EPA-540/1-86-031
                                          	ce of Emergency and
                                          Remedial Response
                                          Washington DC 20460
                     Superfund
&EPA
Off'ce of Research and Development
Office of Health and Environmental
Assessment
Environmental Criteria and
Assessment Office
Cincinnati OH 45268
                       HEALTH EFFECTS  ASSESSMENT
                       FOR  SULFURIC  ACID

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                                           EPA/540/1-86-031
                                           September 1984
       HEALTH  EFFECTS  ASSESSMENT
            FOR  SULFURIC ACID
    U.S. Environmental  Protection  Agency
     Office of Research and  Development
Office of  Health  and  Environmental Assessment
Environmental Criteria  and Assessment Office
            Cincinnati,  OH  45268
    U.S. Environmental  Protection  Agency
  Office of  Emergency and Remedial Response
Office of Solid Waste and  Emergency  Response
            Washington, OC  20460

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                                  DISCLAIMER

    This  report  has  been  funded  wholly  or  In  part  by  the  United  States
Environmental  Protection  Agency under  Contract  No.  68-03-3112  to  Syracuse
Research Corporation.  It has been  subject  to  the Agency's peer and adminis-
trative review, and  1t has  been  approved  for  publication as an EPA document.
Mention of  trade  names or  commercial  products  does  not  constitute  endorse-
ment or recommendation for use.
                                      11

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                                    PREFACE
    This report  summarizes  and evaluates information relevant  to  a prelimi-
nary  interim  assessment of adverse  health  effects associated  with sulfuric
acid.  All estimates of acceptable  Intakes  and  carcinogenic  potency present-
ed in this document  should  be considered as  preliminary  and reflect limited
resources  allocated  to  this   project.   Pertinent  toxicologic  and  environ-
mental data were located through on-Hne  literature  searches of the Chemical
Abstracts, TOXLINE,  CANCERLINE  and  the  CHEMFATE/DATALOG  data bases.   The
basic  literature  searched   supporting   this   document   is   current  up  to
September, 1984.   Secondary  sources of  Information have  also been  relied
upon  in  the  preparation  of  this   report  and  represent  large-scale  health
assessment  efforts  that  entail  extensive   peer  and  Agency  review.   The
following  Office  of Health  and Environmental  Assessment (OHEA)  source has
been extensively utilized:


    U.S. EPA.   1982.   Air Quality  Criteria for Partlculate Matter and
    Sulfur  Oxides.  Vol.  II.   Environmental  Criteria  and  Assessment
    Office, OHEA,  Research Triangle  Park, NC.   EPA 600/8-82-029b.   NTIS
    PB 84-156793.


    The intent In  these assessments  is  to suggest  acceptable exposure levels
whenever sufficient data were available.   Values were not derived  or  larger
uncertainty factors  were employed  when  the  variable data  were  limited  in
scope tending  to generate conservative  (I.e.,  protective) estimates.  Never-
theless, the  interim values presented reflect the relative  degree  of  hazard
associated with exposure or  risk to  the chemlcal(s) addressed.

    Whenever  possible,  two categories of values  have  been estimated for sys-
temic toxicants (toxicants for which  cancer  is  not the  endpoint of concern).
The  first,  the AIS  or  acceptable  intake  subchronic, Is  an estimate  of  an
exposure  level  that would  not  be   expected  to cause  adverse effects  when
exposure occurs  during  a  limited time  Interval  (I.e.,  for  an  Interval that
does  not  constitute  a  significant  portion  of  the lifespan).  This  type  of
exposure estimate  has  not been  extensively  used  or  rigorously defined,  as
previous  risk  assessment   efforts   have  been  primarily  directed  towards
exposures from toxicants in ambient air or  water  where  lifetime  exposure  is
assumed.   Animal  data  used   for  AIS estimates  generally include  exposures
with  durations of  30-90 days.  Subchronic  human data are  rarely  available.
Reported exposures are  usually  from chronic  occupational  exposure  situations
or from reports of acute accidental  exposure.

    The  AIC,  acceptable intake  chronic, is  similar in  concept  to  the ADI
(acceptable daily  intake).    It  1s  an  estimate  of  an  exposure  level  that
would not  be  expected  to  cause adverse effects  when exposure occurs  for  a
significant portion of the lifespan  [see  U.S.  EPA  (1980)  for a discussion  of
this concept].  The AIC  is  route specific and  estimates  acceptable exposure
for a given route with  the implicit  assumption  that  exposure by other routes
is insignificant.
                                      111

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    Composite  scores   (CSs)  for  noncarcinogens  have also  been  calculated
where data permitted.   These  values  are used for  ranking  reportable  quanti-
ties; the methodology for their development is explained  1n U.S.  EPA (1983).

    For compounds for which there  1s  sufficient  evidence  of  cardnogenlclty,
AIS  and  AIC values  are not derived.   For a  discussion  of risk  assessment
methodology  for  carcinogens refer  to  U.S.  EPA  (1980).   Since  cancer  is  a
process that  1s  not characterized by  a threshold, any exposure  contributes
an Increment of  risk.   Consequently,  derivation of AIS and  AIC  values would
be Inappropriate.   For  carcinogens,  q-|*s  have been  computed  based on  oral
and inhalation data 1f available.
                                      1v

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                                   ABSTRACT
    In  order  to  place  the  risk assessment  evaluation  in  proper  context,
refer  to  the preface  of   this  document.   The  preface outlines  limitations
applicable to all documents of  this  series as  well  as  the appropriate Inter-
pretation and use of the quantitative estimates presented.

