ENVIRONMENTAL TOXICOLOGY RESEARCH LABORATORY

                NERC - CINCINNATI
              INTERIM REPORT

 1 Studies on toxicology of catalytic trace metal components
 2 Toxicology of automotive emissions with and without
   catalytic converters
                                       MARCH 1974

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      ENVIRONMENTAL TOXICOLOGY RESEARCH LABORATORY

                    NERC - CINCINNATI
                    INTERIM REPORT
1.  Studies on toxicology of catalytic trace metal components

2.  Toxicology of automotive emissions with and without
    catalytic converters
                                                     March,  1974

                                                     J. F. Stara

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                            TABLE OF CONTENTS


Identification Number                                        Page

Summary	     1-3

A.  Toxicological Studies of Catalyst
    Metal Components	     4-61

    A.I.  "Metabolic and Kinetic Aspects of Palladium
          and Platinum"	     4-23
    A. 2.  "The Acute Toxicity of Palladium Chloride"  .  .    24-33
    A. 3.  "Comparative Toxicity of Noble Metal Compounds
          on Lactic Acid Dehydrogenase and Glutamic
          Qxalaocetate Transaminase in vitro"     .     .    34-37
    A. 4.  "Effect of Noble Metal Compounds on Protein
          Synthesis in Various Organs of Rats"  . .   .  .    38-41
    A. 5.  "Dermal Irritancy of Several Pd, Pt/ and Pb
          Compounds and of MM?"   	» .    .    42-48
    A. 6.  "Dermal Absorption of l91Platmm +4 m HC1
          Solution"   	    49-50
    A. 7.  "Ocular Irritation of Two Palladium Compounds
          in Rabbits"	       51
    A. 8.  "Neurophysiology Summary of Pt and Pd"	    52-53
    A. 9.  "A Preliminary Report on the Cardiovascular
          Actions of Palladium"   	    54-61

B.  Automobile Exhaust Emission Studies With and Without
    Catalytic Converters	   62-140

    B.I.  "Auto Exhaust Facility Modification"  .   ...   62-70
    B.2.  "Catalyst Exhaust Exposure Studies"   	   71-75
    B.3.  "Design and System Performance for Studies of
          Catalytic Emissions"	   76-83
    B.4.  "Exhaust Emissions During Steady Speed Runs
          With the Catalytic Converter in the Exhaust
          System"	   84-90
    B.5.  "Exhaust Emissions from Catalyst-Equipped
          Engines"	   91-98
    B.6.  "Sulfate Emissions from Use of High-Sulfur
          Fuel, TAME-K" 	   99-103
    B.7.  "Comparison of the Biological Effects of Acute
          Exposure to Whole Exhaust Emissions from an
          Automobile Engine Equipped with and without
          A Noble Metal Catalytic Converter"	104-116

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Identification Number                                        Page

    B.8.  "Effect of Exhaust Emission from Catalytic
          Converter on Aryl Hydrocarbon Hydroxylase".  .  .   117-123
    B.9.  "Biochemical Effects of Emissions from an
          Automobile Engine with and without Catalytic
          Converter"	124-129
    B.10. "Exposure of Maternal, Pregnant, and Newborn
          Rats to Exhaust from Modern Automobile Engine
          with Catalytic Converter and Other Emission
          Controls (TAME J)". .     	130-134
    B.ll. "Gross Morphologic and Functional Damage to
          Plant Species by Diluted Exhaust of Automobile
          Engines Operated with and without A Catalytic
          Emission Control Device"	   135-140
                                    11

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                                  Summary

    INHALATION TOXICOLOGY OF AUTOMOBILE EXHAUST EMISSIONS AND THEIR
   TRACE METAL COMPONENTS ASSOCIATED WITH USE OF CATALYTIC CONVERTERS
                                J. F. Stara
Introduction
     The Division of Health Effects, EPA,  instructed the ETRL m July
1973, to reprogram ROAP 21 AFK and develop a new program for toxicologic
assessment of emission products from oxidizing catalysts.

     Members of ETRL staff had compiled early in FY 73 a monograph
entitled,  "Toxicology of Atmospheric Sulfur Dioxide Decay Products."
In July 73,  immediate emphasis was placed  on the metabolism, kinetics,
and biological effects of noble metals, palladium and platinum,
because of the extremely limited data found in the literature on this
subject.

     The definitive toxicological investigations conducted m this
laboratory utilize animal exposures, placing emphasis on those routes
of exposure  that are of major environmental significance.  Other
routes, such as intravenous, are used to obtain comparative toxicological
data.  For this purpose, ETRL developed a  toxicologic matrix which was
geared to  investigate the biological effects resulting from inhalation
of the individual catalytic components and the whole exhaust emissions
after passage through the catalytic converter.   The protocol used for
the toxicologic investigations is outlined in Figure 1.  Whether tms
matrix is  followed in part or in full depends on the theoretical
prediction of toxicity and the amount of knowledge presently avail-
able on the  pollutant m question.
                  1 U>50 LC50 ETC

                  f PHYSIOLOGICAL
                   SCREEN
                   PULMONARY FUNCTION
                   NEUROPHYSIOLOGIC
                   RESPONSE ETC
                  » PATHOLOGY
                   GROSS » LIGHT
                  4 SENSITIVITY
                   DERMAL OCULAR ETC

                  I BIOCHEMICAL SCREEN
GENERATION OF
EXPOSURE
» AUTOMOTIVE
t SINGLE
POLLUTANT

~
EXPERIMENTAL »NIMAL
EXPOSURE
INHALATION
INGESTION ETC

1
—
CHARACTERIZATION
O EXPOSURE
AERO>. LTHY OF
EMiSjlOM AEROSOL
CHURACTEP STICS ETC

!
UBACUTE EXPOSURE
1 PHYSIOLOGY
PULMONARY
1 CHRONIC EXPOSURE 1
SELECTIVE TESTS FROM
WHICH EVER OF THE
BEHAVIORAL NEUflO FOLLOWING IS OEEMEO
. PHYSIOLOGICAL MOST PRODUCTIVE
REPRODUCTIVE ,
t BIOCHEMISTRY
6H7YMES
METABOLITES
3 PATHOLOGY
J
3
4

LIGHT AND EM j
4 METABOLISM

BIOCHEMICAL
PHYSIOLOGICAL
PATHOLOGICAL
ELEMENTAL
ANALYSIS
OTHER AS
APPROPRIATE
KINETICS BODY S"
BURDEN ETC
1
TEST REPORTS
(OPEN LITERATURE
INTERNAL)

/
/
^

S




                  TMC APPROACH FOR ANY GIVEN POLLUTANT(S) WILL VARY SOMEWHAT FROM
                   THIS GENERAL SCHEME DEPENDING ON WHAT IS CUPnruHV KNOWN ABOUT
                   THE POLLUTANT AND THE TYPE OF INFORMATION NlfDEO TO 'l» THE CAPS
                                 Figure 1

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Toxicological Studies of Catalyst Metal Components

     These studies were undertaken to ascertain the relative toxicity
of catalyst metal components such as platinum and palladium.  The
acute and subacute studies are required in any comprehensive evaluation
of the noble metals since data of this type is largely unavilable in
the literature.

     Intratrachael administration of platinum or palladium resulted in
greater body retention than oral dosage (A.I).  Furthermore/ the
differences among the intravenous, intraperitoneal, and oral toxic
dosages of palladium indicated a difference m distribution of palladium
depending on the route of administration (A 2).  Biochemical studies
have shown that the relative toxicity of platinum or palladium on
glutamic oxalaoacetate transammase and lactate dehydrogenase was
dependent upon the chemical form of the metal (A.3)   In addition,
palladium elicited an increase in ^ C-leucine incorporated into heart
and blood serum   Platinum produced a dose-response change in 14C-
leucine incorporation in the lung (A. 4).  Dermal irritancy, dermal
absorption, and ocular irritation tests are being utilized as screen-
ing techniques to determine the relative toxicity of various types of
platinum and palladium compounds  (A 5, A.6, A.7).  Preliminary
neurophysiological screening tests have shown that palladium elicited
short-term changes at higher dosages; these changes may represent
indirect effects produced by changes in other tissues such as the
cardiovascular system (A. 8).  Preliminary cardiovascular studies
have indicated that palladium acted as a non-specific cardiac
irritant as well as a peripheral vasoconstrictor (A. 9).

     In summary, the preliminary results have indicated that platinum
and palladium salts are toxic in high concentrations.  However, the
levels tested in studies reported here will probably not be found in
the ambient atmosphere.  Further work is underway to determine the
atmospheric concentrations of these noble metals that may pose an
environmental hazard.

Auto Exhaust Fmission Studies

     EPA has available at ETRL an auto exhaust generating system for the
production of irradiated and nonirradiated gasoline engine exhaust-air
mixtures.  This system has been utilized in a series of acute and sub-
acute studies which determined the biological effects of exposure of
various experimental animal species to whole automotive exhaust emissions
with fuel additives and/or with or without a catalytic converter  (B.I).

     Furthermore, the system was utilized to determine whether new
pollutants may be emitted through the use of these converters.  These
new emissions may occur under three conditions-  (1) conversion of
organic sulfur compounds present in gasoline into sulfuric acid mist
and sulfates,  (2) platinum and palladium emission due to catalyst
degradation, and  (3) alteration of the emissions with the production
of different quantities and/or new species (B.2).  A report on the
specific design and system performance is included  (B.3).

     Emission studies have indicated that the oxidation-type catalyst
in the exhaust system has resulted in the following changes in exhaust

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emissions.  (1) large reduction of carbon monoxide, total hydrocarbons,
and various organic compounds such as acetylene, (2) a nearly total
elimination of aldehydes,  (3) less photochemical reactions of hydro-
carbons,  (4) the presence of sulfuric acid as a major component in
the particulate  (B.4, B 5, B.6), and  (5) trace emission of Pt and Pd
particulates most of which are in the respirable range.

     The bio-effect studies were undertaken to determine the general
toxicologic effects of an acute exposure to exhaust from engines equipped
with catalytic converters  (catalytic exhaust) vs exposure to exhaust from
engines without catalytic converters  (non-catalytic exhaust)   The results
indicate that aruirals exposed to non-catalytic exhaust exhibited profound
changes in weight of lactating female and infant rats, and in the survival
rate of infant rats.  There were no apparent effects on the rats exposed
to catalytic exhaust with the possible exception of minute weight loss in
lactating female rats  (B.7).

     The clinical data indicates that the only statistical exposure effect
in the catalytic exhaust was an increase in total serum proteins.  In the
non-catalytic exhaust exposure, there were significant effects on total
protein, platelet count, red blood cell and white blood cell count, white
cell differential, alkaline phosphatase, hemoglobin, hematocrit, partial
thrombo plastin tissue, serum glutamic oxalaoacetate transaminase, and
serum glutamic pyruvate transaminase levels   Lung pathology studies
showed a greater incidence of pathological conditions after non-catalytic
exposure than after catalytic exposure  (B.7).  In general, these data
indicate a far greater potential hazard to several organ systems with
prolonged exposure to non-catalyst exhaust.

     The effect of catalytic and non-catalytic exhaust was tested on
several biochemical systems.  Lung aryl hydrocarbon hydroxylase  (an
enzyme which is responsible for the biotransformation of various
carcinogens) activity is depressed with exposure to non-catalytic exhaust
However, the catalytic converter significantly reduced the lung aryl hydro-
carbon hydroxylase depression  (B.8).  Furthermore, serum lactate dehydro-
genase was greatly elevated with non-catalyst exposure but was not
significantly effected with exposure to catalyst exhaust  (B.9).

     Plant damage occurred in both catalytic and non-catalytic exhaust;
it appeared to be somewhat less m the catalytic exposure.  Since plants
were damaged m both types of exposure, it appears that plants are
inherently more susceptible to exhaust damage than animals and that the
effect threshold was exceeded by emissions  (B.ll).

     In summary, the acute whole emission studies have demonstrated that
acute exposures to automotive exhaust without a catalytic converter
elicited a profound effects on physiological and biochemical function
and produced histo-pathological lesions.  In contrast, exposure to exhaust
from a system with a catalytic converter did not result in such demonstrable
physiological or biochemical dysfunction.  One may conclude that the intro-
duction of the catalytic converter has reduced the levels of certain
exhaust constituents.  This has resulted in a decreased biological effect of
exhaust emissions.  However, it should be noted that catalyst-modified
emissions produced changes in plants   In addition, it is now known that
catalyst-modified emissions are highly acidic.  As a result, longer term
studies are needed and are planned for the future  (April, May)   These
studies will test the effect of long-term exposure to the more acidic
catalyst exhaust.

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PALLADIUM AND PLATINUM STUDIES

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 A.I.   METABOLIC AND KINETIC ASPECTS OF PALLADIUM AND PIATINUM



              W. Moore, D. Hysell, W  Crocker and J. Stara






     Automotive manufacturers have indicated that palladium will be used in



exjunction with platinum in automotive catalytic converters.  These converters



are designed to reduce the concentrations of carbon monoxide (CO) and hydrocarbons



 (HC) m the exhaust stream by oxidizing them into carbon dioxide and water   The



control of the concentrations of CO and HC in automotive emissions is necessary



for light duty vehicles to comply with the CO and HC emission standards set



forth in the Clean Air Act - 1970. With the use of palladium and platinum



in automotive catalytic converters, there is the possibility that some of the



material will be emitted to the atmosphere or enter into other segments of



the environment following degradation or disposal of worn-out converters.



1.  Palladium



     Information on the biological effects of palladium is extremely limited.



Meek et al. (1943) have summarized the toxicological findings and presented



additional data on the toxicology following subcutaneous and intravenous



injections in rabbits.  Intravenous infections of PdC^ were extremely toxic,



whereas subcutaneous injections were nontoxic due to the formation of an in-



absorbable complex.  When given in small amounts intravenously, the median



lethal dose in rabbits was 18.6 rcg/kg, with a survival period of 12 days



 (Orestano, 1933).



     The effects of palladium, 5 ppm in drinking water, on the growth and



life span of mice were observed from weaning until natural death  (Schroeder



et^ al. 1971).  No significant differences were found in the body weights of the



females, however, body weights of the exposed male mice were significantly  less



than those of the controls   The life span of the exposed male mice was signifi-

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cantly longer than that of the control male iru.ce.  The incidence of malignancy
and amyloidosis was higher in the exposed animals
     Information regarding human exposure to palladium is also extremely sparse.
In older medicine, palladium has been given orally for the treatment of tubercu-
losis without success, and it has been injected into abdominal fat for the
purpose of reducing obesity (Meek et al. 1943).  Exposure of forearm skin to a
1 mg/ml buffered PdCL, solution for 24 hr. did not result in skin irritation
(Meek et al. 1943).  Men working with platinum salts occasionally developed
an asthmatic response to platinum exposure   These same men had no recurrence
when transferred to jobs involving the handling of palladium (Hunter et al. 1945)
     Palladium has been shown to be highly active in some enzyme systems, and
it is possible that traces of palladium may influence, but not necessarily
unfavorably, enzyme systems in plants and animals including man (Christensen,
1971-72).
     It is apparent from very limited information that palladium is toxic
when it is absorbed and that more information is sorely needed in view of the
possibility of environmental exposure due to catalytic converters   The
purpose of this study was to provide information on the retention, tissue
distribution, excretion and placental transfer of Pd following different routes
of administration.
Animals and Treatments
     The outbred albino rats (Charles River CD-I strain) used in this study
were maintained on a commercial diet (Purina Lab Chow) and tap water ad libitum
except where otherwise noted   The various treatment groups consisted of
     1.  Intratracheal Administration
         Ten fasted male rats, 180-200 g, were anesthetized with pentobarbital
sodium and placed in dorsal recumbency.  The trachea was isolated through a

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ventral midline cervical incision and blunt dissection of the overlying



roasculature.  103PdCl2  (25 yCi m 0.1 ml saline) was injected intratracheally



vath a 1 cc tuberculin syringe and 5/8 in., 25 ga needle.  Following closure



of the incision, the animals were maintained in hanging wire cages for 104



days to determine whole body retention of the 103PdCl2/



       2.  Oral Administration



           twenty fasted male rats, 180-200 g, were lightly anesthetized with



ether and given 25 yCi of -^SpdClj m 0.2 ml saline by stomach tube.  Ten



rats were placed m metabolism cages for collection of 24 hr  urine and



fecal samples to determine routes of excretion  They were maintained 104



days for determination of whole body retention of the PdCl2.  The other ten



rats were sacrificed 24 hrs. following dosage to establish organ distribution



of the PdCl2.  Fifteen non-fasted suckling rats, 30 g, \iere given a sirgle



dose of l^pcic]^ (25 yCi in 0.2 ml saline) by stomach tube   These animals



were maintained for comparison with retention of Pd in the adult rats.



       3.  Intravenous Administration



           Twenty male rats, 180-200 g were given 25 yCi PdCl2 in 0.1 ml saline



intravenously (iv)  in a tail vein with a 1 cc tuberculin syringe and 5/8 m.,



25 g needle.  Ten rats were sacrificed 24 hrs. later for organ distribution,



ten rats were placed in metabolism cages for collection of 24 hr samples of



urine and feces and for whole body counting to determine retention.  Thirteen



female rats  (16 days pregnant) were given 25 yCi -^PdC^ iv and maintained



in metabolism cages for collection of feces and urine.  They were sacrificed



24 hrs after dosage for determination of organ distribution and placental



transfer of the •'-^PdC^.  An additional group of 8 female rats were given

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25 pCi    PdCl2 iv within 24 hrs post-parturition.  The mothers and litters



were maintained 25 days to determine if the ^^Pd was transferred to the



young via the mother's milk.





Sacrifice and Tissue Sampling



    Ml rats were euthanatized with an overdose of chloroform anesthesia.



Samples collected routinely were blood, heart, lung, liver, kidney, adrenal,



pancreas, abdominal fat, spleen, skeletal muscle, bone, brain and testicle



from males, ovary from females.  In the pregnant females, 4 placentas, 4



fetuses and a pooled sample of fetal livers were also saved.  In the young



rats from the milk transfer study, lung, liver, kidney, bone and spleen were



saved.  Tissue samples were placed in pre-weighed glass vials for counting.





Radioactive Determinations



    103p
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                                    8






significantly affected whole body retention.  The percent of 103Pd retained



with time in the rat following three different routes of administration is



presented in Figure 1.  Following oral dosing, the retention curve declined



very rapidly during the first 3 days to about 0.4% of the initial dose.  The



initial rapid clearance is attributed to passage of the non-absorbed   T>d



through the gastrointestinal tract.  Extrapolation of the second component



of the retention curve to the intercept indicated that absorption was less than



0.5% of the initial dose.  Retention of •L03Pd by the suckling rats following



oral administration was similar to the adults, however, the amount absorbed



and retained with time was significantly higher.



    The amount of l"3pd retained following intratracheal dosing was



significantly higher than for oral dosing and also significantly less than



for iv dosing.  The greatest amount of    Pd retained with tune occurred



following iv administration.





Excretion



    Radioactive counts of 24 hr urine and feces samples from the rats



receiving the 103Pd orally showed that almost all of the    Pd was eliminated



in the feces and only a trace amount was excreted in the urine (Figure 2).



With iv administration,    Pd was eliminated both in the urine and feces in



similar quantities.  Toward the end of the study, urinary excretion exceeded



fecal excretion.





Tissue Distribution



    The distribution and concentration of ^^pd was determined for



different tissues following oral and iv dosing   Twenty~four hours after



oral dosing, detectable quantities of 103p
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          Suckling   Rat
        I     Oral
'•     Percent  of Initial
l' \            Retained
                                   103
                                       Pd
                                       Intratracheally
                 8    12    16   20  24  28   32
                  Days  After  Dosing
Fig.  1.  Whole body retention of   Pd in adult rats
        following oral, iv, and mtratracheal admin-
        istration  Also shown is whole body retention
        of 103pd in suckling rats following oral
        administration.

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                             10.
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                Days  After  Dosing
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Excretion of 103Pd following iv and oral
administration.

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                                     11
liver,  the concentration in the kidney was much greater than in the



liver.  Twenty-four hours after iv dosing, -^Sp^ was found in all the tissues



analyzed with the highest concentrations occurring m the kidney, spleen,



liver, adrenal, lung and bone, respectively.



       The rats used in the whole body retention study were sacrificed



104 days post-exposure and the tissues counted.  No significant amounts of



103p3 Were found in any of the tissues from the group receiving the oral



dose.  In the iv dosed rats, the highest concentrations of   'T'd were found



in the spleen, kidney, liver, lung and bone.  For the mtratracheally-dosed



rats, the lung contained the most    Pd followed by kidney, spleen, bone and



liver.





Maternal/Fetal Uptake



       Thirteen pregnant rats (16th day gestation)  were given 25 yCi -^^pd iv



and sacrificed 24 hrs later.  During the 24 hr period, the pregnant rats



excreted 44.2% of the initial iv dose.  The amount excreted by the pregnant rats



was higher than the amount excreted by the fasted adult male rats during



the first 24 hr. period.  The magnitude of the difference in ^^pd concentration



among the maternal organs and also between maternal tissues and the fetuses is



best shown by the counts per g tissue and these values are given in Table 1.

