PA-600/1-78-021
larch 1978
Environmental Health  Effects Research Series

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                RESEARCH REPORTING SERIES

Research reports of the Office of Research and Development, U.S. Environmental
Protection Agency, have been grouped into nine series. These nine broad cate-
gories were established to facilitate further development and application of en-
vironmental technology.  Elimination of traditional grouping  was consciously
planned to foster technology transfer and a maximum interface in related fields.
The nine series are.

      1.  Environmental Health Effects Research
      2.  Environmental Protection Technology
      3.  Ecological Research
      4.  Environmental Monitoring
      5  Socioeconomic Environmental  Studies
      6  Scientific and Technical Assessment Reports (STAR)
      7.  Interagency Energy-Environment Research and Development
      8.  "Special" Reports
      9.  Miscellaneous Reports
This report has been assigned to the ENVIRONMENTAL HEALTH EFFECTS RE-
SEARCH series. This series describes projects and studies relating to the toler-
ances of man for unhealthful  substances or conditions. This work is generally
assessed from a medical viewpoint, including physiological or psychological
studies. In addition to toxicology and other medical specialities, study areas in-
clude biomedical instrumentation and health research techniques utilizing ani-
mals — but always with intended application to human health measures.
This document is available to the public through the National Technical Informa-
tion Service, Springfield, Virginia  22161.

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                                     EPA-600/1-78-021
                                     March 1978
PHYSIOLOGICAL RESPONSE TO ATMOSPHERIC POLLUTANTS
                       by
                  Mary 0. Amdur*
            Department of Physiology
               Harvard University
             School of Public Health
              665 Huntington Avenue
           Boston, Massachusetts 02115

                *Present address:
    Department of Nutrition and Food Science
      Massachusetts Institute of Technology
         Cambridge, Massachusetts 02139
               Grant No. R-802030
                 Project Officer

                 David L. Coffin
             Office of the Director
       Health Effects Research Laboratory
       Research Triangle Park, N.C. 27711
      U.S. ENVIRONMENTAL PROTECTION AGENCY
       OFFICE OF RESEARCH AND DEVELOPMENT
       HEALTH EFFECTS RESEARCH LABORATORY
       RESEARCH TRIANGLE PARK, N.C. 27711

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                         DISCLAIMER
   This report has been reviewed by the Health Effects
Research Laboratory, U.S. Environmental Protection Agency,
and approved for publication.  Approval does not signify
that the contents necessarily reflect the views and policies
of the U.S. Environmental Protection Agency, nor does
mention of trade names or commercial products constitute
endorsement or recommendation for use.
       El
                             11

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                                  FOREWORD

           The many  benefits  of  our modern, developing,  industrial
       society are  accompanied by certain hazards.  Careful  assessment
       of  the relative  risk  of existing  and new man-made  environmental
       hazards is necessary  for the establishment of  sound regulatory
       policy.  These regulations serve  to enhance  the  quality of  our
       environment  in order  to promote the public health  and welfare and
       the productive capacity of our Nation's population.

           The Health  Effects Research  Laboratory, Research Triangle
       Park, conducts a coordinated environmental health  research
       program in toxicology,  epidemiology, and clinical  studies using
       human volunteer  subjects.   These  studies address problems in air
       pollution, non-ionizing radiation, environmental carcinogenesis
       and the toxicology of pesticides  as well as  other  chemical
       pollutants.  The Laboratory develops and revises air  quality
       criteria documents on pollutants  for which national ambient air
       quality standards exist or are proposed, provides  the data  for
       registration of  new pesticides or proposed suspension of those
       already in use,  conducts research on hazardous and toxic mate-
       rials, and is  preparing the health basis for non-ionizing radia-
 x      tion standards.   Direct support to the regulatory  function  of the
'v      Agency is provided in the  form of expert testimony and prepara-
       tion of affidavits as well as expert advice  to the Administrator
       to  assure the  adequacy  of  health  care and surveillance of persons
       having suffered  imminent and substantial endangerment of their
       health.

           Previous  studies have shown  that certain  sulfates and
       sulfuric acid  elicit  greater response in the lung  than
       comparable amounts of sulfur dioxide.  There is  therefore a
       need to develop  information which will relate  these findings
       to  the concentration  of pollutants found in  ambient air.
       This project has performed this function.
                                           John H.  Knelson,  M.D.
                                                Director,
                                   Health Effects Research Laboratory
                                      111

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                           ABSTRACT

     During the period of this grant several materials were
examined as air pollutants of interest for their irritant effects.
These included sulfuric acid, a series of inorganic sulfates, and
a combination of ozone and sulfur dioxide.  Some attention was
also given to the effect of various oil mists on the irritant
response to sulfur dioxide.  The method used for measuring
irritant response was by simultaneous tracings of intrapleural
pressure, tidal volume, and rate of flow of gas in and out of the
respiratory system.  By relating the intrapleural pressure change
to the change in flow rate at points of equal lung volume, it was
possible to calculate the flow resistance; by relating pressure
change to volume at the beginning and end of  inspiration, it
was possible to calculate compliance.  The concentrations used in
these studies are well within the range of human exposure.
These studies indicate that the irritant response previously
observed at higher concentrations of sulfuric acid is also
observed at concentrations below 1 mg/m^. The failure of alter-
ations in resistance to return promptly to control values
following termination of exposure has been a consistent finding
in the work with various irritant aerosols.  The lowest concen-
trations used in these studies (100 jig/m3) are in the range of
concentrations which have been reported as short-term maxima in
urban atmospheres.  Data obtained by the methods used in these
studies can be applied in concept  (although not by direct
extrapolation) to the response of sensitive individuals to
short-term peaks of pollution.
                                IV

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                  CONTENTS
                                          Page
Foreword       	iii
Abstract       	iv
I.   Scope of Work   	   1
II.  Physiological Methods   	   1
III. Sulfuric Acid   	   4
IV.  Inorganic Sulfates  	  13
V.   Ozone and Sulfur Dioxide	26
VI.  Oil Mists and Sulfur Dioxide  ....  33
VII. Preliminary Work on Sulfites  ....  34

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I.  Scope of Work




     During the period of this grant we have examined several



materials of interest as air pollutants for their irritant effects.



These have included sulfuric acid, a series of inorganic sulfates,



and a combination of ozone and sulfur dioxide.  Some support was



also given to a project studying the effect of various oil mists



on the irritant response to sulfur dioxide.  Preliminary work was




done with sulfite and bisulfite.