    Although  considerable  data  are available  concerning  the  effects  of
sulfurlc add,  reported effects  Include  only  localized  Irritant  effects  at
the point of  entry  following  Inhalation {respiratory  tree and  lungs).   Data
regarding systemic toxic effects  are  lacking.  Therefore,  an estimate of AIS
or AIC, which by  definition estimate absorbed dose  In mg/day  1n  relation to
systemic  toxldty,  would   be   Inappropriate.   Available   data,  however,  do
allow  estimation  of   an   acceptable  air  exposure  concentration  of  0.07
mg/m3.  A  CS  of 26.8 was  calculated for  the  effects  of   dental  etching and
erosions that occur  rapidly at relatively  low atmospheric  concentrations.

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                               ACKNOWLEDGEMENTS
    The  Initial  draft  of  this  report  was  prepared  by  Syracuse  Research
Corporation  under  Contract No.  68-03-3112  for EPA's  Environmental  Criteria
and  Assessment  Office,  Cincinnati,  OH.   Dr.  Christopher  DeRosa and  Karen
Blackburn were the Technical Project Monitors  and  Helen Ball  was*the Project
Officer.  The final documents  1n  this  series  were  prepared  for the Office of
Emergency and Remedial Response, Washington, DC.

    Scientists from  the  following U.S. EPA offices  provided  review comments
for this document series:

         Environmental Criteria and Assessment Office, Cincinnati, OH
         Carcinogen Assessment Group
         Office of A1r Quality Planning and Standards
         Office of Solid Waste
         Office of Toxic Substances
         Office of Drinking Water

Editorial review for the document series was provided by:

    Judith Olsen and Erma Ourden
    Environmental Criteria and Assessment Office
    Cincinnati, OH

Technical support services for the document series  was provided by:

    Bette Zwayer, Pat Daunt, Karen Mann and Jacky Bohanon
    Environmental Criteria and Assessment Office
    Cincinnati, OH
                                      v1

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                         TABLE OF  CONTENTS

1.
2.


3.








ENVIRONMENTAL CHEMISTRY AND FATE 	
ABSORPTION FACTORS IN HUMANS AND EXPERIMENTAL ANIMALS . . .
2.1.
2.2.
ORAL 	
INHALATION 	
TOXICITY IN HUMANS AND EXPERIMENTAL ANIMALS 	
3.1.


3.2.


SUBCHRONIC 	
3.1.1. Oral 	
3.1.2. Inhalation 	
CHRONIC 	
3.2.1. Oral 	
3.2.2. Inhalation 	
Page
1
3
. . . 3
3
4
4
. . . 4
4
6
. . . 6
. . . 6
3.3.   TERATOGENICITY AND OTHER REPRODUCTIVE EFFECTS.


3.4.
3.3.1. Oral 	
3.3.2. Inhalation 	
TOXICANT INTERACTIONS 	
4. CARCINOGENICITY 	
4.1.


4.2.


4.3.
4.4.
5. REGULl
HUMAN DATA 	
4.1.1. Oral 	
4.1.2. Inhalation 	
BIOASSAYS 	
4.2.1. Oral 	
4.2.2. Inhalation 	 ,
OTHER RELEVANT DATA 	
WEIGHT OF EVIDENCE 	
VTORY STANDARDS AND CRITERIA 	
	 8
	 8
, 	 8
	 10
	 10
	 10
	 10
	 10
	 10
	 10
	 10
	 10
	 11
                                 V11

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                          TABLE OF CONTENTS (cont.)

                                                                        Page

 6.  RISK ASSESSMENT	    12

     6.1.   ACCEPTABLE INTAKE SUBCHRONIC (AIS)  	    12

            6.1.1.    Oral	    12
            6.1.2.    Inhalation	    12

     6.2.   ACCEPTABLE INTAKE CHRONIC (AICJ	    12

            6.2.1.    Oral	    12
            6.2.2.    Inhalation	    12

     6.3.   CARCINOGENIC POTENCY (q-j*)	    14

            6.3.1.    Oral	    14
            6.3.2.    Inhalation	    14

 7.  REFERENCES	    15

APPENDIX: Summary Table for  SulfuMc  Acid	    22

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                             LIST  OF  ABBREVIATIONS





ADI                     Acceptable dally intake



AIC                     Acceptable intake chronic



AIS                     Acceptable intake subchronlc



CAS                     Chemical Abstract Service



CS                      Composite score



NOEL                    No-observed-effect level



TLV                     Threshold limit value



TWA                     Time-weighted average
                                      ix

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                     1.   ENVIRONMENTAL  CHEMISTRY  AND  FATE