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                                    12
             Table 1.     Pd in Maternal Organs and Fetuses
TISSUE
Kidney
Liver
Ovary
Lung
Bone
Blood
Placenta
Fetal Liver
Fetus
MEAN COUNTS/g
588,479
319,153
29,625
29,211
18,351
3,654
58,321
1,429
757
     The pattern of distribution and concentration of    p(j in maternal organs



was similar to that previously found in the whole body iv experiment.  Most of



the fetuses  (35) contained a small amount of 103pd, and the mean value for these



fetuses is given in Table 1.  However, radioactive counts for 17 fetuses from



5 litters was not significantly higher than background.  The same pattern of



results was obtained for the fetal livers.  The amount of 103Pd found in the



fetuses indicated that Pd does not readily move across the placental barrier



in the rat.



     Within 24 hrs. following the birth of their young, a group of female



rats were given 25 pCi ^^Pd and the litters counted to see if ^^Pd was



transferred to the young via the milk   The retention of -^pcl by the dams



and litters with time following a single iv exposure is shown in Figure 3.

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                                 13
 -C3
 o
 oa

 O)

 o
CO
o
      10
      10
     10
        o
   Adult  Female  Rats
    Suckling  Offspring
8      12     16     20    24

 Days  After  I  V  Dosing
28
       Fig.  3.    Whole body retention of   Pd in nursing feirale

                 rats folia /ing i v. administration and uptake of
                 1n^~'1 in suckling young via the nulk.

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                                     14
It is evident that a small amount of the 103Pd was passed to the young via



the nalk   Twenty-five days after dosing of the dams, the suckling rats were



sacrificed and lung, liver, kidney, bone and spleen taken for analysis   A



very small amount of 103Pd (10-50 counts/gram tissue) was found m the



tissues.  The bone had the highest level of activity followed by the kidney,



spleen, lung and liver.





2.  Platinum






       In discussing the toxicology of platinum, it should be emphasized that



much of the information available in the literature deals with the effects of



complex platinum salts   The effects of the complex Pt salts appear to differ



somewhat from the effects of platinum alone.



       Sodium chloroplatinate, a complex platinum salt frequently encountered



in industry, has been tested in both rats and guinea pigs (Hofmeister, 1945,



Saundelle, 1969).  Immediately following the intravenous injection of 20 mgAg



sodium chloroplatinate into a guinea pig, there occurred an intense attack



of asthma resulting m death within 3 minutes.  Autopsy revealed the lungs



to be pale and inflated as in anaphylactic shock.  The injection of 1-2 mg/kg



resulted in bronchospasm comparable to that caused by 3 ygAg of histamine.



Repeated injections of histamine resulted in reproducible changes in bronchial



motility, whereas sodium chloroplatinate exhibited tachyphylaxis upon repeated



injection   Aerosol exposure of guinea pigs to sodium chloroplatinate also



resulted in an intense asthma attack   Administration of the antihistamine,



pysilnnine, completely blocked the action of sodium chloroplatinate.

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                                    15




    Compared to histanune, sodium chloroplatinate has a long latent period


 (45 seconds following iv infection and 15 seconds following application to


guinea pig ileum).  This long latent period, along with the observed tachy-


phylaxis, suggests that platinum salts do not act by themselves, but instead


are involved in the release of a substance from the tissues.  Evidence that


chloroplatinate may be causing the release of histamme is seen from the fact


that 10 minutes after the intracardiac injection of 40 mg/kg of sodium


chloroplatinate into rats, the plasma histamme level rose to 1500 yg/L


from a norm of 150 yg/L«


    Platinosis is a skin or respiratory reaction or disorder resulting


from exposure to soluble complex platinum salts.  There have also been reports


of dermatitis resulting from exposure to platinum oxides and chlorides


 (Schwarte, 1947) and also to platinum alloys (Scheard, 1955).  Skin lesions


from platinum exposure have been described as a dry, scaling rash associated


with cracking and occasional bleeding   Instances of skm reaction have


been reported from workers in platinum refineries (Roberts, 1951, Milne, 1970,


Parrot, 1969) and by workers in photographic studios, who handled a paper


containing potassium chloroplatinite (Karasek,  1911).


    Scratch tests on human subjects have provided information suggesting


that sensitivity to platinum salts is an acquired reaction precipitated by


previous exposure.  Prior to employment in a platinum refinery, none of the


24 subjects were sensitive to the test solution above a 1 10^ dilution.


Following employment, workers who showed no signs of platinosis remained

                                   2
insensitive to dilutions above 1 10 .  However, subjects with definite signs


of platinosis has positive responses to dilutions of 1 10^ to 1 10^.  The

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                                    16
degree of sensitivity being more or less dependent on the severity of the


subject's syrrptoTis  (Roberts, 1951).


    Respiratory problems resulting from exposure to complex platinum


salts are initiated with irritation of the nose and respiratory tract,


coughing, sneezing and running of the eyes   Continued periods of exposure


nay result in an asthma-like condition associated with wheezing, tightness


of the chest and shortness of breath   The complex platinum salts frequently


responsible for platinosis are sodium, potassium, or ammonium chloroplatinate


(Levene, 1971).


    Symptoms of both dermatologic and respirato>y toxicity have been


reported for a substantial number of workers exposed to complex platinum


salts  (Parrot, 1969, Roberts, 1951, Hunter, 1945).  It has also been


reported that 70% of the exposed staff of a platinum refinery had observable


cases of platinosis (Herbert, 1966).  Hunter et a^. 1945, found that 52 of


91 employees of London platinum refineries had respiratory disturbances.


Roberts has stated the opinion that all workers exposed to platinum salts


have some degree of platinosis, 60% of which are symptomatic and 40% of which


have no obvious symptoms, but who reveal evidence of involvement such as


irritated conjunctivae and hypertrophy of the respiratory lymphatics  (Roberts,


1951).


    With the possibility that platinum may be emitted to the atmosphere and
                        \

the proven toxicity of certain platinum compounds, it is important to determine


the biological fate of platinum

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                                    17
Animals and Treatments



    The same procedures were vised in this study as in the palladium study



except the rats were given 25 yCi of 19-lpt.





Radioactive Determinations



    The radioactive solution was composed of carrier- free 191,193pt -m



0.5 M HCL.



    The solution contained at least 50%    Pt and only the ^^-Pt gamma
was counted.  All values were corrected for decay rPt has a half- life of



3 days) and the same dilutions and counting procedures were followed as m



the 103Pd studies.






Whole Body Retention



    The whole body retention of 191pt following a single exposure was



significantly affected by the route of administration   The percent of -^Ipt



retained with time in rats following three different routes of administration



is presented in Figure 4.  Following oral dosing, the total net gastro-



intestinal excretion was extremely high resulting in a rapid decline of the



retention curve to less than 1 percent at the end of three days.  The data



indicated that the rapid clearance was due to passage of non-absorbed -^Pt



through the gastrointestinal tract.  Extrapolation of the second component of



the retention curve to the intercept indicated that less than 1 percent of



the initial dose was absorbed



    The whole body retention of 191Pt following intratracheal dosing was



significantly higher than for oral dosing   The excretion of approximately



50 percent of the initial dose during the first 24 hours is attributed to



mucociliary and alveolar clearance   Whole body retention of l°lpt was the

-------
   80
                                18
             Percent  of  Initial

                    Retained
                                   191
                            Pt
   60
   40
 c

 O
 V
 v.

 O

Q.
   20
                  Adult

                     Intratracheally
         Oral
               j_
j-Q—O-
                  -Q	I
                8   12   16   20   24  28

                Days  After  Dosing
                                  32
                                   191
       Fig 4   Whole body retention of    Pt in adult rats

               following oral,  iv, and intratrachael admin-

               istration

-------
                                     19
highest following iv dosing, the short half-life precluded an accurate


determination of the biological half-life.




Excretion


       Radioactive counts of 24 hour urine and feces sanples from rats


receiving ^Ip^ orally indicated that almost all of the ^TPt was eliminated


in the feces and only a small amount excreted in the urine (Figure 5).  These


values support the whole body data which showed that total net gastrointestinal


absorption was low.  Following iv administration, 19lPt was excreted in both


the urine and feces.  The urine contained a greater quantity of the 19lPt




Tissue Distribution


       The distribution and concentration of -^Pt in tissues was determined


following oral ard iv dosing   After single oral dose, the kidney and liver


contained the highest concentrations of  °lpt.  The amount of radioactivity


found in the other organs was not significantly higher than background   The


amount of -^Ip^ found in selected tissues following iv dosing is presented on


Table 2.  Most of the tissues did not contain levels of l^lpt appreciably


higher than that found in blood.  However, the fraction of l^lpt in the plasma


that was m an "available" form for movement into the various tissues was not


determined   The large amount of 191pt found in the kidney suggests that this


organ accumulates this element   Concentrations higher than the blood values
                          »

were also found in the liver, spleen and adrenal.  The lower count for the


brain suggested that either 19lPt can be transferred through the blood -bram


barrier only to a limited extent or else much of the circulating l^lpt 1S


complexed to large molecules which do not cross the blood-brain barrier.

-------
                           20


io6
c IO5
.2
X
LU
lio4
_C
g- 3
X
t)
10
«••••
I 0
- \
- \
- \
- \
- \
= \
:SN\
- H\
E <> t°'-D^N;Dx
_ \ \ \ ,-'D^^ ™ i
\ \ V°" \, 1V
=" \ \ Feces ^^ ;
• V°--
\ \
\ \ Feces
1 \ Y 	 °
I V Oral
\
r \
i Urine °
i i i t i i i i i
2 4 6 8 10 12 14 16 18
                    Days After Dosing
                     191
Fig.  5.   Excretion of    Pt following iv and oral

         administration

-------
Table 2.    Counts/g Wet Tissue
1 day
2 days
3 days
7 days
14 days
Blood
Heart
Lung
Liver
Kidney
Spleen
Pancreas
Bone

Brain
Fat
lestis
Mrenal
Muscle
Duodenal Segment
22,147
11,819
18,432
36,848
162,227
41,085
22,208
13,146

1150
4487
4186
45,439
4798
12,725
19,732
12,201
16,139
31,274
160,656
45,840
19,487
12,800

2485
4501
6540
42,363
4671
6044
21,671
15,508
17,638
23,528
162.374
44,033
22,618
13,184
s.
1027
4576
4545
58,596
3930
6045
12,774
8805
11,180
25,732
138,101
55,764
14,802
8932

595
3201
3873
26,667
' 3441
4031
7921
4593
5770
4733
30,195
20,973
,3973
5440

265
429
1431
6190
2146
1410

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                                    22
Maternal/Fetal Uptake
                                                                  191
     Fifteen pregnant rats  (18th day gestation) were given 25 yCi    Pt
intravenously and sacrificed 24 hours later.  During the 24 hour period, the
pregnant rats excreted 18 8 percent of the initial dose   The amount excreted
by the pregnant rats was approximately the sane as the amount (19.3 percent)
excreted by the adult male rats during the first 24 hour period.  The con-
              191
centration of    Pt per gram for different maternal tissues and fetuses is
given in Table 3.
             Table 3    -"pt in Maternal Organs and Fetuses
TISSUE
Kidney
Liver
Lung
Ovary
Blood
Bone
Brain
Placenta
Fetal Liver
Fetus
MEAN COUNTS/g
127,064
43,375
17,981
14,639
10,568
9,193
792
27,750
1,421
432
                                                                      191
     The data indicated that there was some transplacental passage of    Pt,
however, there appeared to be placental binding or accumulation    "^Pt was
present in all the fetuses (60) counted   The hemochorial placental barrier of
rats is more easily traversed than the more complex placental barriers found m
other species of experimental animals

-------
                                    23
 1.   Christensen, G.M.  Effects of Meta/ Cations and Other Chemicals Upon
     the in vitro Activity of Two enzymes in the Blood Plasma of the
     White Sucker, Catostomus commersoni.  Chem. Biol. Interactions £, 351-
     361, 1971-1972.

 2.   Herbert, R.  Affections provoquees par les composes du platine
     Arch  Mai  Prof. 27_  877-886, 1966.

 3.   Hofmeister, F   Ueber die physiologische Wirkung der Platmbasen
     Naunyn-Schmiedebergs.  Arch, exper  Path. Pharmak. 16, 393, 1882

 4.   Hunter, D , Milton, R. and Perry, K.M A.  Asthma Caused by the
     Complex Salts of Platinum.  Brit. J. Industr. Med. 2, 92-98, 1945.

 5.   Karasek, S  R  and Karasek, M.  The Use of Platinum Paper, Report
     of Illinois State Commission of  Occupational Disease, p  97, 1911.

 6.   Levene, G. M   Platinum Sensitivity, Brit. J  Derm. 85_  590-593, 1971

 7.   Meek, F  F , Harrold, C  C  and McCord, C P   The Physiological
     Properties of Palladium.  Indust  Med  Surg. 12_  447, 1943

 8.   Milne, J. E  H   A Case Of Platinosis.  Med. J  Australia 2_  1194-
     1195, 1970

 9.   Parrot, J  L , Herbert R , Saindelle, A , Ruff, F.  Platinum and
     Platinosis   Arch. Environ. Health 19_  685-691, 1969.

10.   Orestano, G.  The Pharmacologic Action of Palladium Chloride.
     Boll  See  Ital. Biol  Sper. 8_  1154-1156, 1933.

11.   Roberts, A. E.  Platinosis.  Arch  Industr  Hyg. 4_  549-559, 1951

12.   Saindelle, A., Ruff, F.  Histamine Release by Sodium Chloroplatinate.
     Brit  J  Pharmacol  35  313-321, 1969

13.   Scheard, C   Contact Dermatitis from Platinum and Related Metals.
     Arch. Derm. Syph  71  357-360, 1955

14   Schroeder, H  A. and Mitchener, M   Scandium, Chromium (VI), Gallium,
     Yttium, Rhodium, Palladium, Indium m Mice   Effects on Growth and
     Life Span.  J. Nutr  101  1431-1438, 1971.

15.   Schwarte, L , Tulipan, L., Peck, S   A Text-Book of Occupational
     Diseases of the Skm   Lea and Fibiger, Philadelphia, 1947.

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                                    24
          A. 2.  THE ACUTE TOXICITY OF PALLADIUM CHLORIDE

                L. Hall, J. Adams, I. Washington, K. Campbell,
              W. Crocker, D. Hysell, W. Moore and J. Stara


Introduction

     As part of the corrprehensive evaluation of the inhalation toxicity

of catalyst emission compounds, acute toxicity studies with palladium

chloride were begun as a rapidly obtained, reliable and inexpensive

first estimate of toxicity in order to quantify the upper limits in terms

of dose and obtain observations for assessing the biological or pharma-

cological effects of these cotpounds.


Pesults

     a.  Single dose studies

         Using the method of Deichman and LeBlanc ^ ' , the approximate lethal

dose (AID) was determined in 200-300 gm rats, (Charles River COBS)  using

intravenous, intraperitoneal, and oral modes of administration.  In addition,

the intravenous AID was determined in the rabbit and the mtratracheal minimum

lethal dose was determined in the rat.  The results are shown in Table 1.
                Table 1.   Acute Lethal Toxicity of
Species
Rat
Rat
Rat
Rabbit
Rat
Approx. LDjQ
5 mgAg slope 'vl.S
70 mgAg slope -vl.5
>200 mgAg
5 mgAg
6 mgAg*
Route
IV
IP
Oral
IV
ITR
         * Minimum lethal dose

-------
                                     25
     Marked differences are noted among the different routes of administration,

ranging from 5 mg/kg for IV to greater than 200 mgAg for oral.

     Using the more precise method of Litchfield and Wilcoxon^' ,  the intra-

venous and intraperitoneal H^Q (14 days) was determined.  Figure 1 shows

the log probit plot of the intravenous data.  The LDso (14 days) was calcu-

lated to be 3.0 mg PdCl2Ag with 95 per cent confidence limits of 2.57-3.49.

The slope was found to be 1.43 with 95 per cent confidence limit of 1 15-1.77.

The (CHI)2 test indicated that the data are not significantly heterogenous.

Following intraperitoneal administration, the I£>50 was calculated to be

123.0 (91.1-166.1) mg PdC^Ag with a slope of 1.84 (1.04-3.27), no signifi-

cant heterogenety was roted (Figure 2).

     A limited number of rats from the intravenous and intraperitoneal studies

were housed in metabolism cages and several toxicometric parameters were

measured during the 14 days observation period.  Survivors of an acutely

toxic intravenous dose of PdCl2 exhibited a 25 per cent decrease in water

intake and urine excretion.  Following intraperitoneal dosing a 7  per cent

reduction in body weight was observed with up to 80 per cent reduction in

food intake.  Water intake was reduced markedly initially and then returned

to control levels or above.  In one rat a 28 per cent increase in urine

volume was noted at 14 days after dosing, with a constant decreased specific

gravity of 1.030.  Proteinuria was noted in all animals following both
                         i
routes of administration.  Elevated urinary ketone bodies were observed in

some animals following both routes of dosing.

     Following intraperitoneal infection, necropsy findings indicated a

chemical type "bum" of the visrora in animals dying within 24 hours.

-------
                                     26
     Gross pathologic examination of intraperitoneally dosed survivors



at 14 days showed prominent peritonitis with numerous adhesions involving



the liver, intestine, pancreas, and spleen.  Involvement did not appear



dose related.  The kidneys showed a yellowish-tan appearing renal parenchyma



with cloudy capsule.  The liver in 30 day survivors showed reduced liver



mass, and yellowish discoloration with thickened, opaque capsules.



     Tissue palladium concentrations were determined by atomic absorption



spectroscopy m rats which died following intraperitoneal injection.  The



concentration for four doses in brain, lung, cardiac muscle, liver, spleen,



kidney and testes are shown in Table 2.  A dose effect was suggested m



some tissue but the sample size was too limited for absolute confirmation.



However, the tissue levels in brain, heart, and lung showed that palladium



was mobilized from the peritoneal cavity.



     In vitro protein binding studies were performed with palladium and



platinum chlorides  (PdCl2 and PtCl^, using the Toribara ultracentrifugation



technique^ '  at concentrations up to 200 yg compound/ml using whole plasma



or plasma equivalent albumin.  Protein binding was greater than 99 per cent



at all concentrations.  Temperature and pH were found not to affect binding.



     Following acutely toxic intravenous doses of palladium chloride, death



occurred very rapidly, with a sharp threshold such that if exitus did not



occur withm five minutes, the animals (both rats and rabbits) survived



the 14 day experimental period  Rapid death may be due to respiratory



arrest, since breathing ceased while a heart beat was still palpable for



some time.  However, cyanosis was not noted; the animals' oral mucosa and



eyes were pink in color.  Clonic and tonic convulsions were noted m rabbits



and rats.

-------
      70
      65
      60
      55
   I 50
   CJS
      45
     40
      35
     30 -
       10
                        i   i  i i i i
10
100
                                         DOSE
                                        (mg/kg)
                                                95

                                                90
                                                85
                                                80

                                                70
                                                60 ^
                                                  C3
                                                50 i
                                                  UJ
                                                  CJ
                                                40 £

                                                30

                                                20
                                                15
                                                10
                                                                                                  NJ
FIGURE 1,   INTRAVENOUS Pd2 MORTALITY DATA PLOTTED BY METHOD OF LITCHFIELD AND WILCOXON (19^9)

-------
         70
         65
         60
         55
      CO
         50
         45
         40
         35
         30
           10
100
1000
                                                 DOSE

                                                (mg/kg)
                                                  98



                                                  95



                                                  90


                                                  85

                                                  80


                                                  70


                                                  60 £
                                                     £
                                                  50 g
                                                     oe
                                                     LU
                                                  40 °-


                                                  30


                                                  20

                                                  15


                                                  10
                                          to
                                          00
FIGURE 2,  INTRAPERITONEAL P
-------
                                     29
                                  TABLE 2
TISSUE PALLADIUM CONCENTRATIONS IN ACUTELY POISONED RATS FOLLOWING
             J15TRAPERITONEAL M2>1INISTFATION (ug/gm Dry Vvt.)




































Total
Dose

30mg



24mg



18mg



12mg



Mean
Day/Died

24hr/l
48hr/5
72hr/0
96hr/0
24hr/0
48)ir/2
72hr/2
96hr/0
24hr/0
48hr/l
72hr/4
96hr/2
24hr/0
48hr/0
72hr/0
96hr/l
Brain

< .04
5 42



5 77
4.18


1 26
2.18
4.77



6.95
Lung

-
86 84



74 46
78.52


41 03
30 60
22 86



3.45
Heart

27.32
37 93



26 62
40 12


17 57
11 15
17 42



0
Liver

185 91
302 68



201 54
277 39


67.79
115 60
51 36



37.24
Spleen

330 56
418 65
-


333 02
272.23


317.18
200 04
196 80



192 09
Kidney

843 39
476 82



478 00
590 86


583 94
202 01
177.83



*
Testes

60 91
67 58



42 34
67.44


14.31
33 56
31 56



12.70

-------
                                     30
     The sharp threshold for mortality following intravenous administration
suggested some conpartmental  (blood) saturation phenomenon.  Therefore, ten
rabbits which had survived the first intravenous dose of PdCl? were re-
                                                             £*
injected six hours after the first dose with a dose less than or equal to
the original dose.  All but one died, and the survivor was the largest
animal used and had received initially the lowest dose.

     b.  Multiple dose studies
         Toxicity of PdCl2 following daily intravenous dosing
             Thirty-three rats weighing 250 g were used in this experiment.
Each rat was given 0.5 mg Pd in .1 ml (2 rng Pd/k9), daily in the tail vein
for five days. Deaths occurred almost ainmediately following injection.  The
mortality during the five day period is given in Table 3.
           Table 3.   Cumulative Intravenous Toxicity of PdCl2
Date
11/26/73
11/27/73
11/28/73
11/29/73
11/30/73
Amount
Injected IV
.5 mg
.5 mg
.5 mg
.5 mg
.5 mg
Total Accum.
Dose mg/kg
2.0
4.0
6.0
8.0
10.0
1
No. of
Acute Deaths
0
2
2
4
3
Accum
Deaths
0/27
2/27
4/27
8/27
11/27
An additional group of six rats was given 0.5 mg Pd on the first day and 1 mg
on the second, five of the six annuals died almost immediately.