II.  Physiological Methods




     The method we use of measuring irritant response has been



described in the literature  (Amdur and Mead, Am. J. Phys. 192:364,



1958).  Simultaneous tracings are needed of intrapleural pressure,



tidal volume, and rate of flow of gas in and out of the respiratory



system.  Intrapleural pressure is measured by recording the pressure




changes in a fluid-filled catheter which is inserted under ether



anesthesia of brief duration.  Tidal volume is measured by record-



ing the pressure changes produced in a body plethysmograph.  Rate



of flow is measured by electrical differentiation of the volume



signal with respect to time.  By relating the intrapleural pressure



change to the change in flow rate at points of equal lung volume,



it is possible to calculate  the flow resistance.  By relating pres-



sure change to volume at the beginning and end of inspiration, it



is possible to calculate compliance.



     The method has certain  advantages.  One  of these is its simplic-



ity,  which permits routine  toxicological use of unanesthetized



animals.  The  fact that each animal serves as its own control per-

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mits the use of paired data for statistical evaluation.  The in-



crease in flow-resistance is related to the concentration of irri-



tant; this permits the development of dose-response curves.  These



curves yield information on such factors as the effect of particle



size on the potency of an irritant material, on the relative irri-



tant potency of different materials, and on the effect of inert



particulate material on the degree of response to irritant gases.



Data such as these dose-response curves resulting from a single ex-



posure of many animals over a wide range of concentrations provide



a tool for the demonstration of potentiation effects and other sub-



tle toxicological phenomena which cannot readily be detected by



experiments on human subjects.  Experimentation with human subjects



is by practical necessity limited both as to number of subjects and



conditions of exposure.



     The method also has certain limitations which should be kept



clearly in mind.   The standard exposure time is one hour; at best,



the preparation can only be used for five or six hours.  Thus, the



results obtained cannot be used to predict  effects of  chronic expo-



sure to the compounds studied.  Although the animals are unanesthe-



tized during the experimental period, an intrapleural  catheter has



been inserted under anesthesia.  That this  surgical procedure per



se causes an increase in resistance was demonstrated by measurements



made by another method before and after the insertion  of the catheter



 (Mead, J. Appl. Physiol.  15^:325, 1960).  The  physiological tech-



nique thus constitutes a stress which might render such animals more



sensitive to irritant exposure.  There  is experimental evidence to



support this suggestion.  Some unpublished  experiments in which the
                               -2-

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response to sulfur dioxide was measured by another method that



did not involve the use of an intrapleural catheter indicated that



the two methods were of equivalent sensitivity at high concentrations



but that at concentrations of 2 ppm and less the intrapleural cath-



eter method was more sensitive.  Thus the stress of the technique



used has rendered the animals more sensitive to low-grade irritant



exposure.  This might be considered an advantage rather than a



limitation, as it is the sensitive segment of the human population



that is most affected by air pollution.  In any effort, to draw



meaningful extrapolations from these data, it should be kept in



mind that  if these guinea pigs are analogous to anything at all, it



is to the  sensitive individual and not to the normal healthy indi-



vidual.




     Random-bred guinea pigs weighing 200-300 g were used in these



experiments.  The plethysmograph was clamped so that the animal's



head projected into the exposure chamber.  Respiratory measurements



were made every five minutes during a half-hour control period.  The



material or materials being studied were then added to the entering



air stream of the exposure chamber.  Respiratory measurements were



again made every five minutes during an exposure period of one hour



(for sulfuric acid or sulfate salts) or two hours (for the ozone-



sulfur dioxide studies).  Each animal thus served as its own con-



trol.  The chamber was cleared of irritant material and measure-



ments were made during a post-exposure period of one-half to one



hour.
                              -3-

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III.   Sulfuric Acid





      A.   Method of Aerosol Generation and Measurement.





     The  sulfuric acid aerosol is  produced by a Rappaport-Wein-



stock condensation type aerosol generator (Rappaport and Weinstock,



Experientia LI: 363, 1955).  The sulfuric acid is first, heated and



nebulized to a heterogeneous aerosol.  The larger particles are



removed by impaction and the smaller particles are carried upwards



through a heating column in which they are vaporized.  Upon emerging



from the  heating column, the vapor cools and condenses into drop-



lets of uniform size.  The size of the aerosol can be controlled



by appropriate adjustments of the amount of sulfuric acid nebulized, of



the temperature of the reservoir, and the temperature of the heating



column.  The mass concentrations can be controlled by regulating



the amount of dilution air.  All air is pre-dried and filtered to



remove foreign particles.  Relative humidity of the chamber was



50% and temperature was 70°F.



     The  mass concentration was measured by collecting a sample of



the aerosol on a type G.S. Millipore Filter, which was then soaked



in 10 ml  demineralized water.  The electrical conductivity of the



resulting solution was then measured and compared with a standard



curve.  All samples were collected throughout the animal exposure



period at a flow rate of 3.5 1pm.  Concentrations were reproducible



within ± 10% or better.



     The particle size of the larger aerosol was determined before



and after each animal exposure with  an ultra-microscope by which



the time of free fall of the aerosol particles across a calibrated



grid could be measured.  The size was then determined by appropri-




                              -4-

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ately inserting the free fall time into the Stokes-Cunningham



equation.  Average sizes were based on counts of 50-100 particles.



The standard deviation was consistently less than 10% of the mean



diameter.  The particle size of the smaller aerosol was determined



by light scattering at each set of experimental conditions.




      B.  Background for Present Studies





     Sulfuric acid is the most irritant of the particulate sulfur



species formed by the oxidation of sulfur dioxide in the atmosphere.



Acute exposure of guinea pigs has demonstrated that the irritant



potency of a given amount of sulfur, as evaluated by changes in



respiratory mechanics, may be increased three- to five-fold when



given as sulfuric acid rather than as sulfur dioxide (Amdur, Am.




Indust. Hyg. Assoc. J. _3_5_:489, 1974).  In two-year exposures of



monkeys to sulfuric acid, pathological changes were produced which




were not observed when corresponding levels of sulfur were given



as sulfur dioxide  (Alarie et al., Arch. Environ. Health 27:16,



1973).   The greater irritant potency of sulfuric acid is thus



indicated in the acute response of a rodent species and the chronic



response of a primate species.  Aerosols of metal salts, which



promoted the conversion of sulfur dioxide to sulfuric acid, poten-



tiated the response to sulfur dioxide three- to four-fold  (Amdur



and Underhill, Arch. Environ. Health 16;460, 1968).



     Our previously-published study of the respiratory response of



guinea pigs to sulfuric acid  (Amdur, Arch. Indust. Health  18:407,



1958) did not examine concentrations below 2 mg/m3 nor particle






                              -5-

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sizes below 0.8 ym (MMD).   The studies reported here were performed



to obtain similar data on concentrations of 1 mg/m  and below at



particle sizes of 1 and 0.3 ym.