    Sulfuric  acid   (CAS  No.  7664-93-9),  H2S04,  is  a  colorless,   viscous
liquid with  a molecular weight  of 98.08  and  a  specific  gravity of  1.8357
(Donovan and  Salamone,   1983).   SulfuMc  acid   1s  soluble 1n  water  in  all
proportions with evolution  of heat and 1t  has a  vapor  pressure  of 1 mm Hg at
145.8°C (Weast,  1980).
    The primary  sources  of  sulfuric  acid  in  the  atmosphere are  vehicular
emissions,  combustion sources, explosive manufacture,  furnace soot, sulfuric
acid manufacture,  steel  manufacture  and volcanic emissions  (Graedel,  1978).
Sulfuric add  is  present  in  the  atmosphere  in  the  form  of aerosols.   The
size  fractionation of  sulfur-containing aerosols  [which  primarily consists
of  H SO   and   (NH4)2   S04]  show  that   in  dry   weather  the  aerosol   is
found  in   sub-0.65 ym  particle  size  fractions, while under  humid   condi-
tions,  the aerosol  is  found  in the  0.65-3.6  vm particle size  range  (U.S.
EPA,  1982).   Size  fraction  analysis  of  sulfate aerosol  in the  atmosphere
also showed that the predominant amount  (70%) of sulfate  ions are present in
the submicron particle  range (U.S.  EPA,  1982).
    The fate  of  sulfuric add aerosols  in the   environment  has  been  studied
by  a  limited  number of  Investigators  (U.S.  EPA, 1982) and  significant data
gaps exist  in this  area.   It  is  likely  that  sulfuric add  aerosol will react
chemically  with  other  species  in  the atmosphere.   The source   of  Inorganic
sulfates 1n  the atmosphere,  particularly  ammonium  sulfate,   has  been  demon-
strated to be due  primarily  to chemical  reactions  In the  atmosphere  (U.S.
EPA,  1982).   Similarly,  depending  upon  the   amount  of  dilution  by  the
moisture in  the  atmosphere, sulfuric acid aerosols  may react  with  organics
in  the atmosphere  to form sulfonates.
                                      -1-

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    Besides  chemical  transformation,  sulfurlc acid  aerosols  in  the  atmo-
sphere are likely  to  be  removed through wet and  dry  deposition;  however,  no
estimate of  the  half-life of atmospheric  sulfurlc  acid due  to  Us  chemical
transformation and  physical  removal processes  was  located in  the  available
literature.
    In  aquatic  media  of  pH  >7,   sulfurlc  add   reacts  with  carbonate,
bicarbonate  or hydroxides  1n the sediment  or  suspended particles,  with  the
formation  of  sulfates.   Since the  majority  of sulfates, with  the  exception
of lead  and  calcium,  are soluble in water,  this  reaction  may remobilize  the
precipitated  metals  from the  aquatic  phase   and  decrease  the pH of  the
solution.  In  aquatic  media  of pH  <7,  at  least a part  of  the  sulfuric acid
may remain Ionized in solution and may be mobile.
    The  majority  of  sulfurlc  acid  1n  soils  is  expected  to be removed  by
reaction with  Inorganic  minerals  or organic matter in  soils.  The  extent of
this  chemical  reaction may  depend  on  the  strength  of  the sulfurlc  acid In
the soil.   As the concentration  of the add  decreases  through  reactions or
dilution  through   water,  the  reactivity  should  also  decrease.  In  highly
sandy soil,  sulfurlc acid probably  leaches Into groundwater.
                                      -2-

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           2.  ABSORPTION FACTORS IN HUMANS AND EXPERIMENTAL ANIMALS



2.1.    ORAL


    Pertinent  data   regarding  the  absorption  of  sulfurlc  add   from  the



gastrointestinal   tract  could  not  be  located  1n  the  available literature.



Since  the  major  toxic  effect  of  sulfurlc  add  1s  local  Irritation,  and



because of the buffering capacity of the blood,  1t  Is unlikely  that  signifi-



cant systemic exposures occur.



2.2.   INHALATION



    Pertinent data  regarding the absorption of  Inhaled  sulfurlc add could



not be located 1n the available  literature.  Since  the major  toxic  effect of



sulfurlc add Is  local Irritation and  since  inhaled sulfurlc  add  1s  largely



neutralized  by   NH   in  the  expired  air,  it  is  unlikely  that significant
                  O


systemic exposure to sulfurlc add occurs.
                                      -3-

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               3.  TOXICITY IN HUMANS AND EXPERIMENTAL ANIMALS

    Carson et  al.  (1981) reviewed  more  than 400  studies  on the effects  of
sulfurlc add  on  humans and  experimental  animals.   A  thorough analysis  of
these data  Is  not possible  within  the  constraints  of  the  current  project.
Therefore,  the following  review  will   concentrate   on  those  studies  that
provide  data  on   the  effects  of  near   threshold doses  of  sulfurlc  add
(Table 3-1).
3.1.   SUBCHRONIC
3.1.1.   Oral.   Pertinent  data  regarding  the  subchronlc  oral  toxidty  of
sulfurlc add could not be  located in the available literature.
3.1.2.   Inhalation.    Schleslnger   et   al.   (1978,   1979)   reported   that
exposure  of   donkeys   to   -0.1   mg  HpS04/m3  (0.102-0.106  mg/m3)   for   1
hour/day, 5  days/week,  for  6  months resulted in erratic bronchial  clearance
1n  the  last  week  of  exposure.   Respiratory  rates were  reduced in  all  four
animals, and two  of  the four  donkeys sustained Impairment of  clearance  with
erratic  improvement  during a  3-month follow-up  period.   Concentrations  as
low  as  0.071  mg/m3   administered  as   "repeated  doses"  were  reported  to
decrease  the rate of  bronchial  mucodliary   clearance,  but  the duration  of
these exposures was not reported.
    Loscutoff  et  al.   (1978)  exposed  dogs to atmospheres  containing  1.0  mg
H-SO./m3  for  "repeated  doses."   The   number   of  animals,  sex,   duration
and number of  exposures  were  not  reported.   No  effects  were  reported and all
exhaled sulfate was in the  form of an ammonium salt.
    Rats appear to be  relatively  insensitive  to the  effects  of sulfuric  add
aerosols.  Lawkowski et  al.  (1979)  exposed groups of 10 male  Sprague-Dawley
rats  to  ambient   atmospheres  or  atmospheres  containing  2.37  mg  H_SO./m3,
                                      -4-

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                                                                   TABLE  3-1



