EPA-600/1-7I-051
NOVEMBEi 107?
Environmental Health Effects iesearcfi Series
LAT1NUM AND PALLADIUM IN
ISSUE: Correlation of Tissue
neentration of Platinum and
Palladium with Biochemical
Effects
Health Effects Laboratory
Prelection Agency
Carolina 27711
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RESEARCH REPORTING SERIES
Research reports of the Office of Research and Development, U.S. Environmental
Protection Agency, have been grouped into nine series. These nine broad cate-
gories were established to facilitate further development and application of en-
vironmental technology. Elimination of traditional grouping was consciously
planned to foster technology transfer and a maximum interface in related fields.
The nine series are:
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2. Environmental Protection Technology
3. Ecological Research
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This report has been assigned to the ENVIRONMENTAL HEALTH EFFECTS RE-
SEARCH series^ This series describes projects and studies relating to the toler-
ances of man for unhealthful substances or conditions. This work is generally
assessed from a medical viewpoint, including physiological or psychological
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clude biomedical instrumentation and health research techniques utilizing ani-
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This document is available to the public through the National Technical Informa-
tion Service, Springfield, Virginia 22161.
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EPA-600/1-77-051
November 1977
CONTENT OF PLATINUM AND PALLADIUM LN RAT TISSUES
Correlation of Tissue Concentrations of Platinum
and Palladium with Biochemical Effects
By
David J. Holbrook, Jr., Ph.D.
Department of Biochemistry
School of Medicine
University of North Carolina
Chapel Hill, North Carolina 2755.4
Contract No. Z804557-01
Project Officer
M.F. Copeland
Environmental Toxicology Division
Health Effects Research Laboratory
Research Triangle Park, N.C. 27711
U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF" RESEARCH AND DEVELOPMENT
HEALTH EFFECTS RESEARCH LABORATORY
RESEARCH TRIANGLE PARK, N.C. 27711
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ABSTRACT
Data have been compiled on the platinum and palladium content
in six rat tissues after the dietary administration of platinum or
palladium salts. The platinum and palladium content in rat tissues does
not appear to correlate with the rates of weight gain of rats, the
organ weights, or the four parameters of drug metabolism which were
studied.
This report was submitted in fulfillment of Order Number
DA-6-99-6142J, Contract Number Z804557-01, by the University of North
Carolina (at Chapel Hill) under the sponsorship of the Environmental
Protection Agency. Work was completed as of July 1977.
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FOREWORD
The many benefits of our modern, developing, industrial society are
accompanied by certain hazards. Careful assessment of the relative risk
of existing and new man-made environmental hazards is necessary for the
establishment of sound regulatory policy. These regulations serve to
enhance the quality of our environment in order to promote the public
health and welfare and the productive capacity of our Nation's population.
The Health Effects Research Laboratory, Research Triangle Park,
conducts a coordinated environmental health research program in toxicology,
epidemiology, and clinical studies using human volunteer subjects. These
studies address problems in air pollution, non-ionizing radiation,
environmental carcinogenesis and the toxicology of pesticides as well as
other chemical pollutants. The Laboratory develops and revises air quality
criteria documents on pollutants for which national ambient air quality
standards exist or are proposed, provides the data for registration of new
pesticides or proposed suspension of those already in use, conducts research
on hazardous and toxic materials, and is preparing the health basis for
non-ionizing radiation standards. Direct support to the regulatory function
of the Agency is provided in the form of expert testimony and preparation of
affidavits as well as expert advice to the Administrator to assure the
adequacy of health care and surveillance of persons having suffered imminent
and substantial endangerment of their health.
This study provides a correlation between platinum and
palladium levels in tissues and their biochemical effects. The
information obtained from this study is important to the Catalyst
Research Program in that it helps establish dose-response
relationships for platinum and palladium salts in animals.
H. Knelson, M.D.
Director,
Health Effects Research Laboratory
lit
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ABSTRACT
Data have been compiled on the platinum and palladium content
in six rat tissues after the dietary administration of platinum or
palladium salts. The platinum and palladium content in rat tissues does
not appear to correlate with the rates of weight gain of rats, the
organ weights, or the four parameters of drug metabolism which were
studied.
This report was submitted in fulfillment of Order Number
DA-6-99-6142J, Contract Number Z804557-01, by the University of North
Carolina (at Chapel Hill) under the sponsorship of the Environmental
Protection Agency. Work was completed as of July 1977.