      C.  Results




     Table 1 presents our data on the effect of sulfuric acid on



pulmonary flow resistance and pulmonary compliance.  All exposures



produced a statistically significant increase in resistance.  The



degree of response was dose-related as shown in Figure 1.  The 0.3 ym



particles produced a greater response at a given concentration than



did the 1 ym particles.  This difference appears greatest at the



lowest concentration of 0.1 mg/m  .



     In animals exposed to 0.1 mg/m3 at the 1 ym particle size, the



resistance values had returned to pre-exposure values by the end of



the half-hour post-exposure period.  In all other  exposures, the



post-exposure value was less than the response at  the end of expo-



sure but was still elevated above control  values.   The time course



of the  post-exposure  resistance increases, expressed as  percent



change  from control,  is shown  in  Figure 2  for the  0.3  ym particles



at concentrations  of  0.1  and  1 mg/m3.   In  both cases,  the values



increased  slightly during the  first  five minutes  of the  post-expo-



sure period then declined to  an essentially  constant  Level  by




 fifteen minutes  after the end of  exposure.



     A  decrease  in pulmonary  compliance was  also  produced by  these



 low  level  exposures  to sulfuric  acid.   In  the exposure to  1 ym par-



 ticles,  the  decrease in compliance  was  not statistically significant



 at concentrations of 0.1 or 0.4  mg/m3.   A decrease in compliance



 was  produced by  the  two higher concentrations of  1 ym particles.





                               -6-

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At a particle size of 0.3 ym, a decrease in compliance was observed



at all concentrations tested.  At corresponding concentrations, the



0.3 ym particles produced a greater decrease in compliance than the



1 ym particles.  When the exposure produced a decrease in compli-



ance, the values were still below control values at the end of the



thirty-minute post-exposure period, although less depressed than



at the end of exposure.



     Detailed data are not presented for tidal volume, respiratory



frequency, or minute volume, as the low concentrations used in



these studies produced no alterations in any of these factors.





      D.  Discussion




     The concentrations used in these studies are well within the



range of human exposure.  Concentrations above 0.1 mg/m^ have been



reported as hourly averages in urban pollution.  A concentration



of 1 mg/m3 is the currently recommended standard for occupational




exposure.



     These studies indicate that the irritant response previously



observed at higher concentrations of sulfuric acid is also observed


                              3                           3
at concentrations below 1 mg/m .  The response to 0.1 mg/m  at the



1 ym particle size is slight and rapidly reversible.  The response



to 0.1 mg/m  at the  0.3 ym  size is greater  in magnitude and is not



rapidly reversible.



     A  concentration  of 1 mg/m  sulfuric  acid contains  0.3 mg/m^



of sulfur.  The percent increase in resistance produced is on  the



order of  80% for  0.3 ym particles and 60%  for 1 ym particles.  The



same order of magnitude of  sulfur  (0.2  mg/m^) given  as sulfur



                              -7-

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dioxide (0.16 ppm) produces a slight resistance increase in the



order of 10%.  Thus, the same amount of sulfur, when given as



sulfuric acid, produces 6 to 8 times the response observed when



given as sulfur dioxide.  Given as 1 ym sulfuric acid, 0.03 mg



S/m  produces a response of the same order of magnitude as 0.2


      3                                                      3
mg S/m  given as sulfur dioxide.  The response to 0.03 mg S/m



as 0.3 ym sulfuric acid is four times the response to 0.2 mg S/m-^



given as sulfur dioxide.



     The failure of alterations in resistance to return promptly



to control values following termination of exposure has been a



consistent finding in our work with various irritant aerosols.



The post-exposure resistance values of animals exposed to sulfur



dioxide and sodium chloride or to formaldehyde and sodium chloride



remained elevated and were related to the total does of aerosol.



This was one of the earlier findings which suggested that the



potentiation of the response to these gases was mediated by for-



mation of an irritant aerosol rather than by simple transfer of



additional gas as such to the lung  (Amdur, Inhaled Particles and



Vap_or_s_ 1:281, 1961; Amdur and Underhill, Arch. Environ. Health



1^:460, 1968).  The response to sulfur dioxide or formaldehyde



alone was readily reversible until extremely high concentrations



were reached.  The only exception to the slow  reversibility of



the response to irritant aerosols was histamine, with which even



very major responses were almost  immediately reversible  (Amdur,



Arch. Environ. Health 13:29, 1966).





                              -8-

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     The lowest concentrations used in these studies  (100 ug/m )



are in the range of concentrations which have been reported as



short-term maxima in urban atmospheres.  Data obtained by the



methods used in these studies can be applied in concept  (though



obviously not by direct extrapolation) to the response of sen-



sitive individuals to short-term peaks of pollution.  Alteration



of pulmonary mechanics is obviously only one manifestation of



irritant response.  Another manifestation is alteration  in regional



deposition or clearance of aerosols.   It is of  interest  to note



that alterations in regional deposition patterns  have been demon-



strated in guinea pigs exposed to concentrations  as  low  as



30 yg/m   (size 0.25 urn) for one hour  (Fairchild et a_l. ,  Amer.



Indust. Hyg. Assoc. J. 3J7:584, 1975).  More recently, Dr. Morton



Lippmann's group at New York University has found that a one hour



exposure to  < 200 ug/m   (size 0.3 ym)  caused a  significant



transient slowing of  tracheobronchial  clearance of ferric oxide



aerosol in donkeys.   Thus, these  levels of  sulfuric  acid produce



irritant effects other than the alterations in  pulmonary mechanics



reported  in  the present studies.
                             -9-

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o
I
                                                         Table  1

                                           Respiratory Response to  Sulfuric Acid
                                    0.70
0.59
0.72
Particle Size HMD
                  o
Concentration mg/m
Number of Animals

Resistance cm l^O/ml/sec

     Control

     Exposure3
     x (E-C)

     ?*<
     % Change
                  b
     Post Exposure
     5 (P-C)
     g_
     PX<
     % Change

 Compliance ml/cm 1^0

     Control
             o
     Exposure
     x (E-C)
     S-
     PX<
     % Change

                  b
     Post  Exposure
     x (P-C)
     <^_
     PX<
     % Change
      a"Exposure":  Average of readings at 55  and  60 min.

       "Post Exposure":  Average of readings at  25  and  30  min.

