TOXICOLOGY

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• Document Creation Date: December 19, 2016
• Document Release Date: January 17, 2006
• Sequence Number: 13
• Publication Date: January 1, 1963
• Content Type: STUDY

INDUSTBrIAL HYGIENE AN>~~RgJeabsd2(OO)e3dOlAiP8oFOOe2?ROOO2OOO3O
Frank A. Patty, Editor
.TOXICOLOGY, David W. Fas~tt and Don D. Irish, Editors
Copyright 1963 - Library of Congress Card No. 58-9223
1182 k1ERBERT L. SPORINU 'R
V2O 5 dust is good. It was originally suggested by Roschin';,2 on the basis of animal
studies of short duration, 'and its suitability was subsequently confirmed in more
extensive animal studies by Stokinger et a1.033 Lewis'':ss has more recently reported
no toxic manifestations from V dusts among workmen exposed to from 0.1 to 0.3
mg. of V/cu. meter. The lower limit for V205 fume is based on the recognized
greater toxicity of fume compared with dusts of larger particle size.
ZINC, Zn
STAT
1. Source and Production
Zn is widely distributed and occurs in small amounts in almost all igneous
rocks. Sphalerite (zinc blende) ZnS is the principal Zn mineral. Depending on Fe
content, natural specimens range in color from light tan to black; above a ratio of
Fe:Zn of 1:5 the mineral is called marmatite; above 5:6 the sphalerite structure
ceases to exist. Next to Fe, Cd is the most common impurity in sphalerite; when
associated with Zn as CdS it is called greenochite. Cd is about 1/200 as abundant
as Zn. Ga and Ge also occur in sphalerite (low-temperature formation), Sn and In
occur in traces from high-temperature deposits. Pb minerals are commonly associ-
ated with Zn minerals; the ratio Zn:Pb varies widely, from 1:7 to 5:1. Other
commonly associated minerals are calcite (CaCO3), dolomite (CaC03?MgC03),
pyrite (FeS2), quartz (Si02), chalcopyrite (CuFeS;r), and barite (_Bar04). Other
oxidized forms of Zn minerals, such as ZnO, ZnSO4'iH2O, ZnCO3, %n4Si207(033_)2
H20, and (Zn,RIn) O'Fe203i can be thought of as alterations from the sulfide, and
are of minor importance.
United States mines produced 412,000 tons recoverable Zn in 1958, 23 per cent
less than in 1957 and the smallest annual amount since 1933. Oversupply, increased
world production, declining consumption, cessation of government stockpiling, and
lower Zn prices contributed to lessened domestic production.
A variety of mining methods are used, which vary with the typ o, ore body.
Underground methods yield macst prar,u.~.tion but sonic spsh-?pit mining is done.
Almost all loading'and transportation are handled by power; at present: electric
or diesel units supply the power. Production of Zn concentrates is done by crushing
and grinding followed.by grav'.t;r sepo? a ior,, flotation, or rcagn^tic.. methods, or
combinations of them, depepding on the co.t?.pieuity of the +..re. Considerable metal
loss occurs on concentrating; losses of 8 to 20 per cent occur with the sulfide and
15 to 90 per cent of the oxidiza: i Zn. To improve recoveries of the la;;ter, a caustic-
leach electrolytic process is use:.: in this, :r. is extracted from the ores by NaOH
solution, the resulting electronelectrolyte is g 1.rific:di with Zn: dust and lime, and the Zn is
electrodeposited. Zn smelting rc-'fErs to troatrnent whereby Zn ores or concentrates
are reduced to refined metal. Suih,?e t~,a ccriceutrates are ,cast. d to eliminate S: in
the process Zn is converted to the oxide and sn..a1i ar.],`..'ue't.s of ZnSO4. The roast
may either`be leached for elec,trclytis deposition of Zn, or combined with coke or
07 I. V. Roschin, Gigiena i Sanit., t 1, 49 (I9, 2).
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THE METALS (EXCLUDING LEAD)
coal and retorted at about 1100?C. Residues from leaching and distillation are
shipped to a lead smelter for further processing if they contain economic amounts
of metals (Pb, Au, and Ag). ? Domestic smelters produce Zn of various grades;
electrolytic plants produce special high-grade or high-grade slab Zn; slab Zn from
horizontal retort plants is mostly prime western grade, although smaller amounts
of other grades are produced; vertical retort plants produce regular high grade; all
other grades are produced as the market warrants.