                                                  Threshold  Doses  for  Sulfurlc  Acid  Toxlclty*
Species rag HpSO^m3
(particle size)
Nonkey -0.1 plus fly ash and/or
S02 (NR)
Donkey 0.102 or 0.106 (0.5 urn)




Donkey 0.071-1.364 (0.3-0.6 tun)
Dog 1.0 (NR)

\
in
1 Dog -0.09 In auto exhausts
(NR)
\ "™ /



Guinea pig 0.08 (0.84*0.60 ym)

Rat 2.37 (0.5*1.0 ,nn)


Rat 0.61 SOf (presumably most
H2S04) In auto exhausts
Exposure
Conditions
22-24 hours/day
1 hour/day;
5 days/week




1 hour by nasal
catheter
"repeated doses*


16 hours/day




22-23 hours/day

continuous


24 hours/day

Length of Length of Comments
Exposure Study
18 months 18 months NOEL for some combina-
tions of pollutants
6 months 6 months Sustained Impairment In
bronchial mucoclllary
clearance In two of four
donkeys. Some Improve-
ment within 3-month
recovery period.
NR NR Bronchial mucoclllary
clearance slowed.
NR NR NOEL (at 3.5 mg/m>).
Increased pulmonary
resistance.

68 months 104 months Emphysema tous and other
microscopic lung changes
3 years after 68-month
exposure.


12 months 12 months Lowered growth rate In
females. NOEL In other
studies.
14 weeks 14 weeks NOEL (lung function,
blood chemistry,
behavior).
7 days 7 days Lower body weight.

Reference
Alarle et al., 1975
Schleslnger et al.,
1979




Schleslnger et al.,
1978
Loscutoff et al.,
1978


Lewis el al., 1974;
Bloch et al., 1972,
1973; Orthoefer et
al.. 1976; Hyde et
al., 1978; Vaughan
et al., 1969
Alarle et al.,
1973. 1975

Lawkowsk! et al.,
1979

Lee et al., 1976

*Source: Carson et al.. 1981



NR = Not reported

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24 hours/day, 7 days/week,  for  14 weeks.  There were  no  significant  effects
on behavior,  as measured  by spontaneous  motor  activity,  lung function  or
blood acid-base chemistry.  Lee et al.  (1976) reported  decreased  body weight
gain   1n  female Sprague-Oawley  rats  (10/group)  exposed  to  0.6  mg  SO^/m3   In
auto   exhausts   24  hours/day for  7  days.   The  S0]j  was,  presumably,  mostly
In the form of H2S04-
3.2.    CHRONIC
3.2.1.   Oral.   Pertinent  data  regarding  the   chronic   oral  toxldty  of
sulfuMc add could not be located 1n the available literature.
3.2.2.   Inhalation.   Alarle   et   al.   (1975)   exposed   groups   of   nine
Cynomolgus  monkeys  of  both  sexes  to  atmospheres  containing 0.09-0.99  mg
H_SO /m3  1n  combination  with  varying  amounts   of  fly  ash  and/or  SO,,.
At   concentrations   of  0.1-0.11  mg  HpSO./m3,    significant   time-related
Increases  1n  pulmonary resistance were  reported  for some  combinations.   No
treatment-related  effects   were  reported  for  any  combination of  exposures
with a sulfurlc add concentration of 0.09 mg/m3.
    Several  Investigators   (Lewis  et al.,  1974;  Bloch et  al., 1972,  1973;
Orthoefer  et  al.,   1976;  Vaughan et  al.,  1969;  Hyde  et  al.,  1978)  exposed
purebred  female  dogs   (12/group,  20  controls)  to  atmospheres  containing
0.09-0.11   mg  HpSO./m3   and   varying   concentrations   of  S02  and  auto
exhaust 16  hours/day,  7  days/week, for  up to  68 months, followed by observa-
tion  for  an additional 32-36 months.   At the end  of  the  3-year  observation
period,  there  was   significant  ciliary  loss,  squamous  metaplasia,  air-space
enlargement and nondllated bronchlolar cell hyperplasla (Hyde et al., 1978).
    Alarle  et al.  (1973,  1975)  Investigated the effects  of chronic  exposure
of guinea  pigs  to  sulfurlc add, with  or without  simultaneous  exposure  to
0.45  mg  fly ash/m3.   Groups  of  50  male and 50  female Hartley  guinea  pigs
                                      -6-

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were  exposed  to  atmospheres  containing 0,  0.08,  0.10  or  0.30 mg  HpSO./m3,
22-23  hours/day  for   12  months.   No  effects  were observed  on  survival,
hematology or  histology  at  any dose level.  Exposure to  sulfurlc acid alone
resulted  In  decreased  growth rates  1n  the  females  exposed to  0.08  or 0.10,
but  not  0.30  mg/m3.   No effects  were  reported  1n guinea  pigs  exposed  to
0.08 mg H SO /m3 and 0.45 mg fly ash/m3.
    Flnklea et al.  (1975a,b) estimated  the  threshold for  Increase In ambient
air  sulfate  with  Increasing  air  pollution  In  terms of  adverse  effects  1n
humans,  based  on  ep1dem1olog1cal  studies  (Table  3-2).  They estimated  that
exposure  to  as  little  as  0.01   mg  H?SO./m3  for  up   to  10  years   can
result 1n an Increased risk of  chronic  bronchitis  In smokers.  Total sulfate
was determined 1n  the  atmosphere,  but  sulfurlc  add 1s  usually  considered to
be a major fraction of the  measured  sulfate.  It  1s also  often  Impossible to
separate  the  effects   of   sulfurlc  add   from  those  of  other  pollutants
(particularly 0„, NO ,  S00,  HC1).
               j    X    c
    Occupational  exposures  have  been  associated  with   Increased  dental
erosion,  eye  Irritation  and effects  on the respiratory  system (Tadzhlbaeva
and GoVeva, 1976;  El-Sad1k  et al.,  1972; Williams, 1970;  Malcolm and Paul,
1961; ten Bruggen  Gate,  1958;  Jones  and Gamble, 1984; Gamble et al.,  1984).
The toxldty of  sulfurlc  add  vapors to the human  respiratory  tract Is  well
recognized.   Williams  (1970)  observed  a slight  Increase  1n  bronchitis among
workers exposed  to  sulfurlc acid  1n  a  battery  manufacturing plant  compared
with nonexposed workers  at  the  same  plant.   Exposure levels had previously
been estimated  at  1.4  mg/m3,  which  1s sufficient  to  cause dental  erosion
1n the exposed workers (Anfleld  and  Warner, 1968).   A higher  Incidence (36%)
of bronchitis  of  apparently greater  severity  was  noted  by  El-Sad1k  et  al.
(1972)  In a group  of  33  workers 1n  two  battery factories.  The Incidence of
                                     -7-

