reference
mg/m3 (ppm) Temperature Exposure Age/Weight Test Animals Controls Exposure Experiment Effects and Rating
HCN 83 (75) 100°F Exposure Swiss 10 10 4 h, once No survivors. All controls Pryor et a1.
C02 30 vol. 'J. Chamber albino, survived the same conditions (1975)
CO 0.075 vol. 'J. Webster except HCN (and another 10 sur- B-13
°2 16 vol. 'J. strain vived for 24 h). In all tests
random- where S02 or N02 was used in-
bred stead of HCN, the microscopic
mice lung and trachea damage was
young male about the same, i.e. t conges-
and female tion. Signs of excitation and
irritability were about the same,
too.
HCN- 66 (60) Exposure Mice 10 Not given 1 h, once LDso. The relationship of Sato et a1.
Chamber ppm X time shows only a small (1955)
variation in the early stages. B-I0
Also, it appears that the
product of concentration X
time for 10'J. deaths is half
that for the case of 50'J.
N deaths and that the effect of
N the HCN itself is greater.*
HCN - 46 (- 42) Exposure Mice 10 Not given 2 h, once LDso. The relationship of Sato et a1.
Chamber ppm X time shows an increase (1955)
of 15 between 1.0-1.5 h.* B-I0
HCN - 42 (38) Exposure Mice 10 Not given 3 h, once LDso. The relationship of Sa to et al.
Chamber ppm"X time shows an increase (1955)
of 10 between 2.5 and 3.0 h.* B-I0
HCN - 39 (35) Expc.sure Mice 10 Not given 4 h, once LDso. The relationship of Sa to et al.
Chamber ppm X time shows an increase (1955)
of 8 between 3.5-4.0 hand B-I0
then decreases again.*
HCN 33 (30) 850F Exposure Swiss 10 0 24 h, OIice 10 d All survived. pryor et al.
Chamber albino (1975)
B-13
(continued)
.,
-------
TALE III -3. (continuec)
Compound(s) and Duration and Total
Concentration(s), Humidity/ Mode of Species/Strain/ No. of No.. of Frequency of Length of Reference
mg/m3 (ppm) Temperature . Exposure Age/Weight Test Animals Controls Exposure Experiment Effects and Rating
HCN 33 (30) lOooF Exposure Swiss. 10 10 4 h, 'once 10 d No survivors Pryor et al.
C02 30 vol. ." Chamber albino, (1975)
CO 0.075 vol. " Webster B-13
02 16 vol. " strain
random-
bred
mice
young male
and female
HCN 22 (20) Exposure Mice' 10 Not given 4.5 h 20" died. Sa to et al.
Chamber (1955)
100-L B-I0
capacity
HCN 17 (15) Exposure Mice 10 Not given 4 h < 10" deaths. The appear- Sato et al.
Chamber ance of mobility hindrance (1955)
occurred at 1 h. B-I0
N HCN 11 (10) Exposure Mice 10 Not given 2 h Mobility hindrance in 2 h. Sato. et al.
W
Chamber. Generally labored respiration. (1955)
B-I0
3 groups of 10 6 h Food intake by the exposed mice
10 was 20 to 65" that of the control
mice. Five mice exposed to 3-10
ppm HCN for 6 h showed a weight
loss of 3.4-4.0 g over the next
2 wkcompared to a weight gain
(1.0 g) by the control group.
HCN 11 (10) 1000F Exposure Swiss 10 10 4 h, once 10 d 2 mice died. Also, estimated Pryor et a1.
C02 30 vol. " Chamber albino, equivalent lethal levels for (1975)
CO 0.075 vol. " Webster humans at 17" 02' 0.01" CO, B-13
02 16 vol. " strain 10" CO2, 110°F, and 10 ppm
random- HCN.
bred
mice
young male
and female.
(continued)
-------
TABLE 1II-3.
(concluded)
Compound(s) and
Concentration(s),
mg/m3 (ppm)
Humidity/
.Temperature
Mode of
Exposure
Species/Strain/
Age/Weight
No. of
Test Animals
No. of
Controls
Duration arid
Frequency of
Exposure
Total
Length of
Experiment
Effects
HCN 5.5 (5)
Reference
and Rating
HCN 5.5 (5)
C02 30 vol. %
CO 0.075 vol. 'J.
02 16 vol. %
HCN < 4.4
N
~
100°F
Exposure
Chamber
Exposure
Chamber
Mice
Swiss
albino,
Io/ebster
strain
random-
bred
mice
young male
and female
Albino mice
10
10
4h, once
< 7 h
4 h
10 d
The amount of food taken was
very much reduced (66-87%)
in comparison to that taken
by a control group; but on
returning to normal air, the
amount of food taken returned
to normal.
All survived.
Survival without any symptoms.
Sato et a1.
(1955)
B-10
Pryor et al.
(1975)
B-13
Lazarev (1971)
C--
*
10
10
The products of ppm X h for the LDso's at 0.5-h intervals from 0.5 h up to 4 h were 50, 52, 67, 82, 95, lOS, 112, 120.
The corresponding values for the LD10's were 25, 40, 45, 50, 55, 60, 60, 60.
-------
TABLE III-4.
RATS--ACUTE ~X ~ERIMENTAL ~X ~OSUR ~ ':0 I CN
Compound(s) and
Concentration(s),
mg/m3 (ppm)
Humidity/
Temper-
ature
Hode of
Exposure
Spedesl
Strain/
Age/Weight
No. of
Test Animals
No. of
controls
Duration and
Frequency of
Exposure
Total
Length of
Experiment
HCN 1,000
Reference
and Rating
IICN 120 (110)
HCN 100
2.0 min
1.5 h
Indefini te
Effects
Letha 1.
Lethal.
Highest "tolerable concentration,"
Barcroft
(1931)
B-11
Dudley et. al.
(1942)
C-9
Barcroft
(1931)
B-11
N
VI
-------
TABLE III-5.
GUINEA PIGS--ACUTE EXPERIMENTAL EXPOSURE TO HCN
Compound(s) and
Concentration(s),
mg!m3 (ppm)
Humidity!
Temper-
ature
Mode of
Exposure
Species!
Strain!
Age!Weight
No. of
Test Animals
No. of
Controls
Duration and
Frequency of
Exposure
Total
Length of
Experiment
Effects.
HCN 1,000
Reference
and Rating
HCN 400
HCN 350 (315)
HCN230 (200)
0.8 min
Indefinite
1.5 h
Letha 1.
Highest "tolerable concentration."
Lethal.
Tolerated without symptoms.
Barcroft
(1931)
B-11
Barcroft
(1931)
8-11
Dudley et. a1.
(1942)
A-9
Dudley et. a1.
(1942)
A-9
N
0">
-------
TA ~ ~ ~ I:: -6 .
RABBIT8--ACUTE EXPERU E I TAL ~X )081 R ~ '~O
.CN
Compound(s) and
Concentration(s),
mg/m3 (ppm)
Humidity/
Temper-
ature
Mode of
Exposure
Species/
Strain/
Age/Weight
No. of
Test Animals
No. of
Contr.ols
Duration and
Frequency of
Exposure
Total
Length of
Experiment
Effects
Reference
and Rating
HCN 1,000
Lethal.
Barcroft
(1931)
8-11 .
HCN 500
HCN 350 (315)
HCN 130 (125)
Rabbit
Rabbit
Rabbits
Rabbits
2 min
15 min
Lethal. Total volume of air in-
haled in that period - 1,902 cm3,
Total quantity of HCN inhaled - 0.95
mg.
Barcroft
(1931)
8-11
Lethal.
Dudley et al.
(1942)
C-9
No marked toxic symptoms.
Dudley et al.
(1942)
C-9
N
-...J
-------
TABLE IlI-7.
RABBITS--REPEATED DOSE EXPOSURE TO HCN
Compound(s) and
Concentration(s),
mg/m3 (ppm)
Humidity/
Temper-
ature
Mode of
Exposure
Species/
Strain/
Age/Weight
No. of
Test Animals
No. of
Controls
Duration and
Frequency of
Exposure
Total
Length of
Experiment
Effects
HCN 0.55 (0.5)
Reference
and Rating
HCN 0.55 (0.5)
CO (200)
HCN 0.55 (0.5)
NO (5)
CO (200)
N
00
HCN 0.55 (0.5)
HCN 0.55 (0.5)
CO (200)
Exposure. Rabbits 24 Ii
Chamber Danish
(Animals country breed
housed in albinos
separate
cages 2.0-2.5 kg
within
it.)
Exposure Rabbits 12 M
Chamber Danish
country breed
albinos
2.0-2.5 kg
Exposure Rabbits 12 Ii
Chamber Danish
country breed
albinos
2.0-2.5 kg
Exposure Rabbits 24 M
Chamber Danish
country breed
albinos
2.0-2.5 kg
Exposure Rabbits 12 M
Chamber Danish
country breed
albinos
2.0-2.5 kg
24 Ii
12 Ii
12 Ii
18 Ii
12 Ii
4 wk
4 wk
2 wk
1 wk
1 wk
Lung morphology unaffected in all
cases. No significant differences
between exposed and control animals
could be established for vascular
sections.
Lung morphology unaffected in all
cases. No significant differences
between exposed and control animals
could be established for vascular
sections.
Lung morphology unaffected in all
cases. No significant differences
between exposed and control animals
could be established for vascular
sections.
Lung morphology unaffected in all
cases. No significant differences
between exposed and control. animals
could be established for vascular
sections.
Lung morphology unaffected in all
cases. No s.ignificant differences
between exposed and control animals
could be established for vascular
sections.
Hugod
(1979 )
C-l1
Hugod
(1979 )
C-ll
Hugod
(1979)
C-l1
Hugod
(1979 )
C-ll
lIugod
(1979)
C-ll
-------
TA 3LE: : 1-8 .
CATS--ACUTE EXPERI~E~~AL ~X)OSURE TO HCN
Compound(s) 'and
Concentration(s),
'mg/m3 (ppm)
No. of No. of
Test Animals Controls
Duration and
Frequency of
Exposure
Humidity/
Temperature
Species/Strain/
Age/Weight
Mode of
Exposure
HCN 1,000 Cat 1 min
HCN 350 (315) Cats 2 min
5-10 min
HCN 290 Cat 11 min
HCN 180 Cat Indefini te
N HCN 140 (125) Cats 6-7 min
\D
HCN 130-165 (120-150) Cats 0.5 h
HCN 55-66 (50-60) Cats 2.5';'5 h
HCN 55 (50) Cats l.Sh
HC~ 33-44 (30-40)
Cats
4-S h
Total
Length of
Experiment
Effects
Reference
and Rating
Letha 1 .
Respiratory paralysis
Death.
Death occurred. To-
tal volume of air in-
haled in that period -
2,547 cm3. Total
quantity of HCN in-
haled - 0.92 mg. '
Highest "tolerable
concentration."
Markl'dly toxic.
Severe symptoms des-
cribed at SS mg/m3"
but recovered after
0.5 h.
,Most died.'
Severe pathological
'symptoms; deep and
slow breathing, sali-
vation, vomiting,
widening of the pu-
pils, spasms.
No effect.
Barcroft
(1931)
B-))
Dudley et. a!.
(1942 )
C-9
Barcroft
(1931)
B-11
,Barcroft
(1931)
B-11
Dudley et. a!.