2. Uses and Industrial Exposures
Zn as metal in slab or pig was used to the extent of 868,300 tons in 1958; ore
and concentrates for pigments and salts, 94,900 tons; as scrap for alloys, Zn dust
pigments, and salts, 178,900 tons; other Zn concentrate is used for galvanizing, the
largest single use (40 per cent of total slab production). Second largest use of slab
Zn is in die-casting: as Zn alloy, of which parts as small as zipper elements or as
large as automobile radiator grilles are made. The automobile industry uses a
great number of Zn die-castings, as do the electric appliance, light machine, tool,
hardware, and toy industries. Large quantities of Zn are used for brass, particu-
larly in wartime for cartridges and shell cases, but developments in weapons and
ammunition are lessening the need for Zn. Zn, in sheet and rolled forms as an
alloy, is used in dry cells; jar caps (whence comes Cd in our diet) ; weather strip-
ping; photoengraving plates; roofing; ship's hulls; pipelines; and heavy plates for
cathodic protection of steam boilers. Zn pigments and salts, chief of which are
ZnO, lithopone (ZnS + BaSO4), ZnC12i and ZnSO4, have innumerable uses; the
major ones are in rubber goods, linoleum, paints, ceramics, cosmetics, textiles,
paper filler, and pharmaceuticals. Leaded ZnO is used in paints, varnishes, coated
fabrics, and textiles; ZnC12, for wood preservation, dry-battery cells, refining oil,
soldering flux; ZnSO4j in rayon, fertilizers, glue, textile dyes, electrogalvanizing
solutions, economic poisons, pure chemicals, and soap. About 30,000 tons of Zn
dust is used as a reducing agent in the synthesis of dye intermediates, of Na and Zn
hydrosulfite, in metallic paints, and cladding of iron and steel products (sherardiz-
Ing). Organic Zn compounds of the type R2Zn have limited application In organic
synthesis.
Industrial hazards arise from exposure to Zn fume, notorious producer of
metal-fume fever, but associated hazards in the metallurgy of Zn, of more serious
consequence, arise from the presence of As, Cd, D/In, Pb, and possibly Cu and Ag.
The frequent presence of As in Zn is a source of exposure to arsine (AsH3)
whenever Zn is dissolved in acids or alkalies; many cases of intoxication by AsH3
have occurred in the pickling of galvanized iron or from the use of powdered im-
pure Zn as a reducing agent in dyeing. It is possible also that effects attributed to
exposure to Zn fume may in part be attributable to those of Cd. Cd occurring
uniformly as a contaminant in Zn is a continuous source of trace amounts of Cd in
man.
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3. Physical and Chemical Properties
The physical and chemical properties of Zn and some of its compounds are
listed in Table 42.
TABLE 42
Physical and Chemical Properties of Zn and Some of Its Compounds
At. or
Chemical mol. M.p., B.p.,
symbol wt. Sp. gr. ?C. ?C. Solubility
Zinc
Zn
65.38
7.14
419.47
907
Insol. hot or cold H2O
Sol. acids, alkalies, acetic
acid
Zinc oxide
i
ZnO
81.38
5.47
>1800
1.6 mg./liter(29?)
Sol. acids, dil. acetic acid,
NH4OH
Z
nc sulfide
h
l
i
e
ZnS
97.45
4.102(25?)
Tr. 1020
0.65 mg./liter(18?)
(sp
a
er
t
)
V. sol. acids
Zinc chloride
ZnC12
136.29
2.91(25?)
262
732
4.32 kg./liter(25?)
6.15 kg./liter(100?)
1 kg./liter alc.(12.5?)
V. so]. ether
Insol. NH3
Zinc sulfate
ZnSO4
161.44
3.74(15?)
Dec. 740
865 g./liter(80?)
808 g./liter(100?)
Dimethyl zinc
(CH3)2Zn
95.45
1.386(10.5?)
-42.2
46
Dec. cold H2O, ale., acids
Sol. ether
Zn is a silvery metal of low to intermediate hardness; rolled Zn, 99.94 per cent
purity, has a scleroscope hardness of 13 to 15; cast Zn of the same purity is slightly
softer. The effect of small amounts of common impurities is to increase corrosion
resistance to solutions, but not in atmosphere. Ordinary Zn is too brittle to roll at
ordinary temperatures, but becomes ductile at elevated temperatures; brittleness
is thought to be associated with impurities such as Sn.
Zn has a standard electrode potential of +0.761 and is thus electropositive to.
most structural metals except Al and Mg. This property is the basis of many
important uses of Zn, for example, in batteries and electrogalvanizing of steel. Zn
is attacked by moist air, C02, and SO2, resulting chiefly in a coating of hydrated
,basic carbonate of variable composition; some H202 may be formed in the process.