IV
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CONTENTS
Foreword iii
Abstract iv
Acknowledgement . . vi
1. Introduction 1
2. Materials and Methods 2
t Animals 2
Metal Analysis on Tissue Samples ... 2
Table 1. Dietary Levels and Total
Consumption during Diet Period . . 3
3. Results 4
Platinum Content in Rat Tissues ... 4
Table 2. Platinum Content in Rat
Tissues after Oral Administration
of Platinum Salts « • 5
Effects of Platinum Salts on
Parameters of Drug Metabolism ... .6
Correlation of Weight Gains by Rats
and Tissue Level of Platinum ... 6
Correlation of Tissue Weights of
Rats and Tissue Level of
Platinum ............. 7
Correlation of DNA, RNA and Protein
Content and Tissue Level of
Platinum 7
Palladium Content in Rat Tissues
after Dietary Administration ... 8
Effects of Palladium Salts on
Parameters of Drug Metabolism ... 8
Table 3. Palladium Content in Rat
Tissues after Dietary
Administration of Palladium Salts • 9
Correlation of Weight Gains by Rats
and Tissue Levels of Palladium . . 10
Correlation of Tissue Weights of Rats
and Tissue Level of Palladium ... 10
4. Discussion ........ 11
References 13
v
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ACKNOWLEDGMENT
The analyses of the rat tissues for platinum and palladium
were conducted by Stewart Laboratories, Inc., Knoxville, Tennessee,
and I am grateful for their participation. Their report as a
Certificate of Analysis was submitted to the Environmental Protection
Agency under code EPA 05575, purchase order number DA-6-99-7341A.
vi
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SECTION 1
INTRODUCTION
Platinum and palladium are used as the active components in the catalytic
converters of air pollution control devices of motor vehicles. The use of
these metals is accompanied by the potential loss of platinum and palladium
into the environment. This laboratory has been involved in studies on the
biochemical effects of these metals. •*
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SECTION 2
MATERIALS AND METHODS
ANIMALS
Male Sprague-Dawley rats, obtained from Zivic-Miller Laboratories, were
used in all experiments. The mean body weights were 100-110 g (4-5 weeks of
age) when the rats were started on the diets.
The dietary administration ad libitum of metallic salts was conducted for
1 week (7.5 - 8.5 days), 4 weeks (28.5 - 32.5 days), or 13 weeks (87 - 93 days).
The rats were housed four rats per cage. Body weights of individual rats and
consumption of feed and water per cage were measured every seventh day. The
metallic salts were administered either in the drinking water or by mixing
in the dry feed (Purina Laboratory Chow).
The dietary levels and total consumption of platinum (Pt) and palladium
(Pd) salts are given in Table 1.
METAL ANALYSES ON TISSUE SAMPLES
Fresh tissue samples were weighed and frozen until analyses. Analyses
for platinum or palladium were conducted by Stewart Laboratories.^ The content
of platinum or palladium is reported as micrograms (yg) of metal per gram (wet
weight) of tissue.
The tissue samples were collected during earlier studies in this
laboratory-'-"^ on the biochemical effects of platinum and palladium. Data
other than the metal analyses were reported in previous reports to the
Environmental Protection Agency. '
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TABLE 1. DIETARY LEVELS AND TOTAL CONSUMPTION OF PLATINUM AND
PALLADIUM SALTS
Group
number
19-
26
87
105
53
17
25
8!5
101
7!i
81
30
77
1021
97
Metallic salt
PtCl4
PtCl4
PtCl4
PtCl4
PtCl4
Pt(S04)2-4H20
Pt(S04)2-4H20
Pt(S04)2-4H20
Pt02
PdCl2
PdCl2
PdCl2-2H20
PdS04
PdS04
PdO
Diet
duration
(weeks)
1
4
4
4
13
1
1
4
4
4
4
1
4
4
4
Dietary levela
319 mg/liter
(1.63)
319 mg/liter
(1.63)
1147 mg/kg
(5.88)
2581 mg/kg
(13.2)
106 mg/liter
(0.54)
106 mg/liter
(0.54)
319 mg/liter
(1.63)
1147 mg/kg
(5.88)
5808 mg/kg
(29.8)
1407 mg/kg
(13.2)
3166 mg/kg
(29.8)
(satd. soln.)
