(Ca 1991?)
Caveat: This documentation was originally produced in a program that is no longer supported.
Extensive editing was necessary to make it readable. In that process, errors and/or loss of content may
have occurred. (April 2013)
JUSTIFICATION FOR ZINC SUBCHRONIC RfC
A subchronic air reference concentration (RfC) has been
developed for inorganic forms of zinc based on available human
and animal toxicological information. Most of the available data
for inorganic zinc have been derived following acute exposure
situations from either occupational studies or animal studies.
No studies were located regarding the cardiovascular,
gastrointestinal, musculoskeletal, hepatic, renal, dermal or
ocular effects in either human or animals following inhalation
exposure to zinc or zinc compounds (ATSDR, 1989). Metal fume
fever associated with welding and smelting processes involving
zinc is frequently reported in the occupational data (ATSDR,
1989). Acute inhalation has been reported to produce nasal
passage irritation, cough, substernal chest pain, persistent
rales of lung base and decreased vital capacity (ATSDR, 1989).
As zinc is an essential element, a certain amount of this element
is essential for proper nutrition. The National Academy of
Sciences has estimated a Recommended Daily Allowance of 15 mg/day
(0.2 mg/kg/day) for men and 12 mg/day (0.2 mg/kg/day) for women
(ATSDR, 1989). Excessive amounts of zinc taken orally can
produce gastric problems. In addition, an excessive dose of zinc
may interfere with the body's ability to absorb and use other
essential minerals such as copper and iron (ATSDR, 1989). There
are no data for either humans or animals, following inhalation
exposure to zinc, which indicate that zinc is a
developmental/reproductive toxicant or is carcinogenic (ATSDR,
1989). Only one report in the literature suggeted adverse
developmental effects after oral exposure to excessive amounts of
zinc (ATSDR, 1989).
A thorough literature search for this compound produced a
number of inhalation and ingestion studies conducted using zinc.
All of the inhalation studies identified involved either acute or
subacute exposure. The majority of the studies located are
summarized in the Agency for Toxic Substances and Disease
Registry Toxicological Profile for Zinc (ATSDR, 1989). The
subchronic RfC was therefore based on a subchronic oral study in
the absence of adequate inhalation data. Other noncarcinogenic
studies identified which were cited in the above publication
include:
Source
H.F.Lam
et al.
Source
Species
male
Hartley
guinea
pigs
Exp. Route
Duration
Effect
Exp Level
Inhalation
(zinc oxide)
3 h, 5
consec.
days
grad. decr.
total lung
capacity
7 mg/m3
Species
Hirano
et al.
rats
(zinc oxide)
P. Kurtz
et al.
6 mo. old
female
NMRJ mice
(ZnSO )
Conner
et al.
male
Hartley
guinea
pigs
T.W.
Graham
et al.
veal
calves
R.J.
Richards
et al.
male
Porton©
Wistar
rats
Exp. Route
intratrach.
adm. to
nasal
cavity
weeks)
inhal.
(noseonly)
(ZnO)
Duration
one dose
2 acute
doses
(4 and 8
3h
(1,2,3
consec.
dly. exp)
Effect
incr. lactate
dehydrogenase
and protein
content in
lavage fluid;
other effects.
decr. learn.
ability
Exp Level
20 ug
10-40 ul
(5% sol)
incr. prot.,
2.3 mg/m
neutroph.,
enzyme activ.,
in lav. fluid;
pulm. damage
oral in
milk
replacer
28 d - then
lower dose
for 23 d
histolog.
chngs.
intratrach.
(ZnC2)
single
dose
edema
706 ug Zn/g;
then 150 ug
Zn/g
2.5 mg/kg
A critical subchronic human study (Hooper et al., 1980) was
identified from this search. In this study, ingestion of 440 mg
of zinc sulfate per day (or 160 mg elemental zinc) by humans for
5 weeks resulted in a reduction of HDL-cholesterol levels in
humans. An oral LOAEL of 2.3 mg/kg/day calculated from this
study was used as the basis for developing a subchronic
inhalation RfC using modified EPA RfC methodology (EPA, 1990).