-------
                                    31
Discussion
    While the goals of this task are to determine the inhalation toxicity
of catalytic components, other routes were examined for a more comprehensive
evaluation.  Intiavenous studies were initiated because of their ease, in-
expensiveness, and rapid information return regarding systemic and comparative
intoxication.  Intraperitoneal studies were also initiated for the above
reasons, and also because of the similarity of mobilization between intra-
peritoneal and pulmonary depots   Oral administration was studied smoe
material deposited m the lung is cleared in part to the gastrointestinal
tract.  Intratracheal dosing is a reasonable model for inhalation studies.
    Palladium chloride was selected for initial study because palladium
compounds are principal contenders for use as catalysts in automotive exhaust
control devices and, therefore, the toxicity and biological effects of
palladium ion are of prime interest as a form of the metal which might distribute
within the organism.
    The large difference between the intravenous, mtraperitoneal and oral
acutely toxic doses suggest a difference in distribution of the palladium ion
depending on the initial depot.  Ihis is supported by the tenacious macro-
molecular binding (> 99 per cent protein bound), the extensive peritoneal
pathology after IP administration, and the sharp threshold for acute intravenous
toxicity.

-------
                                   32
     The signs accompanying intravenous toxicity were suggestive of acute



central respiratory depression, respiration ceased before cardiac arrest



occurred.  Convulsions were noted in some animals which could possibly



have been other than agonal   Further studies are needed to elucidate



the mechanism of acute toxicity.  However, the tenacious protein binding,



coupled with the sharp threshold and the repeat dosing experiment with



rabbits and rats, suggest saturation of some binding sites before distribution



to the ultimate target site(s).



     Two additional effects were observed that merit comment.  Respiratory



arrest was not accompanied by frank cyanosis.  This would suggest some effect



of palladium on metalloporphyrin proteins   Secondly, a pilot study was



performed to determine the effect of palladium chloride on whole blood in



vitro.  The addition of this salt to whole heparinized blood caused clotting



in the sample.  Further studies are necessary to ascertain the significance of



these findings.



     Mortality after intraperitoneal administration appears to involve a



chemical peritonitis, although other direct toxicity may occur, as in the



kidney, since mobilization of the palladium occurred as shown by the tissue



analysis.



     Some cormient is necessary regarding the discrepancy between the intra-



peritoneal ALD5Q as determined by the method of Diechman and LeBlanc^'



and the 1^50 as determined by the procedure of Litchfield and Wilcoxon^).



Assuming the LDso to be the most precise value (123 mg/kg), the value of the

-------
                                     33
      (70 mg/kg) represents a 43 per cent underestimation.  The principal



reason for this discrepancy, although the difference is not particularly



alarming, is thought to be due to the chemistry of PdCLj.  The ALDgQ was



determined using aged solutions which have been shown to be more toxic than



the fresh solutions.  Whereas the LDcQ was performed with freshly prepared



solution of Pdd-2.  In fact, before we were aware of this anomolous



chemical behavior of palladium chloride in solution, an LD^Q determination



was performed according to the method of Litchfield and Wilcoxon'^' with
aged solution.  This procedure produced a value for the LDso m good agree-



ment with the ALD5Q method of Diechman and LeBlancd) .



     These studies suggest that if palladium ion is formed after either



inhalation or ingestion, a great potential for intoxication exists because



of the enormous affinity of this metal ion for biological ^acromolecules .
 References



 1.   Diechman  and LeBlanc.  J A I H.A  25   415,  1943



 2.   Litchfield and Wilcoxon.   J. Pharm. Therap.  9£  99,  1949



 3.   Toribara.   J.  Clin.  Invest. 36   738,  1957

-------
                                    34
        A.3.  COMPARATIVE TOXICITY OF NOBLE METAL COMPOUNDS ON
     LACTIC ACID DEHYDROGENASE AND GLUTAMIC OXALAOCETATE TRANSAMINASE
                               IN VITRO

                       S. D. Lee and R. M  Danner
     An in vitro study was conducted to study the relative toxicity of

palladium and platinum compounds on two enzymes   glutamic oxalaoacetate

transanunase  (GOT) and lactate dehydrogenase (LDH)   The concepts of

correlation between metal-ion toxicity, enzyme inhibition ard serum

enzyme levels as related to cellular damage in certain organs represent

the hypothesis for this study

t    In vitro enzyme test system was as follows   heparinized rabbit blood

plasma was pooled and 5 ml portions were sealed and stored at -20°C until

use.  The test solutions were prepared from stock solutions which contained

one milligram of metal compounds, which was dissolved in dilute hydro-

chloric acid and made up to a final volume of 10 ml with sodium acetate
                                                                                 ^
buffer (pH 7.4, l.OM).  The test system used in this experiment was similar

to that of Christensen (1971/1972) with minor modifications   The concentrations

of stock solutions was 1.0 mg/ml.  Concentrations of 1 x 10~5 through 1 x 10" ^

yg/ml were prepared and tested.

     Various reaction combinations were prepared

     Control = 0 3 mg plasma, 0.1 ml acetate buffer (pH 7.4, l.OM, 100 pi),

               test sample = 0.3 ml plasma, 0.1 ml test solution containing

                noble metal compounds, reagent blank = 0.3 ml acetate buffer and

                100 pi test solution, enzyme blank = 0.3 ml plasma and 4N HC1

                (100 pi), standard = Versatol E  (0.3 ml) and 0.1 ml acetate buffer

-------
                                    35
     The test solutions were incubated for 30 mm  at room tennperature (25°C)


Following incubation, the enzyme activities were determined using DADE reagent sefe


All analyses at each concentration of test solution were performed in duplicate


and average values determined.  The enzyme activities were expressed in


International Units/ml for IDH and Reitman-Frankel Units/ml for GOT following


correction for enzyme and reagent blanks


     Figure 1 shows the inhibitory effects of palladium chloride (PdCl2)f


dutier of propionyl palladium chloride (C^H^-PdCl) 2 and potassium chloro-


palladate (K2PdCl4 on serum IDH   PdCl2 exhibited a "stair-case" type


inhibition pattern and was the most toxic among the three Pd compounds tested,


it reached 80% inhibition at 250 mg/1   (C3H5PdCl)2 was less toxic than PdCl2/


it leveled at a plateau of 35% inhibition between 100 mg/1 and 250 mg/1


K2PdCl4 was the least toxic of the three compounds, it showed a mere 5%


inhibition up to 150 mg/1 and reached 20% inhibition at 250 mg/1.


     Figure 2 shows a comparative inhibitory effect of ^H^PdCl^/ PdCl2/


K2PdCl4, PtCl4 and HgCl2.  HgCl2 was used as a reference compound since its


toxic effect is well known.  The relative toxicity of the five compounds


tested was ranked as follows


       HgCl2 >(C3H5PdCl)2 > PdCl2 > PtCl2 > K2PdCl4


     These tests were performed to ascertain what type of effects one might


expect if sufficient quantity of Pt and Pd compounds were found to be emitted
                         \

into the ambient air.  The in vitro data on inhibition of IDH and GOT may


serve as a useful information as additional data are determined relative to


the emissions of these compounds

-------
                               36
   lOOr
    90
    80
    70
   60
«-  50
 o
 g  40
~  30


*  20
    10
              50
 100
(mg/L
150
200
250
     Figure 1.  Comparative in vitro inhibition of Pd-oxpounds on Serum IDH

-------
                  37




t_
o
CD
uo

M—
o

a
o
«&••
•rS
c
_
,




100
90
80
70

60

50


40


30

20

10

0
(CoHrPdCI)
/
HgCI2 /'
- / /
/ /
/ ,'—/-"" 	 -PtlCI2
X x' /
X x^ / p^pj
y s* / .•••**'** r lUl^
i X .•/'""
- 1 ,''..'•""'/

• 1 ^^<.«* / ^^^**i7 n J f*
"/ ^'*''*' /' ^^*^^ lydk
-* /x '* ^ ^^^^"^
- I - y
/ • ' ^
• ''!• ^
' '' /-'
""""" / t t » 1 1
,50 100 150 200 250
                   mg/L
Figure 2.  Comparative in vitro inhibition of SCOT

-------
                                    38
  A.4.   EFFECT OF NOBLE METAL COMPOUNDS ON PROTEIN SYNTHESIS
                       IN VARIOUS OPJGANS OF PATS

                       S D. Lee and R M. Banner
     Experiments were conducted to detect early biochemical effects of intra-

gastric administration of noble metal compounds (PdC^ and Pt[304]2) on protein

synthesis in various organs as determined by the rate of incorporation of

  C-leucme.  Experimental animals  (rats) were given PdC^ (1 mg/kg body weight)

24 hrs before sacrifice.  Control animals were given saline solution   One

hundred forty yCiAg body weight of -^C-leucine was injected through the tail

vein of all rats  (control and treatment groups) and allowed to metabolize for

one hour before sacrifice,  The -^C content of purified protein m liver, kidney,

lung, heart and blood serum were examined.

     Each of the excised organ samples was homogenized with 0 25 M sucrose

3il v/w.  An aliquot of the homogenate was used to precipitate protein

with 10% trichloroacetic acid v/v   The precipitate was washed twice with

5% trichloroacetic acid v/v and then twice with 95% ethanol   The concen-

tration of protein was determined by the Biuret method.  Radioactivity  levels

were measured in a Packard Liquid Scintillation Spectrometer   The observed

values were expressed in terms of dpm/mg protein and per cent alteration with

reference to control

     As can be seen in Table I, no change was observed in kidney ard lung, and

only a slight decrease in liver.  However, there was a marked increase in ^C-

leucine incorporation into the heart and blood serum protein.  The increases

were 137% ard 49% in heart and blood serum, respectively.

     A different pattern of   C-1-leucine in rats given 0 5,  1.0 and 5.0 mg

per kg body weight of Pt(504)2 was observed.

-------
                                    39
As depicted in Table II, Pt(SO.)2 caused a different response in 14C-1-



leucine incorporation into protein of five organs examined   The most



pronounced change was observed in the lung where a definite dose-response



was observed with increasing concentration   incorporation of ^C-l-



leucine rose 10.3% for 0.5 mg/kg/ 22.7% for 1.0 mgAg and 109 4% for 5 rag/kg



body weight, respectively.



     The incorporation of   C-1-leucine in kidney showed a reverse trend



+16.9% for 0 5 mg, 62% for 1 0 mg/kg and no change for 5 mg/kg body weight,



respectively.  The changes in the brain showed similar pattern as the kidney



There was a 30% increase at 0.5 mg/kg body weight for liver and no other



apparent changes were indicated.  Treatment with 5.0 rogAs body weight of



Pt(SO^^ resulte<3 m a 9% decrease   About 30% and 26% increase for 0.5 mg



and 1 o mgAg levels were observed, respectively   Apparently, Pt(SC>4)2 at



the concentrations used m this study did cause a significant disruption m



protein synthesis in organs tested

-------
                                     40
Table I.   Effect OF PdCJ-2 on -^C-Leucine Incorporation Into Protein
Control
Experimental
% Change
dpm/mg Protein
Liver
1,484 (4)*
1,361 8 (4)
- 8.0
Kidney
1,708.0 (4)
1,728.2 (5)
+ 1.2
Lung
1,566.5 (4)
1,540 6 (5)
- 17
Heart
955 (4)
2,265 (4)
+ 137 2
Blood
Serum
1,877.3 (3)
2,796 5 (4)
+ 49.0
( )  * Denotes number of animals

-------
                                         41
Table II Effect of Pt(S04)2 on 14C-l-Leucine Incorporation
Into Protein
nxjAg B w' ^"^\
0
0.5
% Change
1.0
% Change
5.0
% Change
cpm/mg Protein Corrected for Organ Weight
Liver
1056 (6)*
1374 (4)
+ 30 1
1088 (4)
+ 3.0
1110 (4)
+ 5.0
Kidney
2332 (6)
2807 (5)
+ 16.9
2477 (4)
+ 6.2
2331 (4)
0
Lung
1732 (6)
1911 (5)
+ 10.3
2239 (4)
+ 22.7
3627 (4)
+109.4
Heart
1355 (6)
1356 (5)
0
1326 (4)
- 2.1
1233 (4)
- 9.0
Brain
882 (6)
1142 (5)
+ 29.5
1111 (4)
+ 26.0
949 (4)
+ 7.0
(  )* = number of animals used.

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                                      42
A 5.   DEKMAL IRPJTANCY OF SEVERAL Pd, Pt and Pb COMPOUNDS AND OF MMT



            K.I. Campbell, E L. George, L L. Hall and J.F. Stara








       A necessary aspect of general toxicologic characterization of



   potential environmental pollutant substances is the evaluation of dermal



   irritancy.  A series of such tests were performed on several palladium



   and platinum compounds, for their relevancy to catalytic automotive emission



   control devices, and on two lead compounds and the gasoline antiknock



   additive, 2-methyl cyclopentadienyl manganese tricarbonyl (MMT).



       The test procedure used was essentially that in standard use by



   the National Institute of Occupational Safety and Health,  '  '   a modi-



   fication of the official Food and Drug Administration procedure ' '  In



   each test six (6) healthy, male albino rabbits weighirg 2 to 3 kg tTere



   used   Up to seven (7) pairs of sites 2 x 2 on were used on the closely



   clipped dorsolateral aspects of the trunk of each animal, the sites on



   the right side being abraded and those on the left remaining intact.  Test



   materials in the solid (powder) state were applied in 0 1 gm quantity per



   site, mixed with about 0 1 ml deionized water and spread over the site,



   liquid materials were applied directly in 0.1 ml quantity*  Each application



   was covered immediately with a gauze patch and further secured with tape



    (and overwrap in one test) and use of a leather restraining harness.



   After 24 hours, harnesses and coverings were removed, and test sites were



   washed with mild soap, rinsed, and dried.  The skin reactions were then



   evaluated and scored, and again scored 48 hours later.  Skin reactions



   were evaluated and scored using a grading system summarized in Table 1

-------
                                   43
The assigned rating was calculated as the average of means of the 24 and



72 hour scores for the test group, rated separately for intact and



abraded skin, as illustrated in Table 2.  Ratings were interpreted



according to the scheme summarized in Table 3.



    The materials tested, the dermal irritancy (intact skm) and



cellular toxicity (abraded skin) responses observed, and the corresponding



interpretations are shown in Table 4.  Results were interpreted



conservatively, i.e. based on the test in which the most severe responses



were observed   Many of the test materials showed a delayed healing of



the abrasion lines themselves, in addition to or regardless of the



standard response criteria.



    Severity of response to some of the compounds tested more than



once was quite variable   Skin character and hair gra-rth patterns among



rabbits in the specified weight range were somewhat variable, and



these could be factors in irritancy responses and evaluations.  We



recommend selection of rabbits for uniformity on these additional criteria.



Close but gentle (atraumatic) clipping in preference to shaving, and over-



wrapping in preference to taping for security of patches, are also



recommended.  In addition to tests for dermal irritancy, tests for



sensitization should also be performed.  Sensitizations may be far more



serious or chronic than direct irritation, they may develop at lower and



more common levels of exposure, and opportunity for development may be



greater by virtue of extended or repeated exposure by ingestion and



inhalation as well as cutaneously

-------
                                              44
                                                                                         ~  J
                                       Table 1
                     Evaluation of Skin^ Reaction to ^est !laterial_

                                                       Grac'e Valve ard
           Reaction
nH't}icJra  (regardless of decree)
          and ederra confined to test area
)
  Intact £
       0
(Non -irritant)
       1
(liild imtcuit;
       2
  ('irritant)
          and cdeira extending be^ord test area         3
                                                (Strong imtart)
        (deep reaction involving denras)
                                                   (Corrosive)
                                                                              bradcxl   in
                                                                         (Kild cclliLJeir tc
                                                                           (Cellular t
                                                                        (Strorg cel2u]r^

-------
                      45
Table ?
Exarrple Calculation of
\
\
Test Rating
Intact Skin Peacticn
(Dermal lTitarc\)
nm?l Fiirccr
1
2
3
4
5
C
" K=6
* \
?4 Hr
1
0
2
1
3
JO


72 Hr
1
1
1
0
2
J.


Total
2
1
3
1
3
JL

-
rcan
1.0
0.5
1.5
0.5
1,5
0.5
5,5

traded Skoji Reaction
(Cellular Tc^ic^t-/)
24 Hr.
2
i
\
2
2
2
Jk


72JIr__
»
3
2
2
1
2
J.


Total >3an
*
5 2.5
3 1.5
4 2.0
3 1.5
4 2.0
J2 3.0
10.5

Derrral irritation rct^rq for
intact son - 5 5/6 = 0.9.
In this a^rplG, a ron-
iiiitant.
        imtation rating for
abxac'ed ckn, = 10 5/6 - 1.8.    —
In Uiis e>arple, a raid cellulaM

-------
                                   46
                                     TALI C 3

                        Interpret?J^on of Skin Jest Ratings
Intact Skin
Abraded Skin
        Rating

        0-09


        1  - 1.9
        2-- 4


        0 -0 9



        1 - 1.9
                               2  - 4
        Interpretation

Non-irritant,  probaoly  safe
for intact human skin contact

Mild irritant, may be safe for
use, but appiopriate proactive
measures are recommended during
contact

Too irritant for human  Skin
contact, avoid contact
Non-toxic to cellular conoononts
of abraded skin, probably
for human skin contact
                                                                            safe
Mild cellular toxins,  may be
safe for abraded skin  contact
provided protective measures
are employed

Cqllular IDA ins too imiant
for abraded skin contact,
avoidance of contact is ?Q«nsed
                               MIXED REACTIONS
Intact Sinn

  0-09
  1 - 1.9
  2-4
Abraded SVi n

  0-09
  1-19
  2 - 4


  1 -'1.9


  2-4



  2 - 4
Safe for human skin contact

Safe for intact human skin
contact, may be safe for
skin contact when protection is
maintained                     ,^_

Safe for intact human skinj con-
tact with abraded skin should
be avoided

May be safe for intact and
abraded skin contact \'hen pro-
tection is maintained

May be safe for intact hunan
skin contact ./hen protection
is maintained, but contact with
abraded si in is to be avoided

Unsafe for intact and abraded
human shn contact, avoid contact

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            Table  4   -  Rated Responses to and Interpretation of Direct
              Dermal  Irntancy and Cellular Toxicity Tests in Rabbits
     Material
      Tested
                                Seventy Rating*
                         Intact  Skin     Abraded Skin
                         (Irntancy)   (Cellular Toxicity)
                   Interpretation
Dei om zed water
 (negative control )
Glacial Acetic Acid
 (ethanoic) acid
 (Positive control)

Potassium chloropalladite,
Potassium chloropalladite,
 K2[PdCl6]

Palladium chloride,
 PdCl
Ally palladium chloride
 dimer, (CH
Dichlorodiammine palladium
 (II)Trans,
Ammonium chloropalladite,
 (NH4)2PdCl4
Ammonium chloropalladat
 (NH4)2PdCl6

Palladium monoxide, PdO

Platinum (II) dichloride,
 PtCU
                             0


                             2.6
                             0
                             (0)
                             0
                             (0)

                             0
                             (0 1)
                              0 8


                              0
                             (0)

                              1 5
                             (3 1)

                              2 8
                             (4)
                              0  2
Platinum (IV)tetrachlonde,    1  8
 PtCl4                       {2.7)

Platinum(IV)dioxide,           0
 Pto2
Lead chloride,                 0
 Pd C12
Lead monoxide                 0
 Pb 0
2 - Methyl cyclopentadienyl     0  1
 manganese  tricarbonyl  (HIT)
 0        1)  Safe  for  human skin con-
          tact

 3.2      2)  Unsafe  for human skin
          contact


 1.6      3)  Safe  for  intact human
(1.9)      skin  may be  safe for abrad-
          ed  skin  when protection is
          maintained

 1.6      4)  Safe  for  intact human
(2)       skin  abraded skin contact
          should be  avoided

 06      5)  Safe  for  intact human
(1)       skin  may be  safe for abrad-
          ed  skin  when protection is
          maintained

 1.8      6)  Unsafe  for human skin
          contact

 02      7)  Safe  for  human skin con-
(0 5)      tact

 2.5      8)  Unsafe  for human skin
(3 7)      contact

 3.2      9)  Unsafe  for human skin
(4)       contact

 0       10)  Safe  for  human skin con-
         tact

 06     11)  Safe  for  human skin con-
         tact

 2 6     12)  Unsafe  for human skin
(3.8)     contact

 0       13)  Safe  for  human skin con-
         tact.

