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

-------
                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:

      1.  Environmental  Health Effects Research
      2.  Environmental  Protection Technology
      3.  Ecological Research
     4.  Environmental  Monitoring
      5.  Socioeconomic Environmental Studies
     6.  Scientific and Technical Assessment Reports (STAR)
      7.  Interagency Energy-Environment Research and Development
     8.  "Special" Reports
     9.  Miscellaneous Reports
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
studies. In addition to toxicology and other medical specialities, study areas in-
clude biomedical instrumentation and health research techniques utilizing ani-
mals — but always with intended application to human health measures.
This document is available to the public through the National Technical Informa-
tion Service, Springfield, Virginia  22161.

-------
                                       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

-------
                            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.

-------
                               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

-------
                            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

-------
                          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

-------
                      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

-------
                                  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.  •*

-------
                                  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. '

-------
     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.

-------
                                  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).

-------
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

-------
     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

-------
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.

-------
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.

-------
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.

-------
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

-------
                                  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

-------
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

-------
                                 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

-------
                                    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)
                                             14

-------