(1942)
C-9
Lehmann
(1903)
B-3
Lehmann
(1903)
B-3
Lehmann
(1903)
B-3
Lehmann
(1903)
B-3
-------
TABLE III-9.
MONKEYS--ACUTE EXPERIMENTAL EXPOSURE TO HCN
Compound(s) and
Concentration(s),
mg/m3 (ppm),
Humidity/
Temperature
Mode of
Exposure
Species/Strain/
Age/Weight
No. of
Test Animals
No. of
Controls
Duration and
Frequency of
Exposure
Total
Length of
Experiment
Effects
Reference
and Rating
HCN 1,000
Lethal.
Barcroft
(I 931)
B-ll
HCN 180
HCN 140 (125)
3.5 min
Indefinite,
12 min
Highest "tolerable concentra-
tration."
'Barcroft
, (1931)
B-ll
Distinctly toxic.
Dudley et al.
(1942)
C-9
w
a
-------
TAB~~ III-lO.
)OGS--ACUTE ~X?~RI~EN'~L EXPOSURE TO HCN
Compound(s) and
Concentration(s),
mg/m3 (ppm).
Humidity/
Temperature
Hode of . Species/Strain/
Exposure Age/Weight
No. of
Test Animals
No. of
Controls
Dura.tion and
Frequency of
Exposure
Total
Length of
Experiment.
Effects
HCN 1,000
Reference
and Rating
HCN 550-690
HCN 125 (115)
HCN 100
W
f-I
HCN 100 (90)
HCN 40-70 (35-65)
HCN 35 (30)
0.8 min
0.5 min
1.25 min
1 .5 min
Indefini te
Indefinite
Lethal.
Dog unsteady.
.Unconscious.
Tetanic convulsions (be-
lieved dead and removed from
chamber; however, the dog was
found alive the following day).
Lethal.
Highest "tolerable concentra-
tion."
Hay be tolerated for hours;
death after exposure.
Vomiting, convulsions, recovery j.
may be fatal.
Hay be tolerated.
Barcroft
(1931)
B-ll
Barcroft
(1931)
B-ll
Dudley et al. .
(1942)
C-9
Barcroft
(1931)
B-ll
Dudley et al.
(1942)
C-9 .
Dudley et al-~
(1942)
C-9
Dudley et al.
(1942)
C;'9
-------
TABLE III-H.
GOATS~-ACUTE EXPERIMENTAL EXPOSURE TO HCN
Compound(s) and
Concentration(s),
mg/m3
Humidity/
Temperature
Mode of
Exposure
Species/Strain/
Age/Weight
No. of
Test Animals
No. of
Controls
Duration and Total
Frequency of Length of
Exposure Experiment
Effects
Reference
and Rating
HCN 1,000
HCN 360
HCN 240
W
N
Exposure
Chamber
Exposure
Chamber
Exposure Goat
Chamber
Goat
Goats
4
4 .
4
3 min, once
15 min, once
20 min, once
24 min, once
Indefinite
Lethal.
1 died, 3 recovered.
3 died, 1 lived.
All died.
Highest approximate concentra-
tion that could be b~eathed
indefinitely.
Barcroft
(1931)
B-11
. Barcroft
(1931)
B-11
Barcroft.
(1931)
B-11
-------
TABL~ III-12.
DON
-------
SECTION IV
HUMAN EXPOSURES
This chapter reviews the literature on occupational studies in detail,
while selectively reviewing case histories and related reports. There were
no epidemiology studies of HCN exposure of the general public. None of the
accidental-exposure papers correlated HCN levels with effects. Except for
two occupational studies; accidental overexposures are not included.
Many reviews (see references in Table IV-I) have cited data from orig-
inal documents when compiling human dose response tables, but it is usually
not clear who performed the. original observation. In a few instances, com-
piled values varied as if the author(s) had performed a unit conversion incor-
rectly. Table IV-l uses the values most often cited. Note that headache
'and vertigo (dizziness) have been observed at values below the 1981 ACGIH
threshold limit value (ACGIH, 1981). The occupational studies are charted
in Table IV-2 and most are discussed in the SUmmary. .
35
-------
TABLE IV-I.
HUMAN DOSE-RESPONSE DATA AS GENERALIZED IN THE
. LITERATUREa
Dose of HCN
mg/m3
ppm
Response
22,000
20,000
7,000-12,000 6,360-
10,900
5,000 4,550
3,750 3,410
3,600 3,270
2,500 2,270
~ 1,000 < 909
550 500
400 364
300 270
200 180
150 140
120-150 110-135
110 100
50-60 45-54
Even though breathing is through a gas
mask, vertigo, weakness, and tachy-
cardia occur after 8-10 min. Loss of
work capacity for 2~3 d.
Level dangerous after 5 min even though
a gas mask is used because of skin
penetration.
Safe for 1 min.
Safe for 1.5 min.
Safe for 30 min with a gas mask.
Safe for 2 min.
Safe for an experienced fumigator in-
definitely.
No serious consequences after 1 min ex-
posure.
Tolerable for 1.5 min without vertigo.
Immediately fatal. Lazarev (1971)
[2-0144] stated that this concentra-
tion is tolerable for 2 min without
headache. Lazarev (1956) [2-0145]
stated a person at rest would with-
stand this concentration for 2 min
without dizziness. ..
Fatal after 10 min.
Fatal after 0.5 h.
Fatal after 0.5-1 h.
Fatal in 1 h.
Tolerated for 0.5-1 h without immediate
or late effects.
(continued)
36
-------
TABLE IV-I.
(concluded)
Dose of HCN
mg/m3
. ppm.
Response
0.4-50
0.4-45
20-50 18-45
20-40 18-36
5-20 4.5-18
10 10
0.2~5.5 0.2-5.0
0.11-0.99 0.1-0.9
Headache, vertigo, nausea, regurgitation,
heartburn, general weakness, . sensation
of pressure in the epigastric region,
sweating of the hands, instability of
the autonomic ne+vQus system, decrease
in vascular tone, slowing of blood cir-
culation. .
Headache, nausea, vomiting, and tachy-
cardia after several hours.
Slight symptoms (headache) after several
hours.
Headache and vertigo.
Threshold limit value (ACGIH, 1981).
Odor threshold.
. b
No effect.
a
Aghoramurthy and Mehta (1977), Dudley et a1. (1942), Einhorn
(1975), Flury and Zernik (1931), Henderson and Haggard (1943),
Hamilton and Hardy (1949), Lazarev (1971) [most levels> 300
mg/m3], McNamara (1976).
b
Attributed to Lazarev by Czechoslovak Committee of MAC (Wills
et a1., 1976).
37
-------
TABLE IV-2.
OCCUPATIONAL EXPOSURE TO HYDROGEN CYANIDE
Compound(s) "
Concentration(s),
mg/m3 (ppm)
Duration
Description
of Workers
Exposed
Controls
Effects
Remarks
Reference and
Rating
Cyanide gas 28-83
(25-75) This was
likely higher due
to added ventila-
tion before testing.
Cyanides: 7-14
(Yugoslav MPC 5)
6-9
w.
00
Worker in photographic
darkroom; wet plate
process
Workers in the electro-
plating department in
the electronics indus~
try of Nis, Yugoslavia
Workers in the annealing
shop of the same plant.
1 M
28
(18 smok-
ers; 10
nonsmokers r
20
same 20
as above
15
(5 non-
smokers;
10 smokers)
Symptoms/complaints of numb-
ness, weakness, vertigo, nau-
sea, rapid pulse, and flush-
ing of the face occurred on
three different occasions
at the end of the work week
followed by headache and
vague gasttic distress.
Complaints of exposed workers
included fatigue, headache,
body weakness, tremor of the
hands and feet, pain, and
nausea. Hore pronounced com-
plaints came from workers
who had worked for a long
time with cyanides. More
thiocyanate was eliminated
by those who were exposed to
CN- over the controls. The
annealing shop was found to
be less of a risk than the
electroplating shop. The
avg. thiocyanate values in the
urine for nonsmoking exposed
electroplaters and annealing
shop workers were 3.10 and
1.90 mg/L; the smokers in
these job categories had avg.
thiocyanate values 10.00 and
8.00 mg/L, respectively.
The values for the controls
were 0.17 mg/L for nonsmokers
and 4.40 mg/L for smokers.
The differences between the
exposed and control concen-
trations were all statisti-
cally significant (P < 0.01).
Workers who had been exposed
to cyanides for a longer time
generally excreted more thio-
cyanate in their urine.
(continued)
Case report showed indivi-
dual hypersensitivity. In-
dicating an industrial stan-
dard applicable to the
general case" may not always
apply in individual situa-
ations.
Parmenter
(1926) "
B--
Symptoms sound like long-term
stress exposure. Interest-
ing that cigarette smoking
produced urinary thiocyanate
levels higher than work ex-
posure, yet the complaints
were working-related not smok-
ing related. Smoking hand-to-
mouth may be portal of entry
and account for higher levels.
Radoj icic
(1973)
B-9
Workers constantly exposed to
cyanide" as HCN consistently ex-
crete low levels of thiocyanate
in the urine. Average range
from 6 to 13 mg/L (Hardy et a!. ,
1950 [B-7].
Haehly and Swenson (1970)
[C-12], who did not re-
port on exposure symptoms,
found an average total 20.0 or
23.0 mg SCN-/L urine when HCN
levels were 3.8 or 5.1 ppm,
respectively. "
-------
TABLE IV-2.
(continued)
Compound(s)
Concentration(s),
mg/m3 (ppm)
Duration
Description
of Workers
Exposed
Controls
Effects
Remarks
Reference and
Ra ting
Combined copper.
cyanide and NaCN.
Mean CN- concen-
tration in breath-
ing.zones:
0.4 (10.375)a
7.1 (6.416)
8.9 (8.083)
W
\D
,-
Electroplating sections
of three factories
36 M
20 M
Prevalence data were used to
assess exposure. . It woul d
have been helpful to use thio-
cyanate levelb to correlate
with symptoms.
E1 Ghawabi
et al.
(1975)
B-9
Incidence of symptoms in work-
ers significantly greater
than in controls: head-
ache, weakness, changes in
taste and !
-------
.j:o-
a
TABLE IV-2.
(continued)
Compound(s)
Concentration(s),
mg/m3 (ppm)
Duration
Description
of Workers
Exposed
Controls
Effects
Remarks
Reference and
Rating
HCN Average
daily concen-
trations for
the 12 shops
ranged from
0.05':0.09
to 0.36-2.7.
. .
Work area:
Cyanide (HCN and
particulates) ,
0.2-0.8; mean 0.45
General workroom:..
0.1-0.2; mean 0.15
Relative humidity
29.0 - 61.0%;
mean .45.0%
Workers in 12 galvaniz-
ing shops in metal-
lurgic industry,
electric, and radio-
technical apparatus
plants. .
Workers engaged in
Electroplating and
casehardening, ages
23-40 y. Control
workers from same
factory had never
been exposed to
chemical hazards
and belonged to
the same age group,
sex, and socioeconomic
status.
Both groups avoided
cyanogenic foods such
as cabbage, mustard,
and almond for> 48 h
before collection of
blood and urine samples.
63 H
11F
23 H
8 Smok-
. ers
15 Non-
smokers
11 H
45 F
20 H
10 Smok-
ers
10 Non-
smokers
223 determinations on 73
working posts revealed
46 had ratio of actual
concentration to maximum
allowable (0.3 mg/m3) from
1.1 to 9.0. Rhodanase de-
terminations.showed only
two case values above normal
range. Clinical and labor-
atory investigations showed
no characteristics of acute
or chronic occupational HCN
poisoning.