 0       14)  Safe  for  human skin con-
         tact.
 0.1     15)  Safe  for  human skin con-
         tact.

 08     16)  Safe  for  human skin con-
         tact
 *Rating in parentheses indicates  the most  severe test result where tested more than
  once, those without indicate  the single test rating or average of 2 or 3 test
  ratings
 HBased on most severe or single  test result

-------
                                     48
References

1.  Course Manual   "Toxicologic Investigative Techniques"  Occupational
    Health Research and Training Facility, Division of Occupational
    Health, U.S  Department of Health, Education and Welfare, 1964

2.  Johnson, G T , Perone, V B , Busch, K.A , Lewis, T R  and Wagner, W D
    Protocols for Toxicity Determinations, Unit 1, Acute Projects
    Toxicology Branch, NIOSH, Cincinnati, Ohio, 1973   (Draft)

3.  Perone, V.B.  Personal communication, 1973

4.  Code of Federal Regulations, Chapter 1, Paragraph 191.11

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                                   49
     A. 6.   DERMAL ABSORPTION OF 191PLATINUM+4 IN HC1 SOLUTION
        K. Campbell, E  George, W  Moore, W. Crocker, F. Truman

    In conjunction with tests of dermal imtancy of platinum compounds
an experiment to assess transcutaneous absorption of ionic platinum was
performed   In each of 5 rabbits, 10 yl of a solution containing 191Pt+4
in 0.5M HC1 was spread over a closely clipped 1 on square area of dorsal
skin in the scapular region   The nuclide dose was 8 36 yCi, a Packard
gamma scintillation spectrometer (Model 5375) was used for counting
Samples of blood before application and at 4, 24, 48 and 72 hours post-
application, and 72-hour terminal samples of skin (incorporating the
site of application), liver and kidney were counted.  Counts were
corrected for background and decay, expressed as counts per minute (CPM)
per gm of sample (except for the skm specimen for which only total count
was pertinent), and the fraction of the original applied dose was calculated
    Results showed that at the 72 hour terminal period, on the average,
53.41% of the original dose was in or on the skin at the site of application
and that very small fractions appeared in the blood or in the tissues.  Of
the sequential blood samples, the earliest  (at 4 hours post-application)
contained by far the greatest fraction of the applied dose  (0 0074%),  sub-
sequent samples contained less than 1/10 as much   Among the tissues at
sacrifice, the concentration of activity in kidney was about 2.7 times that
in liver and 14 3 times that in blood.  The results are summarized in Table 1.
Data of this experiment do not permit conclusions as to total amounts absorbed
vs  lost from the s'-in, the fractional distribution to other tissues,  and the
amounts excreted, they do suggest early minor transcutaneous absorption, with
distribution to blood, liver and kidney   There was no visible sign of
dermal irritation at the site of application.

-------
        Table 1.   Tissue Levels of ^  Pt Activity Following Dermal
                    Application of 191piatmum+4 ^ HCl Solution
Specimen
Blood
Pretreatxnent
4 Hr. post- treatment
24 hr. " "
48 Hr. "
72 Hr. " " (terminal)
Skin, terminal
Liver, terminal
Kidney, terminal
CPM/gm
mean

0
92.4
1.4
6.8
2.1
594,493
Total*
11.35
30.3
Proportion of Dose Applied, Dec. Fract.xlO"
Mean Range

C
74.0
1.24
6.60
1 82
534,100
10.25
27.0

0
0
0
0
0
274,000
3
6

- 0
- 240
- 3.2
- 30
- 8
- 732,200
- 16
- 48
Remark

n=5
"
"
"
"
Ave. 53.41% of
orig dose
n=4
n=5
*Based on entire skin sample.

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                                    51




 A 7.  OCULAR IRRITATION OF TWO PALLADIUM COMPOUNDS IN RABBITS




              D  Hysell, S  Neiheisel and D  Cmehil






     The test was performed as outlined in the Code of Federal Regulations,



Title 21, part 191 12, revised as of April 1,  1973   Six albino rabbits,



having no known ocular abnormalities, were restrained and 100 mg of the



test material was deposited on the surface of the right eye   The left



eye was maintained as a control.   The animals were examined for ocular



inflammation 24, 48 and 72 hours following application of the material



     In the case of PdO (Table 1)  no reaction was noted in any of the six



rabbits   In one animal, the test material was still present in the



corgunctival sac at the end of 72 hours, but was completely covered with



a thick rrucous material



     All six animals receiving PdCl showed a severe corrosive type lesion



of the conjunctiva with severe inflammation of the cornea and anterior



chairber of the eye (Table 1)   This was noted at 24 hours and persisted



throughout the test period.



     These test results would indicate that at the dosage levels used,



PdCl was a severe irritant, PdO was not
                                 Table 1
Compound
PdO
PdCl
Fraction of animals shaving reactions at specific test intervals^
24 hours
0/6
6/6
48 hours
0/6
6/6
72 hours
0/6
6/6

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                                    52
           A.8.   NEUROPHYSIOLOGY SUMMARY OF Pt AND Pd
                      J  LewkovvSki, T  Wessendarp,
                          W  Moore and J  Stara
     The visual evoked potential in the rat is being utilized as a

screening technique to test the relative short-term effects of various

toxic agents   Over 120 anesthetized rats have been exposed via intra-
venous iT3ection in the past year   The resultant changes in the visual

evoked potential has been analyzed using various methods including computer

averaging techniques

     The results have indicated that this screening technique may be

important in assessing the significant acute effects of various pollutants

on central nervous system function   The table below indicates the mean

threshold dose of a particular cation which elicited a reproducible change

in the visual evoked potential in 50% of the animals studied.


                     VISUAL EVOKED POTEOTIAL SCREEN
                                   Mean Reproducible Dose-Effect Threshold
                 Ion               	(mg/kgj	
                 Co                               0 010
                 Cd                               0 10
                 Pd                               0 40
                 Cr                               0.80
                 Ba                               20
                 Mn                               20
                 Pt                          Minimal effect
     Therefore, the relative short-term effect of the intravenous adminis-
tration of these cations on the rat visual evoked potential may be ranked

as follows
                    Co > Cd, Pd, Cr > Ba, Mn > Pt

-------
                                    53
     Assuming a similar blood level of Pd and Pt, it would appear that Pd



has a greater effect on the central nervous systeir. function under the



experimental conditions of this particular screening technique   It should



be noted that this effect may not necessarily be a direct effect on central



nervous system function.  Further experimentation is underway to determine



whether these effects are direct or are due to indirect factors, such as



changes in blood pressure or some other physiological changes



     In addition, more quantitative and less subjective methods to determine



these thresholds are currently being utilized in an attempt to more pre-



cisely determine the relative central nervous system toxicity of these metals

-------
                                      54
A. 9.   A PRELIMINARY REPORT ON THE CARDIOV2\SCULAR ACTIONS OF PALLADIUM



                                M. J. Wiester



Introduction



     Palladium chloride has been shown to be extremely toxic when given



intravenously (I.V.).  Rabbits, rapidly injected with 0.6 mg/Kg quickly



die with damage chiefly to the heart.     The nature of the heart damage



was not further defined and there is very little other information in



the literature addressing this subject.  The purpose of this study was



neasure the effects of different palladium chloride solutions on heart



rate, ECG pattern, blood pressure, cardiac contractility (dp/dt) and



breathing for one hour following intravenous injection.



Methods



     Sprague Dawley (f rats (300 + 50g) were surgically prepared one day



prior to use.  Surgery consisted of catherization of the abdominal aorta



with tubing (#50 P.E.) for measurement of blood pressure and tubing



 (#10 P.E.) v/as inserted into the femoral vein to acoomodate I.V. injections



Both catheters were guided through the subcutaneous tissue to the bacK region



and via a puncture wound through the skin to the outside.  Six small silver



electrodes, fitted with micro-strip connector pins, were inserted under the



skin and sutured.  Electrodes were arranged laterally so that four were



near the lutfos to record the BOG and two were on the lateral surface of



the rib cage for respiratory measurements.  After surgery, the rats were



returned to their cages and given food and water ad libitum (Purina Lab



Chow and tap water).



     For testing, an unanesthetized animal was placed m a plastic tubular



holder for the duration of the experurent and sensor leads fed to a recorder



 (Figure 1).  The measurement system is diagrammed in Figure 2.  After a

-------
                              55
FIGURE 1.  PLASTIC RAT HOLDER.    HOLDER WITH RAT AND POLYGRAPH LEADS

-------
                            56
/x
PRESSURE
TWWSbUCLR
\/
^
t
rz


f
sr
DIFFCRCtmATOR
dp/clt
V
\
f
\1
'


V
IMPEDANCE
PHeiMOGRflPH
^7
1
f
\7
'


^
ECG-
PREflMPUFIER
^
\
^
7"^
^
RECORDER
      FIGURE 2   Block Diagram of Recording System
  Pressure Transducer
       Differentiator
Impedance Pneumograph


     ECG Preamplifier
            Polygraph
For measurement of arterial blood
pressure - calibrated with a Hg
manometer   (Miller Insttument)
For a recoid of  maxinum rate of
change of aortic piessute - time
constant of 1  msc   Calibrated
with an osciloscope
Monitors rate  and relative depth of
respiration (Narco Bio-Systems)
(Grass) Lead 2 was recorded
(Grass 7C)

-------
A  COHTROU  rc
                                                 ,t

                                                            B_tO &6COMD5 AFTFn DOSS
                                                                                                                           ,-U'
                                                                                                                         \  /   !
                                                                                                                             I  '   I
C  60 MIM /"=ieR DCSS
                                                                                                                                       01
    Fig  3 Pat i?4      A  Polygraph recording 25 minutes into the control  period   Aortic blood pressure is 165/i25
    Electronic differentation of tne blood pressure signal is displayed as dp/dt   The uptsard deflection shov.s maximum rate
    ofpressure development, wmch for this pressure pulse is 3,000 trmHg/sec  dp/dt reflects the contractile state of cardiac
    rusc'^   The respiration record sho,vs the rate and relative depth of breatmng   The ECG is derived from lead 2   For
    this lead a proiiinant P wave and R wave can be defined   The Q, S, and T \a/es are soirc\ hat less specific   However, the
    pattern is dependable ana remains unchanged throughout control periods   heart Rate = 460 beats/mm
    B   This section she /s the Measurements inr^diatoly following tne I V  injection of 2 04 mg/kq PdCl2   Gross abnormalities
    can be seen in the ECG   PVC's are not frequent enough to cause a detrimental fall in blood pressure   Breathing was not
    altered   Similar irregularities continued for approximately 3 minutes   The animal survived
    C   One hour following the injection blood pressure haa increased to 185/140 irarllg, dp/dt = 3660 imHg/sec , tne ECG showed
    no gross abnormalities, heart rate = 408 beats/irin  and bieathing was uncranged

-------
                                      58
thirty minute stabilization or control period the palladium solution



was injected and washed in with saline.  Hie total volume of the dose



and wash solution Wcis 1 ml. and total infusion time was one minute.



Effects of the injection were then observed for 60 minutes.  Control



animals were injected with 1 ml. of saline and treated the same.



Results and Contrente>



     Palladium chloride exerted an immediate cardiovascular effect in



the unanesthetized rat.  The most pronounced effect was seen on the



electrical integrity of the heart.  A total of ten animals were dosed



in amounts ranging laetween 1.14 - 5.9 mg PdCl2/Kg and in each instance,



premature ventricuLir contractions (PVC) were noted within one minute



after dose initiation.  PVCs were never seen during the 30 minute control



periods or in control animal experiments (5 rats).  Doses between 1.14 -



1.75 ng/Kg resulted in mild episodes of PVCs following the injection



with no consequential fall in blood pressure.  These arrhythmias



continued for 3-4 minutes then the BCG stabilized.  This stability,



however, was dependant on the quiet state of the animal.  If the rat



moved or showed signs of distress, PVCs> reappeared.  Rats that received



doses between 1.75 - 5.9 mg/Kg experienced gross alterations in the BCG



pattern following injection.  If the cardiac arrhythmias were inter-



mittent or of sucn a nature as to allow adequate filling and pumping,



then the animal survived  (Figure 3).  These surviving animals were able



to maintain sufficient blood pressure levels during the critical 3-4



minute period following injection.



     These surviving rats also reestablished a stable ECG during the one



hour observation period, and like the low dose animals, were susceptible



to arrhythmias, if they became agitated.  Rats that succumbed after

-------
                                     59
receiving PdC]^ intravenously suffcred gross alterations in the EGG


acxsompanied by a precipitous fall in blood pressure.  After the aortic


pressure fell, breathing became erratic and the EGG continued to


deteriorate  (Figure 4).  Death usually occurred within four minutes


after infection.  Additional EGG abnormalities, other than PVCs, that


were seen after injection of Pdd^ were extra p waves, large S waves


and various degrees of A-V block.


     Rats surviving a PdCl9 injection developed elevated blood pressures
                          t*

which persisted throughout the one hour observation period.  Systolic


pressure increased 20-50 ranHg and diastolic 10-20.  Heart rates


correspondingly decreased, and dp/dt changed very little.


     Intravenous PdCl^ appeared to have no initial effect on respiration.


Changes in breathing were seen, however, the changes followed gross cardiac


arrhythmias and falling blood pressures.  If the rat reestablisned a


steady and productive heartbeat, thus, survived the injection, breathing


returned to control values and remained stable.


     Results from preliminary experiments described above indicate that


PdCl^f when injected I.V., acts as a non-specific cardiac muscle irritant


as well as a peripheral vasoconstrictor.  Since the chloride salt strongly


dissociates in solution  (PdC^ % Pd** + 2 C1-) the palladium ion itself


nay be the irritant.  Effects seen might be due to the release of
                         i

catecholamines or to stimulation of adrenergic receptors located in the


cardiovascular system by the metal ion.

-------
           '_  'A1
      A  COWTROI.  PERIOD
/v/
                                                                Bieoo  PRE4SURE
                                                      "HIM i/nMvii'iMiH  < '  ,.,, ;,,
                                                      f 17.  rf,• r,/1cfnn,ri tfr
-------
                                   61
1.  Orestano, G.   The Phannacologic Actions of Palladium Chloride,
    Boll. Soc. Ital. Biol.  Sper.  8   1154-1156, 1933

-------
WHOLE EXHAUST EMISSION STUDIES

-------
                                   62
             B.I.   AUTO EXHAUST FACILITY MODIFICATICN



                     R. G  Hinners and J. K  Burkart





Introduction



     The auto exhaust generating system has recently been modified at this


                                                     (1 2)
laboratory and the following will update other papers  '   describing the



earlier facilities for the production of irradiated and nonirradiated



gasoline engine exhaust-air mixtures   It is also intended as a reference



for biologically oriented papers discussing health effects of completed



studies   The Toxicity Assessment of tobile Emissions (TAME) project



represents a series of acute and subacute bio-effect studies which test



exposures of experimental anurals to whole automobile exhaust emissions



with fuel additives ard/or with or without a catalytic converter   Briefly,



the exhaust gases are generated by an engine-dynamometer unit and mixed



with clean conditicned air in a dilution system to produce the desired



concentration   The exhaust gas mixture is divided with one part flowing



direct to animal exposure chambers, and the remainder flowing through



irradiation chambers to other animal chambers.  The changes include an



air dilution tube for the immediate mixing of the entire raw exhaust



emissions with conditioned air and a large mixing chamber after the dilution



tube.  Information is also provided on air supply, engine cycle, fuel supply



and other minor changes that have been made.





Dilution Tube



     The effluent from the engine exhaust system is passed into an air



dilution tube, through flexible stainless steel tubing, connected to the



muffler   The dilution tube is 23 in  in diameter and made from 10 ga  SS

-------
                                   63
plate, rolled and welded.  Dilution air enters the tube through a 90° elbow

from a remote supply source.  Located between the flanges of these two tube

sections is a mixing baffle plate, with a 7-1/4 in. diameter hold bored in

the center   Ihe incoming dilution air under pressure, is forced through

this hole to mix with the raw exhaust   The tailpipe exhaust inlet elbow

enters 90° to the tube axis and is bent 90° again, so that the flow axis

of the exhaust outlet coincides with the center line axis of the dilution

tube   The exit end of the 2-in  diameter SS exhaust elbow is in the same

plane as the baffle   Located on top and outside the dilution tube, at

the baffle plate, are two quick-disconnect couplings   One allows the

end of the flexible 2-in. I D. exhaust pipe from the muffler to connect

with the dilution tube and the other connects to the outside atmosphere.

A blank plug is installed in the disconnect to the dilution tube when the

exhaust is vented outdoors   System back pressure at this point is 4 in.

water   This feature provides the capability of varying the modes of engine

operation for aerometry and allows interruption of animal exposures.

     By closing a damper m the air supply line, the dilution ratio can be

controlled.  To retain the particulate matter in suspension and prevent

condensation, it is necessary to dilute the whole exhaust with at least 8

parts of air to 1 part of exhaust   For each pound of fuel burned, approxi-

mately a pound of water is formed and some condensation occurs if the exhaust
                         \
is not immediately diluted with dry air   Also to prevent condensation, the

outside of the dilution tube is insulated since engine room temperature often

exceeds 90°F and dilution  air temperature averages 50°T and 67% relative

humidity   The main portion of the dilution tube consists of two 7 ft. long

flanged sections before reducing through a transition to a 6-in. diameter and

entering the mixing chamber

-------
                                   64
Mixing Chamber



     The diluted auto exhaust enters the mixing chamber, formerly used as



an irradiation chanter, through a 6-in  diameter SS pipe opening in the



side wall   An elbow discharges the exhaust in front of and parallel



with a tube-axial ian, controlled at a low rpm by a Zero Max unit, to



mix the entering auto exhaust with the chamber atmosphere



     The chamber is, 23-1/2 ft  long, by 4 ft wide, and 8 ft high, with a



volume of 683 ft^   The sides consist of a framework of aluminum structural



members holding metal panels to replace the plastic windows   The aluminum



sheet metal panels are clamped and sealed by means of pressure screws and



gasketed channels.  Previous studies with a reference fuel, to which had



been added methylQclopentadieny1 manganese tricarbonyl ^M?) as an



antiknock additive required darkress, due to the light sensitivity of the



MMT.  The top, bottom, and ends of the chamber are formed of 1/4 m  thick



aluminum plate welded on both sides at all seams to prevent leakage



     At the end of the chamber opposite the entry port is a 6-in  diameter



line with a motori2ed damper control vented to the atmosphere.  Another



6-in. diameter outlet pipe from the chamber supplies the exhaust either to



irradiation chambers or to raw exhaust animal exposure chambers   A pressure



sensor, which is ad} us table and located downstream of the chamber exit line,



controls the motorized damper in the vent line to maintain 2-m  of positive



water pressure in the chamber





Irradiation Chambers



     The photochemical reactions that result from the exposure of the diluted



raw exhaust to artificial sunlight take place in five irradiation chambers

-------
                                    65
Fluorescent lighting panels composed of blue lamps, black lamps and sun



lamps outside the chamber pass intense ultraviolet radiation through



windows of Teflon FTP fluorocarbon film.  One irradiation chamber is



needed to provide the atmosphere for each animal exposure chamber   Normal



flow through the irradiation chambers is 11 cfm, which results in 15 air



changes per hour in the animal exposure chambers   In some instances,



however, the flow has been reduced by one-half that of normal, which, of



course doubles the irradiation time   One of the original irradiation



chambers used in previous exhaust studies has been converted into a mixing



chamber which is described separately



     At a volume of 683 ft3 and 11 cfm flow, 43 minutes is needed to



achieve 50% of inlet concentration when "building up" from zero   Approxi-



mately five times 43 minutes (3-1/2 hours) are needed to reach equilibrium



at the inlet concentration, decay tune is also 3-1/2 hours





Air Supply



     The air purifier unit provides, at maximum, 550 cfm of CBR (chemical,



biological, radiological) filtered and conditioned air   Inside building air



is passed through a cooling coil to lower the temperature to 40°F (saturated



at coil outlet), there is no reheating or humidification.  Therefore, if the



relative humidity of the outside air drops below 36 grains of moisture per



pound of dry air, the relative humidity in the final exposure chamber will



also vary   Most of the tune, there is no problem maintaining constant



relative humidity, but occasionally on very dry days, there is a change

-------
                                    66
     The humidifiei is turned off, because of the constant reed for cool



dry air to mix with hot wet raw exhaust.  Exposure chambers on control air



are supplied from a separate CBR filtered source, with controls set to



maintain 72° + 2°F and 55 + 5% relative humidity in the animal chambers.



The same air is also ducted to the air filter inlet of the engine being



used for the study smce a change in humidity effects the NC^ emissions



from the engine






Engine Cycle



     The dynamometer driving schedule for the Chevrolet engines consists



of a repetitive series of idle, acceleration, cruise, and deceleration



modes of fixed tune1 sequences and rates   The following Table I and



Figure 1 is the modified "California Cycle" used m the fuel emission studies.