Zn is resistant to attack by dry F2, C12, and Br2 but combines rapidly in presence
of water vapor. Zn is attacked by acid gases and acids. Zn is an active reducing
agent for many ions such as Fe+++, Mn04-, and Cr04 -. Hot caustic solutions
form zincates of uncertain composition. Zn vapor reduces CO:! to CO, the amount
depending on the temperature; above 1100?C., the retort temperature of Zn distil-
lation, essentially all CO2 is reduced to CO, in the presence of excess C. Zn and S
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THE METALS (T.xCLLTDINC LEAD) 1185
will explode when mixed .as a powder and warmed. A protective coating of ZnS is
formed on masses of Zn by either S or H?_S. When Zn or one of its alloys is burned,
melted, or heated to temperatures above 930?F., Zn metal oxide fume of particle
diameter 1 ? and below is formed.
4. Analytical Determination
Samples of fumes of Zn, ZnO in air may be collected by means of an impinger,
electrostatic precipitator, molecular-membrane filter, or by passing air through a
cotton plug moistened with dilute HNO3. Analysis may be made colorimctrically,
using dithizone or di-,3-naphthyithiocarbazone, or poiarographicaliy.c53
5. Physiological Response
A brief review by Vallee (6 pages, 28 references) touching on many of the
salient features of Zn and its biological significance to man appeared in 1957.854
Sufficient evidence has accumulated to show that Zn occurs in the body in two
different protein combinations: (a) as a metalloenzyme in which Zn is an integral
part of an important enzyme system, such as carbonic anhydrase for the regula-
tion of CO2 exchange, and (b) as a metal-protein complex in which Zn is loosely
bound to a protein, which acts as its carrier and transport mechanism in the body.
The possible relation of these Zn-protein combinations in a variety of altered
metabolic conditions and diseases is pointed out, and will be discussed in more
detail here in the appropriate sections.
Toxicity. Zn salts are astringent, corrosive to the skin, and irritating to the
gastrointestinal tract. Because of the last, when ingested they act as emetics. Zn
ion, however, is ordinarily too poorly absorbed to induce acute systemic intoxica-
tion. After large doses have been ingested, fatal collapse may occur as a result of
serious damage to the buccal and gastroenteric mucous, membranes. Mass poison-
ings have een repeatedly recorded655 from drinking acidic beverages made in
galvanized containers; fever, nausea, vomiting, stomach cramps, and diarrhea
occurred in 3 to 12 hours following ingestion. The emetic concentration range in
water is from 675 to 2280 p.p.m.; the threshold concentration of taste for Zn salts
approximates 15 p.p.m.; 30 p.p.m. soluble Zn salts impart a milky appearance to
water, and 40 p.p.m., a metallic taste.658 The lethal dose of Zn ion administered
orally to mice is 57 mg./kg s.,7 When parenterally administered, Zn depresses the
central nervous system, causing tremors and paralysis of the extremities; sub-
cutaneous injection of Zn lactate or valeratein a dose a uivalent to-57_.mg..- of
-' J. Cholak, D. Hubbard, and R. Burkey, Ind. Eng. Chem. Anl. Ed., 15, 754 (1943).
?64 B. L. Vallee, A.M.A. Arch. Ind. Health, 16, 147 (1957) ; Physiol. Revs., 39, 443 (1959).
166 G. E. Callender and C. J. Gentkow, Military Surgeon, 80, 67 (1939); J. W. Sale and
C. H. Badger, Ind. Eng. Chem., 16, 164 (1924) ; U. S. Natl. Ofc. Vital Statist., Communicable
Diseases Summary, for Sept. 11, 1954.
?`? J. J. Hinman, J. Am. Water Works Assoc., 30, 484 (1938).
?6P H. Jaeger, Arch. exptl. Pathol. Pharmakol., 159, 139 (1931).
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1186 HERBERT E. STOKINGER
Zn/kg. killed a cat after 3 days.657 Orally, soluble Zn salts are more. than 100 times
Tess toxic than corresponding salts of Cd, with which Zn is commonly contaminated.
Drinker, Thompson, and Marsh658 gave from 175 to 1000 mg. of ZnO/day for
periods of from 3 to 53 weeks to dogs and cats, and it was tolerated; glycosuria
occurred in the dogs, and fibrous degeneration of the pancreas in some of the cats
was found at autopsy. No manifest injury occurred in rats from administration of
from 0.5 to 34.4 mg. ZnO/day for periods of 1 month to 1 year. Similar lack of
response from ZnCO3 is reported. On the other hand, Waltner and Waltnerf59
reported that feeding the same salt induced anemia and osteoporosis in rats; 2
per cent metallic Zn in the diet of rats, however, resulted in no injury. Zn acetate
fed to rats for 4 months in doses of 10 to 15 mg. daily, and 50 mg. of Zn malate fed
to cats for 10 days to 2 months caused no intoxication, according to Salant.66?