625 mg/kg
(5.88)
3164 mg/kg
(29.7)
3166 mg/kg
(29.8)
Total consumption
during diet
period
(mg Pt or Pd/rat)
59
255
743
1616
389
26
78
716
4308
873
2020
—
407
1868
. 2276
aDietary level is expressed
drinking water. Values in
as mg Pt or Pd/kg feed or
parentheses are mmoles/kg
as mg Pt or Pd/liter
or mmoles/liter.
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SECTION 3
RESULTS
PLATINUM CONTENT IN RAT TISSUES
The platinum content in various tissues after dietary administration is
given in Table 2.
After the dietary administration of any of the platinum salts, the metal
contents in the tissues were in the following order: kidney > liver, spleen >
blood, testis > brain. After four weeks on platinum-containing diets,
the platinum content in the kidney generally was about 8-fold greater than
the liver and spleen, and at least 16-fold greater than in the blood and
testis, except when the highest dose of platinum was administered (group 105),
and the content in the kidney was 3.5 to 5-fold greater than in the liver and
spleen.
The dietary administration of platinum tetrachloride (PtCl*) at 319 mg
Pt/liter for one week resulted in low levels of platinum in the tissues. The
continuation of the same diet for 4 weeks increased the total platinum intake
by 4.3-fold and the platinum content in kidney, spleen and blood by at least
7-fold.
When the PtCl4 was placed in the dry feed, and the platinum consumption
during 4 weeks was increased greater than 2-fold (groups 87 versus 105,
respectively), the platinum content in kidney showed no increase, but the
contents in liver and spleen increased at least 2-fold.
The platinum content in the tissues was not appreciably different,
although it was administered in the form of two different very water-soluble
salts, PtCl4 and platinum disulfate (Pt(S04)2) (namely, groups 19 versus 25,
and groups 85 versus 87).
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TABLE 2. PLATINUM CONTENT IN RAT TISSUES AFTER ORAL ADMINISTRATION OF PLATINUM
SALTS
Group
19
26
87
105a
53*
17C
25d
85
101
Salt Liver
PtCl4 : 2.2
PtCl4 2.5
±0.9
PtCl4 3.2
±0.9
PtCl4 8.9
±1,2
PtCl4 1.3
±0.3
Pt(S04)2-4H20 0.07
Pt(S04)2-4H20 0.85
Pt(S04)2-4H20 3.5
±6.4
Pt02 <2.2
Platinum Content
(yg/gram wet weight; mean
Kidney Spleen Testis
4.8
±0.2
33.7
±3.5
33.5
±6.3
32.4
±4.6
14.9
±0.4
0.26
±0.02
4.6
43.4
±8.3
<2.2
0.24
4.8
±1.5
3.1
±0.9
6.4
±3.0
1.6
±0.3
<0.02
0.13
3.2
±0.5
<0.02
—
1.5
±0.5
1.1
±0.4
1.7
±0.3
0.94
±0.20
<0.04
—
1.1
±0.1
<0.07
± SE)e
Brain
—
0.11
±0.07
<0.02
0.12
±0.08
<0.06
—
<0.02
0.33
±0.18
<0.02
Blood
0.23
2.1
±0.4
1.5
±0.4
1.6
±0.2
0.90
±0.08
0.05
0.22
1.6
±0.3
<0.04
aHeart, 2.4
bHeart, 0.20 ±0.09
cHeart, <0.02
AHeart, 0.25
BSE is given for four values; only the mean is given when two values are
available
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When platinum dioxide (PtC^) was administered in the diet, only small
quantities of the platinum of this water-insoluble salt were found in any of
the tissues even when the salt was administered at a very high level in the
diet (group 101).
EFFECTS OF PLATINUM SALTS ON PARAMETERS OF DRUG METABOLISM
Effects of the dietary administration of platinum and palladium salts on
parameters of drug metabolism have been reported previously by this laboratory,*
All four parameters (activities of aniline hydroxylase and aminopyrine demethylase
and the contents of cytochrome P-450 and cytochrome be,) were expressed "per
mg microsomal protein."