0.11
20
1
0.40
20
pm
0.69
•20

0.85
20
0.
0.10
23
3 urn
0.51
20

1.
25

0

0.68
0.80
0.72
                                    0.23
0.24
0.20
0.21
0.22
0.24
0.74
0.80
0.10
0.039
0.02
+14
0.77
0.07
0.041
NS
+ 10
0.77
0.18
0.033
0.001
+30
0.71
0.12
0.051
0.05
+20
1.06
0.34
0.042
0.001
+47
O.S9
0.17
0.047
0.001
+24
1.09
0.41
0.051
0.001
+60
0.86
0.18
0.053
0.01
+26
1.13
0.33 '
0.048
0.001
+41
1.01
0.21
0.059
0.01
+26
1.15
0.43
0.052
0.001
+60
1.09
0.37
0.058
0.001
+51
1.32
0.58
0.063
0.001
+78
1.20
0.46
0.067
0.001
+62
0.20
0.20
•0.03
0.015
NS
-13
0.21
0.02
0.018
NS
-9
0.22
-0.02
0.016
NS
-8
0.23
-0.01
0.012
NS
-4
0.15
-0.05
0.014
0.01
-25
0.17
-0.03
0.011
0.02
-15
0.15
-0.06
0.017
0.01
-28
0.17
-0.04
0.013
0.01
-19
0.16
-0.06
0.012
0.001
-27
0.17
-0.05
0.013
0.01
-22
0.16
-0.08 '
0.017
0.001
-33
0.18
-0.06
0.016
0.01
-25
0.12
-0.08
0.019
0.01
-40
0.14
-0.06
0.021
0.01
-30

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O



O
O
ro
P
CO
g
P
Ol
P
00
P
CD
                              -ii-

                 % Change  in Resistance
 o
—r~
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                      CO
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 00
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                                           co ^
                                                        \
                                                     rocx
                                                     Ol   \
                                                                    M
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                                                          W O
                                                          > O
                                                          O cn
                                                          K W
                                                            I
                                                          »Td W
                                                          O W
                                                          H W
                                                          2! ^
                                                          H O
                                                            3
                                                          H cn
                                                          2J W
                                                          G
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                                                          O G
                                                          > »
                                                          H <
                                                          W td
                                                                  a ^d
                                                                  M O
                                                          G cn

                                                          8 tr1
                                                          W *T|
                                                                  O H
                                                                  *d o
                                                          2 n
                                                          H H
                                                          is o
                                                          cn

                                                          H
                                                                   H 2
                                                                   a G
ro
                                                          Q
                                                          Jd
                                                          O
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                                                                    tn
                                                                    H

-------
                    -2T-
O
H

m —
x o
o
m
 i
a
3 o
  FO
  en
  CM
  O
       % INCREASE IN RESISTANCE
         ro
         O
                         CO

                         O
o
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          I Hour  EXPOSURE
                                    x ©

                                    - o
                                    o-
                                    3 3
                                      «o
                                        ro
                                    330
                                    ui 01 ^1
                                      ro  _,
                                    HI ii!  3

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IV.  Inorganic Sulfates




     A.  Methods of Aerosol Generation and Measurement




     These aerosols were produced with Dautrebande D~Q aerosol



generators.  These produce a heterogeneous aerosol of sub-micron



size.  The several models we have have slightly different charac-



teristics in terms of mean size produced with a given concentra-



tion of solution.  To vary size, we utilized this fact in combina-



tion with the use of O.I/ 0.3 and 1% solutions of the various



salts.  The size was measured by collecting a sample on a



carbon-coated EM grid by electrostatic precipitation.  The size



was measured from electron micrographs.



     The mass concentration of the sulfate salts was measured by



various methods following collection on a Millipore filter.  For



the copper sulfate, copper was measured by atomic absorption.



Ammonium sulfate and ammonium bisulfate were measured with an



ammonium ion electrode, by direct weighing on a Cahn electro-



balance or by increase in electrical conductivity.



     Sulfur dioxide was generated by metering gas from a tank



containing 0.1% sulfur dioxide in air.  The concentration was



measured by collecting a sample in dilute sulfuric acid-hydrogen



peroxide solution and measuring the increase in conductivity.



The collecting bubbler was preceded by a membrane filter to



remove the aerosol, which would have also altered the conductivity.
                           -13-

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     The main air stream entering the exposure chamber was



filtered to remove extraneous particles and dried.  The relative



humidity of the exposure chamber atmosphere was 50%.




     B.  Background




     Data on the comparative toxicity of sulfate salts are of



importance because sulfur dioxide in urban atmospheres is con-



verted into particulate sulfur species.  The rather meager ex-



isting toxicological data indicate that some, but not all, sul-



fate salts are respiratory irritants and that the irritant



potency of a given sulfate increases with decreasing particle



size.



     Zinc ammonium sulfate causes an increase in pulmonary



flow resistance in guinea pigs  (Amdur  and Corn, Amer. Indust.



Hyg. Assoc. J.  2_4_:326, 1963).  Over the size range studied



 (0.29  to 1.4 ym, mean size by weight)  the change  in flow  resis-



tance  increased as the particle size decreased.   In cats, zinc



ammonium sulfate also caused an increase in  flow  resistance



and  a  decrease in pulmonary compliance (Nadel et  al., Inhaled



Particles and Vapors 11:55, 1965).  These changes were  similar



to the response to an aerosol of histamine,  but were  of lesser



magnitude.



      Zinc sulfate  and ammonium  sulfate (0.3  pm  in size)  produced



 an increase  in  flow  resistance  in  guinea pigs  (Amdur  and Corn,



 1963)  as  did ferric  sulfate  (Amdur and Underhill,  Arch. Environ.
                            -14-

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Healthy 16_:460, 1968).  Neither ferrous sulfate nor manganous
sulfate was irritant  (Ibid.).
     In the present studies we have examined the comparative
irritant potency of ammonium sulfate, ammonium bisulfate, cupric
sulfate and sodium sulfate.  We have also determined whether
or not these sulfate salts potentiate the response to low concen-
trations of sulfur dioxide.
     C.  Results
     The effects of the four sulfate salts on resistance and
compliance are presented in Table 2.  In order that the various
salts may be compared in irritant potency, the response is also
expressed as percent change per microgram of sulfate.
     Ammonium sulfate caused a statistically significant de-
crease in compliance  at all the concentrations and particle
sizes tested.  Two of the exposures produced an increase in
resistance and two did not.  The resistance increase produced
by the 0.3 ym particles at a concentration of 1 mg/m  was in
good agreement with values found on a smaller group of animals
in a previous study (Amdur and Corn, 1963).  With the exception
of the fact that there was a minimal response to the 0.2 \im
particles, the response per ug of sulfate was greater as the
particle size decreased.
                            -15-

-------
     Ammonium bisulfate was also a mild respiratory irritant.



All the exposed groups showed a statistically significant in-



crease in resistance and decrease in compliance.  The; degree of



response per microgram of sulfate increased as the pcirticle size



decreased.  As was the case with ammonium sulfate, the response



was minimal to the 0.8 um particles.  An overall consideration



of the data suggests that ammonium bisulfate is less irritant



than ammonium sulfate.  At the smallest size  (0.13 urn) the



percent change in resistance per ug of sulfate was 0.. 063 for the



sulfate and 0.019 for the bisulfate; the corresponding values



for compliance were -0.074 and -0.019.  A similar pattern emerges



when one compares the data for 0.3 um ammonium sulfate with the



data for 0.5 um ammonium bisulfate.  For what it's worth, these



comparisons would tend to suggest that the response to ammonium



sulfate is of the order of three times that to ammonium



bisulfate.