HCN-exposed women had no
circulatory system pathol-
ogies reported, but had
neurosis (CNS symptoms) as
frequently as controls.
HCN-exposed males had cir-
culatory system problems as
frequently as controls but
no neurotic symptoms which
were seen in control males.
Hean blood thiocyanate level
in.smokers of exposed and
control groups were 0.48
and 0.10 mg/100 ml, re-
spectively, in nonsmokers,
0.42 and 0.04 mg/lOO ml,
respectively. Correspond-
ing cyanide levels were
56.0, 4.8, 18.3, and 3.2.
~g/lOO ml, respectively.
The mean 24-h thiocyanate
in urine of smokers of the
exposed and control groups
were 0.62 and 0.41 mg/lOO ml,
respectively; in nonsmokers,
0.57 and 0.08 mg/lOO ml, re-
spectively. Corresponding cy-
anide levels in urine were 6.23,
3.2, 5.4, and 2.15 ~g/lOO ml,
respectively.
(continued)
Neuros i s may be rela ted to
multiple job-related stresses
having little association with
HCN. Job comparability of
workers and controls exposed
should have been evaluated.
Ju'zwiak
et at.
(1979 )
B-8
. .
Although the author abstract
states that the "workers com-
plained of typical HCN poi-
soning" arid there is a similar
statement in the conclusions,.
no health effects are reported.
Since detaled clinical examina-
tions and pulmonary function
tests are stated to have been per-
formed, perhaps the results will
be reported in a future paper.
Chandra et al.
(1980)
8-11 .
-------
TABLE IV-2.
(con:inued)
Compound(s)
Concentration(s),
mg/m3 (ppm)
Duration
Description
of Workers
Exposed
Controls
Effects
Remarks
Reference and
Rating
3.1-37.0oC; mean
4S.0oc [sic),
presumably 35°C.
Duration: 2 mo,
June and July
.p-
I-'
1966: avg. acry-
lonitrile exceeded
the MPC (0.5) by an
avg. 'S-10X.' Major-
ity of HCN concen-
trations < MPC of
0.3, but the HPC was
exceeded in one-
. third of the samples.
1971: avg. acrylo-
nitrile concentra-
ioil 0.75. HCN
concentrations all
at or below the HPC.
Venous blood was col-
lected at the end of
the work shift and
urine samples were
collected throughout
the workday and at
home. .
Workers employed 4-6 y
in an acrylonitrile
plant.
75 M&F
Blood.vaJ.uesin exposed work-
ers (P < 0.001) whether smok-
ers or nonsmokers were signif-
icantly higher than among the
control group workers. The
differences in urine cyanide
values were statistically not
significant, but the thiocya-
nate level differences were
significant (~ < 0.001),
There was no consistent pat-
tern in thiocyanate levels
found in samples collected at
2-h intervals, so a 24-h urine
sample should be used.
25 M&F
Complaints included indispo-
sition, headache, reduced
. work capacity, poor sleep,
irritabIlity, compressive.
pains in the region of the
heart, poor appetite, skin
pallor. Some irritation of
the skin had occurred but
subsequently disappeared.
Reduced nos. of erythrocytes,
leukocytes, and hemoglobin
values were observed. Also
noted were changes in the
oxidation processes in the
tissues. .
(continued)
It would be difficult to
attribute effects solely to
inhalation since liquid
acrylonitrile may be ab-.
sorbed through the skin.
Zotova
(1975)
C-8
-------
TABLE IV-2.
(continued)
Compound(s)
conceritr~tion(8),
!IIs/lIa (ppm)
Duration
Description
of Workers
Exposed
Controls
Effects
Remarks
Reference and
Ra ti ng
Over a 5-y period,
the avg. concen-
tration was 0.26
(MPC = 0.3)
~
N
Acrylonitrile
0.55 tbO.03
(23.5)
HCN O.gS:t 0.006
(3.7)
NH3 7.g:t 0.7
(3.0)
Total hydro-
carbons
41.0 6 3.S
(0)
Unsaturated
hydrocarbons
20.2 6 1.2
(0)
1972-1974
numerous mea-
surements
HCN 0.01 (0.091)
NH3 2.9
Acid mist
Avg. length of occupa-
tion 5.4 y at an elec-
troplating plant.
Workers in a~ryloni-
trile production.
Workers' in Massachusetts
jewelry plating opera-
tions, February 1974.
12 M
31 F
Not given
No figures given.
3-4
Results of tests demonstrate
'noticeable decline of leuko-
cytochrome oxidase, reduction
to peroxidase and succinic
dehydrogenase activity, and
a reduction of blood catalase
levels. These findings dem-,
onstrate that HCN inhibits the
activity of certain redox en-
zymes in somatic cells.
Increased frequency of dis-
orders of the nervous sys-
tem. Neurasthenic and
asthenic syndrome with
vegetative-vascular dis-
turbances. Increase in
sympathetic nerve system
reflexes. Increase in
flabby heart and cardiac
weakness (both significant
'at 0.05 level). Changes
in the functional condition
of the liver. Methemoglo-
binemia was increased.
Tendency to lowering of
total work capacity sup-
ported by dynamometric data.
No hazard exists to employees
working in the plating area
exposed to HCN, NHa, and
acid mists. "No adverse
health effects were evident."
Employees interviewed ex-
perience "occasional irri-
tation from anunonia'."
(continued)
Good study" The degree of
enzyme depression, however,
was not related to age
categories.
Symptom list includes eva-
nescent signs of nervous
system change. The pro-
gressive symptoms and
changes reported, without
any good epidemiologic data
collection, hint at a toxic
effect on long-term human ex-
posure to the levels of the
mixture described. Relevance,
of the signs to HCN toxicity
cannot be assessed from data.
A NIOSH Health Hazard Eval-
uation. Paper did not de-
scribe the health effects
they evaluated or the method
of evaluation.
Dinca et ai,
(1972)
A-12
Boklag
(1975)
C-6
Burton
(1974)
B-3
-------
TABLE. :V-2.
(continued)
Compound(s)
Concentration(s),
mg/m3 (ppm)
Duration
Description
of Workers
Exposed
Controls
Effects
Remarks.
Reference and
Rating
Exposed:
HCN
0.00035-0.00087
(0.00032-0.00079)
Phenol. .
0.00875-0.9154
~
W
H2S .
0.0075-0.0093
(0.0050-0.0062)
Controls:
HCN
0.00012-0.00083
(0.00011-0.00075)
Phenol
0.00504-0.01701
H2S
0.0032-0.0063
(0.0021-0.0038)
HCN concentration
not given;
infrequent
toxication
cidents in
in-
.in-
1953.
Bulgarian farm workers
- 1973-1975
Bulgarian farm workers
- 1973-1975
17 workers in fumigation
employment of miscella-
neous job classifications.
Ages - 24-59 y
Periods of service -
< 2--27 y.
No numbers given.
Suffered more acute infec-
tions of the upper respi-
ratory pathways and neurosis
than workers exposed to the
less contaminated air. In
this period, 65.7% of the
workers exposed to the more
contaminated air experienced
. morbidity of average dura-.
tion 14.3 d compared to
50.5% of the workers exposed
to the lesser contamination
experiencing sickness of
average duration 9.3 d.
13 M.
4 workers employed. 7-8 y and
24-27 y had: not inhaled HCN
gas on any occasion, and.
showed no symptoms or phys-
ical changes resulting from
employment. Of the 13 ex-
posed workers ,. 12 showed
some signs of gastritis.
Objective signs of disturb-
ance included dizziness,
headache, tremors, pain
around the heart, Romberg's
sign, nystagmus, heartburn,
dyspnea, cough, tachycardia,
and diarrhea. 3 or more. of
those exposed had odd atrio-
ventricular lead patterns (as
shown by EKG). Other param-
eters were tested and results
given. Loss of consciousness
was reported in one subject
for a period of :i! 10 min. .
(continued) -
Multiple factors besides air
quality could have con-
tributed to the observed
variation of "sickness dur-
ation." Job comparability.
between the groups is not
given.
Kiryakov
. et a!.
(1978)
C-5
Carmelo.
(1955)
C-6
-------
TABLE IV-2.
(continued)
Compound(s)
Concentration(s),
, mg/m3 (ppm)
Durlition
Description
of Workers
Exposed
Controls
Effects
Remarks
Reference and
Rating
HCN concentration
not given.
Serum thiocyanate
'(SCN-) levels
measured after
CN- exposure in
fumes while
fighting major
fires: Oct. I,
1973 - Mar. 31;
1974
.p..
.po
HCN concentration
not given.
Serum thiocyanate
(SCN-) levels
measured after
CN exposure in
fumes while fight-
ing major fires.
HCN concentration
not given.
Serum thiocyanate
(SCN-) levels
measured after
CN- exposure in
fumes while fight-
ing major fires.
HCN concentration
not given.
Serum ~hiocyanate
(SCN ) levels
measured after
CN- exposure in
fumes while
fighting major
fires.
Baltimore, Maryland
firefighters popula-
tion (not stratified
by cigarette use)
Baltimore, Maryland,
firefighters (heavy
smokers category)
Baltimore, Maryland,
firefighters
(light-to-moderate
smokers category)
Baltimore; Maryland,
firefighters
(nonsmoking category)
479 46
Presumably all male.
114
132
193
11
13
20
28% showed minor symptoms
after a fire: 7%, cough
and increased sputum; 2%,
nausea and vomiting; 8%,
headache; and 10%, other
symptoms. Significantly
higher mean serum SCN-
levels (5.6 vs. A.36
~g/ml). Occupational ex-
posure also related to
shift in range of serum
SCN- evidenced by 12% of
the exposed having levels
above the highest values
for controls (9.9 ~g/ml).
Increase iri serum SCN- levels
for heavy smoking exposed
firefighters (7.8 ~g/ml)
over heavy smoking unex-
posed control; (6.53 ~g/ml).
Increase in serum SCN- levels
for light-to-moderate smok-
ing exposed firefighters
(6.74 ~g/ml) over smoking un-
exposed controls (4.61 ~g/ml).
Increase in serum SCN- levels
for nonsmoking exposed, fire-
fighters (3.75 ~g/ml) over
unexposed nonsmoking controls
(3.21 fig/mI).
( continued)
No attempt was made to cor-
relate minor symptoms with
serum,SCN- levels due to
,concomitant CO exposure.
The population studied was
quite small after strati-
fication for smoking. There
was a lack of age correspon-
dence with the controls, who
were fire academy students
and administrative personnel.
~ 10-15% of the exposed men
had values above the high-
est control values in each
smoking group.
Levine and
Radford
(1978)
A-10
Levine and
Radford
(1978)
A-lO '
Levine and
Radford
(1978)
, A-10
Levine and
Radford
(1978 )
A-10
-------
TABLE:V-2.
(concluded) .
Compound(s)
Concentration(s),
mg/m3 (ppm)
Duration
Description
of Workers
Exposed
Controls
Effects
Remarks
Reference and
Rating
HCN vapors from hot
liquid bath of
cyanide salts.
Dusts of the latter.
No concentrations.
given.
Subject 1: 1910-1920
1941-1943
Subject 2: 1940-1948
(less frequent
exposure 1942-
1948)
~:
VI .