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bronchitis was 21%  1n  unexposed  controls (what size not  reported).   Some  of
the  increased  incidence of  bronchitis  in the  exposed  workers and  the  high
incidence  in  controls  appeared  to  be  related  to  smoking  habits.   Dental
Infections and  tooth  discolorations  were also  observed  in exposed  workers
and  the  incidence  and  severity   appeared   to  correlate  positively  with
duration of exposure.
    Malcolm and  Paul  (1961)  also  reported  severe  tooth  erosion among  160
acid-battery factory  workers.   The  incidence  and  severity were  more  severe
at  concentrations  of  3-16 mg/m3  than  at  0.8-2.5  mg/m3.   In some  workers
exposed  to  the  higher  levels  the  height of  their incisors was decreased  by
as much  as  50%.   In a  more  recent investigation of the  effects  of  sulfuric
acid on  the teeth,  erosions  were observed in  workers  exposed  to  atmospheres
of  0-1.7 mg/m3  (average  0.18 mg/m3)  (Jones  and   Gamble,  1984; Gamble  et
al.,  1984).   Exposure  to  0.23  mg/m3  for  4  months  was   sufficient  to
initiate erosion.
3.3.   TERATOGENICITY AND OTHER REPRODUCTIVE  EFFECTS
3.3.1.   Oral.  Pertinent  data regarding the teratogenicity or other  repro-
ductive  effects of orally  administered  sulfuric  add could not be located In
the available literature.
3.3.2.   Inhalation.   Pertinent  data regarding  the  teratogenicity  or  other
reproductive effects  of inhaled sulfuric acid could  not be  located  in the
available literature.
3.4.   TOXICANT INTERACTIONS
    The  toxidty  of inhaled  sulfuric  acid  is  heavily influenced  by,  among
other factors, the presence  of other  particulates  in the  air  (Carson et al.,
1981).   Due to  the  hygroscopic nature of  sulfuric acid,  there is a tendency
for  sulfuric acid  droplets to absorb water  from  the breath,  creating larger
                                      -8-

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droplets  that  Impact  high  1n  the upper  respiratory  tract where  they  cause
less damage.   When  the sulfurlc  add  1s  absorbed to other  partlculates,  1t
may be carried deeper  Into the respiratory tract.
    Inhaled  sulfurlc   acid  mists  are  rapidly neutralized  by  NH3  1n  the
expired air  (Barrow and  Stelnhagen,  1980).   This neutralization  1s  reduced
when the sulfurlc add 1s absorbed to airborne partlculates (Lawther,  1980).
    Synerglsm  has   also   been  demonstrated  between   sulfurlc  add  and  the
pollutants normally  found 1n auto  exhausts  (SO^, ozone,  metallic  aerosols)
(Carson et  al., 1981).   The specific  Interactions   Involved  have not  been
fully  elucidated  and  studies  In humans  have not consistently  demonstrated
the synerglstlc effects observed 1n experimental  animals.
                                      -9-

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                             4.  CARCINOGENICITY
4.1.   HUMAN DATA
4.1.1.   Oral.   Pertinent  data   regarding   the  cardnogenldty  of  orally
administered sulfurlc add could  not  be  located  1n  the available literature.
4.1.2.   Inhalation.    Pertinent   data  regarding   the   cardnogenldty   of
Inhaled sulfurlc add could not be  located 1n  the available literature.
4.2.   BIOASSAY
4.2.1.   Oral.   Pertinent  data   regarding   the  cardnogenldty  of  orally
administered sulfurlc add could  not  be  located  1n  the available literature.
4.2.2.   Inhalation.    Pertinent   data  regarding   the   cardnogenldty   of
Inhaled sulfurlc add could not be  located 1n  the available literature.
4.3.   OTHER RELEVANT DATA
    One  study  was located  1n which  Escherlchla  coll  (strain  unspecified)
were treated with 0.002-0.005% sulfurlc acid  solutions  for  3 hours  (Oemerec
et al., 1950, 1951).   No  Increase In mutation  frequency was observed.
4.4.   WEIGHT OF EVIDENCE
    IARC  has  not  evaluated  the risk  to  humans  associated with  oral  or
Inhalation exposure  to sulfurlc  add.   Data  were not available regarding the
cardnogenldty  of   sulfurlc  add   1n  humans  or  animals.   Applying  the
criteria for evaluating the overall  weight of evidence of cardnogenldty to
humans proposed by the Carcinogen Assessment  Group of  the U.S.  EPA  (Federal
Register, 1984), sulfurlc add 1s most  appropriately  designated  a  Group D -
Not Classified chemical.
                                    -10-