     The data for copper sulfate permit the direct comparison of



two concentrations at similar particle sizes  and of two particle



sizes  at similar concentrations.  At a particle size of 0.1  um a



concentration of 0.4 mg/m  produced a slight  but  statistically
                            — 16 —

-------
significant decrease in compliance.  The slight decrease in resis-



tance was not statistically significant.  At a higher concentration



of 2 mg/m  both an increase in resistance and a decrease in com-



pliance were observed.  Exposure to 2 mg/m  at a particle size of



0.3 urn produced a statistically significant change in resistance



and compliance, but the response was slightly less than that produced



by the smaller particles.



     Sodium sulfate at a particle size of 0.1 ym produced no change



in resistance.  The slight decrease in compliance was not statisti-



cally significant.



     Data for sulfur dioxide alone at a concentration of 0.3 ppm



and for the combination of sulfur dioxide and the aerosols at a



particle size of 0.1 pm at the lowest concentration used are presented



in Table 3.  In all exposures there was a statistically significant



increase in resistance and decrease in compliance.  Figure 3 com-



pares the responses to the combined exposure with the sum of the



responses to the sulfur dioxide and aerosol given alone.  The com-



bination of the copper sulfate and sulfur dioxide was more than



additive.  The response to the other combinations could be predicted



on the basis of a simple additive response.




     D.  Discussion





     Of the four sulfate salts examined, ammonium sulfate appeared



to be the most irritant, followed by ammonium bisulfate, copper sul-



fate, and sodium sulfate.  There is evidence that isolated guinea



pig lung fragments release histamine when incubated with solutions



of  ammonium sulfate but not when incubated with solutions of sodium






                              -17-

-------
sulfate (Charles and Menzel, Arch. Environ. Health 31:314, 1975).



Intratracheal injections of ammonium sulfate solutions produced



bronchoconstriction in isolated perfused lungs but sodium sulfate



did not.  Ammonium ions also increased the absorption of sulfate



by the rat lung in vivo (Charles and Menzel, Res. Comm. Chem. Path.



Pharm. 12_:389, 1975).  Sulfate removal was differentially enhanced



and presumably there was increased flux by various associated cat-



ions across the mast cell where histamine is stored.  Among the



most active in this regard were ferric and zinc ions.  In earlier



work in our laboratory  (Amdur and Corn, 1963; Amdur and Underhill,



1968), both ferric sulfate and zinc sulfate were found to be irri-



tant.  The pharmacological findings correlate well with the data



obtained in our studies using mechanics of respiration as a means



of determining relative irritant potency.



     None of the sulfate salts tested in the present studies or in



our earlier work are as irritant as sulfuric acid itself.  The per-



cent increase in resistance per ug of sulfate as sulfuric acid



is 0.432 for 0.1 um particles and 0.410 for 0.3 vim particles  (Amdur,



Proc. 4th Symp. Statistics  and the Environment, pg.  48, 1976).  Data



for all the sulfates tested in these and earlier studies  are  avail-



able at the 0.3 ym size except sodium sulfate, which was  only studied



as 0.1  urn particles.   If one  assigns a value of 100  to the 0.410



obtained with sulfuric acid and relates the values  for the sulfate



salts to it,  it is possible to rank these  compounds  for irritant



potency as shown in  Table  4.  The ten-fold less  irritant  potency



of ammonium sulfate  as compared to sulfuric  acid would fit the
                            -18-

-------
observation made twenty years ago that neutralization with ammonia



eliminated the lethality of sulfuric acid to guinea pigs (Pattle,



Burgess and Cullumbine, J. Path. Bact. 72:219, 1956).



     The irritant potency of the sulfate species varies so widely



that the term "suspended sulfate" is toxicologically meaningless.



The practical implication of this fact is that a better analytical



measurement than "suspended sulfate" will be needed in research



epidemiology before definitive data relating to health effects of




particulate sulfur species are likely to emerge.



     The range of particle size of the aerosols used in the present




study  (0.1 to 0.8 ym) was too narrow to demonstrate a rational



relationship between particle size and degree of reponse.  Such



relationships were reported earlier for zinc ammonium sulfate over



a size range of 0.3 to 1.4 ym (Amdur and Corn, 1963) and for sul-



furic acid over a size range of 0.1 to 2.5 ym  (Amdur, 1976).  The



data for any given compound in the present study, however, showed in



general a greater degree of response at a smaller particle size.



Overall, data from various studies in our laboratory indicate that



measurement of mass median diameter would be much more meaningful



than "respirable size" in attempts to assess the health effects  of




atmospheric aerosols .



     Ammonium sulfate, ammonium bisulfate, and sodium sulfate in



these  studies did not  potentiate  the  response  to sulfur dioxide.



These  exposures were all  performed  at an exposure  chamber  relative



humidity  of 50%.  There  is  evidence that increasing the relative



humidity  to 80% markedly  increases  the  potentiating effect of sodium



chloride  (McJilton,  Frank and Charlson,  Science  182:503,  1973).
                             -19-

-------
Whether or not increased relative humidity would effect these sul-

fate salts in a similar manner is not known.

     It was previously reported that salts of manganese, vanadium,

and ferrous iron were strong potentiators of the response to sul-

fur dioxide (Amdur and Underhill, 1968).  At concentrations of 1.4
           _ o
to 1.8 x 10   millimoles of metal per cubic meter the metal salts

increased the response to 3 to 4 times that observed in exposures

to sulfur dioxide alone.  These metals were known to promote the

conversion of sulfur dioxide to sulfuric acid.  Under our exposure

conditions about 10% conversion was found at sulfur dioxide concen-

trations of 0.2 ppm.  When this amount of sulfuric acid was combined

with 0.2 ppm sulfur dioxide, the response observed from sulfur di-

oxide and the metal aerosols was reproduced  (Amdur, Amer. Indust.

Hyg. Assoc. J.  35^:589, 1974).

     It had been reported that copper sulfate also promoted the

conversion of sulfur dioxide to sulfuric acid (Cheng et al., Atmos.

Environ.  5^:987, 1971).  On this basis, our observation that aero-

sols of copper sulfate potentiated the response to sulfur dioxide

would have been predicted.  It is interesting, however, to note

that copper appears to be a more powerful potentiator of sulfur

dioxide than the other metals.  The concentration of copper used

was 1.3 x 10   millimoles/m , or about one  tenth of the concen-

tration of the other metals.  The response  increased four-fold.  A

possible explanation for the greater effectiveness of copper may

be  provided by the  observation made at the  Center  for Thermochemi-

cal studies  at Brigham  Young University  that  aerosols containing
                             -20-

-------
copper can complex with sulfur dioxide in such a manner that the



sulfur is relatively stable as S   and is to some extent protected



from further oxidation (Hansen et al., Proc. Int. Conf. Environ.