                                 Table I
Mode
Idle
Accelerat lor
Cruise
Decelerat-ion
Cruise
Acceleration
Peak
Decelerat-ion
Speed, M P H
0
0 to 30
30
30 to 15
15
15 to 49
49 to 50
50 to 0
Tame, seconds
20
14
15
11
15
29
1.5
31.5
                                         Total          137 sec.

-------
            67
         TIME  (SECONDS)
FIGURE  1   CYCLE  SPEED  TRACE
             (137  SECONDS)

-------
                                    68
     Replacement oi the California Cycle with the IA-4 cycle controller



was considered at one time.  However, after consultation with other



experts in the field, it was decided to continue with the California Cycle



because the exhaust is being further diluted to prescribed levels and both



cycles are very similar sauce they reflect transient as well as cruise



operation.  The key to this research is comparative toxicity   either



cycle is satisfactory to achieve this goal   A simple repetitive cycle



that is easily cont_rolled over long periods of time (weeks) is of prime



importance to toxicologic investigations





Fuel Selection



     The gasoline selected for use in the Chevrolet engines as a standard



reference, baseline* fuel for evaluation of engine, fuel and additive



variables was American Oil Co.  Unleaded 91 Octane Test Fuel, Intermediate



Grade Indolene Clear   As a reference it was important that it be of quite



precise and reproducible composition and character, including absence



of lead and other additives  (except as specifically noted), and similar to



high-volume regular market gasoline   This gasoline has been used for such



purposes m research and development by industry and other agencies   The



lubrication oil se Lected was Texaco Havoline 30W, API service specification



SE.  Table II shown below, represents a comparison and product analysis of



the two gasoline deliveries used for exhaust emission studies during 1973.

-------
                                     69
                     Table I.  Fuel Properties
Shipment No.
Date Delivered
Quantity, gallons
Octane No., research
Octane No., motor
Lead Atm. Abs., gir/gal.
Phosphorus, gm/gal.
Sulfur, wt. %
Aromatics, Vol   %
Olefins, Vol.  %
Gum, Existent, mg/100 cc
Gravity/ °API
Oxidation Stability, minutes
Ried Vapor Pressure, Ibs
  #1
3/30/73
 2,000
   91.4
   82.9
    0.01
    0.002
    0 04
   25.4
   11.8
    0.8
   61.4
  600+
    9.1
  #2
10/29/73
 1,500
   91.3
   82.5
    0.01
    0.00
    0.05
   23.5
    9.9
    1.0
   61.5
  600+
    9.0
   Note.  Shipment #1 used for studies G, H, I and J. Shipment #2
          used for study K with Thiophene added to produce 0.10%
          by weight sulfur
  Fuel Storage and Handling
       Local fire and safety regulations require  flammable liquids to be
  stored outside the building,  so two underground fuel storage tanks were
  installed on the property near a blacktop  surface driveway.  To promote
  chemical stability of the fuel during storage,  the tanks are maintained
  under slight positive pressure with nitrogen  supplied from cylinders and

-------
                                    70
controlled by a pressure regulator.  A double acting pressure and vacuum

relief valve on the vent outlet compensates for changes due to fuel being

pumped out or temperature increase, which would alter the pressure of the

nitrogen gas cover   Each tank is of 2000 gallon capacity and equipped with

an electric fuel pvitp rated at 15 gallons per minute

     Outside the bvalding wall and next to the engine room is an 18-gallon

marine fuel tank setting on a weight scale and connected to a remote electric

fuel gauge located in the instrument panel.  Transportation of the test fuel

from the main underground storage supply to the one-day supply tank is

effected by a mobile safety dispenser cart made especially for transporting

flammable liquids   The 60-gallon-capacity cart carries the Underwriters

Laboratories' approval as a portable flammable liquid tank and is equipped

with transfer pump and grounding reel.  The cart also has a drain, and

removing the pump gives access to a 4" handhole for reaching and cleaning

the tank interior between fuel changes.  Similarly, the 18-gallon marine

tank can easily be inverted for cleaning when required.

     An alteration in the composition of the reference fuel for a study is

made by the addition of the required amount of chemical to a full cart

batch.  Thus studies requiring the testing of fuel additives such as

methylcyclopentadienyl manganese tricarbonyl  (MMT) or thiophene to increase

the sulfur content can be conducted by mixing only the amount of fuel necessary.


References

1.  Hinners, R. G   Laboratory Produced Automobile Exhaust Facility.
    Biomed. Sci. Instrum. _!  53, 1963

2   Hinners, R  G  , Burkart, J  K  and Centner, G  L   Arimal Exposure
    Chambers in Air Pollution Studies.  Arch  Environ  Health. 13_  609-615,
     (Nov ) 1966.

-------
                                                                        \
                                                                         1
                                   71
             B.2.  CATALYST EXHAUST EXPOSURE STUDIES



                     R G. Hinners and J.K  Burkart



    During 1973, animal exposure studies were conducted in ETRL, NERC-



CincinnatL, to assess the relative health hazard of automobile exhaust



emitted from engines equipped with and without catalytic converters using



similar engine settings.  Automotive exhaust catalysts were developed to



lower exhaust emissions of carbon monoxide, hydrocarbons by oxidation, and



oxides of nitrogen by reduction.  They are the three pollutants specifically



listed in the Federal Clean Air Act of 1970.  The regulations also require



that no pollution control device shall emit "noxious or toxic" substances



Three possible conditions could result m such emissions   1) As the hot



catalysts promote the oxidation of carbon monoxide and hydrocarbons in



automotive exhaust, converting them to carbon dioxide and water, it may



simultaneously convert the organic sulfur compounds present in all gasoline



into sulfuric acid mist and eventually sulfates  2)  The metals used in



the converter, such as platinum and palladium, may be emitted under conditions



of catalyst degradation from the exhaust pipe in fine particles and be



suspended in the air.  3) The total emissions may be altered and may produce



different quantities or new species.



    In order to perform the assigned tasks, this laboratory recently



acquired and installed two new engines equipped with catalytic converters



from General Motors Company* and the Ford Motor Company * (See Table 1)

-------
                                   72
                               Table 1

FORD - 400 C.I D   (1975 Prototype) R-6 Engine with R-14  Calibration and
                        the Following Controls
          (1)  EGF  (exhaust gas recirculation)

          (2)  Air Puitp

          (3)  Fli,.idic spark delay valve

          (4)  Various tenperature sensing triggers

          (5)  Catalytic converter of monolith, noble metal
              oxadation type.  IWo converters of  thjs  type
              are required, one for each bank of  cylinders.
               (Cc'talyst by Matthey-Bishop Co )
         GENERAL MOTORS - 350 C I.D.  (1973 Production Engine)


           (1) EGR

           (2) Art Purp

           (3) Caialytic converter, pelletized type,  noble metal
              ox.dation catalyst.  One converter  after Y pipe
               (Catalyst by Engelhard Co.)

-------
                                    73
The schematic plan view of the engine-dynamometer unit and dilution tube



is presented in Figure 1.



    During TAME studies H, I, J and K, the 1973 Chevrolet engine was



operated continuously for 7 days using the California Cycle   Comprehensive



data for comparison of study engine operating conditions is given m Table 2



    TAME 'K' was designed to test emissions and bioeffects of a high-sulfur



gasoline free of other undesirable substances such as lead.  Thiophene was



added to produce a sulfur content of 1000 ppm m the control fuel, Indolene



Sulfur compounds present in gasoline are mainly in the form of polysulfides



and thiophene compounds with an insignificant amount of hydrogen sulfide



    It was reported and confirmed by our testing procedures that the addition



of oxidation catalysts to the automotive exhaust system causes an increase in



the emitted particulate material (consisting mainly of hydrated sulfuric



acid droplets) as a result of the oxidation of organic sulfur compounds in



gasoline.  Recent national averages of the sulfur content are between 210



and 260 ppm for premium gasoline, and between 390 and 440 ppm for regular



gasoline   The "Indolene" motor fuel used at the ETRL facility had a sulfur



content 0.04% by weight or 400 ppm.

-------
DOUBLE ENGINE-DYNAMOMETER UNIT
               (PLAN VIEW)
   -a       R
1 Vibration Isolating Stand
2 1973 Chev  V-8 350 C I D
3 Turbohyd romatic Transmission
4 Dynamometer Absorption  Unit
5 Flywheel
6 Catalytic Converter
                       7  Muffler
                       8  Dilution Tube
                       9  Baffle  Plate
                      10  Dilution Air Supply
                      11  1975 Ford V-8  400 C I D
                      12  Catalytic Converters
              FIGURE  1

-------
TAME H
TAME I
TAME J
TAME K
Dates
Fuel
Engine
Engine Hrs.
Study Hrs.
Eng. Miles
Cuirm Catalyst
Hrs.
Catalyst Miles
Total Fuel
(Ibs)
Fuel, tb/Hr.
Exh. Oxygen (%)
Air/Fuel Ratio
Oil Consunption, qts.
Dilution Ratio
Dilution Air Flow
Average, SCFM
Dilution Tube Temp.
Average, °F
9/10 - 17
Ref . Only
' 73 Chev.
w/catalyst
62-230
168
4600
244

4880
1533

9.10
4.9
—
1-1/8
8.0/1

318
106
10/10 - 17
Ref. Only
'73chev.
No catalyst
255-425
170
8500
244

4880
1545

9.08
N.A
14 4 cycling
12 4 idle
1/2
9.6/1

305
101
10/24 - 31
Ref. Only
'73Chev.
w/catalyst
444-615
171
12,300
465

9300
1601

9.40
4.2
—
1/4
8.7/1

310
114
11/14 - 21
Ref. + Sulfur
1 7 3 Chev.
w/catalyst
675-841
166
16,820
632

12,640
1495

9.02
4.7
—
1/4
9.5/1

324
101
                                                                                           Ul
 Table 2.  Comparison of Study Engine Operating Conditions

-------
                                    76
B.3. DESIGN AND SYSTEM PERFORMANCE FOR STUDIES OF CATALYTIC EMISSIONS



                       J. Burkart and R  Hinners





    All of the catalyst studies m this report were performed with the 1973



Chevrolet engine, new headpipe, standard muffler and fabricated stainless



steel tailpipe   New road load data supplied by the EPA Motor Vehicle



Emissions Lab were used, they are equivalent to an increase of inertial



weight from 3400 Ibs  (used on 1972 Chev) to 4000 Ibs.  No attempt was



made to adjust idle mixture, as in earlier TAME A through G studies and



carburetor "limiters" remained in place.  In TAME "H1 the engine was run



"as received" except for setting idle speed, dwell and timing.  Maintenance



performed before T'AME I, J and K consisted of oil and filter change, new



points, condenser, spark plugs and setting hot idle speed, dwell and



tuning   In addition, before TAME 'K' new spark plug wires were installed



    For each of t±e continuous one week studies shown in Table 2 of the



article B-2, approximately 3400 miles were accumulated on the California cycle



Separate cumulative ergine miles and catalyst miles are reported since



the catalyst was removed in TAME 'I1 and additional steady speed runs



(without animal exposures) were made to characterize emissions   The dilution



ratio is determined by the ratio of average tailpipe C02 "to dilute CO^



    Because the variability of tailpipe C02 throughout the cycle is small,



the problem of obtaining a proportional sample is negligible.  Samples for



CO- detection flow at a constant 1 liter per minute thru a refrigerated



cooler, dessicant dryer and paper filter to the Beckman 1R Model 315.  This



instrument, converted for OX^, is calibrated 15% CO- full scale and zeroed

-------
                                    77
on dilution air, however, because of the cooler some C02 loss ln



condensate was unavoidable



    For all studies a continuous trace at constant sample flow on two-



Mosley  (2 pen) recorders was made of the following emissions



            (1)  tailpipe CO



            (2)  dilute CO



            (3)  tailpipe THC



            (4)  tailpipe C02



The above, along with "spot" checks of tailpipe oxygen and dilute C02,



monitored engine and dilution system operation.



    TAME schematic Figure 1 shows sampling points throughout the system



starting with engine (E), catalytic converter  (C) and standard muffler  (M).



The numbers will be referred to for aerometry sample identification except



when exposure chambers are sampled, the chamber number and treatment  (I, NI,



clean air) is used   Average total particulate losses on a percentage basis-



are also shown starting with 100% at point 5 in the dilution tube   An



overall loss of 39% occurs by the tune the NI chamber is reached.  The



diagram shows only part of the exposure chambers receiving autoexhaust and



there are control chambers which receive filtered air from a separate supply



    During the studies, the entire tailpipe volume was mixed with the



quantities of air given in Figure 2 and resulted in the dilution tube



temperatures shown   The dilution air temperature for all studies ranged



from 48° to 55°F.  Figure 3 depicts tailpipe conditions of exhaust oxygen



content and average catalyst temperature (on center line of tailpipe one-



inch from catalyst oftlet)   At the tailpipe, the seven day trend during



the catalyst studies (H, J, K) was oxygen decrease, C02 increase and catalyst



temperature increase.

-------
                                   78
    Table 1 shows the GM catalyst efficiency when TAME 'I1  (w/o catalyst)

average emissions are used as the basis for comparison   It is noted that

the catalyst is mere efficient in terms of CO than for HC under the hot

cycling condition.

    Some initial loss of efficiency may be due to the higher oil consunption

during TAME 'H1, also by the end of that study #3 plug had "fouled."
              Table 1    GM CATALYTIC CONVERTER EFFICIENCY
    Average Tailpipe Concentrations* (PPM)


                                       S.    I     £      £

       Carbon Monoxide                56  5376   400    380

       Hydrocarbons (as methane)      96  1056   191    171


    Total Per cent Reduction Below TAME I


       Carbon Monoxide                99%   X    93%     93%

       Hydrocarbons                   91%   X    82%     84%
      *Calculated from dilute concentrations multiplied by
       dilution ratio.

-------
                                    79
    Basic specifications  for the  1973 Chevrolet engine are shown below
 in Table 2.


                   Table  2   Chevrolet Engine System
                                                     1973
           Displacement                       350 C.I.D.
           Compression  Ratio                     8.5/1
           Carburetor Type                     Roch. 2GV 1-1/2
           Carburetor No.                        #7043114
           Distributor*                         # 1112168
           Mech. Adv. Unit                       C 4815
           Vacuum Adv.  Unit                    C6020(46914)
           Dwell                                  30°
           Initial Timing                       8oBTC
           Maximum Vacuum Advance                 14°

               Emission Control Equipment   Air Pump
                                         Rich tune  (A/F M.4.5/1)
                                         Tuned port Vac. Adv.
                                         EGR 11633  (IF 7040437)
   Data for exposure chamber temperature and relative humidity are presented
in Figure 4   The temperature profiles appear favorable,  however,  the
relative humidity for chambers receivug exhaust were consistently above
60 per cent relative humidity while the reverse was true for control air
chambers

-------
                     /      /
 VENT
                ®76
                  DILUTION AIR
                                      IRRADIATION  CHAMBERS
                                                                          .
                                                                    --O
V,
 EXPOSURE CHAMBERS
                                                                                            CO
                                                                                            o
MIXING CHAMBER  DILUTION TUBE
             FIGURE 1. TAME SCHEMATIC SHOWING SAMPLING POINTS -.-O

-------
    330
  E
 %*•
  V
    320--
 Oi
 <
 z
 o
310--
    300
             DR=8/1
012345678
    TAME H
   (CATALYST)
 u.  120°
 o

 O.

 LU
 I—

 UJ  HO°J
 Z
 O
    100°--
 Q

 O

 <   90°
                        DR=9 6/1
DR=8 7/1
                             TAME I
                          (NO CATALYST]
                                         TAME J
                                        (CATALYST)
                                                       DR=9 5/1
                  TAME K
              (CATALYST W/
              HIGH SULFUR FUEL)
        012345678  012345678  012345678  012345678
             DAYS             DAYS            DAYS             DAYS

FIGURE 2-DILUTION AIR  FLOW AND  DILUTION TUBE  TEMPERATURE
                                                                                          oo

-------
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         CATALYST
          /
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           DAYS
          TAME H
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           DAYS
                         CATALYST
                          TAME J
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                                     4

                                     3

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                                     1

                                     0
                                        CATALYST
                                          WITH
                                          HIGH
                                          SULFUR
                                           FUEL
                                         TAME K
                                                                         CO
                                                                         to
          FIGURE 3  TAILPIPE  CONDITIONS

-------
                          83
 70% 80°FH
  60% 75°F-
  50% 70°F
                              IRRADIATED EXHAUST
             i   (  I   i  i  I  1
             1234567
i   i  i   i  i   i  i
1234567
ji   r^  i  i   i  i
1234567
570% 80°F-]
                           NON IRRADIATED EXHAUST
1U
360% 75°F-
0£

efi

u.
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ce
  50% 70°F
              i  i   i  r i  i  i
              1234567
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1   234567
  70% 80°F_|
                            CLEAN CONTROL AIR
UJ
  60% 75°F-
  50% 70°F
              1234567     1234567    1234567
                    DAYS                DAYS                DAYS
                   TAME  I              TAME J              TAME K

           •	• SOLID LINE  TEMPERATURE
           *--•• DASH LINE   RELATIVE HUMIDITY

  FIGURE 4  EXPOSURE CHAMBER TEMPERATURE

              & RELATIVE HUMIDITY

-------
                                    84
  B.4.    EXHAUST EMISSIONS DURING STEADY SPEED RUNS WITH THE
                CATALYTIC CONVERTER IN THE EXHAUST SYSTEM

             M. Malanchuk, N  Berkley, G  Centner,
                  M. Richards and R  Slater
Introduction

     In preparation for studies on the exposure of animals to the exhaust

emissions from catalytic-equipped systems, preliminary runs were made with

the 350 C I.D. Che\Tolet engine operating at constant speeds.  Information

was sought that would indicate the levels of constitutents different from

those of previous i~uns made under different engine operating conditions

The data were needed particularly with reference to sulfur compounds and

acidity of the emissions   Preparations were made to test for sulfates,

sulfur dioxide, suJfuric acid and nitrate components   Sample procedures

were adapted with £>uch changes as were considered expedient to get

quantitative result.


Experimental Procedure

     The main effort was directed to the sampling of particulate in order to

establish the natuie of the anticipated changed character of the particulate.

     Since membranes-type filters used to collect aerosol from the catalytic

converter system deteriorated from the corrosive action of the sample, quartz

fiber material was used and found favorable for such samplings.  Not only

did the material resist breakdown, but also in the aqueous extraction medium

it did not show any resulting changes in the nature of the solution  (e.g  pH)

upon standing for as long as 20-30 hours.

     The sample fiLters were handled m two different ways   Every filter was

weighed immediately after sampling   Some were permitted to stand overnight.to

equilibrate in the room atmosphere  (70-75°F, 40-60% R.H.) until the weight

-------
                                    85
had stabilized.  These final weights were used to calculate the particulate



concentrations in the sairpled atmospheres   Other filters, immediately after



they were weighed following the sampling, were placed in a measured volume of



distilled, deionized water.  Conductance and pH measurements were then



made to determine ion concentrations mainly, the acidity of dissolved



samples.  The aqueous extracts were also used for analysis of particular



ion radicals like the sulfate and nitrate groups



     Analytical procedures included the barium chloranilate method^ ' and


                                                               (2)
also nephelometry for sulfate, the phenol-hypochlorite reaction    and



ion-specific electrode for amroma and ammonium compounds, and the


                  (3)
hydrazine reaction    for nitrate



     Bubblers containing distilled water or a weak acid solution were used



to scrub sampled atmospheres for nitrate - and for ammonium-producing



components.  A sampling train of bubblers similar to that used in stack



sampling'^ was arranged for separation of 862 from SCU m atmospheres



drawn from the exhaust pipe before and after the catalytic converter and



from the arimal exposure chambers.  The first bubbler in the train, con-



taining isopropanol, collected 803   The succeeding two bubblers, containing



hydrogen peroxide, collected the SC>2 ard converted it to the sulfate form.



In some cases, the follow-up bubblers contained tetrachlormercurate instead


                                                                   (4)
of peroxide to trap the SO- for analysis by the West-Gaeke method



     None of the animal exposure chambers from which the atmosphere was



sampled contained any animals.  These chambers previously were hosed down



thoroughly with hot water to minimize, if not eliminate, sources of contaminating



deposits.

-------
                                     86
Results



     The effects of different engine speeds and of different concentrations



of sulfur in the fuel are seen in the concentratior values of exhaust



emission conponents in Table I.