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                     5.   REGULATORY STANDARDS AND CRITERIA







    The  ACGIH   (1980)  has  recommended  a  TLV  of   1  mg/m3.   This  value  1s



recommended to  "prevent  pulmonary  Irritation  and Injury to  the  teeth."   The



USSR  has  established  an  average  maximum  allowable  concentration for  the



ambient  air  of  populated  places  of  0.1  mg  H2S04/m3  with  an  allowable



peak  value of  0.3  mg/m3  (USSR  State Committee  of  the  Ministers  for  Con-



struction,  1972).   The  ACGIH  (1980)  reports  that  both the  USSR  and  Czecho-



slovakia   have  recommended   a   limit  of  1   mg   H  SO /m3   for   Industrial



exposures.   The  U.S.   Occupational   Safety  and  Health  Administration  has



established  an  8-hour   TWA  of  1  mg  H2S04/m3  (Code  of  Federal  Regula-



tions, 1981).
                                     -11-

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                             6.  RISK ASSESSMENT
6.1.   ACCEPTABLE INTAKE  SUBCHRONIC  (AIS)
6.1.1.   Oral.    Pertinent  data  regarding  the  subchronlc  oral  toxldty of
sulfuMc add could not be located  1n  the  available  literature.
6.1.2.   Inhalation.    The only  reported  effects   of   exposure  to  Inhaled
sulfuMc  add  were  localized  effects  at  the  point   of  entry.   Since an
Interim  AIS  1s  based  on the  absorbed  dose,  It 1s  Inappropriate  to  derive
these numbers  from local irritant  effects.   Based  on  studies with  donkeys,
which have  respiratory  systems  anatomically  similar  to  humans,  subchronlc
exposure  to  atmospheric  concentrations   as   low   as   71   yg  H_SO./m3   may
produce a measurable decrease  in the  rate of  bronchial  mucodliary  clearance
(Schlesinger et a!.,  1978, 1979).
6.2.   ACCEPTABLE INTAKE  CHRONIC (AIC)
6.2.1.   Oral.    Pertinent  data  regarding   the chronic   oral   toxicity of
sulfuMc acid could not be located  in  the  available  literature.
6.2.2.   Inhalation.    The only  reported  effects   of   chronic   exposure to
Inhaled sulfuric add are localized effects at  the  point  of  entry.   Since an
Interim  AIC  1s  based  on the  absorbed  dose,  it is  Inappropriate  to  derive
these  values  from the  available  data.   There are  some  Indications  that
tolerance to the  Irritant effects  of sulfuric  add develops with  repeated
exposures (Hackney,  1978; Bushtueva,  1957).   Thus,  individuals may be  able
to  tolerate  chronic  exposure  to concentrations of  sulfuric add which would
produce  significant  irritation during the  initial  exposure.   Carson  et al.
(1981)  estimated that  "a  lower  exposure  level  that appears  to be  safe for
man  1s  1n the range of  0.066-0.098 mg/m3."   They  point out  that  this value
may  be  influenced  by a number  of factors,  including particle  size,  frequency
and  duration of exposure and synerglstic  effects.
                                     -12-

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    This estimate  correlates  with  the  monkey data  of  Alarle et  al.  (1975)
which  showed  a NOAEL  of 0.09  mg/m3 even  when sulfuMc  add was  combined
with various  combinations  of  fly ash  and/or  S0? which would  be  expected  to
exacerbate  pulmonary  Irritation.   In  addition, the  TLV has  been set at  1
mg/m3;   therefore,  this  suggested range  Incorporates  a  minimum of  a  10-fold
uncertainty factor for  protection  of more sensitive  segments  of  the  general
population. Still  troubling  are the donkey  data (Schlesinger et  al.,  1978,
1979),   which   show  decreases  in bronchial  mucociliary  clearance at  0.071
mg/m3.    It is  uncertain  whether   the  donkey  Is   unusually   susceptible  to
sulfuric  acid  irritation  or  whether   this  study  evaluated   more  sensitive
endpoints  than  the other reports.   The  decrease  In  clearance  could represent
a metaplastic  response  of  the  bronchial  epithelium  to  Irritation, and  this
would  not  be  detected as a  deficit in pulmonary function.   This  deficit  In
clearance  capacity,  however,  could compromise  the  ability  to  clear  other
resplrable pollutants.
    For  these  reasons,  the  range  suggested  by   Carson  et   al.   (1981)  of
0.066-0.098  mg/m3  should   be  protective  for   exposures   to  sulfuric  acid
alone.    As more  data  become  available  revision  of this  estimate  may  be
required.
    A  CS was  calculated  for  the respiratory tract  effects observed in humans
and  animals  and for  the tooth  erosion and etching  that  occurred in  battery
manufacturing workers exposed for  as little as  4 months  to sulfuric  acid at
0.23 mg/m3.   In  the  latter   case,  the  exposure was  expanded  to continuous,
assuming  workers  inhale 10  m3  of  air  during  working hours  on  5 days/week.
An  uncertainty  factor   of  10  was  applied to  convert  from short-term  to
chronic exposure  since  1t  seems certain that  prolonged  exposure would result
                                     -13-

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1n increased  severity  of  the effect.  A human  MED  of  0.16 mg/day resulted,
corresponding to  an  RV.  of  6.7.   Tooth  erosion and  etching  were assigned
an RV  of 4.   A  CS of  26.8,  the  product of  RV. and RV , resulted.
     e                                      u       e
6.3.    CARCINOGENIC POTENCY  (q^)
6.3.1.   Oral.   Pertinent  data  regarding the  cardnogenicity  of  orally
administered  sulfuric  add could not be located  in the  available literature.
6.3.2.   Inhalation.    Pertinent  data  regarding   the  cardnogenlcHy   of
inhaled sulfuric add  could  not  be located  in the available literature.
                                     -14-

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                                7.   REFERENCES

ACGIH  (American  Conference  of  Governmental  Industrial  Hyg1en1sts).   1980.
Documentation  of  the   Threshold  Limit  Values,  4th  ed.    Cincinnati,  OH.
p. 377-378.