Sensing and Assessment, 1975).  Their samples were from within a



smelter or from the atmosphere when wind patterns brought material



from known point sources.  It has also been reported that sodium



bisulfite is a much more powerful irritant than sulfur dioxide



(Alarie, Wakisaka and Oka, Environ. Physiol. Biochem. 3_:182, 1973).



These data raise the interesting speculation that perhaps the



copper potentiation is mediated by the formation of a sulfite or



bisulfite complex rather than by the formation of sulfuric acid.



     Overall, these data emphasize the importance of analysis of



specific trace metal content of atmospheric aerosols in studies



attempting to unravel the complexities of the health effects of the



sulfur oxides-particulate pollution complex.
                             -21-

-------
                                                                              Table  2

                                                                  Respiratory Response   to guifato salts
 Sol fate Salt                                     ft«4>J«>4


                                              020           0.30           0.81             0.13         0.52            0.77           0.11           0.13           0.33           0.1)
 HUD -|i n                      "   .  n         214 + 023   102 + 011    9.54 + 0.94    0.93+_0.09   2.60  + 0.29   10.98 +_ 1.64    0.43+0.17    2.05j_0.?n     7.41 «_ 0.31   0.90^0j.l]

 Salt - nxy™3                  ifi-l            1553"  "     '«&"           6926~            775           2168           9157            2"            12K            1™R          fit)8 i
lig S04/m3                      Jo              10             10             10              19              10            1O             23              30              35           10
 No. of Animals



 Resistance cm II 0/ml/sec

control
exposure
airterence
S x 3
r < h
% change
\ change/ w SO4
0 43

+ 0 . 10
O.041

0.05
+ 23
0.063
0.53
0.51
-0.02
0.043

N.S.
-4

0.65
0.83
+ 0.18
0.052
0 01
+ 29
0 039

0.60
0.60
0
-

0
o

0.60
0.69
+ 0.09
0.035
O.O2
+ 15
0.019

0.87
1.11
+ 0.24
0.059
0.01
+27.5
0.013

0.59
0.73
+0.14
0.043
O.O2
+23
0.002

0.44
0.40
+0.04
0.021
NS
<9


0.44
0.55
HO. 11
O.O32
0.01
125
0.07.0

0.49
0.5C.
+0.07
O.OPl
0.01
H4
0.009

O.G6
0.67
+0.01
~
MS
1-2
O.OO.l

 CompJ i ance  ml/cm
control
exposure
di f fer once
S v a
X
„ x b
p <
% chanqe
0.29
0.21
-0.08
0.019
0.01

-0 . 074
0.23
0 .20
-0.03
0.013
0.05
-13
-0.008
0.30
0 23
-0.07
0.012
0.001
-23
-0.032
0.26
0.23
-0.03
0.013
0.05
-12
-0.002
0.26
0.22
-0.04
0.011
0.01
-15
-0.019
0.23
0.16
-0.07
O.O13
0.001
-30
-0.014
0.26
0.21
-0.05
0.011
O.01
-19
-0.002
0.27
0.24
-0.03
0.017
0.02
-11
-0.043
0.77
0.23
-0.04
O.OOS
0.001
-15
0.012
0.77
0.74
-0.01
O.O06
0.001
-11
-0.000
0 . 26
0.24
-0.02 .
0.01'f
NS
-7
-0.01(1
  a  stiindnrrt F.rror of Difference


  b  Students paired tost

-------
                             Table 3

             Response to 0.1 ym Sulfate  Salts and SO2
SO2 - ppm           0.32
Sulfate Salt
Cone. mg/m3
Number of Animals    10
                              0.30
                             (NH4)2S04
                              0.5
                               10
  0.32
NH4HS04
  0.9
   10
 0.36
CuSO4
 0.4
  10
 0.31
Na2SO4
 0.9
  10
Resistance -
CmH20/ml/sec
control
exposure
difference
Sx
P <
% change
0.62
0.69
+0.07
0.023
0.02
+12
0.50
0.66
+0.16
0.051
0.02
+31
0.61
0.74
+0.13
0.047
0.05
+ 21 '
0.49
0.78
+0.29
0.067
0.01
+59
0.53
0.59
+0.06
0.024
0.05
+11
Compliance -
control
exposure
difference
Sx
P <
% change
                    0.22
                    0.20
                    0.02
                   0.012
                    NS
                    -10
0.23
0.18
•0.05
0.020
0.05
-22
0.28
0.21
-0.07
0.019
0.01
-25
0.30
0.19
-0.11
0.021
0.001
-37
0.31
0.27
-0.04
0.017
0.05
-13
                                  -23-

-------
               Table 4

Relative Irritant Potency of Sulfates
Sulfuric Acid                  100
Zinc Ammonium Sulfate3          33
Ferric Sulfateb                 26
Zinc Sulfate3                   19
Ammonium Sulfate                10
Ammonium bisulfate               3
Cupric Sulfate                   2
Ferrous Sulfate                0.7
Sodium Sulfate0                0.7
Manganous Sulfate^            -0.9d
  Data of Amdur and Corn, 1963

  Data of Amdur and Underbill, 1968
  Particle size  O.lym
d
  Resistance decreased; change N.S.
                 -24-

-------
                                           SULFATE
                          COMBINATION
I

NJ

U1

I
ncrease %
Resistance
ance c&crease
        E
        o
       o
                      A\\\

                      A\\\
                      A\\\
A\\V

                                       --
                                  \\\v •:>•••:•:•:•"•
NH4 HS04     Cu  S04
                                                                     Na2 S04
                                      \\\V

                                      \\\\

                         FIGURE 3 - COMPARISON OF RESPONSE TO COMBINATION OF SO, AND

                                  SULFATES WITH SUM OF THE RESPONSES TO EACH  GIVEN

                                  ALONE.

-------
V.  Ozone and Sulfur Dioxide





    A.  Methods of Generation and Measurement





     The ozone was generated by passing oxygen through a high voltage



electric field.  To prevent interference from sulfur dioxide, a



chemiluminescent ozone detector was used to measure ozone concentra-



tions.  The method of generation and measurement of sulfur dioxide



was as described in Section IV.  The ozone and sulfur dioxide were



mixed with the main air stream prior to contact so that there was



no chance for chemical interaction of the two gases at high concen-



trations.  During one run at levels of 0.8 ppm of both gases, a



sample was collected on a Millipore filter and analysed for par-



ticluate sulfate.  No detectable amount of sulfate was present.