Subject 1: Case hard-
ener exposed continu-
ously, at work. Heavy
cabbage eater. From known
. area of endemic goiter. Age
62 in 1946, the year his
goiter was removed. .
Subject 2: Worked in ma-
chine shop where case
hardening was performed..
Began iodine treatment
for neck swelling 5 mo
after beginning of expo-
sure.. Age 36 in 1948,
when admitted to hospital
with goiter. Heavy pipe
smoker until 1945. Sis-
ter had a simple colloid
goiter.
2 M
None.
Case 1:. Persistent headache,
sweating, chest pains, dizzi-
ness, fatigue, weakness,
mental confusion, disturbed
moto~ function (e.g., tremor),
nervousness, coughing, sneez-
ing, cramping in lower ab-
domen, paralysis, auricular
fibrillation, thyroid en-
largement 2~3 X normal, high
blood pressure. After a
thyroidectomy, the. patient
did not resume contact with
cyanides.
Case 2:
Thyroid enlargement.
Case reports of goiter in two
men occupationally exposed to
unquantitated HCN vapors.
Family history, endemic
goiter region, and dietary
history combined make these
reports of doubtful value in
establishing thyroid toxicity
ofHCN vapors.
Hardy et al.
(1950)
B-7
a
No local exhaust system.
b
Percent of measurements that exceeded the USSR maximum allowable concentration.
-------
2-0035
2-0001
2-179
2-0034
2-0066
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Au.
Recommended time-weighted TLV of 10 mg/m3.
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C--. . Review of toxicity of HCN and other materials that would be
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i
D--. Summary of various exposure standards such as TLV's toxicity
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C-11. Two donkeys were exposed for ~ 30 min to puffs of ciga-
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Anonymous. 1966.
Cosmet. Toxicol.
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Food
*
Numbers in the left margin are MRI acquisition numbers.
47
-------
2-0071
2-0120
5-191
2-0036
2-0020
2-0037
2-0032
D--. Acceptable daily intake of 0.05 mg CN-/kg body weight in
food for man given; no data for the choice or reason behind it.
Aoyama, M. 1975. Effect of Anti-Flame Treated Cloths at
Combustion on the Living Body. Nagoya Med. J. 20:1-10.
D-11. Time of death was recorded for mice exposed to mixed
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Barcroft, J. 1931. The Toxicity of Atmospheres Containing
Hydrocyanic Acid Gas. J. Hyg. 31:1-34..
B-11. Classic. LDso - concentration - time studies. Multi-
species comparison very good.
Battista, S. P., and C. J. Kensler. 1970. Mucus Production and
Ciliary Transport Activity. In Vivo Studies Using the Chicken.
Arch. Environ. Health 20:326-338.
C-9. In vitro, a
. 8 puffs inhibited
of control hens.
puff for 8 puffs.
for HCN is given.
dose of 10 ~g HCN/40 ml puff [250 mg/m3] for
ciliary activity to 50% that of the trachea
The corresponding EDso in vivo was 38 ~g/40 ~l
A log concentration - percent inhibition curve
Baxter, R. 1977.
53(12) :38-41.
Cyanide Can Be Handled Safely.
Ind. Finish.
C--.
The odor threshold for HCN is 2 ppm.
Review.
Boklag, E. P. 1975. Hygienic Characteristics of Working Condi-
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C-6. Group changes upon exposure to acrylonitrile, HCN, NH3,
and hydrocarbons included evanescent signs of increased immu-
nity, premature aging, an~ borderline central nervous system
change. One assumes the mixture to which this population was
exposed was slightly toxic.
Brunnemann, K. D., L. Yu, andD. Hoffmann. 1977. Chemical.
Studies on Tobacco Smoke. XLIX. Gas Chromatographic Determina-
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C--. A "standard" cigarette contained 479 ~g HCN in mainstream
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Burton, D. J. 1974. Health Hazard Evaluation/Toxicity Determina-
tion Report 73-147-134, H.F. Barrows Company, North Attleboro,
Massachusetts. PB-246 459, U.S. Nat. Tech. Inform. Servo U.S.
Dept. of Commerce, Springfield, Virginia. 6 pp. .
48
-------
2-0121
2-0003
2-0178
2-0122
B-3. Three or four electroplaters were exposed to acids, 0.01 mg
HCN/m3, and 2.9 mg NHs/m3. No ill effects were noted. Paper did
not describe the health effects evaluated or any method of evalu-
ation, which is a shortcoming. .
Carmelo, S. 1955. Nuovi Contributi a110 Studio de11a Intossica-
zione Subacuta-Cronica da Acido Ciandrico nell'Uomo [New Contri-
butions to the Study of Subacute-Chronic Hydrocyanic Acid Intoxica-
tion in Man]. Rass. Med. Ind. 24:254-271.
C-6~ Most fumigators who had inhaled sufficient HCN to experience
symptoms of poisoning within the past 2 y suffered from gastritis.
Those who had never inhaled HCN showed none of the CNS and cardio-
pulmonary symptoms observed in the exposed fumigators.
Castello, C., A. Giussani, and A. Berti. 1969. Avvelenamento
da Acid Cianidrico. Considerazioni Clinic6-Terapeutichee Presen~
tazione di un Caso. [Poisoning by Hydrocyanic Acid; Clinical and
Therapeutic Considerations and Present~tion of a Case]. Minerva
Anestesiol. 35:437-447.
D-2. Paper describes the medical treatment of a sailor found
unconscious in his berth onboard ship after disinfection of the.
ship with HCN.
. Chandra, H., B. N. Gupta, S. K. Bhargava, S. .H. Clerk, and P~ N.
Mahendra. 1980. Chronic Cyanide Exposure--A Biochemical and
Industrial Hygiene Study. J.Anal. Toxicol. ,4(4):161-165.
B-ll. Case hardeners and electroplaters were exposed to cyanide
at concentrations up to 0.8 mg/m3. They showed significantlyele-
vated thiocyanate in blood and urine and significantly elevated
cyanide in blood. There were only small differences between values
for exposed smokers and nonsmokers. Although this article men-
tioned that HCN toxicity symptoms occurred, the full report was
cited as having been communicated (by these authors with Gupta
first) in 1979 to an obscure journal that we tried ~ut failed to
locate: Indian J. Occup. Health.
Chaumont, A. J. 1960. L'intoxication chronique par, les cyanures
et l'acidcyanhydrique [Chronic Intoxication Caused by Cyanides
and by Hydrocyanic Acid]. Soc. Med. D'Hyg. Trav. 660-662; copy-
righted English translation provided by the National Institute
for Occupational Safety and Health, Rockville, Maryland.
C-4. Review of work by Koopman (1936) [2-0173] and Teleki. Addi-
tional ca~e histories given, but no HCN concentrations given.
. Paper demonstrates definite low level symptoms that are secondary
to low oxygen-carrying power of red blood cells: increased heart
. size, increased red blood cell count, enzyme change. Poor, sci-
entifically. Not strong numbers. .
49
-------
2-0123
2-0172
2-0124
2-0068
2-0006
2-0111
Colle, R. 1972. L'intoxication cyanhydrique chronique [Chronic
Hydrogen Cyanide Poisoning]. Maroc. Med. 50:750-757; copyrighted
English translation provided by the National Institute for Occu-
pational Health Science, Rockville, Maryland.
C--. Good review of symptoms of occupational chronic exposure to
HCN, but research and control level are deficient.
Columba, D. 1940. Die erstenklinischen Beobachtungen uber die
Blausaure bein Menschen verursachten chronis chen Veranderungen
durch. [First clinical observations on the chronic changes in
man due to hydrocyanic acid]. Ber; Gesamte Physiol. Exp. Pharmakol.
120:176. .
C-3. Pneumo-cardio-diaphragmaticchanges,hematologic changes,
and changes occurring in carbohydrate metabolism were observed
in 15 workers who had been extermirlating with HCN for 2 to 7 y.
Changes included widening of the lungs and bronchi, a change in
the position of the diaphragm, hypotension, hyperhemolysis followed
by hyperchromy, a diminution of the neutrophil polynuclei, a re-
duction in perpxidase levels, lymphocytosis accompanied by mono- .
cytosis, and hyperglycemia.
Creel, R. H., F. M. Faget, and W. D. Wrightson. 1915. Hydro-
cyanic Acid Gas--Its Practical Use as a Routine FUmigant. Public
Health Rep. 30:3537-3550.
D-9.
Lethality experiments with rats were performed.
Dalhamn, T. 1972.
of Cigarette Smoke.
Factors Influencing the Respiratory Toxicity
J. Nat. Cancer Inst. 48:1821-1824.
D-8. Cats were exposed tracheally to mixed combustion products
from nonfilter cigarettes containing 60-480 ~g HCN/cigarette.
Physiological effects on bronchial clearance were studied. The
number of 10-ml puffs to produce ciliostasisranged from 39 to
154. Acrolein, tar, CO, nicotine, and HCN concentrations were
highly correlated with the number of puffs required.. .
Delga, J., J.Motin, p~ Bouletreau, and 1. M. Rouzioux. 1970.
Actual Problems of Hydrocyanic Acid Poisoning. . Therapeutique
46:887-892.
D--. Review. Chronic HCN poisoning is similar in its manifes.
tations to carbon monoxide poisoning.
, Dequidt, J., D. Furon, F. Wattel, J.
B. Gosselin, and A. Ginestet. 1974.
trile with a Report on a Fatal Case.
Hyg. 7:91-97.
M. Haguenoer, P. Scherpereel,
Intoxication with Acetoni-
Eur. J. ToxicoL Environ.
50
-------
2-0126
2-0029
2-0127
2-0128
2-0039
2-0021
D-12. Well-followed fatal case report. Conc~ntrations of free
HCN were determined in the victim's tissues. Acetonitrile,CH3CN,
was used by the fatally intoxicated worker and others to clean a
floor. Upon pouring boiling water on the floor, hydrolysis caused
the release of HCN and HCHO. .
Dinca, C., L. Pod, and I. Galetariu. 1972. [Considerations on
Leukocytic Oxidative Enzyme Changes in Subjects Exposed to the
Prolonged Action of Cyanhydric Acid in Industry]. Med. Int.
24:1385-1392; Copyrighted English translation provided by the
National Institute for Occupational Safety and Health, Rockville,
Maryland.
A-12. The case is convincing--a human population exposed at
moderate levels (0.26 mgfm3) to HCN had significantlydepresserl
enzymes.
DiPasquale, L. C., and H.V. Davis. 1971. Acute Toxicity of
Brief Exposures to Hydrogen Fluoride, Hydrogen Chloride, Nitrogen
Dioxide, and Hydrogen Cyanide Singly and in Combination with Car-
bon Monoxide. AD-751 442, National Technical Information Service,
U.S. Department of Commerce, Springfield, Virginia. 13 pp.
C-10.
Data same as those in MacEwen and Vernot (1971)[2-0027].
Drinker, P. 1932. Hydrocyanic Acid Gas Poisoni~g by Absorp-
tion Through the Skin. J. Ind. Hyg. 14:1-2.
.D-8. Industrial gas masks give respiratory protection in atmo-
spheres containing 2% HCN, but unprotected skin should not be ex-
posed to such concentrations.
D~dley, H. C., T. R. Sweeney, and J. W. M{ller, 1942.
Acrylonitrile (Vinyl Cyanide). II. Studies of Effects
Inhalation. J. Ind. Hyg. Toxicol. 24:255-258.