     Values of gaseous conponents are listed first - carbon monoxide (CO),



total hydrocarbons, as methane  (THC), nitrogen oxides  (NC^) with a break-



down into nitric oxide (NO) and nitrogen dioxide  (IC^)/ the aliphatic



hydrocarbons of the 04-^5 grofp examined, olefins of the C2-C^ group, and



acetylene   Values of particulate material are listed as total particulate



and the sulfate and nitrate concentrations in that particulate



     The first three column groups of concentration values were obtained



from the operation of the engine with the base fuel, Indolene gasoline, and



the use of the catalytic converter unit in the immediate exhaust system.  The



last two column groups show the concentrations obtained when the Indolene



gas was "spiked" with an organic sulfur compound to double the concentration



of sulfur in the fvel, in one case, the catalytic converter unit vras retained



in the exhaust system, in the second case, the unit was removed before the



run was started



     The samples were mainly collected from the animal exposure chambers



receiving the diluted exhaust emissions that had been exposed to the irradi-



ation lights, I, and those chambers receiving diluted emissions not treated



to the irradiation effects, N-I.  Some samples were collected from the



exhaust system in -the immediate range of the engine, viz , the particulate



samples identified as diluted exhaust  (Dil'd  Exh )

-------
                                     87
     In order to relate the values from the higher engine speeds and the



runs with higher gasoline sulfur to the "base" 15 irph with its 7 5/1 dilution,



the actual values of those runs have been adjusted to equivalent values



for a 7.5/1 dilution which are given m brackets.  Thus, for total



particulate weight in the diluted exhaust, it is seen that the significantly



different values of 6 10 irg/M3 at 30 mph and of 8.40 mg/ta3 at 50 nph



become nearly the same value as the 5 03 mg/M3 at 15 nph when the dilution



adjustments are made for the 6 2/1 and 4.9/1 at 30 itph and 50 mph, respectively.



     Since the data applies to only single runs at each of the five different



sets of conditions (except the "base" 15 nph with regular Indolene fuel,



there were two runs for which the average values were calculated), the



information must be considered as tentative   Duplicate runs will be made



to establish reproducibility and to confirm the results presented



     Nevertheless, large differences in the results between runs were



seen which may be acceptable for what they indicate.  The large increase in



the nitrogen oxides at the highest speed of 50 mph was to be expected (see



columns 1-3 of Table 1).  There was a concomitant decrease in hydrocarbons.



Particulate levels remained about the same with the changes in engine speed



Apparently particulate sulfate concentrations also renamed the same at



different speeds, however, they seem to make up most of the total bulk of



the particulate   Nitrate was present at much loser concentrations.

-------
                                                                                _»_ i,

                                      88




     With the high s.ulfur (2 x) Indolene gas as fuel, the carbon monoxide

and hydrocarbons  (total and individual) levels remained the same  (column 4).

The big difference was seen in the total particulate and sulfate contents,

about 1-1/2 - 2 times as much.

     The engine operating with the high-sulfur fuel but without the

catalytic converter had, as expected, much higher levels of carbon monoxide

and hydrocarbons   The nitrogen oxide levels were at similar concentrations

as those for the 15 mph with regular Indolene fuel.  The particulate levels,

column 5, were only 1/3 to 1/4 of those for the catalytic converter, column 4.

Sulfate in the partxculate was almost negligible by comparison.

     Measurements of acidity of the particulate from the catalytic-equipped

exhaust emissions was, without exception, high enough to allow for all the

sulfate to be consi'3ered present as sulfuric acid   That is to say, that the

hydrogen ion concentration as  (2H+) that was measured with a pH meter v/as

greater than the sulfate  (SO^-) concentration, sometunres by a factor as high

as three times.  Such high acidity was found unaccountable on the basis of

the anionic components measured and of the total particulate determined, so

that additional study is needed to resolve that phenomenon.  An indication of

relative acidity levels with different operating conditions is shown in Table 2.

The particulate, column 5 of Table 1, in the no converter condition, on the

other hand, was almost completely neutral as measured by pH meter on its
                         \
aqueous extract.

     Measures of sulfur components, SO , in the undiluted exhaust before and
                                      J*L

after the catalytic converter showed 50-90 per cent decrease of sulfur across

the converter   That is to say, that there is a considerable hold-up of

sulfate in the catalyst bed itself

-------
TABLE 1.    COMPARISON OF EXHAUST EMISSIONS, STEADY SPEED RUNS
Exhaust Dilution Ratio

CO,ppm*
        Exp. Ch   N-l
THC,ppm
        Exp. Ch:  N-l
     ppm
        Exp. Ch:  N-l
NO, ppm
N0,
        Exp. Ch:  N-)
        Exp. Ch:  N-I
Al Iphatlcs  ppm
  C4-C5 Exp. Ch:  N-l

Olefins ppm
  C2-Ci, Exp. Ch:  N-l

Acetylene ppm
        Exp. Ch:  N-l
                  I
Particulate, mg/M^ -
      - Dll'd Exh
        Exp  Ch   N-l
                  I

Sulfate, mg/M3-Dll'd Exh.
        Exp. Ch   N-l
                  I

Nitrate, mg/m3-Dll'd Exh,
        Exp. Ch   N-l
                  I
                              Regular Indolene Gasoline
                              With Catalytic Converter
High-Sulfur  Indolene
w/catalytic	w/o catalytic
15 mph
7.5/1
7
7
9
8
20.0
19.4
14.7
13.2
5.3
6.2
0 107
0 108
0 450
0.426
0.025
0.024
5.03
2.24
1.98
4.33
4.80
3.01
0.32
0.01
0.01
30 mph
6 2/1
8
8
9
9
28.4
31.8
21.2
21.8
7 2
10.0
O.I 13
0.113
0.465
0.456
0.018
0 020
6 10
5.00
4 72
6 18
5 00
3.94
	
50 mph
(7.5/1)
(7)
(7)
(8)
(8)
(23.5)
(26.3)
(17 5)
(18 0)
(6 0)
(8.3)
(0 093)
(0.093)
(0.385)
(0 377)
(0 015)
(0 017)
(5 04)
(4.14)
(3 90)
(5 II)
(4 14)
(3.26)
!:::!
4.9/1
10
10
4
4
102.0
104.8
71.9
63.6
30.1
41.2
0.031
0.026
0.204
0.195
0.012
8.40
6.25
5 71
6.93
4.90
2 72
0.47
0.00
0.31
1(7 5/1)
•*
(7)
(7)
(3)
(3)
(66.6)
(68.5)
(46.9)
(41.6)
(19.7)
(26.9)
(0 020)
(0.017)
(0.133)
(0 127)
(0.008)
(5.49)
(4.08)
(3.73)
(4.53)
(3.20)
(1.78)
(0.31)
(0.00)
(0.20)
15 mph
8.1/1(7.5/1)
7 (8)
7 (8)
8 (9)
8 (9)


0.109(0 1 18)
0.115(0. 124)
0.433(0.467)
0.447(0.483)
0.018(0.020)
0.028(0 030)
6.46 (6.97)
7.63 (8.24)
5.79 (6 25)
13.16 (14.20)
11.86 (12 80)
10.65 (1 1.50)
0.36 (0.39)
0.01 (0.01)
0.01 (0.01)
15 mph
8/0/1(7.5/1)
491 (522)
93 (99)
21.1 (22.5)
20.3 (21.6)
13.3 (14.2)
9.6 (10.2)
7.8 (8.3 )
10.7 (11.4) oo
VD


1.92 (2.05)
2 50 (2.66)
2 33 (2 48)
0 54 (0 58)
0 49 (0 52)
0 49 (0.52,
0 28 (0.30)
0.04 (0.04)
0.17 (0.18)

-------
                                                                                 -  i
                                      90
References
1.  Kufta, R. J   "Stationary Source Testing."  Apollo Chemical Corp.
    September 1, 19"'2

2.  Weatherburn, M W.  "Phenol-Hypochlorite Reaction for Determination
    of Armenia"  Anal. Chem. 39_ 971, July, 1967

3.  Hauser, T.R   "tiethod for Analysis for Nitrate by Hydrazine Peduction"
    Water Research _L_ 1816, 1956

4.  West, P.W  and Gaeke, G.C.  "Fixation of Sulfur Dioxide as Disulfito-
    mercurate  (11), Subsequent Colorametric Estimation"  Anal. Chem. 28.
    1816, 1956

-------
                                    91
     B.5.   EXHAUST EMISSIONS FROM CATALYST-EQUIPPED ENGINES

           M  Malanchuk, N. Barkley, G. Centner, M  Richards,
                    R. Slater, J. Burkart and Y  Yang
Introduction

     Some early studies in the automobile industry have indicated that

oxidation-type catalysts in auto exhaust systems generated high levels of

sulfuric acid aerosol, as much as 0.1 gram of the acid per vehicle mile

It was hypothesized that the engine combustion process converted organic

sulfur compounds in the gasoline into sulfur dioxide, and that the dioxide

was oxidized by the catalyst to sulfur trioxide which reacted with water

vapor in the exhaust to produce sulfuric acid droplets.

     Therefore, unlike the constant engine speed runs as descirbed in the

previous article, cycling speed runs more nearly simulating automobile

operation in the streets were used for the animal exposure studies

Measurements of exhaust emission components were made to determine the

levels of such toxic components to which the animals in the studies were

exposed   The effective changes in exhaust composition were determined

when the catalytic converter unit was added to the exhaust system, and when

high-sulfur fuel was substituted for the reference Indolene gasoline

     Emission components present in relatively high concentrations were

monitored in much the same way as in previous runs

Sampling and Analytical Procedures

     The instrumentation and methods used for key components are summarized

in Table I   Atomic absorption spectrophotometry was used for trace metal

determinations in particulate.

-------
                                      92
         Table I.  AJZROMETRIC CHARACTERIZATION OF EXHAUST EMISSIONS
   Pollutant compone-vt    Analytic method   Automatic  Manual  Where determined*
Carbon monoxide  (CO)
Total hydrocarbons
 (THC) , as CH4
Nitrogen oxides
includes NO ard N02)
QI to 05 hydrocarbons
 (several compounds)

Cg to CIQ aromatic
hydrocarbons  (several
compounds)

Aldehydes, total
Particulates, total
mass

Particulate size
distribution
Aerodynamic

Photonomeric
Particulate compo-
sition

Ozone, "oxidant"
Nondispersive         X
Infra-red spec-
troscopy

Flame lonization      X
spectroscopy

Chemiluminescence     X        X
spec , coloruretry
using Saltzman
reagent

Gas chromatography             X
Gas chroroatography             X
MBTH according to              X
Hauser

Filtration gravimetry          X
Stage impaction                X
 (Anderson)
Photoelectronic                X
 (Royco)

Infra-red and ultra-
violet spectrophotometry       X

Chemiluminescence spec.
                                        EPM, EC



                                        EPM, EC


                                        EPM, EC
                                        EC
                                        EC
                                        EC
                                        EC
                                        EC
                                        EC
                                        EC
 *EPM - Exhaust or priirary exhaust   air mixture, EC - exposure chamber

-------
                                    93
     Particulate saitples were collected on pure quartz fiber filters



after early rneirbrane filters deteriorated from exposure to the high



reactivity of the collected sample of catalyst-treated emissions.



     Bubbler and unpmger samples of the atmospheres were used for



collecting ammonia- and sulfur-based gases.






Results



     Table II lists the concentrations of various engine exhaust components



measured during the series of studies of the catalytic converter system



Individual hydrocarbons measured by gas chromatography are shown in



Table III, the aromatic compounds were not measured after it was discovered



that those concentrations were so low in the catalyst-equipped system



atmosphere as to be near or below detection level.



     TAME J and TAME H (see Hinners report) were run under the same



engine operating conditions, i e  they were "duplicate" runs   However,



reference to the data of Table I shows considerable differences in values



between the two runs.  When TAME H was performed, the engine was probably



not fully broken in and the catalyst was quite new, the piping system for



conducting the emissions to the exposure chambers probably had not as yet



attained equilibrium conditions of surface exposure characteristics  (i e.



mainly deposition of particulate and adsorption of organic vapors) for the



new engine system.  TAME J, run at a later date, when a more stable system



should have been established, was considered to have the more accurate



atmospheric component values than TAME H.  Therefore,the concentration values



from TAME J were used for comparison to those from TAME I for the purpose of



evaluating the effect of the catalytic converter upon the make-up of the

-------
                                    94
auto exhaust emissions reaching the animal exposure chambers.  That comparison



is emphasized by the large percentage reduction values of several atmospheric



components due to the use of the Pt-Pd coated, pelleted catalyst converter



 (Table IV), and also seen m the greatly reduced concentrations of individual



hydrocarbons, TABLE III



     Since the dilution of the raw exhaust with clean air was not as great



in TAME J (8.7/1 as in TAME I (9.6/1), the reduction values listed in the



third column of Table IV were adjusted by a factor appropriate to the



differences in dilution values,  about ten per cent of the TAME J values,



to obtain the more accurate "normalized" values listed in the fourth column



     A barely detectible concentration of platinum, 0.029 yg/m3, was



measured in the diluted emissions of the animal exposure chamber



     A barely de-cectible concentration of platinum, 0 029 yg/rrH, was



measured in the diluted emissions of the animal exposure chamber - this



result, of course, for a system using a catalytic converter unit that was



quite new and that was shown to be adsorbing a large proportion of the



sulfur gases in the exhaust gases



     On the basis of an average flow of 1 W^/mm of raw exhaust produced



at a calculated average speed of 22 mph on the engine dynamometer, it was



estimated that the 0 029 yg Pt/m3 represented a loss of nearly 0 62 yg/Pt/mi



     If it is estimated that there is 0 04 troy ounce of the noble metal in



the catalytic unit (1 244 gm, i e ) then 0.5 x 10~4 per cent of the



platinum was lost per mile   Such a loss over 50,000 miles of operation



would mean a total loss of 2 5 per cent of the platinum originally present.

-------
                                                                                .. 1.
                                    95
Conclusions
     The incorporation of the oxidation-type catalyst m the exhaust system
resulted in drastic changes in the exhaust emissions
     a.  The effectiveness of the catalyst was revealed in the large
reduction of   carbon monoxide, total hydrocarbons and various individual
organic compounds (such as acetylene)
     b.  An almost total elimination of aldehydes was achieved.
     c.  In TAME I (without catalyst), the high value of particulate in the
irradiated atmosphere along with the low value of nitric oxide, NO, and
the measurpd presence of ozone indicated that much more photochemical
reaction of hydrocarbons occurred than in TAME J  (with catalyst)   That
activity was greater m the case of the olefins than in the acetylene, and
negligible for the aliphatics.
     d.  Gross evidence (color, weight stability) of the particulate in
TAME I, indicated that the nature of the sample was mainly organic   The
particulate in TAME J, on the other hand, was strongly acidic, liquid in
nature and lost significant weight upon standing   Analysis showed sulfate
to be the primary constituent   Such facts suggested the presence of sulfuric
acid as the major component in TAME J particulate.
     More detailed reports of sulfate and acid measurements are given in the
related articles, "Sulfate Emissions from Use of High-Sulfur Fuel, TAME-K"
and "Exhaust Emissions During Steady Speed Runs with the Catalytic Converter
in the Exhaust System."

-------
                                96
                             TABLE II.



ENGINE EXHAUST EMISSION VALUES FOR CATALYTIC CONVERTER SYSTEM STUDY


Exhaust Dilution Ratio
CO, ppm.
Exp. Ch

THC, ppm
Exp. Ch.

NOV, ppm.
x Exp. Ch.

NO, ppm. Exp. Ch.

NO,, ppm Exp Ch'
£
Aldehydes ppm
Exp. Ch

Methane, ppm
Exp. Ch

AHphatics
ppm C,-C5
Exp. Ch

Oleflns
ppm C2-C4
Exp. Ch.

Acetylene, Exp. Ch

Ozone, ppm
Exp. Ch

3
Particulate, mg/M
011 'd. Exh.
Exp. Ch


N-I
I

N-I
I

N-I
I
N-I
I
N-I
I

N-I
I
*
N-I
I


N-I
I


N-I
I
N-I
1

N-I
T
X

N-I
I
TAME-H
10-16 Sept.
'73
8/1

7
8

12
13

11.0
11.0
8 5
8.0
2.5
3.0



.....









.....








.....






1.86
2.05
TAME-I
10-16 Oct.
'73
9.6/1

651
559

110
95

11.9
5.1
6.7
C0.5
5.2
4.6

10.20
14.62





1.30
1.32


13.24
9.23
3.28
3.06

0.0
OA
«•»
1.08
0.69
3.19
TAHE-J
24-30 Oct.
'73
8.7/1

46
41

22
22

"12.9
12.6
11.1
9.6
1.8
3.0

0.08
0.10





0.61
0.58


0.89
0.79
0.03
0.03





1.02
0.96
1.09
TAME-K
14-21 Nov.
'73
9.5/1

40
38

18
18

12.6
11.2
10.8
9.7
1.8
1.5

0.18
0.11

6.53
6.13


0.44
* 0.39


0.91
0.82
0 04
0.04





5.97
6 53
5.85

-------
                             97
                         Table III.



      Gas Chroratographic Measurements of Hydrocarbons,ppm
Component
n-Butane
i-Butane
n-Pentane
i-Pentane
Acetylene
Ethylene
Propylene
Butane-1
Isobutylene
1,3-Butadiene
Methane
TAME-I
N-I
0
0
0
0
3
6
1
0
0
0

.61
.08
.20
.41
.28
.85
.81
26
.63
.41

0
0
0
0
3
5
0
0
0
0

I
.61
.08
.23
.40
.06
.10
.71
.08
.20
.08

TAME-J
N-I I
0
0
0
0
0
0
0
.30
.05
.09
.17
.03
.82
.04
Bid
Bid
Bid


0.29
0.05
0 09
0.15
0.03
0.72
0.04
Bid
Bid
Bid

TAME-K
N-I I
0
0
0
0
0
0
0



6
.21
.03
.05
.15
.04
.81
06
-
-
-
53
0.
0.
0.
0.
0.
0.
0.
-
-
-
6.
18
03
05
13
04
74
04



13
Bid - Below level of detection

-------
                      98



                 TABLE IV.



COMPARISON OF EXHAUST EMISSIONS. TAME-I AND -J

Exhaust Dilution
CO, ppm
Exp. Ch

THC,PPM
Exp. Ch

NO.ppm _
x Exp. Ch

NO, ppm Exp. Ch

N09,ppm Exp. Ch
C
Aldehydes, ppm
Exp. Ch

Aliphatlcs, ppm'
C4-C,
H ° Exp. Ch

Olefins, ppm
Exp. Ch

Acetylene, ppm
Exp. Ch

Ozone, ppm
Exp. Ch

Parti cul ate, mg/M
DiTd. Exh.
Exp Ch


Ratio

: N-I
I

N-I
I

N-I
I
N*I
I
N-I
I

N-I
I


N-I
I

N-I
I

N-I
I

N-I
I
3

N-I
I
TAME-I
10-16 Oct.
'73
9.6/1
t
551
559

110
95

11.9
5.1
6 7
0.5
5 2
4.6

10.20
14 62


1.30
1.32

13 24
9.23

3.28
3.06

' 0.0
0.4

1 08
Q.69
3.19
TAME-J
24-30 Oct.
'73
8.7/1

46
41

22
22

12.9
12.6
11.1
9.6
1.8
3.0

0 08
0 10


0.61
0.58

0 89
0 79

0 03
0.03




1 02
0.96
1 09
% Conc'n
Reduction
I-vJ


91.7
92.7

80.0
76.9








99.9
99.9


53.1
56.1

93.3
91.4

99.1
99.0







Normalized
% Reduction
Value


92.4
93.3

81.9
79.0








99.9
99 9


57.7
60.0

93 9
92.2

99 2
99 1








-------
                                   99
  B.6.   SULFATE EMISSIONS FFOM USE OF HIGH-SULFUR FUEL, TAME-K
         M. Malanchuk, N. Barkley, G. Contner and M. Richards
Introduction
    To supplement the data on exhaust emissions from catalyst-equipped
systems studied in which regular Indolene fuel was used, in study TAME-K
a high-sulfur content gasoline was substituted   In  that  study  a
quantity of thiophene was added to the reference Indolene fuel to provide
a sulfur level twice as great, 0 10 percent, as that normally present.  A
more detailed analysis of the particulate was made m order to establish
the concentration of sulfate and of the expected high acidity.

Experimental Procedure
    The high acidity of the aerosol produced in the exhaust emissions from
oxidative catalytic equipped systems was indicated in preliminary runs of
the 350 C I D  Chevrolet engine.  Aerosol collected from an exposure chamber
onto an electrostatic precipitator plate was a water-white liquid and proved
to be very acid by pH-paper test.  Also, membrane- type filters used to
sample the exposure chamber atmospheres remained an undisoolored white and
deteriorated upon standing several hours, sometimes to the point of breaking
into fragments.
    Therefore, quartz fiber filter material (Pallflex type 2500-QAO) was
used to collect aerosol samples at all the sampling points of the piping
system.  Every filter was weighed immediately after sampling   Some were
weighed again after several hours or overnight standing to allow for
equilibration with the room atmosphere and stabilization of the sample
weight.  Others that were used for aerosol acidity measurements were  (total

-------
                                   100
or portions of) then placed without delay after the early weighing into a


beaker of a specified quantity of distilled, deionized water   At


least 30 minutes was allowed for water extraction of the sample before


the initial measurements of conductance and of pH were made   Final


measurements of ion concentration were made 16-40 hours later.


    The aqueous extracts were subsequently used for determination of


sulfate  (SO."), of airmonium (NH4+), and of nitrate (NC^")   Sulfate was


analyzed by the barium chloranilate method '^ ', ammonium by phenolhypochlorite


reaction,^' and nitrate by hydrazine reduction.^ '


    Alternate analytical methods were used in some cases to confirm the


concentrations determined.  A nephelometric method was adapted to sulfate


measurement, and ion specific electrode applied to ammonium measurement.