    B.  Background for Present Studies





     Hazucha and Bates  (Nature 3_3_:50, 1975) reported that human



subjects exposed for two hours with intermittent exercise  to a



combination of 0.37 ppm ozone and 0.37 ppm sulfur dioxide showed



greater effects on pulmonary function than could be accounted for



on the basis of simple addition.  It was suggested that these



effects might have occurred in response to sulfuric acid formed



in the respiratory tract by chemical interaction of ozone and sul-



fur dioxide.



      The guinea pig preparation we use is very sensitive to  sulfuric



acid.  Thus it appeared worthwhile  to expose animals to the com-



bination of ozone  and  sulfur dioxide.  The backlog of dose-response



data  on  small-size sulfuric acid would permit a possible estimation
                               -26-

-------
of the amount formed.  Our initial protocol was to expose groups



of animals for two hours to 0.2,  0.4, or 0.8 ppm of each gas or to



combinations of the two at equal concentrations.  On the basis of



the results of the exposures to the two higher levels, the planned



experiments on the combination of the lowest concentration were




not carried out.





    C.  Results




     The response to ozone alone is shown in Table 5.  As had been



previously observed, ozone concentrations of this order of magnitude



do not alter pulmonary flow resistance.  The two higher concentra-



tions produced a decrease in compliance of 22-24% below control val-



ues after one hour of exposure and 28-29% below control values by



the end of the two-hour exposure.  The post-exposure period of



30 minutes was not long enough for complete reversal.  Earlier



work showed that control values would be reached within two hours



after exposure.  The decrease in compliance resulted in a decrease




in the time constant of the lungs and was accompanied by an increase



in respiratory frequency.  At the lowest concentration the increase



in frequency was the only statistically significant change produced



by the two-hour exposure.



     The response to the exposure to sulfur dioxide alone is shown



in Table 6.  In these particular groups of animals the response



was minimal and no statistically significant alterations in respira-



tion were produced.  There was no progressive  increase in flow-



resistance produced by the extension of the exposure time to two



hours.
                               -27-

-------
     The response to the combined exposures to 0.4 and 0.8 ppm



of each gas are shown in Table 7.  The responses observed are



essentially the same as those produced by the exposure to these



concentrations of ozone alone.  This response pattern is not



typical of the response pattern produced by sulfuric acid.




    D.  Discussion





     The results of the exposure to the combination of ozone and



sulfur dioxide do not indicate a synergism between the two gases



under the exposure conditions prevailing in these experiments.



The response typical of ozone exposure, i.e. an increase in fre-



quency, a decrease in compliance, minimal change in resistance



and a decrease in the time constant, was observed in response to



the combination of ozone and sulfur dioxide.  This pattern of



response is not similar to the changes produced in the quinea pig



by exposure to sulfuric acid.




     Since this work was done, Bill and Hackney at Rancho Los Amigos



in Los Angeles have done further exposures of human subjects to



combinations of ozone and sulfur dioxide.  Their overall finding



was that the effect was much less dramatic than that originally



observed by Hazucha and Bates in Montreal.  Together the two groups



explored the various possible reasons for the observed difference.



The most likely explanation appears to be the fact that the condi-



tions in the Montreal exposure chamber led to the production in the



exposure atmosphere of perhaps up to 200 yg/m  of acid sulfate, most



likely sulfuric acid  (Bill e_t al. , Am. Indust. Hyg. Assoc. J., in



press).  The negative results obtained in our studies, in which no






                              -28-

-------
sulfate was present in the chamber, suggest that there was no



interaction of the ozone and sulfur dioxide after inhalation,



as was originally postulated, at least in the guinea pig lung.
                               -29-

-------
                            Table 5

                      Response to Ozone
PPM
Number of Animals

Resistance
  cm H-O/ml/sec
Compliance
  ml/cm H20
R x C
  sec
Frequency
  breaths/min
Tidal Volume
  ml
Minute Volume
  ml


Control
1 hr
2 hr
Post Exp.
Control
1 hr
2 hr
Post Exp.
Control
1 hr
2 hr
Post Exp.
Control
1 hr
2 hr
Post Exp.
Control
1 hr
2 hr
Post Exp.
Control
1 hr
2 hr
Post Exp.
0.2
10
0.74
0.62
0.56
0.56
0.25
0.23
0.22
0.22
0.185
0.143
0.123
0.123
80
89
94*
93*
2.3
2.3
2.3
2.1
184
205
216
195
0.4
10
0.67
0.65
0.67
0.50
0.25
0.19*
0.18*
0.20*
0.167
0.123
0.120
0.100
84
93
99*
96*
2.4
2.2
2.0
2.3
201
205
198
221
0.8
10
0.60
0.50
0.44
0.47
0.27
0.21*
0.19*
0.21*
0.162
0.105*
0.084*
0.099*
86
97*
115*
113*
2.6
2.2
1.8
2.0
223
213
207
226
*Statistically significant:  p < 0.05 or better.
                                -30-

-------
                            Table 6
                   Response to Sulfur Dioxide
PPM
Number of Animals


Resistance
  cm H20/ml/sec
Compliance
  ml/cm H_0
R x C
  sec
Frequency
  breaths/min
Tidal Volume
  ml
Minute Volume
  ml


Control
1 hr
2 hr
Post Exp.
Control
1 hr
2 hr
Post Exp.
Control
1 hr
2 hr
Post Exp.
Control
1 hr
2 hr
Post Exp.
Control
1 hr
2 hr
Post Exp.
Control
1 hr
2 hr
Post Exp.
0.2
10
0.62
0.64
0.59
0.58
0.24
0.21
0.21
0.20
0.149
0.134
0.124
0.116
87
93
94
89
2.3
2.2
2.3
2.1
200
204
216
187
0.4
10
0.59
0.63
0.57
0.56
0.20
0.20
0.19
0.18
0.118
0.126
0.108
0.101
89
95
92
94
2.0
2.1
2.0
2.1
178
199
184
197
0.8
10
0.62
0.66
0.64
0.60
0.23
0.23
0.24
0.22
0.143
0.152
0.154
0.132
78
80
76
74
2.1
2.3
2.2
2.1
169
184
167
155
                              -31-

-------
                           Table 7

              Response to Combination of Ozone
                    and Sulfur Dioxide
PPM
Number of Animals

Resistance
  cm H20/ml/sec
Compliance
R x C
  sec
Frequency
  breaths/min
Tidal Volume
  ml
Minute Volume
  ml


Control
1 hr
2 hr
Post Exp.
Control
1 hr
2 hr
Post Exp.
Control
1 hr
2 hr
Post Exp.
Control
1 hr
2 hr
Post Exp.
Control
1 hr
2 hr
Post Exp.
Control
1 hr
2 hr
Post Exp.
0.4
10
0.42
0.40
0.33
0.31
0.27
0.23
0.22*
0.28
0.113
0.092
0.072*
0.087*
91
104*
108*
111*
2.6
2.2
2.1
1.9
237
229
227
211
0.8
10
0.55
0.56
0.42
0.37
0.28
0.23
0.21*
0.24
0.154
0.129
0.088*
0.089*
71
89*
88*
99*
2.6
2.4
2.1
2.1
184
214
185
208
*Statistically significant:  p < 0.05 or better.
                             -32-

-------
VI.  Oil Mists and Sulfur Dioxide




     This work is described in detail by Daniel L. Costa in a



thesis:  The Physical and Physiological Effects of Oil Mists and



Sulfur Dioxide (Harvard School of Public Health, May, 1977).  Two



manuscripts for publication are currently being prepared from this




material.