Toxicology of
of Daily
C-9. The effects of inhaled acrylonitrile
comparable levels to HCN in several animal
mental protocol is given for the.HCN tests
. bably only a review of the literature. .
are quite'similar at
species: No experi-
so that they are pro-
Einhorn,
of Smoke.
Environ.
I. N. 1975. Physiological and
Produced During the Combustion
Health Perspect. 11:163-189.
Toxicological Aspects
of Polymeric Materials.
C--.
The human HCN dose-response data are reviewed again.
Eitingon, A. I., L. T. Poddubnaya, L. S. Naumova, and G. P.
Gribunova. 1977. Toksichnost i Sostav Produktov Goreniya
Nekotorykh Khimicheskikh i Prirodnykh Tkanei i Volokon [Toxicity
and Composition of Combustion Products of Some Synthetic and Na-
tural Fabrics and Fibers]. Khim. Volokna No. 4:49-51.
51
-------
2-0129
2-0130
2-0131
2-0132
2-0133 .
2-0134
D-6. . Lethal doses were determined for mice exposed to mixed com-
bustion products.
El Ghawabi, S. H., M. A. Gaafar, A. A. El-Saharti, S. H. Ahmed,
K. K. Malash, and R. Fanes. 1975. Chronic Cyanide Exposure: A
Clinical, Radioisotope, and Laboratory Study. Br. J. Ind. Med.
32:215-219.
B-9. Controlled study reports multiple symptoms in exposed
group. Prevalence data were used to assess exposure. It
would have been helpful to use thiocyanate levels to cor-
relate with symptoms. Twenty (56%) of 36 electroplaters had
mild to moderate thyroid enlargement after long-term exposure
to 4.2-12.4 ppm CN- in the air. .
Etteldorf, J. N. 1939. The Treatment of Gaseous Hydro-
cyanic Acid Poisoning by Sodium Thiosulfate and Sodium Nitrite
Combination. J. Pharmacol. Exp. Ther. 66:125-131.
D-9. Exposure of dogs to convulsing concentrations of HCN (~ 500
ppm) for> 0.25 h was lethal.
Fairley, A., E. C. Linton, and F. E. Wild. 1934. The Absorp-
tion of Hydrocyanic Acid Vapour Through the Skin with Notes on
Other Matters Relating to Acute Cyanide Poisoning. J. Hyg.
34:283-294. .
C-7. The skin of guinea pigs and rabbits was exposed to an atmo-
sphere "saturated with" HCNvapor. This is a lethality study; no
other effects were well studied.. .
Fassett, D. W, 1963. Cyanides and Nitriles. In: Industrial
Hygiene and Toxicology, Vol. 2, F. A. Patty, ed. Interscience
Publishers, New York, New York. pp. 1991-2036.
C--.
Review of effects of high HCN concentrations.
Flury, F., and F. Zernik. 1931. Cyanwasserstoff (Blausaure,
Ameisensaurenitril) [HCN (Hydrocyanic Acid, Prussic Acid)]. In:
Noxious Gases--Vapors, Mist, Smoke, and Dust Particles. Verlag
von Julius Springer, Berlin, Germany. pp. 400-415.
.. .' ~
C--. A good review of early literature on animal and human poi-
soning by HCN.
Gettler, A. 0., and J.O. Baine. 1938.
Cyanide. Am. J. Med. Sci.195:182-198.
The Toxicology of
C--. ,The distribution of HCN in a 68.30 kg human female who had
died inhaling HCN was (in mg/kg):' brain, 0.032; lungs, 0.075;
blood, 0.041; liver, 0.021; kidney, 0.033; heart, 0.42; and stomach
wall, 0.10. Distribution in dogs poisoned fatally by HCN inhala-
tion was similar. .
52
-------
2 - 0 135
2-0040
2-0136
2-0137
2-0138
2-0061
Gordh, T., and B. Norberg. 1947. Studies on Oxygen Treat-
ment in Connection with Experimental Hydrocyanic Poisoning.
Physiol. Scand. 13:26-34. .
Acta
D-IO. Rabbits were exposed to lethal HCN concentrations (284-
1,290 mgjm3).
Goii, G. B. and C. J. Lynch. 1978. Toward Less Hazardous
Cigarettes. J. Am. Med. Assoc. 240:1255-1259.
Cn. Compare data with Brunnemaim et al. (1977) [2"':'0037], where
smoke was analyzed. In this study, the range of HCNfound in 27.
modern brands of U.S. cigar~ttes was 9 to 141 ~gjcigarette.
Grabois, B. 1954.
of Apricot Kernels.
33:33-36, 1954.
Exposure to Hydrogen Cyanide in the Processing
NY State Dept. Labor Mon. Rev., Div. Ind. Hyg.
D--. No exposure effects are described in the plant personnel ex-
posed to ~ 17 ppm HCN. Since the paper is mainly an analytical
methods development paper, no attempt. was made to examine the
. workers. In fact, we had totally discarded this paper until we
found the observed levels described as tlNo observed effects" in
Table XIV-5, p. 178, of Wills et al. (1976) on human responses.
Grubbs, S. B. 1917. Detection of Hydrocyanic Acid Gas--Use of
Small Animals for This Purpose. Weekly Public Health Rep.
32:565-570. .
D-9. Several species, but few doses and single animals. Guinea
pigs were resistant to HCN concentrations that may be dangerous
to man. Mice and tame rats were almost as susceptible as the
"most .delicate live indicatorstl--sparrows or. other small birds.
Hamilton, A., and H. L. Hardy. 1949. In: IndustrialToxi-
cology, ed. 2. Paul B. Hoeber Inc., New York, New York. pp.
248-262. .
C--. Good review.
1963 [2-0132]).
Human symptoms (more applicable than Fassett,
Hanzal, R. F., andJ. W. Howard. 1955. Chronic Toxicity for
Rats of Food Treated with Hydrogen Cyanide. J. Agric. Food
Chern. 3:325-329. .
D--. Survivors of 20 rats (10 of each sex) fed 2 y a diet containing
~ 100 or 300 ppm HCN (HCN ~aporized from the fumigated food) showed
significant amounts of SCN in tissues but no pathology that was
not linked to their advanced age: Specifically, the thyroid was
one of the organs studied histologitally. Hatdl et al. (1950)
[2-0175] had s~ggested goiter in chronically CN exposed humans
was due to SCN toxicity.
53
-------
2-0175
2-0072
2-0139
2-0140
2-0028
Hardy, H. L., W. M. Jeffries, M. M. Wasserman, and W. R. Wadell,
1950. Thiocyanate Effect Following Industrial Cyanide Exposure.
Report of Two Cases. New England J. Med. 242:968-972.
B-7. Two case studies are presented, and other so-called chronic
cyanide poisoning studies are reviewed. Many of the symptoms
ascribed to chronic cyanide poisoning may be due to the toxicity
of its metabolic product thiocyanate. . Both of the cases described
exhibited goiter, presumably due to the mimicking of iodide by
thiocyanate. Heavy smoking and eating of cabbage~related vegetables
may exacerbate the symptoms of occupational cyanide exposure due to
additional formation of thiocyanate.
Haroz, R. K., and L. Mattenberger-Kreber. 1977. Fassett, 1963
[2-0132]. Effect of Cigarette Smoke on Macrophage Phagocytosis.
Energy Research and Development Administration Symp. Ser. 43
(Pulmonary Macrophage Epithelial Cells):36-57.
D--.
The decrease in immunity was not adequately related to HCN.
Haymaker, W., A. M. Ginzler, and R. L. Ferguson. 1952. Re-
sidual Neuropathological Effects of Cyanide Poisoning. A Study
of the Central Nervous System of 23 Dogs Exposed to Cyanide Com-
pounds. Mil. Surg. 111:231-246. .
D-7. Two of five dogs exposed for 1.75-2.0 min to 590 to 700 ppm
HCN survived 24 and 28 h (until sacrificed), whereas the other 3
died within 16-20 h. Another dog, exposed to 165 ppmHCN for 10
min survived 26 h until sacrificed. All were rendered comatose
and apneic.
Henderson, Y., and H. Haggard. 1943. In: Noxious Gases and
the Principles of Respiration Influencing Their Action, ed. 2, No.
35, ACS Monograph Series. Reinhold Publishing Corporation, New
York, New York. pp. 172-176.
C--. Old review with commonly given human dose-response data.
The rapidly fatal dose is in error, being> 10-fold higher than
the 270 ppm value or 0.3mgjL value given by Flury and Zernik
(1931) [2-0133].
Higgins, E. A., V. Fiorica, A. A. Thomas, and H. V. Davis. 1971.
Acute Toxicity of Brief Exposures to Hydrogen Fluoride, Hydrogen
Chloride, Nitrogen Dioxide and Hydrogen Cyanide Singly and in
Combination with Carbon Monoxide. AD-735 160. National Technical
Information Service, U.S. Department of Commerce, Springfield,
Virginia. 9 pp.
C-12. LCso for HCN and HCN plus toxic dose of CO.
only 5-min. exposure.
Good data but
54
-------
2-0095
2-0041
2-0096
2-:-0043
2-0031
2-0074
Higgins, E. A., V. Fiorica, A. A. Thomas, and H. V. Davis. 1972.
Acute Toxicity of Brief Exposures to Hydrogen Fluoride, Hydrogen
Chloride, Nitrogen Dioxide, and Hydrogen Cyanide with and without
Carbon Monoxide. Fire Technol. 8:120-130.
C-12. Lethality studies of rats and mice expoied to HCN a~d HCN
plus CO. Data duplicated in Higgins .et 31. (1971) [2-0028].
Hilado, G. J., and H. J. Cumming. 1978. Short-term LC50 Values:
An Update on Available Information. Fire .Technol. .14:46-50.
D--. Review of 4 lethality studies in mice and rats. Values taken
from a curve representing LC50 values for 250-g rats showed that
at -5 min the LC50 was -500 ppm; at 10 min, - 350 ppm; at 20 min,
- 210 ppm; at 30 min, - 180 ppm; and at 60 min, - 140 ppm. Note
that Barcroft (1931) had teported that 100 ppm was a
level that rats could "breathe indefinitely."
Hoffmann, L. D., and E. L. Wynder. 1972. Smoke of Cigarettes
and Little Cigars: An Analytical Comparison. Science. 178:
1197-1199. .
C--. . The HCN content of single puffs of cigarettes and littie
cigars was 36.1 to 88.7 ~g.
Hoffmann, D., L. D. Sanghvi, and E. L. Wynder. 1974. Compara-
tive Chemical Analysis of Indian Bidi and American Cigarette Smoke.
Int. J. Cancer. 14:49-53.
C--. Cigarettes (200) of a U.S. non-filtered brand purchased in
. 1973 contained 445 and 240 ~g HCN when smoked mechanically at the
rates of.2 and 1 puff/min, respectively.
Hollett, B. A. 1976. Health Hazard Evaluation Determination.
Report Number 75-182-334, New England Foundry, Lawrence,
Massachusetts. . PB-273 778, National Technical Information Service,
U.S. Dept. of Conunerce,Springfield, Virginia. 25 pp.
C--. Core makers exhibited respiratory problems due more prob-
ably to Si02 than to HCN, whose concentrations were well within
accepted exposure limits.
Hugod, C. 1979. Effect of Exposure to 0.5 ppm Hydrogen
Cyanide Singly or Combined with 200 ppm Carbon Monoxide and/or 5
ppm Nitric Oxide on Coronary Arteries, Aorta, Pulmonary Artery,
and Lungs in the Rabbit. Int. Arch. Occup. Environ. Health.