Sutton and Nelson6C1 found that 0.1 per cent Zn was tolerated in the diet of rats,
but that more than 0.5 per cent reduced their capacity to reproduce, and 1 per cent
inhibited growth, caused severe anemia, and death. Zn salts in the diet are some-
what more toxic to pigs.662
Metabolism. Human intake of Zn is about 10 to 15 mg./day, which is mainly
excreted through the intestines. The feces contain about 10 mg. and the urine
about 0.4 mg. The normal Zn content of human tissues varies from 10 to 200 ,ag./g.
of fresh tissue. Most organs, including the pancreas, contain around 20 to 30
?g./g.654 The liver, bone, and voluntary muscle contain from 60 to 180 ?g. of Zn/g.
of tissue. Exceptionally large amounts are present in the prostate (860 - 100
?g./g.) and the retina (500 to 1000 ?g./g.). The total amount of Zn in the human
adult is estimated to be 2 g. No tissue preferentially stores Zn. Whole blood of man
contains about 900 pg. per cent of Zn, of which the serum contains from 80 to 160
?g. per cent. Leukocytes contain 3 per cent of total blood Zn. Blood Zn values
exhibit no seasonal or diurnal variations nor do they differ between the sexes.
Diabetics have normal Zn blood levels.
Only very small amounts of Zn were absorbed and stored in the tissues of
dogs, cats, and rats fed Zn compounds for long periods;633 chief sites of storage
were the liver and pancreas. Intravenously injected radioactive Zn65 showed that
liver, pancreas, and kidney stored large amounts of Zn65, but that the muscular
and mucosal layers of the small intestine contained relatively large amounts;
more than 50 per cent of the dose was excreted by mice in the feces and 2 per cent
in the urine in 170 hours 663
069 K. R. Drinker, P. K:-Thompson, and M. Marsh, Am. J. Physiol., 80, 31, 65 (1927), 81,
284 (1927).
w K. Waltner and K. Waltner, Arch. exptl. Pathol. Pharmakol., 141, 123 (1929) ; 146, 310
(1929).
'0' W. Salant, J. Ind. Hyg., 2, 72 (1920).
081 W. R. Sutton and D. E. Nelson, Proc. Soc. Exptl. Biol. Med., 36, 211 (1937).
R. E. Grimmett, et at., N. Z. J. Agr., 54, 216 (1937).
G. E. Sheline, I. L. Chaikoff, H. B. Jones, and M. L. Montgomery, J. Biol. Chem., 147,
409 (1943), 149, 138 (1943), J. Exptl. Med., 78, 151 (1943).
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THE METALS (EXCLUDING LEAD)
Zn is apparently transported in the blood stream as a loosely bound metal
globulin complex;-664 blood serum also contains a firmly bound Zn-protein com-
ponent, which amounts to about 50 per cent of that of the loosely bound fraction.
Ethylenediaminetetraacetate (EDTA) administered to rats intraperitoneally
greatly increased the urinary excretion of Zn. Of the various tissues analyzed, only
the pancreas and ileum showed a decreased concentration of Zn after EDTA.665
Mechanism. Zn is an active component of carbonic anhydrase; removal of
Zn results in irreversible inactivation of the enzyme, which is responsible for rapid
exchange of CO2.654 Zn is also a component of carboxypeptidase that splits termi-
nal amino groups from peptides; 1 atom of Zn is combined to 1 molecule of enzyme.
Four dehydrogenases contain Zn that is essential for their action: alcohol dehydro-
genase of yeast and liver, lactic acid dehydrogenase, and glutamic dehydrogenase;
2 to 4 moles of Zn are contained per enzyme molecule. Their presence in liver and
retina may explain the high concentration of Zn at these sites.