The following adjustments were made:
Human LOAEL (subchronic, adult) = 2.3 mg/kg/day
Converted to concentration (based on human parameters inhal. rate: 20 m3/day; and body weight: 70 kg) = 8.1mg/m3
Human NOAEL (10) = 0.81 mg/m3
Adjust for sensitive individual (10) = 0.081 mg/m3
Low confidence in database (10) = 0.0081 mg/m
SUBCHRONIC RfC = 8.1 ug/m3
JUSTIFICATION FOR ZINC CHRONIC TEL
The Chemical Health Effects Assessment Methodology and the
Method to Derive Allowable Ambient Limits (CHEM/AAL) can be used
to derive a threshold effects exposure limit (TEL) which
represents a concentration in air to which the general public can
be exposed day after day for a lifetime and experience no adverse
threshold health effects. The TEL therefore, is analogous to a
chronic RfC. However, occupational limits are used as the basis
for a TEL rather than primary toxicity studies. The occupational
literature contains exposure limits for four forms of zinc: zinc
oxide, zinc chloride, zinc stearate and zinc chromates. Zinc
chromate is known to be carcinogenic due to the carcinogenicity
of the chromate ion; and the exposure limit for this compound is
based on carcinogenicity. Thus, zinc chromate was not judged to
be an appropriate basis for a guideline for zinc. Of the
remaining forms, zinc stearate is an organic form but its
exposure limit is greater than those for the other compounds.
Based on relative exposure limits, zinc chloride is the most
toxic form so it was chosen as the basis for the guideline. The
most appropriate occupational exposure limit (MAOL) for zinc
chloride was selected and adjusted to account for continuous
exposure and for protection of children and high©risk groups to
derive an adjusted MAOL of 0.014 mg/m3.
MAOL = 1 mg/m3
Adjustment for continuous exposure (4.2) = 0.24 mg/m3
Adjustment for childhood exposure (1.75) = 0.14 mg/m3
Adjustment for high©risk groups (10) = 0.014 mg/m3
Adjusted MAOL = 0.014 mg/m3
The adjusted MAOL was further modified to account for
reproductive/developmental effects not accounted for in setting
the occupational exposure limit and for relative source
contribution which is also not applied in the derivation of the
occupational limit. Based on available developmental and
reproductive studies, zinc was given a hazard score of "A" and
assigned a threshold effects uncertainty factor (TEUF) of 10.
TEUF adjustment (10) = 0.0014 mg/m3
Relative source contribution (x 0.2) = 0.00027 mg/m3
TEL = 0.3 ug/m3
REFERENCES
Agency for Toxic Substances and Disease Registry, Toxicological
Profile for Zinc. U.S. Department of Health and Human Services.
Public Health Service. December 1989.
Conner, M.W., Flood, W.H., Rogers, A.E. and Amdur, M.O. 1988.
Lung injury in guinea pigs caused by multiple exposures to
ultrafine zinc oxide: changes in pulmonary lavage fluid. J.
Toxicol. Environ. Health. 25: 57-69.
Environmental Protection Agency. 1990. Interim Methods for
Development of Inhalation Reference Concentrations.
Environmental Criteria and Assessment Office. EPA 600/8-90/066A.
Graham, T.W., Holmberg, C.A., Keen, C.L., Thurmond, M.C. and
Clegg, M.S. 1988. A pathologic and toxicologic evaluation of
veal calves fed large amounts of zinc. Vet. Pathol. 25:484-491.
Hirano, S., Higo, S., Tsukamoto, N., Kobayashi, E. and Suzuki,
K.T. 1989. Pulmonary clearance and toxicity of zinc oxide
instilled into the rat lung. Arch. Toxicol. 63: 336-342.
Hooper, P.L., Visconti, L., Garry, P.J. and Johnson, G.E. 1980.
Zinc lowers high©densisty lipoprotein©cholesterol levels. JAMA.
244: 1960-1961.
Kurtz, P., Schuurman, T. and Prinz, H. Loss of smell leads to
dementia in mice: is Alzheimers's Disease a degenerative
disorder of the olfactory system? International Symposium on
Receptors and Ion Channels - Short Communications. J. Prot.
Chem. 8: 448-451.
Lam, H.F., Chen, L.C., Ainsworth, D., Peoples, S. and Amdur, M.O.
1988. Pulmonary function of guinea pigs exposed to freshly
generated ultrafine zinc oxide with and without spike
concentrations. Am. Ind. Hyg. Assoc. J. 49: 333-341.
Richards, R.J., Atkins, J., Marrs, T.C., Brown, R.F.R. and Masek,
L. 1989. The biochemical and pathological changes produced by
the intratracheal instillation of certain components of zincªhexachloroethane smoke. Toxicology. 54:
79-88.
Sittig, M. Handbook of Toxic and Hazardous Chemicals. Noyes
Publications. 1981.