44: 13-23.
55
-------
2-0119
2-0044
02-0142
2-0165
2-0099
C-11. Rabbits were exposed for 1-4 wk in an interaction study at
low levels; only morphological effects sought; none found, which
. limits usefulness. Same design with more data, especially physio-
logical, would be very useful. .
Hugod, C., and P. Astrup. 1980. Exposure of Rabbits to
Carbon Monoxide and Other Gas Phase Constituents of Tobacco Smoke.
Influence on Coronary - and Aortic Intimal Morphology. MMW,
Muench. Med. Wochenschr. 122:18-24. .
C-11. Identical experiments for HCN were reported by Hugod
(1979).
Hugod, C., L. H. Hawkins, and P. Astrup. 1978.
Passive Smokers to Tobacco Smoke Constituents.
Environ. Health. 42:21-29.
Exposure of
Int. Arch. Occup.
D--. People were exposed to ~ 0.014 mg HCN/m3 from sidestream
cigarette smoke for up to 2.5 h. Authors have attempted to quan-
titate "annoyance"; no control on cigarette type. They concluded
that a passive smoker would require 50 h to inhale as much HCN as
an active smoker would from inhaling the mainstream smoke of one
cigarette.
Jandorf, B. J., and O. Bodansky. 1946.
phylactic Effect of Methemoglobinemia in
Hydrogen Cyanide and Cyanogen Chloride.
28: 125-132. .
Therapeutic and Pro-
Inhalation Poisoning by
J. Ind. Hyg. Toxicol.
D-10. Dogs were exposed to lethal concentrations (500 to 2,200
ppm) of HCN without an antidote. The protective action of
methemoglobin was not so marked for HCN poisoning as for CNCI
inhalation.
Jaroschka, R., and R. Kropp.
[Chronic Cyanide Poisoning].
22:202-207. .
1966. Chronische Cyanidvergiftung
Int. Arch. Gewerbepath. u. Gewerbehyg.
C--. One case history of exposure to KCN, trichloroethylene,
H2S04' HC1, HN03' bleaching lye, and caustic soda. No concentra-
tions were given. Extensive description of his blood chemistry
.and EKG. The victim must have had a toxic hepatosis.
Jouglard, J., G. Fagot, B. Deguigne, and J. A. Arlaud. 1971.
Acute Hydrogen Cyanide Poisoning and Its Emergency Treatment. Mars.
Med. pp. 571-575.
C-7. The accidental inhalation exposures of 5 humans to HCN are
described, but the symptoms are discussed with those for cyanide
salts.
56
-------
j-
2-0019
2-0100
5-367
2-0018
Ju'zwiak, I., B. Pollak-Korkus, J. Bugajska, M. Menzel-
Lipi'nska, H. Go'zdzik, J. Suchowiak, W. Pelc, Z. Kaplicka, B.
Rybacka, Z. Pruszy'nska, and A. Gruszka. 1979.. Badania nad
Zagrozeniem Zawodowym Cyjanowodorem PracownikowGalwanizerni
Przemyslowych [Occupational Exposure to Hydrogen Cyanide in
Workers of Industrial Galvanizing Workshops]. Pol. Tyg. Lek.
34(9):337-340.
B-8. Electroplaters exposed to HCN had a different health
profile than the control group: HCN-exposed women had no
circulatory system pathologies reported, but had neurosis
(CNS symptoms). as frequently as controls. HCN-exposed men,
on the other hand, had circulatory problems as frequently
as controls but none of the neurotic symptoms that were seen
in control males.
Kensler, C. J., and S. P. Battista. 1966. Chemical and Physical
Factors Affecting Mammalian Ciliary Activity. Am. Rev. Resp. Dis.
93:93-102.
B-9. Ciliary activity in. rabbit trachea was inhibited to 50%
that of the controls when exposed to 200 mg HCNfm3 for 18 s~
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. Hasselbarth,
E. Lahmann, G. Muller, and W.Niemitz, eds. Erich Schmidt Verlag,
Berlin, Germany. pp. 448-453 (Ger).
C--. Maximum
Acrolein
NH3
HCN
HCHO
MeOH
allowable indoor air in the USSR:
0.1 mgfm3
.0.2
0.002
0.01
0.5
Kiryakov, K., T.S. Vodichenska, V. Markovska, and E.
Tsutsulova. 1978.. Contamination of the Atmospheric Air and Mor-
bidity with Temporary Loss of Working Capacity Among Agrarian
Work~rs. Khig. Zdrave6paz. 21:42-48.
C-5. Bulgarian article. Workers were exposed to H2S, phenol,
and HCN. The details that were understandable to a reader
facile in Russian are given in Table IV-2. Multiple factors
besides air quality could contribute to the variation in
"sickness duration" observed. Job comparability between
groups is not given.
57
-------
2-0047
2-0024
2-0173
2-0145
2-0144
Kishitani, K., and K. Nakamura. 1974. Toxicities of Combus-
tion Products. J. Fire Flammability/Combust. Toxicol. Suppl.
1:104-123.
D-12. Mice were exposed to lethal concentrations of mixed com-
bustion products in almost all tests. However, the mice survived
~ 1 week in fresh air after the tests when the HCN concentrations
were 9 to 60 ppm and the CO concentrations were low. In some
tests at > 100 ppm HCN, the mice survived; yet in others, where
the combustion constituents were nearly the same, they died.
.
Kondrashov, Y. A. 1978. 0 Sootnosheniyakh Opasnosti
Otravleniya Parami i Gazami Toksicheskikh Veshchestvpri Kozhnom
i Ingalyatsionnom Putyakh Vozdeistviya [Relative Hazards of Poi-
soning with Fumes and Gases of Toxic Substances with Their Dermal
and Inhalation Routes of Action]. Gig. Tr. Prof. Zabol. No.
2:34-38.
D-2. The LCso for rats by inhalation of HCN is ~ 200 mg/m3 com-
pared to~. ~2,000 mg/m3 by skin absorption.
Koopman [no initial]. 1936. Beitrag zur Frage der chronichen
Blausavievergiftung [On the Question of Chronic Cyanide Poisoning].
Deut. Z. ges. gerichtl. Med. 36:382-384.
D-6. Complaints of employees that had been in contact for years with
the rooms that had been used for disinfection with cyanide are enum-
erated. They included eye itching and watering, headache, light
coughing, and various gastrointestinal symptoms. The conclusions
are broad and sweeping without the data base that is expected in
current studies. No HCN concentrations are given.
Lazarev, N. V. 1956. [Harmful Substances in Industry-Part II -
Inorganic and Organometallic Compounds]. State Technical Publish-
ings, Warsaw, 1956, pp. 224-235; copyrighted English transiation
.by the National Institute for Occupational Safety and Health, Rock-
ville, Maryland. .
C--.
Review duplicated in 1971.
Lazarev, N. V. 1971. Toxic Substances in Industry. Inorganic
and Elementary Compounds. A Manual for Chemists, Engineers and
Physicians. ed. 6. Khimiya, Leningrad, pp. 228-240; copyrighted
English translation provided by the National Institute for Occupa-
tional Safety and Health, Rockville, Maryland.
C--.
Review.
. .
Duplicates information in Lazarev (1956).
58
-------
L
2-0146
2-0080
2'""0048
2-0149
2-0148
Lehmann, K. B. 1903. Ueber die Giftigkeit der gasformigen
Blausaure und des Phosphorwasserstoffs mit Demonstration [About
the Toxicity of Gaseous HCN and Hydrogen Phosphide with a Demon-
stration]. Klin. Wochensch;40:918-919; copyrighted" English trans-
lation provided by the National Institute of Occupational Safety
and Health, Rockville, Maryland.
. .
B-3. Cats tolerated 30-40 ppm HCN for 4-5 h, but more
toms appeared at higher concentrations.
severe
symp-
Leuchtenberger, C., R. Leuchtenberger, I. Zbinden, and E. Schleh.
1976. Significance of Oxides of Nitrogen and Sulfhydryl Reactive
Components in Pulmonary Carcinogenesis. An Experimental Study
Related to Tobacco Smoke. Colloq. Inst. Nail. Sante Rech. Med.
52(Environ. Pollut. Carcinog. Risks):73-79. .
C-14. A good paper; a valuable assay for lab, workers. Not
useful for identifying a level of concern for HCN in automo-
bile emissions.
Levine, M. S., and E. P. Radford. 1978. Occupational Expo-
sures to Cyanide in Baltimore Fire Fighters. J. Occup. Med.
20:53-56.
A-10. Exposure to a fire atmosphere was correlated with a
significant increase in mean serum thiocyanate levels over
controls in each smoking category. The population studied.
was quite small after stratification on smoking. There was
a lack of age correspondence with controls. Theblood
. thiocyanate levels could not be correlated with the exposure
composition (materials burned in fire), symptoms in fire-:-
fighters (undescribed), or mask use (safety protection). The
authors hypothesized that there are some individual differences
in response, which sounded theoretical and unbased but possible.
Levine, S., and W.Stypulkowski. 1959.. Experimental Cyanide
Encephalopathy. Arch. Pathol. 67:306-323. .
D-10. Rats were exposed to lethal and near-lethal conc~ntrations
and the brain histopathology was described.
Levine, S., and B. Weinstein. 1959. Neurotoxicity of Hydro-
gen Cyanide. J. Am; Pharm. Assoc. 48:224-226.
D-7. Rats were exposed to near-lethal and lethal concentrations
of HCN. The concentrations were varied according tp the condi-
tion of the animal so as to produce a high incidence of brain
lesions. . .
59
-------
2-0102
2-0009
2-0027
2-0150
2-0167
2-0152
Levine, S., A. Hirano, and H. M. Zimmerman. 1967. Experi~
mental Cyanide Encephalopathy: Electron Microscopic Observations
of Early Lesions in White Matter. J. Neuropath. Exp. Neurol.
26:172-174. .
D-2. ,Rats were acutely exposed to unknown HCN concentrations.
Lutsenko, L. A. 1970. Voprosy Gigieny Truda pri Obagashchenii
Sul'fidnykhMednykh Rud na Fabrikakh Urala [Industrial Hygiene in
the Concentration of Sulfide Copper Ores at Mills in the Urais].
Gig. Tr. Prof. Zabol. 14:11-15.
D--. Workers were exposed to numerous agents
H2S, noise, vibration, and low temperature as
containing free silica [and probably numerous
in the ore minerals].
including HCN, CS2,
well as the ore dusts
accessory elements
MacEwen, J. D., and E. H. Vernot. 1971. Toxic Hazards Research
Unit Annual Technical Report. AD 734543. National Technical Infor-
mation Service, U.S. Department of Commerce, Springfield, Virginia.
102 pp.
C-10. Acute toxicity (mortality) study of rats and mice exposed
to high levels of HCN alone and combined with CO.
Maehly, A. C., and A. Swensson. 1970.. Cyanide and
Levels in Blood and Urine of Workers with Low-Grade
Cyanide. Int. Arch. Arbeitsmed. 27:195-209.
Thiocyanate
Exposure to
C-12. "Total" SCN in urine of 13 exposed workers (including five
nonsmokers) averaged 20.0-23.0 ~g/L whe~ the HCN levels were 3.8-5.1
ppm. Concentrations of free CN or SCN in the urine vary and
cannot be used for detecting undue chronic exposure to workplace
cyanide. Average urinary thiocyanate values in nonsmokers not
exposed in the workplace were 1.1-3.8 mgfL and were 3.1-6.5 mg/L
in nonexposed smokers.