The platinum content in liver shows little correlation with the parameters
of drug metabolism. The highest platinum content in liver, 9 yg Pt/g tissue,
was observed in group 105 (PtCl4» 2581 mg Pt/kg feed for 4 weeks). In this
group the cytochrome P-450 .content and the activity of microsomal aniline
hydroxylase were normal and the activity of microsomal aminopyrine demethylase
and the content of cytochrome bs were both increased. After 4-week diets of
the soluble platinum salts, intermediate levels of platinum (2.5 - 3.5 yg Pt/g
tissue) were found in groups 26, 85 and 87. All of the measured parameters
of drug metabolism in liver were within normal limits. The administration of
PtCl4 for 13 weeks (group 53) resulted in a low level of tissue platinum (1.3
yg Pt/g tissue), normal levels of cytochromes P-450 and bs, and increased
levels of aniline hydroxylase and aminopyrine demethylase. The only group to
show a reduced drug metabolism—reduced aniline hydroxylase—contained less
than 1 yg Pt/g tissue; these animals showed reduced weight gain and the reduced
drug metabolism may have been due to reduced feeding in group 25 *
Correlation of Weight Gains by Rats and Tissue Level of Platinum
The weight gain by rats receiving PtCl4 at a level of 319 mg Pt/liter
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in drinking water (comparable to groups 19 and 26) showed reduced weight gain
during the first week (p < 0.01) and a normal rate of weight gain during the
second, third and fourth weeks on the diet. During the latter three weeks, the
platinum content in kidney, spleen and blood were increasing at least 7-fold
but: the liver content was not appreciably changed. Likewise, rats receiving
an equal molar level of Pt(804)2"4H20 (group 25) showed a reduced weight gain
during the first week which was comparable to that observed in the PtCl4~treated
rats during the first week. Rats treated with PtCl^ at a level of 2581 mg Pt/kg
feed showed markedly reduced weight gains during the first.two weeks on the
diet and a total weight gain during the four weeks of approximately two-thirds
of the control animals.
Correlation of Tissue Weights of Rats and Tissue Level of Platinum
After adjustment of organ weights of platinum-treated rats for the
observed body weight, treatment with platinum salts at the levels given in
fable 1 did not alter the weights of any of the organs studied: liver, kidney,
sple:en, heart or testis. The lack of effect was observed in kidney even though
the content was 30-45 yg Pt/g wet tissue.
Correlation of DNA, RNA and Protein Content and Tissue Level of Platinum
The contents of DNA, RNA and protein were determined in liver, kidney and
spleen of two groups of platinum-treated rats and their corresponding controls.
The dietary administration of PtCl4 (2580 mg Pt/kg feed) (group 105) or Pt(S04)2*
4H20 (1147 mg Pt/kg feed) (group 85) did not alter the tissue content of DNA
(pmoles DNA-nucleotide/g wet tissue), RNA (ymoles RNA-nucleotide/g wet tissue)
or protein {mg protein/g wet tissue) in any of the three tissues examined
(liver, kidney or spleen). Thus, the levels of platinum attained in these
tissues (Table 2) did not alter the content of these macromolecules.
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Palladium Content in Rat Tissues after Dietary Administration
The palladium contents in various tissues after dietary administration
are given in Table 3.
After the dietary administration of either of the slightly water-soluble
palladium salts, namely PdCl2 and PdSO^j, the metal contents in the tissues
were in the following order: kidney > liver > spleen > testis > blood and
brain. After 4 weeks on the palladium-containing diets, the Pd content in the
kidney was at least 7-fold greater than in the liver and at least 18-fold
greater than in the spleen.
The 4-week administration of very high and equal levels of PdCl2 and PdS04
resulted in comparable levels of palladium in the .tissues of the two groups
(namely, groups 81 versus 103). In contrast, the administration of the water-
insoluble PdO salt at a very high level resulted in only a trace amount of
palladium in the kidney and generally nonmeasurable levels in the other tissues.
Effects of Palladium Salts on Parameters of Drug Metabolism
The highest level of hepatic palladium was observed in group 103 (PdS04,
3164 mg Pd/kg feed, 4 weeks) but animals in this group showed no alteration in
drug metabolism. In two groups of rats treated with. PdCl2 (group 75 and a
similarly treated group), all four parameters of drug metabolism exhibited
appreciable increases. When the administered level of PdCl2 was increased
(group 81), the hepatic content of palladium was approximately the same
(approximately 2 pg Pd/g tissue) but none of the parameters of drug metabolism
were altered.
Two groups received a saturated solution of PdCl2'2H20 as the drinking
water, similar to group 30. Both groups showed an appreciable reduction in
aniline hydroxylase and in aminopyrine demethylase even though only a trace
of palladium was found in the liver of rats in group 30 (Table 3) and these
rats showed normal weight gain during the 4-week diet period. We do not have
an explanation for the reduced drug metabolism in these rats.