AlaMe,  Y.,  W.M.  Busey,  A.A.   Krumm and  C.E.  Ulrich.   1973.    Long-term
continuous exposure  to  sulfuMc add mist  1n cynomolgus monkeys  and  guinea
pigs.  Arch.  Environ. Health.  27:  16-24.   (Cited  1n  Carson  et  al.,  1981)

Alarle,  Y.C.,  A.A.  Krumm,  W.M. Busey,  C.E.  Ulrich and  R.J.  Kantz.   1975.
Long-term exposure to sulfur dioxide, sulfurlc add mist, fly  ash,  and their
mixtures.  Results  of  studies  1n  monkeys  and guinea  pigs.  Arch.  Environ.
Health.  30:  254-262.  (Cited in Carson et  al.,  1981)

Anfleld, B.D.,  and C.G. Warner.  1968.  A  study of  Industrial  mists contain-
ing sufluric  add.  Ann. Occup. Hyg.  11:  185-194.   (Cited  in  Gamble et al.,
1984)

Barrow,  C.S.  and  W.H.  Stelnhagen.   1980.   Ammonia  concentrations   in  the
expired air of the rat: Importance  to inhalation  toxicology.   Toxicol.  Appl.
Pharmacol.  53(1): 116-121.   (Cited  In Carson  et al.,  1981)

Bloch,  W.N.,  Jr., T.R.  Lewis,  K.A.  Busch,  J.G.  Orthoefer  and  J.F.  Stara.
1972.   Cardiovascular  status of  female  beagles  exposed  to air pollutants.
Arch. Environ Health.  24:  343-353.   (Cited in Carson  et  al.,  1981)
                                     -15-

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Bloch, W.N.,  Jr.,  S.  LassHer,  O.F.  Stara  and  T.R.  Lewis.   1973.   Blood
rheology  of  dogs  chronically  exposed  to  air pollutants.   Toxlcol.  Appl.
Pharmacol.  25:   576-581.   (Cited 1n Carson et al.,  1981)

Bushtueva, K.A.    1957.  The  determination  of the  limit of allowable  concen-
tration  of  sulfuric  acid  In  atmospheric  air   [Materialy  k  Ustanovleniyu
Predel'no  Dopustlmoi  Kontsentratsil  Aerozolya Sernoi  Klsloty Atmosfer  nom
Vozdukhe].   Predel'no  Dopustimye   Kontsentratsl   Atmosfernykh   Zagryazenii
[Limits of Allowable  Concentrations of Atmospheric  Pollutants].   33:  23-43.
(Cited in Carson et al.,  1981)

Carson, B.L., B.L.  Herndon,  H.V. Ellis  III, L.H. Baker and E.  Horn.   1981.
Sulfuric  Add Health Effects.   Prepared under  Contract  68-03-2928 by Midwest
Research  Institute, Kansas City,  MO.   Prepared for  Emission  Control Technol-
ogy Division, Office of  Mobile Source Air  Pollution  Control.   U.S. EPA,  Ann
Arbor, MI.  EPA 460/3-81-025.  NTIS PB82-113135.

Code  of  Federal  Regulations.   1981.   OSHA Safety and  Health  Standards.   29
CFR 1910.1000.

Demerec,  M.,  E.M. Witkin,  B.W. Catlin, et  al.  1950.  Methods  development
paper  for Demerec et  al.  (1951).   The  Gene. Carnegie  Institute Washington
Yearb.  49: 144-157.  (Cited 1n Carson et al., 1981)

Demerec,  M., 6. Bertanl and  J.  Flint.   1951.  Negative results for mutagene-
s1s   study  with  0.002-0.005%  H-S04  and   Escherichia  coll.   A   survey  of
chemicals  for mutagenic  action  on  E_.  coli.  Am.  Nat.   85:  119-136.  (Cited
in Carson  et al., 1981)

                                     -16-

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Donovan, J.R. and  J.M.  Salamone.   1983.   Sulfurlc acid and  sulfur  trloxide.
In.:  K1rk-0thmer  Encyclopedia  of Chemical  Technology,  3rd ed.,  Vol.  22,  M.
Grayson, Ed.   John Wiley and Sons,  Inc.,  NY.   p.  190-232.

El-Sad1k, Y.M., H.A. Osman  and  R.M.  el-Gazzar.  1972.  Exposure  to  sulfurlc
add  1n manufacture of storage  batteries.    J.  Occup.   Med.   14:  224-226.
(Cited In Gamble et al., 1984)

Federal Register.   1984.   Environmental  Protection  Agency.   Proposed  guide-
lines for carcinogenic  risk assessment.   Federal  Register.  49:  46294-46299.