Those methods had lurated use for the present group of samples because of


sensitivity and reproducibility requirements.


    Gas samples for nitrate - and for ammonium - producing components in


the atmospheres were collected by absorption into distilled water or into


a weak acid solution   For separation of SC>2 from SO-j, the procedure   /of


drawing the gas through a bubbler containing isopropanol and then through


hydrogen peroxide, ^0-, solution or through tetrachlormercurate, TCM,


contained in two follow-up bubblers was applied   The ammonium and the


nitrate product concentrations were determined by the same methods cited


for the aerosol analysis.  The SO^ sulfate in the first bubbler and the


SC>2 sulfate in the peroxide bubblers of the three bubbler-train were analyzed


by the chlorarilate method   The SO^ m the TCM absorption liquid was analyzed

                          (4\
by the West-Gaeke method.v '

-------
                                                                              -  i

                                   101





    The animal (population) occupancy of an exposure chairiber was noted by


the number of cages and activity wheels   A cage might have three adult


rats, or a litter of recently-born rats with their mother, or a group of


four hamsters   An activity wheel was associated with a single mouse.  A


record of the animal occupancy was kept for comparison with levels of


ammonium and acidity of the particulate in the atmosphere of the exposure


chamber.



Results


    A condensation of the analytical values for several ionic components


is given in Table 1.  Gas and particulate values are listed for the


diluted atmosphere sampled immediately after the exhaust pipe and for the


atmospheres in each of several exposure chambers.


    Total particulate for TAME-K is shown in the fourth column of values


of Table 1 of the article, "Exhaust Emissions from Catalyst-Equipped Engines."

                                                                      o
The sulfate value for the diluted exhaust pipe emissions, 46.5 y mol/fa , m


Table 1 of this article represents almost 75 per cent of the weight of the


total particulate, 5.97 mg/M .  Considering the very highly acid nature of


the aerosol (particulate), one must assume that the sulfate is most likely,


totally, sulfuric acid.  On the basis of an average emissions volume generated


by the engine of 1 M /mm  and an average of 22 m.p.h  equivalent road


speed for the engine operation (California cycle), the total particulate


value of the diluted exhaust was calculated as approximately 0.16 gm/mile.


    Actually, the acidity is so high that at the present tune it is un-


accountable in terms of the amount of aerosol reported   Further work is


required to explain this phenomenon   The point should be made that those

-------
                                   102
filter samples which were not used in the extraction scheme did lose, after

standing overnight, as much as 50 per cent of their weight sometimes.  It

was this final weight upon which the total particulate calculations were

made.

    Although values are given for  (NH.+) and  (NO^") in the gas phase,

Table 1, it is assumed that the analytical procedures are accounting mainly

for ammonia  (NH3) and for the contribution of nitrogen dioxide  (NO2) to

these ion concentration values.  The SO^ in most cases is probably a fine

mist of acid aerosol in the submicron size range of 0 1 micron or less.

    The particulate analyses of Table 1 show that the aerosol in the

diluted exhaust pipe emissions (first column) is a highly acid sulfate.

The aerosol m exposure chamber #15 (second column) is non-acidic and

contains ammonium  (2^K^+) nearly quantitative to the sulfate  (804") measured.

It is not unreasonable to think, therefore, m terms of the acid such as

sulfuric acid H2SC>4 or of the salts such as ammonium sulfate  (NE^^SO^

The amount of sulfate measured in the exposure chambers themselves represented

an average of at least 15 per cent of the sulfur present m the fuel.



References

1.  Kuffa, R  J   Stationary Source Testing.  Apollo Chemical Corp  Sept  1972

2.  Weatherburn, M  W.  Phenol-Hypochlorite Reaction for Determination of
    Ammonia   Anal  Chem  39_  971, July 1967
                        \
3.  Hauser, T. R   Method for Analysis for Nitrate by Hydrazine Reduction.
    Water Research !_  205-216, 1967

4.  West, P. W. and Gaeke, G. C   Fixation of Sulfur Dioxide as Disulfito-
    mercurate  (11), Subsequent Colormetric Estimation.  Anal  Chem  28_  1816,
    1956.

-------
                 Table 1



K - Atmospheric Component Concentrations,

GAS



PARTICULATE




(NH4+)
(N03-)
(S04=)
(S02)
(2NH4+)
(N03")
(S04=)
(2H+)
Exh.Pipe
Emissions
Diluted

-


1.6
0.2
46.5
170.6
Exp.Ch#15
Irrad.
15-10 cages
0 4
7.3
15 0
2.0
38.6
1.2
32.8
0.2
Exp Ch #18
Non-Irrad.
2-0 cages
0.1
2.4
28 0
0
4.6
0
34.3
122 9
Exp.Ch.#6
Non-Irr.
No Animals




1.1
0
35.0
109.9
Exp.Ch.#22
Irrad.
4-2 cages
+ 6 wheels
0.22
8.70


7.9
0
34.2
54.7
Exp.Ch.#24
Non-Irrad
2 cages
+ 6 vheels
0.33
6.25


21.9
0.2
31.3
-
Exp.Ch.#23
Non-Irrad.
12 cages




41.2
0
25.5
0
Exp.Ch.#17
Irrad.
6 wheels




11.4 S
0.6
31.3
97.0

-------
                                     104
B.7.   COMPARISON OF THE BIOLOGICAL EFFECTS OF ACUTE EXPOSURE TO WHOLE
       EXHAUST EMISSIONS FROM AN AUTOMOBILE ENGINE EQUIPPED WITH AND
                WITHOUT A NOBLE METAL CATALYTIC CONVERTER

          D. Hysell, W  Moore, L  Garner, D. Cmehil, S. Neiheisel,
                      H. Ball, Y  Yang and J  Stara
      This study was undertaken to compare the biological effects which

 might result from an acute exposure to catalyst treated exhaust  (TAME J)

 vs. nontreated exhaust  (TAME I).  The exposure facility and emission

 chemistry are discussed in detail in other reports (See Hmners, et al.

 and Malanchuk et al ).  The experimental animals included young adult male

 rats and hamsters, lactating female rats and their sud- Img young   Biologic

 parameters studied included mortality, body weight, hematology and blood

 chemistry, and pathology.


 Body Weight and Mortality

      The animals in this portion of the study were exposed to treatment

 atmospheres 24 hrs/day for 7 days   There were 7 treatment groups consisting

 of clean air (CA), irradiated exhaust  (IH), and non-irradiated exhaust  (RH) for

 both TAME I and J and a carbon monoxide control (CO)  with CO levels comparable

 to those encountered in the emissions produced in TAME I   Each treatment group

 consisted of 10 lactating female rats and their 2-week old litters (10 suckling

 rats/litter) which were weighed at the beginning and end of the study   Each

 treatment group was examined several tunes daily for possible mortality

      The results indicate that the IH and RH treatment groups in TAME I showed

 the most severe changes in weight of lactating female  (Fig. 1) and infant

 rats  (Fig. 2), ard survival rate of infant rats (Fig. 3)   There appeared to

 be minimal changes in infant survival in the high CO group  (Fig  3).  There

-------
        TAME I (no catalyst]
-CO
    350
GO
s
ca
1,250
QQ
   200
    150
    100
           j	I	I	I
                                     I	I	I	I
TAME J (catalyst)
                                                                                             RH

           01234567
                          Days of Exposure
                     01234567
                                   Days of Exposure
                              FIGURE 1,    BODY WEIGHT OF LACTATING FEMALE RATS

-------
    55
    50
    45

 E
 eg
j^  35

f  30
^
    25

    20

    15
    10
     5
o
OQ
        TAME I (no catalyst]
                                                            TAME J (catalyst]
      01234567
                      Days of Exposure
                                                          01234567
                                                                           Days of Exposure
                                 FIGURE 2,    BODY  WEIGHT OF INFANT RATS

-------
 TAME I (no catalyst)
   100

    90

    80
"r5

I  7°
^  60

    50

    40

    30

    20

    10
           i     i     i
                                     IH
                                    ....
                                                          TAME J (catalyst)
                                                                                         IH&RH
                                                                                         CA
0123456
              Days of Exposure
                                                              01    234567
                                                                           Days of Exposure
                                FIGURE 3,   SURVIVAL OF INFANT RATS

-------
                                    108
were no apparent effects in TAME J with the possible exception of weight



loss in IH and EH lactating female rats (Fig  1).



Henatology and Blood Chemistry



     For this portion of the study, adult irale rats were maintained m six



treatment atmospheres  (CA, RH, IH for both TAME I and J) 24 hrs./day.  Five



animals per group were removed on days 1-5, anesthetized and exsanguinated by



abdominal aorta catheterization.  The clinical laboratory determinations



included hemoglobin  (HB), hematocrit  (KCT), red (EEC) and white blood cell



(WBC) counts, platelet counts, reticutocyte counts, white blood cell



differential, partial thromboplastin time (PIT), prothrombin tune  (PT),



fibrinogen determination, total serum protein, alkaline phosphatase, SCOT,



SGPT, blood urea nitrogen  (BUN), Na, K, Cl, and Ca.  Standard laboratory



procedures were used in these determinations   The results are presented



in Tables 1 and 2.



     Examination of the results indicates that in TAME J, the only statistically



apparent treatment effect was an increase in total serum proteins in exhaust



exposed animals.  In TAME I there were statistically significant treatment



effects in both raw and irradiated exhaust exposures on total protein, platelet



count, BBC and WBC counts, white cell differential, alkaline phosphatase,



hemoglobin, hematocrit, partial thromboplastin time, SCOT and SGPT levels



The irradiated exhaust exposure also produced a treatment effect on levels



of BUN fibrmogen.  It should be emphasized that while the treatment effects



were statistically significant, the data may not be physiologically significant



They do, however, indicate a potential hazard to certain organ systems with



prolonged exposure.  In explaining the effects, the RBC related changes and



alkaline phosphatase levels could relate to the high levels of CO, the WBC

-------
                                    109
                           TABLE I.

        Treatment Mean Values for Selected Heraatologic
                    Parameters in Male Rats

KBC/otm (x 106) •


WBC/otm (X 103) :


Platelets/arm (x 106)


Lyrnphocyte neutraphil
ratio

HB (gin %) •


ICT (%).


CA*
RHb
IH c
CA
RH
IH
CA
RH
IH
CA
PH
IH
CA
KH
IH
CA
RH
IH
Without
catalyst
7 074
7.616
7.784
9.1
11.9
12.0
0.95
1.07
1.10
5.3
1.7
1.0
14.9
16 5
16.7
41.6
46.6
47.4
With
catalyst
7.141
7.004
7.073
9.3
9.0
8.7
0.93
0.97
0.92
5.3
5.1
5.3
14.6
14.7
14.5
40.8
41.0
40.1
a:  clean air control atmosphere
b:  Nonirradiated exhaust atmosphere
c:  Irradiated exhaust atmosphere

-------
                                       110
                             TABLE  II.
         Treatment Mean Values for Selected Blood Chemistry
                      Parameters in Male Rats

Total protein, (gm %)
Alkaline phosphatase
(Int. t/nits)
SCOT (R-F Units)
SGPT (R-F Units) :
Fabrinogen (mg/dl) .
BUN (mg %) .
PTT (seconds) •
CA a
RHb
CA
RH
IH
CA
RH
IH
CA
RH
IH
CA
RH
IH
CA
RH
IH
CA
RH
IH
Without
catalyst
6.0
6.3
6.8
79.1
54.2
40.8
161.6
185.3
196.7
48.5
60.5
53.7
170
165
220
23.8
21.0
28.3
19.9
21.7
22.4
With
catalyst
5.8
6.1
6.0
80.9
91.4
83.4
169.7
174.4
174.8
40.0
40.7
42.0
175
175
170
22.5
21.8
21.4
19.9
19.3
19.2
a*  Clean air control atmosphere
b:  Nonirradiated exhaust atmosphere
c:  Irradiated exhaust atmosphere

-------
                                    Ill
changes would suggest a rather severe acute uiflanmatory response,  the



other changes relate to hepatic and/or renal dysfunction.





Pathology



     Tissues from the adult male rats used in the Hamatology and Blood



CHemistry Section of this study were saved m 10% formalin for pathology.



]ji addition, an equal number of adult male hamsters were exposed and



tissues saved for pathology   Sections of hematoxylin and eosm stained



]ung, liver and kidney were examined microscopically for abnormalities.



     In TAME I, 2 of 5 IH hamsters shewed acute inflammatory pulmonary



changes after one day exposure.  The lesion was characterized by an



infiltrate of polymorphonuclear neutraphils  (PMN) into alveoli at the



level of the terminal bronchioles   After 2 days, the lesions consisted



of prominent macrophage and EMN exudate in alveoli at the level of the



terminal bronchioles plus a patchy acute purulent bronchiolitis and



pneumonia with some ulceration of bronchiolar epithelium.  By the end of



5 days, the IH animals had a subacute purulent bronchiolitis and pneumonia



(Fig. 4).  The alveoli at the level of the terminal bronchioles had



thickened septae with some crescentic epithelial caps.  Many were plugged



with an admixture of fibrin, macrophages and PMN.

-------
                                112
             -;%&»
              C 4) ""•
         Figure 4.  Subacute purulent bronchiolitis and pneurtoraa in
                   hamsters exposed to irradiated exhaust in TAME I
                   for 5 days
     In the RH hamsters,  the pulmonary changes were not apparent until day 2,
and thoughout the study the changes were confined to the alveoli at the level
of the terminal bronchioles.  The lesions were not as severe as in the IH group
and tended to be more proliferative than exudative.  By the end of 5 days, there
were some alveoli with thickened septae with an increase in alveolar macro-
phages (Fig. 5).

-------
                      113
Figure 5.  Pulmonary changes in hamsters e>q?osed
           5 days to non-irradiated exhaust in
           TAME I.

-------
                                    114
      In both the PH and IH hamsters from TAME I, no treatment related

changes were noted in liver and kidney until 5 days of exposure.  In

the IH group, all 5 animals showed vacuolar change  (possibly lipidic

degeneration) in hepatic parenchymal cells (Fig. 6).  Two FH annuals

showed similar changes.
        Figure 6.  Cytoplasrnic vacuolar change in livers frcm
                   hamsters exposed 5 days to exhaust in TAME I.

-------
                                    115


Three of the IH animals also had sutular vacuolar changes in renal

tubular cells  (Fig. 7).
         Figure 7.  Renal tubule cytoplasmic vacuolar change in
                    hamsters exposed 5 days to irradiated exhaust
                    m TAME I.
     Pulmonary changes noted in TAKE I rats paralleled those noted m the

hamsters but were not apparent as early in the study and were not as severe.

Extramedullary heiratopoeisis was present m the livers of the IH and RH rats

by day 4 probably as a result of the high CO levels.

-------
                                     116
     Tissues from TAME J have not yet been examined.  For the purpose of
coinparison, TAME H  (identical to TAME J in design) results are included.
No pulmonary changes were noted in IH and RH rats.  The changes noted in
hamster pulmonary tissue were rather mild and mainly present in the IH
group only after 2 days of exposure.  The lesion was confined to the
alveoli at the level of the terminal bronchioles and consisted of an
increase in macrophages, thickened septae and some crescentic epithelial
caps.  The changes were rather typical of lesions ascribed to exposure
to N02-  No changes in liver or kidney were noted.

-------
                                    117
         B.8.  EFFECT OF EXHAUST EMISSION FROM CATALYTIC CONVERTER
                         ON ARYL HYDROCARBON HYDROXYIASE

             L. Hall, I. Washington, J. Adams, K. Campbell and Y  Yang


Introduction

    Chemical carcinogenesis is of considerable concern in relation to

exposure to environmental pollutants.  Due to the association of microsomal

metabolism with carcinogenesis the effect of catalytical modified auto

exhaust on aryl hydrocarbon hydroxylase  (AHH), one of the mixed function

oxidase  responsible for the biotransformation of some known potent

carcinogens was determined

METHODS

    Male Syrian hamster retired breeders [>8 mos. old] were exposed

continuously for five days to automobile exhaust using the system described

by Hinners et al   (ETRL)   These exposures were carried out in the three

studies, TAMEs I, J, K, described elsewhere in the Catalytic Report

    In each study after five days continuous exposure to either clean

air  (CA), nonirradiated (MI), or irradiated  (I) exhaust, the hamsters were

sacrificed with pentobarbital (IP), exsanguinated, and the puncture, and the

lungs were removed in_ toto and quickly immersed in cold saline (4°C)   The

lungs from three animals were then trummed of bronchi and connective tissue,

weighed,and placed in cold 0.15 M KC1 for homogenization   Aryl hydrocarbon

hydroxylase was assayed as described by Dixon et al *  ' using a homogenate

concentration of 25 mg/ml and an incubation period of 60 minutes.  The

results are expressed as the fluorescence equivalent to picomoles of

3-hydroxy-benzo pyrene formed/min/mg tissue

-------
                                  118
RESULTS


    Table 1 shows the hamsters ' lung AHH activity following exposure to


either clean air, nonirradiated, or irradiated exhaust in TAMEs I, J and K.


    Statistical analysis of the data showed that significant enzyme reduction


occurred as a result of exposure to both nonirradiated and irradiated


atmospheres in the reference study  (TAME I - without catalyst)   Exposure


to catalyst-modified exhaust (TAKE J) resulted in a depression of mixed


function oxidase (MFC) activity in both experimental groups, but statistically


significant (p =  05) depression was noted only in the group exposed to


irradiated exhaust   The use of high sulfur fuel with the catalyst (TAME K)


produced a depression following exposure to irradiated exhaust, although

                                                             <
the decrease did not reach statistical significance at the p = / 05 level.


    Due to the innate variability in enzyme activity of control animals


berween experiments, the data were normalized to percent of control for


further comparison between studies   Following exposure to nonirradiated


exhaust a reduction in AKH activity of 52, 12 and 0 per cent was seen m


TAMEs I, J, and K, respectively   Following irradiated exhaust exposure, the


depression in TAME I was 55 percent, 28 percent in J, and 18 percent m K


Duncan's multiple range test revealed that TAMEs J and K effects were


similar and different from TAME I


    Table 2 shows the lung weight/body weight ratios for the three studies


Only in TAME I (without catalyst) was a significant increase in the ratio


noted   The severity of this exposure was also evident in the mortality of some


of the other experimental animals, which did not occur in the other studies.

-------
                               119
    Table 1.  Aryl Hydrocarbon Hydroxylase  in Hamster Lung
Clean Air
Non-irradiated
Exhaust
Irradiated
Exhaust
I
0.01192
0.00579*
0.00529*
J
0.01789
0 01671
0.01352*
K
0.01134
0.01150
0.00974
1  Activity expressed as equivalent to the formation of
   3-hydroxy-BP in piconnoles/nan/nig tissue
*  Significantly different from control at p'=  .05

-------
                                  120
IUU
90
80

70

g 60
£
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0
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oc
LU
a.
30
20

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*















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t— 4
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-------
                                 121
Table 2.  Lung Weight/Body Wsight Ratio in Hamsters Exposed to Auto Exhaust
TAME
I
J
K
n.
12
12
12
CA
.536
.505
.521
Non-Irrad.
.696*
.498
.531
Irrad
.725*
.492
.528
   * Significantly different from control at p = .05

-------
                                    122



DISCUSSION


     TAME I, the reference study, shewed profound toxicological and biological


effects as manifested by death, lung weight/body weight ratio changes, and


depression of AHH activity.  However, no gross effects were noted in TAMEs J


and K.  Ozone  (0.4 ppm) and N02  (4.6 ppm) was measured m the exhaust chamber


atmospheres in TAME I.  Palmer et al. ^ ^' noted a 33 per cent decrease in


hamster lung AHH activity following a three-hour exposure to 0.75 ppm ozone,


but no effect on bronchial AHH was noted for N02 concentrations up to 50 ppm


for three hours.' ^'  Thus ozone probably had significant effect on AHH


activity in TAME I.  The contribution by the other exhaust components, many


with known biological effectiveness, is not known.  No ozone was detected,


and no significant change m N02 concentration was found in TAME J or K


which would account for the depressed AHH activity.  The biological effective-


ness as reflected in AHH activity/ therefore, may reside in the organic


fraction of the atmospheres.  Further work is necessary to resolve this problem.


     Two additional comments are needed.  The lack of statistical significance


in the AHH depression in the NI atmosphere of TAMEs J and K and in the


irradiated exposure in TAME K is thought to be due to the small sample size


(4/treatment) rather than to lack of effect.  Depression of AHH activity has


been a consistent finding following exposure to auto exhaust in several


studies (ETKL Annual Report, 1972).


     The apparent lack of AHH induction is curious, since Holt and Keast  ^'
                         \

found induction of AHH in the lungs of mice exposed to cigarette smoke,


which contains several components such as N02/ aldehydes and polycyclic hydro-


carbons, also present in the exhaust.  The significance of the depression and


lack of induction is not clear, but due to the association of this enzyme

-------
                                    123
system with carcinogenesis it seems important to determine the impact of

effects on aryl hydrocarbon hydroxylase and its relationships to cancer

initiation and promotion.