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TABLE 3. PALLADIUM CONTENT IN RAT TISSUES AFTER DIETARY ADMINISTRATION OF
PALLADIUM SALTS
Group
75
81
30
77
103
97
Salt Liver
PdCl, 1.8
±0.3
PdCl2 2.0
±0.1
PdCl2-2H20 <0.08
PdS04 <0.03
PdS04 3.2
±0.6
PdO <0.02
Palladium Content
(yg/gram wet weight; mean
Kidney Spleen Testis
27.6
±2.5
34.6
±3.4
0.50
±0.07
0.08
±0.01
21.9
±3.1
0.15
±0.02
0.15
±0.01
0.72
±0.21
<0.01
<0.02
0.94
±0.17
<0.01
0.14
±0.00
0.24
±0.03
<0.01
<0.01
0.26
±0.07
<0.01
± SE)a
Brain Blood
<0.01 <0.02
<0.01 <0.04
<0.01 <0.01
<0.01 <0.01
<0.01 0.16
±0.06
<0.01 <0.01
aMean ± SE for four values.
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Correlation of Weight Gains by Rats and Tissue Levels of Palladium
The dietary administration of PdCl2 or PdS04 at 3166 mg Pd/kg feed (groups
81 and 103, respectively) resulted in palladium levels in tissue (yg Pd/g wet
tissue) of 22-35 in kidney, 2-3 in liver, 0.7-1.0 in spleen and 0.25 in testis
(Table 3) . The PdC^-treated rats (group 81) exhibited restricted weight gain
during the first, second and third weeks. The total weight gain at the end of
4 weeks was three-fourths of that observed in controls. In the PdS04~treated
rats (group 103), the total weight gain at the end of 4 weeks was one-half of
that of controls.
Correlation of Tissue Weights of Rats and Tissue Level of Palladj.um
The dietary administration of PdCl2 or PdS04 at fc^e levels given in Table
1 and resulting in the tissue levels of palladium given in Table 3 did not
alter consistently the tissue weights of liver, kidney, spleen, heart or testis
when adjusted for the body weight. A small decrease in liver and kidney
weights were observed in rats treated with PdCl2 at 1407 mg/kg feed (group 75);
however, no decrease was observed at a higher dietary level of PdCl2 (3166 mg/kg
feed) (group 81).
10
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SECTION 4
DISCUSSION
The dietary administration of PtCl4 in the drinking water at 0.54 milli-
moles/liter for 13 weeks (group 53 of Table 1) resulted in the accumulation of
platinum in the kidney to 76 nanomoles/g wet tissue. The kidneys were not
enlarged significantly in these animals. Likewise, the dietary administration
of Pd^+ salts does not result in kidney enlargement. In an earlier study, the
dietary administration of PbCl2 in the drinking water at' 3.7 millimoles/liter
for 13 weeks resulted in the accumulation of lead in the kidney to 64 nanomoles/g
wet tissue. In contrast with the results with platinum or palladium, however,
the kidneys were approximately 25% larger (p < 0.01)'in lead-treated rats than
in the corresponding control animals.
The dietary administration of water<-soluble salts of platinum—platinum
tetrachloride and platinum disulfate tetrahydrate—results in a rate of
weight gain less than in control rats for the first few weeks on the diet and
is accompanied by some accumulation of platinum in the tissues. During later
periods (e.g., third and fourth weeks) on the diet, the rate of weight gain
(g/week/rat) by platinum-treated rats is equal to that of control animals even
when the accumulation of platinum in the tissues is increasing. Such a
finding is consistent with the proposal that the synthesis of a platinum-
binding protein is induced during the first week of dietary administration.
The binding of platinum to the metal-binding protein during the latter weeks
may sequester the platinum and prevent the manifestation of its toxicity.
The proposal is made here (see also reference 1) that there is an
inducible metal-binding protein for platinum and palladium, by analogy with
the findings for other toxic metals. Such metal-binding proteins have been
found for Cd2+, Zn2+ and Hg^+ (i.e., metallothionein) and for Cu2+ (i.e.,
11
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copper-chelatin). These metal-binding proteins contain 25-33 mole percent
cysteine, and Pt^+ and Pd2+ may bind to the same or similar proteins. The
following indirect evidence is consistent with the existence of metal-binding
protein(s) for Pt4+ and/or Pd2+. (a) The prior injection of a low level of
platinum salt before the injection of a normally lethal dose of platinum
salt protects against the acute lethality of the latter treatment.^ (b)
Although rats on Pt4+- or Pd -containing diets often show reduced weight
gain during early dietary administration, the rate of weight gain often
returns to normal after continuation of the diet for several weeks. (c)
Although acute administration (and occasionally 1-week dietary administration)
results in a decrease in xenobiotic metabolism, longer term dietary
administration of Pt4+ or Pd2+ does not decrease the capabilities for
xenobiotic metabolism.