     When simultaneous exposures were made to 1 or 10 ppm sulfur



dioxide and 10 mg/m  motor oil, the irritant effects of sulfur



dioxide  (resistance increase) were antagonized.  Mineral oil



 (medicinal grade napthene oil) did not protect against sulfur di-



oxide.  When either the detergent or the dispersant component of



the "additive package" used in the motor oil were added to mineral



oil, partial protection was obtained.  The addition of both of these



components to mineral oil essentially reproduced the protection re-




sulting from the motor oil.  We were unable to elicit true coopera-



tion from the manufacturers due to the proprietary nature of their



product.  Our attempts to negotiate with them bore more resemblance,



to a game of twenty questions  than to a scientific inquiry.



     Neither motor oil nor medicinal mineral oil protected animals



from the irritant effects of  formaldehyde, suggesting that the



protection observed with the motor oil was specific  for sulfur di-



oxide  and not a  general protection against irritant  action per se.



     One curious  finding, which was not included  in  the thesis



write-up, was the fact that  the  addition of a-tocopherol to  the



medicinal mineral oil would  protect against the irritant action of



 sulfur dioxide.   We  currently  have no  rational  explanation  to offer
                             -33-

-------
for this.  It is probably worth further work to determine whether


it was a local effect in the lung or would also be observed if


vitamin E were administered by more usual routes.



VII.  Preliminary work on Sulfites



    The finding by the group at Brigham Young University that


in the presence of some trace metals, sulfur remains as SIV


rather than being oxidized to S   points up the need for toxicolog-


ical work on sulfites and bisulfites.


    Alarie e_t al. (Environ. Physiol. Biochem. 3^:182, 1973) reported


that sodium bisulfite was more irritating than sulfur dioxide and


that sodium sulfite was not irritant.  They were using reduction


of respiratory frequency in mice as the criterion of irritant


response.  The concentrations are all reported as S09 equivalents.


    If one aerosolizes a solution of sodium bisulfite, one ends


up by generating sulfur dioxide, with no sulfur in a particle


mode.  Alarie used a glycol to stabilize the aerosol phase, but
i

the paper does not define how much sulfur was in the aerosol phase


and how much was present as sulfur dioxide gas.  A phone call


indicated that as they had not used a filter in their sampling


system, no effort had been made to determine this factor.  We


tried their system, using the glycol.  With the bisulfite, some


was indeed present on the filter, but some was also present as sul-


fur dioxide gas  (unless of course it came off the filter rather


than being present in the chamber atmosphere).
                             -34-

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     The system had other disadvantages, as there is evidence



that some liquid aerosols capable of dissolving sulfur dioxide will



cause potentiation of response to the gas.  In order to properly



cope with this possibility, we would have had to run a separate



series with the glycol plus sulfur dioxide gas.  Overall, the



system seemed too inoptimum to spend further time on at this



moment.  We also had a problem with an infection in our supply



colony of guinea pigs.  These factors, combined with problems of



moving myself and my lab from Harvard to M.I.T., led me to throw



in the sponge on this project for the time being.  I plan to



return to the problem of S  -aerosol complexes, but not via this



particular generation system.
                           -35-

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TECHNICAL REPORT DATA
/Please read Instructions on the reverse before completing)
1 REPORT NO.
EPA-600/1-78-021
2
4. TITLE AND SUBTITLE
PHYSIOLOGICAL RESPONSE TO ATMOSPHERIC POLLUTANTS
7. AUTHOR(S)
Mary 0. Amdur
9. PERFORMING ORGANIZATION NAME Al>
Department of Physiology
Harvard University School c
665 Huntington Avenue
Boston, Massachusetts 021 IE
•ID ADDRESS
f Public Health
12. SPONSORING AGENCY NAME AND ADDRESS
Health Effects Research Laboratory RTP,NC
Office of Research and Development
U.S. Environmental Protection Agency
Rpsearr.h Triangle Park, NT ?7711
15. SUPPLEMENTARY NOTES
3 RECIPIENT'S ACCESSION NO.
5. REPORT DATE
March 1978
6. PERFORMING ORGANIZATION CODE
8. PERFORMING ORGANIZATION REPORT NO.
10. PROGRAM ELEMENT NO.
1AA601
11. CONTRACT/GRANT NO.
R-802030
13. TYPE OF REPORT AND PERIOD COVERED
14. SPONSORING AGENCY CODE
EPA 600/11


16. ABSTRACT
During the period of this grant several materials were examined as air pollutants of
interest for their irritant effects. These included sulfuric acid, a series of
inorganic sul fates, and a combination of ozone and sulfur dioxide. Some attention
was also given to the effect of various oil mists on the irritant response to sulfur
dioxide. The method used for measuring irritant response was by simultaneous
tracings of intrapleural pressure, tidal volume, and rate of flow of gas in and out
of the respiratory system. By relating the intrapleural pressure change to the
change in flow rate at points of equal lung volume, it was possible to calculate
the flow resistance; by relating pressure change to volume at the beginning and
end of inspiration, it was possible to calculate compliance. The concentrations
used in these studies are well within the range of human exposure. These studies
indicate that the irritant response previously observed at higher concentrations
of sulfuric acid is also observed at concentrations below 1 mg/m^. The failure
of alterations in resistance to return promptly to control values following
termination of exposure has been a consistent finding in the work with various
irritant aerosols. The lowest concentrations used in these studies (100 yg/nr)
are in the range of concentrations which have been reported as short-term maxima in
urban atmospheres.
17.
a. DESCRIPTORS
KEY WORDS AND DOCUMENT ANALYSIS
b. IDENTIFIERS/OPEN ENDED TERMS
air pollution
sulfuric acid
sul fates
lung
toxicity
13 DISTRIBUTION STATEMENT
RELEASE TO PUBLIC
19. SECURITY CLASS (This Report)
UNCLASSIFIED
20. SECURITY CLASS (This page )
UNCLASSIFIED

c. COSATI Held/Group
06 F, P, T
21. NO OF PAGES
40
22. PRICE
EPA Form 2220-1 (9-73)
                                                            36

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