Mattina, C. F., Jr. 1972. Potentiometric Method for the Deter-
mination of Hydrogen Cyanide and Hydrogen Sulfide in Cigarette
Smoke. Tob. Sci. 16:113-114.'
C--. Nonfilter cigarettes were consumed by a: smoking apparatus
in 32 puffs. Each puff contained 4.3 ~g H2S and 35 ~g HCN. [If
this is drawn into the lungs with ~ 0.7 L air/puff, the resultant
HCN concentration in the lungs would be ~ 50 mg/m3 (which exceeds
the 1979 TLV for HCN).] .
McNamara, B. P. 1976. Estimates of the Toxicity of Hydro-
cyanic Vapors in Man. ADA 028501. National Technical Information
Service, U.S. Department of Commerce, Springfield; Virginia. 25
pp.
60
-------
2-0151
2-0049
2-0154
2-0114 .
6-124
A--. Good review of old animal and human data as regards human
exposure. Estimated I-min LCso of 3,404 ppm~
Merzbach, G. 1899. Ueber einen Fall von gewerblicher
chronischer Blausaurevergiftung [On a Case of Chronic Industrial
Hydrocyanic Acid Intoxication]. BeiL Hyg. Rundsch. 9: 45-56.
D--. The patient, an electroplater, was chronically exposed not
only to HCN fumes but also toa AgCN-KCN solution. From the des-
cription of hi:;; ash-gray colored face with a bronze-colored luster,
he might have suffered from argyria. .
Mohler, S. R. 1975. Air Crash Survival: Injuries and Eva- ,
cuation Toxic Hazards. Aviat. Space Environ. Med. 46:86-88.
C--. The importance here is the author's conclusions that HCN is
dangerous as a combu~tion product in a large fire - say on an air-
plane. At"" 5 f./g CN Iml blood, death occurs in mammals. Incapaci-
tation occurs at about half that level. .
Moss, R. H., C. F. Jackson, and J. Seiberlich. 1951. Toxicity
of Carbon Monoxide and Hydrogen Cyanide Gas Mixtures--a Pre-
liminary Report. Arch. Ind. Hyg. Occup. Med. 4:53-64.
D-6. Interaction study of combustion products in rats; superceded
by later work. .
Myers, W. G., J.
llC Distribution
in High Specific
F. Lamb, R. W. James, and H. S. Winchell. 1973.
in Dogs Visualized after Intravenous llC-Cyanide
Activity. Nucl.Med. 12(2):154-162.
D--. High llC uptake by some organs (heart, fundus of stomach,
kidneys, and parotid glands) may be due to complex formation
between HCN and ferricytochrome oxidase.
Newsome, J.R., V. Norman, and V. L. Zaratzian. 1965. Vapor
Analysis of Cigarette Smoke. Tob. Sci. 9:102-110; or Tobacco
161(4): 24-32. . .
Phase
D--.
Levels in tobacco smoke (f./g/40 ~l puff):
methanol
HCHO
acrolein
HCN
H2S
NH3
Unfiltered
13
4.1.
8.2
32
3.4.
12
61
Filtered
10
3.6
7.9
29
3.1
13
-------
I
I.
2-0026
2-0109
2-0030
2-0155
2-0050
2-0157
Nishimaru, Y., M. Shimada, and Y. Tsuda. 1973. Experimental
Examination on the Case of Inhaled Hydrogen Cyanide Gas. Yokohama
Igaku. 24:1-8.
D-5. Time-lethality study at very high levels. Rats more resis-
tant than rabbits. Not all of the rabbits were killed after 30
min at ~ 80 ppm HCN, but ~ 150ppm HCN killed all the rabbits
within 3-5 min. Rats required 30 to 50 min. to expire from < 500
to 700 ppm HCN. [Comments based only on English summary.]
Owsianowski, M. 1975. Cholesterol Metabolism in the Rat
Brain During Experimental Cyanide Encephalopathy. Neuropatol.
Pol. 13:423-431.
D-I0. Rats were dosed to unconsciousness. About 30% died within
24 h of intoxication. No HCN concentration was given.
Paabo, M., B. Pitt, M. M. Birky, A. W. Coats, and S. E. Alderson.
1976. Measurements and Observations of the Toxicological
Hazard of Fire in a Metrorail Interior Mock-up. PB-250768. Na-
tional Technical Information Service, U.S. Department of Commerce,
Springfield, Virginia. 20 pp.
D--. Acute exposures of rats to combustion products (HCl, CO,
C02' HCN) from a full-scale mock-up. . .
Parmenter, D.C. 1926.
ing: Report of a Case.
Observations on Mild Cyanide Poison-
J. Ind. Hyg. 8:280-282.
B--. A case report showed individual human hypersensitivity.
Indicating an industrial standard applicable to the general
case may not always apply in individual situations.
Pryor, A. J., D. E. Johnson, and N. N. Jackson. 1975. Hazards
of Smoke and Toxic Gases Produced in Urban Fires. Combust. Toxi-
col. 2: 64-112.
.B-13. Mixed combustion products and HCN alone - good interaction
study. Good effort at separation and interaction of variables -
. see Table 21 and 23. .
Radojicic, B. 1973. [Determining Thiocyanate in Urine of Workers
Exposed to Cyanides.] Arh. Hig. Rada 24:227-232; copyrighted
English translation provided by the National Institute for Occupa-
tional Health Science, Rockville, Maryland.
B-9. Smokers and long-time cyqnide workers eliminated more thio-
cyanates (CNS) in their urine., The test was valuable for quanti-
tating chronic exposure if the smoking history was also known.
62
-------
i ----_u_-.
2-180
6-036
2-0051
2-0081
2-0159
Rickert, W. S., and J. C. Robinson. 198i. Estimating the Hazards
of Less Hazardous Cigarettes. II. Study of Cigarette Yields of
Nicotine, Carbon Monoxide, and Hydrogen Cyanide in Relation to
Levels of Cotinine, Carboxyhemoglobin, and Thiocyanate in Smokers.
J. Toxicol. Environ. Health 7(3-4):391-403.
C--. Study calculated that a person smoking < 10 cigarettes/d is
. exposed to ~ 1.4 mg HCN/d; 17.5-22.5 cigarettes, ~ 3.2 mg HCN/d;
and smoking> 37.5 cigarettes resulted in exposure to ~ 8.4 mg
HCN/d. In small groups of smokers studied no significant differ-
ence was found in blood thiocyanate level of those smoking high.
HCN cigarettes versus those smoking low HCN cigarettes.
Rickert, W. S., J. C. Robinson, and J.C. Young: 1980. Estimating
the Hazards.of "Less Hazardous" Cigarettes. 1. Tar, Nicotine, Carbon
Monoxide, Acrolein, Hydrogen Cyanide, and Total Aldehyde Deliveries
of Canadian Cigarettes. J. Toxicol. Environ. Health 6(2):351-366.
C--. Canadian cigarettes (102 brands purchased in March and April
1978) smoked usually to a 30-nuit butt length contained 4-269 IJg HCN/
. cigarette and 3-85 IJg acrolein per cigarette. . Average values were
.168 and 65 I-/g, respectively, or 432 and 78 ppm [it is not clear how
these latter values were derived; presumably the alveolar concentra-
tions were meant]. Smoking 20 cigarettes per day would give 4 and
68% of the total exposure in the workpiace for an 8-h day at the OSHA
limits. .
Rylander, R. 1973. Toxicity of Cigarette Smoke Components:
Free Lung Cell Response in Acute Exposures. Am. Rev. Respir. Dis.
108:1279-1282.. .
D-5. Guinea pigs were acutely exposed to HCN in mixed combustion
producti from 5 cigarettes containing 60-260 IJg HCN/cigarette.
The numbers of free macrophages and leukocytes in the lungs after
exposure to th~ smoke from unfiltered cigarettes were inversely
correlated to HCN and other smoke compo~ents except NO.
Sakai, T., and A. Okukubo. 1979. Application of a Test for.
Estimating the Relative Toxicity of Thermal Decomposition Products.
Fire Retardants: Proc. 1st Eur.Conf. Flammability and Fire Retar":'
dants, Belgium, 1977. pp. 147-153. .
D-6.
Lethality study with mice of mixed combustion products.
Sato, T., T. Fukyama, and M. Yamada. 1955. The Allowable Concen-
tration of Hydrogen Cyanide in Air. Bull. Inst. Public Health
(Tokyo) 4(4):3-5; copyrighted translation provided by the National
Institute for Occupational Safety and Health, Rockville, Maryland.
63
-------
2-0052
2-0160
2-0115
2-0078
2-0084
2-0053
B-10. Very good; the paper would have been excellent had it con-
tained more data on gas concentrations. Sublethal effects were
studied in mice exposed to HCN at and near the TLV.
Schmeltz, I., D. Hoffmann, and E. L. Wynder. 1974. Toxic and
Tumorigenic Agents in Tobacco Smoke: Analytical Methods and Modes
of Origin. Proc. Univ. Mo. Annu. Conf. Trace Subst. Environ. Health
8:281-295.
C--. A U.S. nonfilter cigarette contained 240 ~g
in the gas phase.of the smoke and 74 ~g/cigarette
late phase. .
HCN/cigarette
in the particu-
Smith, A. R., 1932.
Bull. 11:169-170.
Cyanide Poisoning.
N.Y. Dept. Labor Ind.
D--. Symptoms of poisoning by exposure primarily to cyanide salts
are reviewed with a few case histories.
Smith, L., H. Kruszyna, and R. P. Smith. 1977 ... The Effect of
Methemoglobin on the Inhibition of Cytochrome Oxidase by Cyanide,
Sulfide or Azide. Biochem. Pharmacol. 26:2247-2250.
D-6.Azide and sulfide are more toxic cellularly in vitro than
--
cyanide on cytochrome £ oxidase system.
Smith, P. W., C. R. Crane, D. C. Sanders, J. K. Abbott, and B. Endecott.
1976. Effects of Exposure to Carbon Monoxide and Hydrogen
Cyanide. Nat. Academy Sciences, Nat.. Res. C<:mncil, Comm. Socio-
tech., Comm. Fire Res., eds. Physiological and Toxicological
Aspects of Combustion Products: Int. Symp., Utah. 1974. pp.
75-88.
D-12. Lethality study of rats exposed to HCN and HCN plus CO.
Times to physical incapacitation at lethal concentrations were
also recorded. .
Spurgeon, J. C. 1978. The Correlation of Animal Response Data
with the Yields of Selected Thermal Decomposition Products for
Typical Aircraft Interior Materials. AD-A062938, Iss. FAA-NA-
78-45, FAA-RD-78-131. National Technical Information Service,
U.S. Department of Commerce, Springfield, Virginia. 40pp.
C-12. LDso of mixed combustion products. Sixteen percent of the
lethal HCN dose produced incapacitation of a 200 g rat in 5 min.
The calculated incapacitating concentration was 193 ppm HCN.
Swinyard, E. A. 1975. Noxious Gases and Vapors. Carbon Monoxide,
Hydrocyanic Acid, Benzene, Gasoline, Kerosene, Carbon Tetrachloride,
and Miscellaneous Organic Solvents. In: The Pharmacological Basis
of Therapeutics. L. S. Goodman and A. Gilman, eds. MacMillan Publish-
ing Co., New York, New York. pp. 900-911.