12
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REFERENCES
1. Holbrook, D. J., Jr., Washington, M, E., Leake, H. B., and Brubaker, P. E.
Effects of Platinum and Palladium Salts on Parameters of Drug Metabolism
in Rat Liver. J. Toxicol. Environ. Health, 1^: 1067-1079 (1976).
2. Fisher, R. F., Holbrook, D. J., Jr., Leake, H. B., and Brubaker, P. E.
Effect of Platinum and Palladium Salts on Thymidine Incorporation into
DNA of Rat Tissues. "Environ. Health Perspect., 12; 57-62 (1975).
3. Holbrook, D. J., Jr., Washington, M. E., Leake, H. B., and Brubaker, P. E.
Studies on the Evaluation of the Toxicity of Various Salts of Lead,
Manganese, Platinum, and Palladium. Environ. Health Perspect., 10; 95-101
(1975).
4. Holbrook, D. J., Jr. Assessment of Toxicity of Automotive Metallic .
Emissions. Volume I. Assessment of Fuel Additives Emission Toxicity via
Selected Assays of Nucleic Acid and Protein Synthesis. Publication Number
EPA-600/l-76-010a. Environmental Protection Agency, Research Triangle
Park, N. C. January 1976. 61 pp.
5. Holbrook, D. J., Jr. Assesment of Toxicity of Automotive Metallic
Emissions. Volume II. Relative Toxicities of Automotive Metallic
Emissions Against Lead Compounds Using Biochemical Parameters. Publication
Number EPA-600/l-76-010b. Environmental Protection Agency, Research
Triangle Park, N. C. January 1976. 59 pp.
6. Yoakum, A. M., Stewart/ P. L., and Sterrett, J. E. Method Development
and Subsequent Survey Analysis of Biological Tissues for Platinum, Lead
and Manganese Content. Environ. Health Perspect., 10: 85-93 (1975).
13
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TECHNICAL REPORT DATA
(Please read Instructions on the reverse before completing)
1. REPORT NO.
EPA-600/1-77-051
3. RECIPIENT'S ACCESSIO(*NO.
4. TITLE AND SUBTITLE
CONTENT OF PLATINUM AND PALLADIUM IN RAT TISSUE
Correlation of Tissue Concentration of Platinum and
Palladium with Biochemical Effects
S. REPORT DATE
November 1977
6. PERFORMING ORGANIZATION CODE
7. AUTHOR(S)
8. PERFORMING ORGANIZATION REPORT NO.
David J. Holb.rook, Jr.
9. PERFORMING ORGANIZATION NAME AND ADDRESS
Department of Biochemistry, School of Medicine
University of North Carolina
Chapel Hill, North Carolina 2751A
10. PROGRAM ELEMENT NO.
1AA601
11. CONTRACT/GRANT NO.
Z804557-01
12. SPONSORING AGENCY NAME AND ADDRESS
Health Effects Research Laboratory
Office of Research and Development
U.S. Environmental Protection Agency
Research Triangle Park. N.C. 27711
13. TYPE OF REPORT AND PERIOD COVERED
RTP,NC
14. SPONSORING AGENCY CODE
EPA-600/11
15. SUPPLEMENTARY NOTES
16. ABSTRACT
Data have been compiled on the platinum and palladium content in six rat
tissues after the dietary administration of platinum or palladium salts. The
platinum and palladium content in rat tissues does not appear to correlate with
the rates of weight gain of rats, the organ weights, or the four parameters of
drug metabolism which were studied.
17.
KEY WORDS AND DOCUMENT ANALYSIS
DESCRIPTORS
b.IDENTIFIERS/OPEN ENDED TERMS
c. COSATI Field/Group
platinum
palladium
metabolism
toxicity
06 A, F, T
13. DISTRIBUTION STATEMENT
RELEASE TO PUBLIC
19. SECURITY CLASS (This Report)
UNCLASSIFIED
21. NO. OF PAGES
20. SECURITY CLASS (This page)
UNCLASSIFIED
22. PRICE
EPA Form 2220-1 (9-73)
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