     In summary, the use of the catalytic device significantly reduced

but did not eliminate the depression of lung aryl hydrocarbon hydroxylase

by exposure to auto exhaust   Whether this residuum of biological

activity in catalytic modified exhaust reflects the lower part of the dose

response spectrum, or the formation of potent new chemical species, is not

yet clear   Additional research is necessary for insight into this aspect

of catalyst evaluation.
     AOOX3WLEDGMENT

          We acknowledge with gratitude the sample of 3-hydroxy-benzpyrene
     from Dr. H.V. Gelboin, National Cancer Institute, that was used to
     standardize our work.
References

1.  Dixonetal   Cancer Pes. 30_  1068, 1970

2.  PaJjter et al  Cancer Res. 31^  730, 1971

3.  Arch, Environ. Health 25_  489, 1972

4.  Holt and Keast, Expenentia 29_  1004, 1973

-------
                                    124
B.9.   BIOCHEMICAL EFFECTS OF EMISSIONS FROM AN AUTOMOBILE ENGINE
                 WITH AND WITHOUT CATALYTIC CONVERTER

       S. D. Lee, V. N. Finelli, L. McMillian, and R. M. Danner
     As a part of the toxioologic studies of automobile engines with and

without catalytic converters, the biochemistry group, in collaboration

with Dr. Finelli of the Department of Environmental Health at the University

of Cincinnati, has studied early biochemical alterations in rats exposed

to auto exhaust emissions.

Materials and Methods

     Experimental Animals - Each exposure experiment consisted of thirty

female Sprague-Dawley rats, each group weighing approximately 200 grains,

divided into three groups of ten animals   Clean Air  (CA), non-irradiated

(N-I), and irradiated (I).

     Exposure Conditions - The exposure system has been described by

Hinner et. al., earlier in this report.  The concentrations of major

exhaust components in the exposure chambers were also described in a

earlier report by Malanchuck, et. al.  Temperature and humidity in the

exposure chambers were kept constant throughout the experiment at 22°C

and 50 percent relative humidity respectively.  The exposures were conducted

24 hours a day, for 7 consecutive days.  Two animal exposure experiments

were conducted using the exhaust from the same engine with and without

the catalytic converter.  In addition, an experiment was performed by

exposing a group of animals to carbon monoxide alone  (experiment CO) at

a concentration of 575 mg/m3  (500 ppm) which approximately reflects the

carbon monoxide level observed in exposure chambers when emissions from

the engine without the catalytic converter was tested.

-------
                                   125
     The following parameters were determined:  hematocrits, serum



latate dehydrogenase  (LDH), serum glutanic oxaloacetate transaminase



(SCOT), and serum lysozyme.  Serum IDH and GOT were determined by



using DADE reagent sets (American Hospital Supply Corp., Miami, Florida,



white lysozyme was assayed with Worthington kit (Wbrthington Biochemical



Corp., Freehold, N. J.).  Blood samples were obtained from animals by



tail vein puncture.



Results and Discussion



     Figure 1 shows the drastic effects of the exposure to emissions from



the engine without the catalytic converters on the hematocrit.  At the end



of the 7-day exposure, very high hematocrit levels were observed in the



experimental animals, 62.3 + 1.5 percent for N-I and 66.2 + 0.5 percent



for I, as compared to a normal value of 43.2 + 0.9 percent for the clean



air group.  During a recovery period of 3 weeks, the hematocrit values



were obtained weekly and a gradual return to normality was seen in the



animals of both N-I and I groups.  The animals exposed to carbon monoxide



showed a average hematocrit of 62.5 + 0.9 which is equal to the value



found for N-I group in the experiment without converter.



     The hematocrit in the animals expsoed to emissions from the engine



when equipped with the catalytic converter did not differ from control



values.  From the above data it seems that the elevation of the hematocrit



is due to the carbon monoxide concentration in the exposure chambers.  The



levels of carbon monoxide in N-I and I groups in the experiment without



the catalytic converter were 551 and 559 ppm, respectively, while for



N-I and I with the catalytic converter the carbon monoxide levels were



reduced to 46 and 41 ppm.  The increased hematocrit may be due to poly-



cythemia and/or dehydration.  Total serum protein or albumin analyses

-------
                                  126
      
-------
                                   127
were not obtained and therefore the occurence of dehydration cannot be



confirmed; however the data collected from histological examination of



the experimental animals, presented in a report by Hysell et. al.,



revealed the presence of a large numbers of reptured red blood cells



which may indicate a polycythenic response.



     In order to assess organ damage in exposed animals, the activity



of LDH, GOT, and lysozyme in serum was assayed.  These intracellular



enzymes are characteristic of appropriate organs and an increase of



enzymatic activity in serum would indicate presumably a leakage of



enzymes from injured cells.  Serum GOT was not significantly elevated



in any of the exposed animals, this would indicate that neither liver



nor heart were damaged by exposure to various types of emissions and to



carbon monoxide.  Serum LDH was elevated in the anmals exposed to



emissions from engine without catalytic converter.  Figure 2 shows that,



at the end of the exposure period, the animals from both N-I and I groups



presented approximately 200% increase in serum LDH activity.  In the



recovery period, while the N-I group values tended to return to normal,



the I group values presented an unexplained erratic behavior, moreover



we cannot explain the low value obtained in the third week for the CA



group.  No significant changes in LDH activity were observed in the



experimental animals when the converter was used and in the animals



exposed to 00.  Serum Lysozyme activity was not assayed in the experiment



conducted without catalytic converter, however, in the experiment with



converter, the exposed animals did not show any statistically significant



elevation.  From the above preliminary results it appears that the target



organs of the toxic components present in the emissions from engine



without catalytic converter are probably the lungs and/or kidneys.

-------
                                    128
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Fig. 2     Serum LDH values fron animals exposed to automobile
           emissions without catalytic converter.

-------
                                    129
     It can be concluded that the introduction of catalytic converters

into the automobile exhaust system, not only has reduced the levels of

certain exhaust constituents but has effectively decreased or eliminated

biological effects studied.
Reference

1.  Stara, J. F. and R. Hinners   Toxicology of Atmospheric Pollutants

    Associated with the Use of Automobile Catalytic Converters, Annual
    Report, Environmental Research in 1973, U S. Environmental Protection
    Agency, National Environmental Research Center, Cincinnati, Ohio

-------
                                     130
B.10.   EXPOSURE OF MATERNAL, PREGNANT, AND NEWBORN RATS TO EXHAUST FROM
              MODERN ADTCMBIIE ENGINE WITH CATALYTIC CONVERTER AND
                        OTHER EMISSION CONTROLS (TAME J)

                 K. Canpbell, E. George, L. Hall and J. Stara
       Toxicity to newborn and pregnant rats of diluted exhaust from a proto-

   type automotive engine system including oxidative catalytic converter was

   evaluated by two experiments in the TAME J study.  Details as to test atmo-

   sphere generation and characterization are provided in preceding reports

   (See Hinners et al., Malanchuk et al.).  Similar studies were performed in

   TAME K (high sulfur fuel used) but data are not sufficiently complete to

   permit a comparative evaluation of the sulfur effect.


   Experiment A

       Ten litters of day-old Charles River COBS suckling rats and their

   dams were exposed for six days in each of three atmospheres   purified air

   (controls), nonirradiated (NI) exhaust, and irradiated (I) exhaust.

   Dams and litters were weighed and pups were counted when placed in exposure

   (Day 0),  when removed to clean air (Day 6), and subsequently while housed

   in purified air  (on Days 11, 15 and 19).  On Day 19 the young were 20

   days of age and this was designated as "weaning date."  Maternal body weight

   and infant survival and growth of treated groups were compared to control

   values.

       Results, which are summarized in Table 1, are preliminary in the sense

   that the data has not as yet been subjected to statistical analysis   Neverthe-

   less, the largest contrasts between treated and control means are 7 per cent

   for maternal weight gam deficit (for Day 6), 3 per cent for infant growth

   deficit,  and 8 per cent for infant survival to weaning, all in NI.  Without

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Table 1.   Maternal Body Vfeight and Infant Growth and Survival in Rats Exposed to
           Catalytic Converter-Treated Automotive Emssions m TAME J, Experiment A.
                                                  Treatment
Bioef feet Criterion (Clean Air (Control)
Maternal Lactating Rats:
Pre- treatment body weight,
grrs (mean)
Mean fraction of pre-treat-
nent. body weight Day 0
Day 6 (End of Expos.)
Day 11
Day 15
Cay 19 (Weanling)
Infant Growth:
Pre- treatment body weight,
gms (mean)
Fean fraction of above
Eiy 0
Lay 6
Day 11
Day 15
Day 19
Infant mortality & Survival:
Original No.
No lost, % survival to age 7 Days
No lost, % survival to weaning
275.1
1.00
1.163
1.270
1.245
1.283

8.76

1.00
2.139
3.337
4.257
5.708

100
0, 100
1, 99
Non- Irradiated

292.0
1.00
1.085
1.252
1.172
1.262

9.09

1.00
2.138
3.285
4.112
5.666

99
1, 99
8, 91.9
Irradiated

310.0
1.00
1.105
1.208
1.212
1.226

8.74

1.00
2.191
3.310
4.252
5,707

98
0, 100
0, 100

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                                  132


additional data by which a consistent pattern might be discerned as a

basis for interpretation and validation, these relatively snail differences

are suspected as being neither statistically* nor toxicologically significant

Most infant deaths in NI  occurred between 16 and 20 days of age.  The

cause of these was not clear, and they are not as yet considered as clearly

treatment-related   It would thus appear, at least tentatively, that despite

the low exhaust dilution ratio, the test atmospheres from this engine and its

emission controls were not sufficiently harmful to be detected by the

methods used   It should be noted that in the previous study (TAME I)

in which the catalyst was not used, there were obvious body weight deficits

and morbidity in exposed anomals, suggesting a oeneficial effect of the

catalytic converter m regard to the latter criteria.


Experiment B

    Twelve Charles River COBS female rats pregnant 15 days were exposed

for 6 days to each of 3 atmospheres   purified control air, nonirradiated

(NI) exhaust, and irradiated (I) exhaust, as with Experiment A   After

exposure, all were transferred to brood cages and housed in clean room air.

Body weight of the maternal animals were recorded when they were placed

in to exposure (Day 0), when removed from exposure to room air  (Day 6), and

subsequently on days 11, 15, 19, 25 and 29.  Offspring were counted at

parturition following exposure  (Day 8), and weighed and counted on days

11, 15, 19, 25 and 29. 'On Day 29 the offspring were 20 days of age, this

date was designated as the weaning date   Maternal body weights and infant

survival and growth in exhaust-exposed groups were compared to those in the

control group.
*Subsequent statistical analyses indicated that the infant survival on NI was
significantly less than in CA and IR, however, this suspicious pattern was not
observed in a subsequent experiment  (TAME K)   The weight-data analyses suggested
no significant treatment effects

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                                  133
    The resulting data, which are summarized in Table 2, and which have

not yet been statistically analyzed, are tentatively interpreted as in-

dicating no significant effect by either treatment (NI or I)  on maternal

body weight, litter size, or infant survival or growth.  The largest

contrast noted was a mean 9% smaller litter size in NI, but litter size

varied considerably in all groups, and the mean I litter size was 3.5%

larger than control.  The largest single contrast m maternal body weights

was -4.5% in I, and in infant body weight was +8.2% in NI.  Without

additional data to establish a clear pattern it is doubtful that the

pattern and magnitudes of mean differences observed in this experiment are

statistically or toxicologically meaningful.   Since this experiment was

not performed in TAME I, a comparative evaluation of converter-no converter

emission toxicity en these criteria is not yet possible, but it is speculated

from other observations in TAME I that effects might well have been demonstr-

able with this system.
 + Subsequently completed statistical analyses indicated no significant
   treatment effects on maternal or infant body weights or on infant
   survival in this experiment

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                             134
Table 2.   Maternal Bcdy Vcaght and Infant Ocwth and Survival
           in Rats After Jn Dtoro Exposure to Catalytic Converter-
           Treated /utcnotive Emissions in TAMC 3,  Experiment B

fioeffect Criterion

Maternal rats — Body VJsight
lilln body weight (gir) and
faction of initial (pre-
e>pos) weight. N=12
^ay 0 (Pre-e>cposuLe)
Day 6 (Post-exposure)
•ay 11 (3 day after partur)
Day 15
fay 19
Day 25
•ay 29 (v;eanmg)
Lo^-ng orrspring —
I'ftn body \ eigit (gm) and
fraction of 1st weight
(age 3 days)
%ay 11 (3 days of age)
Cy 15
y 19
l)ay 25
Day 29 (weaning, age 20 days)
•
IrBant mortality and survival
Sginal No. and mean litter size
lost and % survival 1st 3 days
I'M lost and % survival to v^eanmg
Treatment
lean Air (Control)




227.5 1.00
303.3 1.333
278.6 1.225
301.5 1.325
318.9 1.402
331.2 1.456
321.8 1.415

-


9.08 1.00
16.25 1.790
24.26 2.672
36.78 4.051
46.63 5.135

115 9.58
2 98.3
3 97.4
Non-irradiated


4(

221.0 1.00
299.4 1.355
262.8 1.189
285.9 1.294
308.9 1.398
327.0 1.480
310.9 1.407




8.71 1.00
16.03 1 840
24.24 2.783
37.96 4.358
48.38 5.555

105 8.75
1 99.0
2 98.1
Irradiated




234.6 1.00
297.4 1.268
280.1 1.194
297.0 1.266
322.5 1.375
326.7 1.392
316.9 1.351




8.46 1.00
15.68 1.853
23.70 2.801
36.37 4.299
46.29 5. 472

119 9.92
0 100.0
1 99.2

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                                     135
B.ll. GROSS MORPHOLOGIC AND FUNCTIONAL DAMAGE TO PLANT SPECIES BY DILUTED
          EXHAUST OF AUTOMOTIVE ENGINES OPERATED WITH AND WITHOUT A
                      CATALYTIC EMISSION CONTROL DEVICE

                     K. Campbell, R. Miller and J  Enright


      Effects on vegetation of automotive exhaust from engines with and

  without an oxidative catalytic converter, and operated on low-sulfur Indolene

  fuel, were assessed by exposing multiple plant species to clean air (control),

  irradiated and nonirradiated atmospheres in each of the two sequential

  "TAME" experiments 'I1 (without converter) and 'J1 (with converter)   Details

  concerning the experimental atmosphere generation and characterization are

  provided in preceding reports  (see hinners et al. and Malanchuk et al ). In

  TAME 'K1, in which the atmospheres were produced by the same engine fitted

  with converter, but usung high-sulfur Indolene, the time-related aspects of

  vegative damage by exhaust to a single plant specie were investigated   These

  studies were conducted collaboratively with faculty and student representatives

  of the Department of Biology (Botany), University of Cincinnati   Results

  reported are based on preliminary data evaluation.


  Experiment A   Damage to vegetation by automotive exhaust from an engine

  operated on low-sulfur fuel with  (TAME J) and without (TAME I) an oxidative

  catalytic converter.

      Phytotoxicity in exposed plants was evaluated on the basis of
                         \
  morphologic alterations (gross visible alterations of leaf and stem character)

  m all species and functional changes (C^-determined photosynthetic activity)

  in some.  Post-exposure recovery was also observed   Effects of irradiated (I)

  and nonirradiated  (NI) atmospheres were compared in each experiment and

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                                  136
between experiments   Nine species in varying young stages of development
were used in duplicate in each experiment.  Of these, five were the same
in both and four were different, and developmental stages were comparable
between exposures.  The species used in each experiment are shown in Table 1.
Duration of exposure was 127 hours for TAME 'I1, and 151 hours for TAME 'J'


             Table 1.   Plant Species Used in TAME 'I1 and 'J'

                     TAME 'I* - Without Catalytic Converter
               Taxas cuspidata                     Japanese yew
               Picea abies                         Norway spruce
               Ilex hetzi                          Japanese hollyberry
               Cotoneaster lofast                  Cotoneaster
               Euonymus coloratus
               Alianthus altissntia                 Tree of heaven
               Episcia cupreata (Silver Sheen)      Episcia
               Pinus strobus                       VJhite pine
               Easilico

                    TAME 'J1 - With Catalytic Converter
               Dancus carota                      Red-cored chantenay carrot
               Phaseolus mungo                    Bean
               Oxalis corniculata                 Oxalis
               Coleus blumei                      Coleus
               Cotoneaster lofast                 Cotoneaster
               Euonymus coloratus
               Episcia cupreata (Silver Sheen)     Episcia
               Alianthus altissima                Tree of heaven
               Basilico

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                                  137
    In both experiments, exposure to both NI and I atmospheres damaged



all species with varying degrees of severity.  Although modes of damage



were also variable, the most generally common were wilting, bleaching and



loss of leaves.  In some species, younger leaves were damaged first and in



others the older leaves showed earliest damage   Generally, even though



exposure duration was a little longer in TAME 'J1 than in 'I1, damage was



somewhat less in TAME 'J' (with converter) than m TAME 'I1 (without converter).



However, this difference m severity was less remarkable than the difference in



gross toxic severity shown by animals, suggesting that the plants were



fundamentally more susceptible subjects than animals and that their damage



"thresholds" were greatly exceeded in both studies   Three of the five species



used in both studies showed less damage in the converter-treated emissions than



in the non-converter emissions   TAME 'I' atmospheres killed Cotoneaster,



Allanthus and Episcia with no post-exposure recovery, in TAME 'J' atmo-



spheres Cotoneaster showed slightly less damage even though it was wilted



badly, and Alianthus and Episcia showed post-exposure recovery,  i.e., formed



new buds after apparent death with loss of original leaves.  Basilico



seedlings, however, recovered after the 'I1 exposure but died from the 'J1



and Euonymus damage was similar in both exposures.



    In TAME 'I' damage produced by the NI atmospheres was generally more



severe than that by I   Five of nine species showed greater visible damage



by NI than by I while the reaminder were about equally damaged by NI and



I.  There was a drastic depression of C  -measured photosynthetic rate and,



in Euonymus, photosynthesis was depressed more by NI than by I,  while the



reverse was true for Picea.  In three species visible damage was delayed

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                                 138
until about one week post-exposure, at which tine needle burn was observed


in Pinus and Picea, and bleach m Taxus.  In Ilex there was direct damage


to petioles.


    In TAME J, also, all nine species were damaged by both NI and I


but the visible damage severity by NI and I was generally not as distin-


guishable as in TAME I.  Photosynthetic depression by I was greater than by


NI in Euonymus, while the reverse was true for Cotoneaster   The species


showing delayed effects in I were not used in J


    Within the context of the vegetation damage from the severe exposure


conditions in TAME studies I and J, it is tentatively concluded that,


in general, there is a detectable but minor advantage to the use of the


catalytic emission control system.




Experiment B   The tune course of severe damage to Episcea Cupreata by


diluted automotive exhaust in TAME K


    Since plant species exposed for several days to the TAME I and


J atmospheres exhibited severe to fatal damage, specimens of one of the


most susceptible species were exposed for varying durations in this experi-


ment in order to better understand the temporal "dose-response" relationships


of the damage at similar pollutant levels   In each of the control (clean air),


nonirradiated  (NI) and irradiated  (I) atmosphere chambers duplicate


Episcia Cupreata  (Silver Sheen) plants were exposed for periods of
                       t

six days, one day, sax hours and one hour.  The six-day plants were examined


daily.  Degree of visible damage was subjectively rated on a scale of 0-12,


Degree of visible damage was subjectively rated on a scale of 0-12, essentially


as described previously  (Campbell, 1973)   After exposure, photosynthetic


rate and recovery were also assessed

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                                 139
    As noted in previous studies, foliar damage was distinctly visible



as early as six hours of exposure, and progressively became severe as



exposure continued.  In this study, generally, the I plants were damaged



more than the NI plants.  There was a visually distinguishable difference



in the pattern of damage shown in the two types of atmosphere, as well,



in terms of spacial pattern of discoloration and of degree of wilt and



turgor.  There appeared to be a somewhat steeper slope to the degree of



damage x duration of exposure curve than in the previous studies (TAME I



and J).  Preliminary results are illustrated in Figure 1.



    A subsequent study of duration - and concentration - related effects,



using the new Ford engine {with catalyst), shorter exposure periods and



multiple lower exposure levels (greater dilution), was conducted recently.



Preliminary data evaluation suggested grossly visible effects at 3 hours



of exposure or less in the high-level atmosphere (corresponding to those



reported above), and duration and concentration relationships in both gross



and functional effects.  CO and total HC levels were substantially lower,



and NCjx levels higher, than in TAME K

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12 -
TOTAL INJURY

                                   Without converter/
                                     low sulfur (TAME I)

                                   With converter,
                                     low sulfur (TAME J)

                                   With converter,
                                     high sulfur (TAME^K)
                                                     Non-
                                                  irradiated
                                                     O
                                                                       Irradiated
                                                                                             *».
                                                                                             o

                       2345

                              DURATION  OF EXPOSURE, DAYS
                                                           6
        FIGURE 1,  D/WAGE TO FOLIAGE OF EPISCIA PLANTS EXPOSED TO AUTOMOTIVE EXHAUST

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