64
-------
2-0177
2-0161
2-0015
2-0169
5-425
Cn. . Brief review of HCN metabolism and therapy covers the same
material that Fassett (1963) did.
Towill, L. E., J. S. Drury, B. L. Whitfield, E. B. Lewis, E. L. Galyan,
and A. S. Hammons. 1978.. Reviews of the Environmental Effects of
Pollutants. PB-289-920. National Technical Information Service,
U. S. Department of Commerce, Springfield, Virginia.
Cn. Review of effects of HCN, metal cyanides, and organic
nitriles.
Trautman, J. A. 1933. Methylene Blue in the Treatment of HCN Gas
Poisoning. Public Health Rep. 48:1443-1447.
D-10. Guinea pigs, rats, and rabbits were exposed to lethal con-
centrations of HCN. Methylene blue injections were of no value
as on antidote.
Truhaut, R., C. Boudene, and J. M. Jouany. 1975. Etude de la toxi-
cite aigue, par voie aerienne, des toxique majeurs.pouvant etre
liberes lors d'incendies [Toxicity of Combustion and Pyrolysis
of Materials Used in Construction. I. Acute Toxicity by Pulmonary
Route of Major .Toxicants Released During Fires]. Arch. Mal. Prof.
Med. Trav. Secur. Soc. 36:707-738.
C-6. Elaborate interaction study; mostly dose-lethality studies
on rabbits and rats. i
Ubisch, H. von. 1968. The Assessment of Environmental Hazards
from Large-Scale Storage of Hydrogen Cyanide. .Nord. Hyg. Tidskr.
49(1) :31-35;
Not rated. Experiments showed the rate of evaporation of HCN from
simulated spills. Health effects were not considered.
Urban~ C. M., and R. J. Garbe. 1980. E~haustemissions from mal-
functioning three-way catalyst-equipped automobiles. SAE Tech.
Pap.Ser. 800511. 11 pp.
C--. Maximum emission rates (mg/m3) in 4 malfunctioning, 3-way
catalyst-equipped automobiles:
NH3 254
CN 67
H2S 8
HCRO 3
65
-------
3-094
2-0162
2-0056
2-0057
2-0170
2-0059
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 Stroitel'stvu [Publishing House of Lit-
erature on Construction]. Moscow. 96 pp.
C--. In the USSR, the MAC for HCN in workplaces was 0.3 mg/m3, and
0.01 mg/m3 .as the average limit in populated places..
Valade, P. 1952. Lesions du systeme nerveux central dans les in-
toxications chroniques experimentals par l'acide cyanhydrique
gazeux [Injuries to the Central Nervous System in Chronic Experi-
mental Poisoning by Hydrocyanic Acid Gas]. Bull. Acad. Natl. Med.
Paris. 136:280-285.
D-8. Five of 17 dogs died after repeated short exposures to 50
ppm HCN. The morphology of the vascular and nervous systems was
described. There were no controls. .
Vernot, E. H., J, D. MacEwen, C. C. Haun, and E. R. Kinkead. 1977.
Acute Toxicity and Skin Corrosion Data for Some Organic and In-
organic Compounds and Aqueous Solutions. Toxicol. Appl. Pharma-
col. 42:417-423.
D-11. The inhalation 1-h LCso for male rats was 484 ppm HCN.
The 5-min LCso for male mice was 323 ppm.
Vettor*zzi,F. G. 1977. State of the Art of the Toxicological
Evaluation Carried Out by the Joint FAO/WHO Expert Committee on
Pesticide Residues. III. Miscellaneous Pesticides Used in Agri-
culture and Public Health. Residue Rev. 66:137-184.
D--. Review. No-effect level for man of oral HCN is 0.05 mg/kg
. or3.5 mg/day for 70-kg Reference Man.
Vickroy, D. G., and G. L. Gaunt, Jr. 1972.. Determination of Cya-
nide in Cigarette Smoke by a Cyanide Ion-Selective Electrode.
Tob. Sci. 16:22-25.
C--. An average 306~g CN was determined in each standard domes-
tic brand cigarette by analyzing the smoke.
Wagner, R. P., C. H. Haddox, R. Fuerst, and W. S. Stone. 1950.
The Effect of Irradiated Medium, Cyanide, and Peroxide on the
Mutation Rate in Neurospora. Genetics.. 35:237-248.
D-6. Treating the conidia of Neurospora crassa with a nutrient
broth that had been pre-irradiated by ultraviolet light produced
biochemical mutations at a rate significantly higher than the
control rate. . Biochemical mutations were also produced at a
higher rate by treating with KCN or H202' The mutation rates
induced by these treatments were not much different from each
other but were significantly lower than the rate induced by
. direct ultraviolet irradiation. .
66
-------
2-0163
2-0113
2-0117
2-0060
2-0017
2-0070
Walton, D. C., and M. G.Witherspoon. 1926. Skin Absorption of
Certain Gases. J. Pharmacol. Exp. Ther.26:315-324.
D-8. The skin of individual dogs was exposed to very high con-.
centrations of HCN (5,500-16,900 ppm). Somedied; some survived,
showing no symptoms or facial twitching during the test.
Wender, M., A. Piechowski, and A, Wajgt. 1974, The Activity
of ,Arylsulphatases in Experimental Cyanide Encephalopathy. Exp.
Pathol. (Jena). 9: 122-124. .
D-11. The effect of cyanide on sulfatase activity appears not to
be a decisive factor in demyelination resulting from experimental
cyanide encephalopathy in rats. The HCN concentrations inhaled
were not given.
Wender, M., J. Stanislawska, and H. Filipek-Wender.
bral Cholesteryl Esters in Cyanide Encephalopathy.
Pol. 16:163-172. .
1978. Cere-
Neuropatol.
D-11. Encelphalopathywas induced in rats by unknown HCN concen-
trations. .
Will~, J. H., F. L. Mitchell, and B. J. Vos. 1976. Criteria for a
Recommended Standard. Occupational Exposure to Hydrogen Cyanide,
and. Cyanide Salts (NaCN, KCN, and Ca (CNh). U. S. Dept. of Health,
Education, and Welfare, Public Health Service, Center for Disease
Control, National Institute for Occupational Safety and Health,
Cincinnati, Ohio. Vol. 77-108. .191 pp. .
No rating.
Bibliography used for source of documents.
Yamamoto, K. 1976a. Acute Combined Effects of HCN and CO, with
the Use of the Combustion Products from PAN (Polyacrylonitrile)-
Gauze Mixtures. Z. Rechtsmed. 78:303-312.
D-11. Interaction of HCN and CO was studied in rats and mice,
mostly at maximum concentrations of HCN >200 ppm. In one test,
all nine mice survived when a maximum concentration of 37 ppm was
attained within 18 min. . .
Yamamoto; K. 1976b. Acute Combined Effects of Hydrogen 'Cyanide
and Carbon Monoxide, with Special Reference to a Theoretical Con-
sideration of Acute Combined Effects on the Basis of the Blood
Cyanide and Carbon Monoxide-Hb Analyses. Nippon Hoigaku Zasshi.
30:401-406;Chem. Abstr. 1977. 87:79238 m. . .
D--. This Japanese interaction study was not rated in detail.
Rats were acutely exposed to HCN and CO in combustion products.
The HCN concentration was not given. Blood cyanide in the rats
dying from the exposure was 3.14 to 3.70 ~g/ml.
67
-------
2-0013
2-0014
2-0025
Yamamoto,K., and Y. Yamamoto. 1971. Toxicity of Gases Released
by Polyurethane Foams Subjected to Sufficiently High Temperature.
Nippon Hoigaku Zasshi. 25:303-314.
C-12~ Studies of acute inhalation exposures of rats to mixed com-
bustion products and HCN alone. HCN seems to be the most toxic
component of the mix because thiosulfate predosing protected.
One dose - death curve for HCN.
Yamamoto, K., and Y. Yamamoto. 1978. On the Acute Toxicities of
the Combustion Products of Various Fibers, with Special Reference
to Blood Cyanide and Po Values. Z. Rechtsmed. 81:173-179.
2
C-9. Dose-lethality for Eabbits and HCN and mixed combustion pro-
ducts, with some blood CN measures.
Zotova, L. V. 1975. Working CObditions in the Production of
Acrylonitrile and Their Influence on the Workers. Gig. Tr..Prof.
Zabol. No. 8:8-11; copyrighted English translation provided by
. the National Institute for Occupational Safety and Health, Rockville,
Maryland. . .
C-8. Workers were exposed to vapors of acrylonitrile and HCN
as well as to acrylonitrile absorbed via the skin.
68
-------
,. REPORT NO.
EPA 460/3-81-026
TECHNICAL REPORT DATA.
(Please read IRs.l!1ICtiolls on the re~'erse beforecompletingj
3. RECIPIENT'S ACCESSION-NO.
12.
Hydrogen Cyanide Health Effects
5. REPORT DATE
- . 1QP'1
6. PERIfORMING ORGANIZATION CODE
4. TITLE AND SUBTITLE
7. AUTHOR(S)
Bonnie L. Carson,' Larry H. Baker,
'D~"''''''. Tn' U",.,..,." U 1<'11; C! TTT
9. PER-FORMING ORGANI,ATION NA~E AND ADDRESS
8. PERFORMING ORGANIZATION REPORT NO.
Eileen M.. Horn
and
10. PROGRAM ELEMENT NO.
Midwest Research Institute
425 Volker Boulevard
Kansas City, Missouri 64110
12. SPONSORING AGENCY NAME AND ADDRESS
Environmental Protection Agency
Office of Mobile Source Air Pollution Control
Emission confro1 Technology Division'--
2565 P1Vrnouth Road Ann Arbor Michi2an 48102
15. SUPPLEMENTARY NOTES
11. CONTRACT/GRANT NO;
68-03':'2928
.
13. TYPE OF REPORT AND PERIOD COVERED
Final Report
14. SPONSORING AGENCY CODE
16. ABSTRACT
Health effects literature primarily related to inhalation exposures to hydrogen
cyanide was collected, eva1u~ted, tabulated and summarized. Approximately 170 documents
were collected from computerized and manual literature searches covering the period
1899-1981. Pharmacologists and an M.D. epidemiologist rated the documents according
to their applicability to the study and the.ir methodology. The approximately 20 docu-
ments considered useful for deriving a range of concern for human exposure to hydrogen
cyanide from automotive emissions were tabulated. The 25 pages of tables detail the
results of acute and repeated dose testing of mice, rats, guinea pigs, rabbits, cats',
monkeys, dogs, goats, donkeys and humans as well as human occupationaistudies. Most
of the documents evaluated are described in an annotated bibliography.
17.
a.
DESCRIPTORS
KEY WORDS AND DOCUMENT ANALYSIS
b.IDENTIFIERS/OPEN ENDED TERMS
C. COSA TI Field/Group
Toxicity
Hydrogen cyanide
Cyanides
Mammals
Bibliographies
Toxic Tolerances
Occupational
diseases
Respiratory
system
Inhalation Health Effects
06 T
18. DISTRIBUTION STATEMENT
Release unlimited
19. SECURITY CLASS (This Report)
Unclassified
20. SECURITY CLASS (This PQge)
TTnf"lassified
21. NO. OF PAGES
69
22. PRICE
EPA Form 2220.1 (9.73)
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