Serum Zn level is lowered in experimental CS2 poisoning,666 in pneumonia,
bronchitis, erysipelas, in pyelonephritis, and in untreated pernicious anemia.654
Industrial Experience. Batchelor, Fehnel, Thomson, and Drinker found no
acute or chronic illness in their examination of 24 men who had been exposed to
ZnO at levels of 0.3 to 1.64 mg./cu. ft. for from 2 to 35 years.667 The mean Zn
content of the blood of the exposed men was only slightly greater than that of
unexposed men. Exposure to mists or fumes of Zn salts may give rise to irritation
of the respiratory or the gastrointestinal tracts, but the evidence for these effects
is inconclusive. It has been stated that ZnO as dust may block the sebaceous-gland
ducts and give rise to a papulopustular eczema in men engaged in packing ZnO in
barrels.66s Sensitivity to ZnO is extremely rare.669 Unlike ZnO, ZnCI2 has a caustic
action, may result in u cl oration of the fingers, hands, and forearms of those who
use it as a flux in soldering. Affections of the skin have been noted among men
.handling railway ties impregnated with ZnC12. Zn stearate has been implicated as
a causative agent in pneumoconiosis.610
Metal-Fume Fever. Inhalation of fumes of ZnO results in a malaria-like
illness with onset some hours after the exposure.671 Metal-fume fever is not con-
fined to the inhalation of ZnO but may follow exposure to metal fumes of Sb, As,
Be, Cd, Co, Cu, Fe, Pb, Mg, Mn, Hg, Ni, and Sn. ZnO fume is a more frequent
??' I. Vikbladh, Scand. J. Clin. & Lab. Invest., 3, Suppl. No.2, 2,1 (1951).
' M.J. Millar, et al., Nature, 174, 881 (1954).
??? A. E. Cohen and L. D. Scheel, et al., Am. Ind. Hyg. Assoc. J., 20, 303 (1959).
?B7 R. P. Batchelor, J. W. Fehnel, R. M. Thomson, and K. R. Drinker, J. Ind. Ilyg., 8, 322
(1926).
J. A. Turner, Public Health Repts. U. S., 36, 2727 (1921) ; J. G. Downing, J. Ind. Hyg.,
17, 147, 150 (1935).
H. E. Freeman, J. Am. Med. Assoc., 119, 1016 (1942).
U. Uotila and L. Noro, Folia Med. Naples, 40, 245 (1957).
Q71 C. C. Sturgis, P. Drinker, and R. M. Thompson, J. Ind. Hyg., 9, 88 (1927) ; P. Drinker,.
R. M. Thompson, and J. L. Finn, J. Ind. Hyg., 9, 98, 187, 331 (1927) ; 10, 13 (1928).
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cause, however. The symptoms include chills and fever, which rarely exceeds
102?F., nausea and sometimes vomiting, dryness of the throat, cough, fatigue,
yawning, weakness, and aching of the head and body. After a few hours, the
victim sweats profusely, and the temperature begins to fall. The condition lasts a
day and is never fatal. Occasionally glucose is found in the urine; albuminuria is
rare. Mental confusion and convulsions may be present. The vital capacity (lung)
may be reduced, a condition which may persist for 15 hours. In 36 of 100 cases
observed by Natvig,C72 the condition recurred weekly or more frequently. Leuco-
cytosis (12,000 to 16,000 leucocytes/cu. mm.) persists for 12 hours after the tem-
perature has returned to normal.671 While the condition persists there is a measure
of immunity. Workers are more susceptible on Mondays, and on week-days follow-
ing a holiday, than on other workdays. A postulated mechanism that seems most
reasonable today is that of Lehmann '673 who suggested that the inhaled Zn-fume
particles liberated modified protein from the lung into the blood stream. The
subsequent distribution and absorption of the modified protein results in the
characteristic response resembling that from the injection of a foreign protein. A
recent review of the problem of metal-fume fever from inhaling ZnO, with reports
of cases, is given by Rohrs.674
6. Hygienic Standards of Permissible Exposure
A limit of 15 mg. of Zn/cu. meter air accepted by the American Conference of
Governmental Industrial Hygienists was suggested by Drinker, Thomson, and
Finn671 as the maximal concentration that can be inhaled daily without the pro-
duction of metal-fume fever. In laboratory experiments, a concentration of 45
mg./cu. meter was tolerated for 20 minutes by man.
7. Flammability
Powdered Zn presents a hazard of explosion. If stored in damp places, there is
danger of spontaneous combustion. Residues from reduction reactions may start a
fire if thrown into combustible waste (see also Vol. I, pages 560, 562, 565, 567, 570,
and 575).
ZIRCONIUM, Zr
1. Source and Production
Zr is associated with other metals in many minerals, but is recovered only
from zircon (Zr02?SiO2) and baddeleyite (brazilite) (Zr02). Hafnium, Hf, is
invariably associated with Zr. Zircon occurs in all igneous rocks but is more com-
mon in granite, sylnite (complex silicates), and diorite (alkaline-earth silicates).
Zircon is a common constituent of river gravels and beach sands, whence it is
H. S. Natvig, J. hid,. llyy. Toxicul., 19, 227A (1937) (abstr.),
? K. B. Leliuuuui, Arch. Ilyy, 72, 358 (1910).
L. C. Rolirs, AMA. Arch. Int. Mcd., 100, 44 (1957).
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