Flnklea,  J.F.,   J.  Moran,  J.H.  Knelson,  D.B.  Turner  and  I.E.  Memeyer.
1975a.   Estimated  changes  1n human  exposure  to suspended sulfate  attribut-
able  to  equipping  light-duty   motor  vehicles   with  oxidation   catalysts.
Environ. Health Perspect.  10:  29-34.  (Cited  1n  Santodonato  and Lande,  1977)

Flnklea,  J.F.,   J.  Moran,  J.H.  Knelson,  D.B.  Turner  and  I.E.  Nlemeyer.
1975b.  Environmental  Quality  — The Sixth Annual  Report of the  Council  on
Environmental Quality,  December  1975, p. 327-334.  Available from  U.S.  GPO,
No.  040-000-00337-1.  (Cited 1n  Santodonato and Lande, 1977)

Gamble,  J.,   W.   Jones,  J.  Hancock   and  R.  Meckstroth.   1984.    Ep1dem1o-
loglcal-envlronmental   study of  lead  acid battery   workers.   III.  Chronic
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                                     -17-

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Graedel,  T.   1978.   Chemical  Compounds  1n  the Atmosphere.   Academic  Press,
NY.  p. 27.

Hackney,  J.O.   1978.    Effects  of  Sulfate  Aerosols  Upon  Cardiovascular
Function  1n  Squirrel  Monkeys.   Final  Report.   APRAC  Project  CAPM-20-74,
Coordinating  Research  Council,  Inc.,  New York.   (Cited  1n  Carson et  a!.,
1981)

Hyde, 0., J.  Orthoefer, 0. Dungworth,  W.  Tyler,  R.  Carter  and H.  Lum.   1978.
Morphometrlc  and morphologic  evaluation  of  pulmonary  lesions  1n  beagle  dogs
chronically exposed to high  ambient levels  of air  pollutants.  Lab.  Invest.
38: 455-469.  (Cited 1n Carson et al.. 1981)

Jones, W. and J. Gamble.   1984.   Ep1dem1olog1cal-env1ronmental  study  of  lead
acid  battery  workers.   Environmental  study  of  five  lead  acid  battery
plants.  Environ. Res.   35(1): 1-10.

Lawkowski,  J.P.,  M. Malanchuk,   L.  Hastings, A.  Vinegar  and G.P.  Cooper.
1979.  Effects  of  Chronic Exposure of Rats  to Automobile  Exhaust,  Sulfuric
Add,  Sulfur  Dioxide,  Aluminum  Sulfate, and Carbon  Monoxide.    Assessing
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Arbor  Science  Publishers,  Inc.,  Ann Arbor, MI.   p.  187-217.   (Cited  In
Carson et al., 1981)

Lawther,  P.J.   1980.   The Effects  of Sulfur  Dioxide, Sulfuric  Acid,  and
Particulate Matter  on  Lung   Function.   Comm. Eur.  Communities,  [Rep.]  EVR
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                                     -18-

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Lee, S.O.,  M.  Malanchuk  and V.N.  Flnelll.   1976.   Biologic effects of auto
emissions.  I. Exhaust from engine with and without catalytic converter.   J.
Toxlcol. Environ. Health.   1:  705-712.   (Cited  1n  Carson  et  a!.,  1981)

Lewis,  T.R.,  W.J.  Moorman,  Y. Yang  and  J.F.  Stara.  1974.  Long-term  expo-
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function  1n  the beagle.   Arch.  Environ. Health.   29:  102-106.   (Cited  1n
Carson  et a!., 1981)

Loscutoff,  S.M.,  F.6.  Burton  and  8.W.  KUland.   1978.   Neutralization  of
Inhaled sulfurlc add aerosols by ammonia 1n the  lung.   Fed. Proc.   37: 867.
(Cited  1n Carson et a!.,  1981)

Malcolm,  D.  and  E.  Paul.   1961.  Erosion of  the  teeth due to sulfurlc acid
In  the battery  Industry.   Br.  0.  Ind.  Med.   18: 63-69.   (Cited  In  Carson  et
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Orthoefer,  J.G.,  R.S.  Bhatnagar,   A.  Rahman,  Y.  Yang,  S.D.  Lee  and J.F.
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MD.
                                     -19-

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Schleslnger, R.B., M. Uppmann and R.E.  Albert.   1978.   Effects  of  shortterm
exposure  to  sulfurlc  add  and  ammonium  sulfate  aerosols  upon  bronchial
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Schleslnger, R.B., M.  Halpern,  R.E.  Albert  and  M.  Uppmann.  1979.   Effect
of chronic  Inhalation of  sulfurlc  acid mist upon mucoclllary  clearance  from
the  lungs  of  donkeys.   J. Environ.  Pathol.  Toxlcol.   2:  1351-1367.   (Cited
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Tadzhlbaeva, N.S. and I.V. GoVeva.  1976.   Industrial hygiene and  condition
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                                     -20-

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U.S. EPA.   1983.   Methodology and Guidelines for  Reportable  Quantity Deter-
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Vaughan, T.R., Jr., L.F  Jennelle  and T.R.  Lewis.   1969.   Long-term exposure
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Williams, M.K.  1970.   Sickness  absence  and ventilatory  capacity  of  workers
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Carson et al.,  1981)
                                     -21-

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                                                         APPENDIX
                                             Summary Table for Sulfurlc Acid

Inhalation
AIS
AIC
Maximum
composite
score
Species Experimental
Dose/Exposure



human 0.23 mg/m3
occupational
(0.16 mg/kg/day)b
Effect Acceptable Intake Reference
(AIS or AIC)

NDa
N0a
tooth etching and 26.8 Jones and
erosion (RVe = 4) Gamble, 1984;
Gamble
I\J
I
(RVd  =  6.7)
et al., 1984
       Oral
         AIS
         AIC
                                                  ND
                                                  ND
       aSee  text  for  suggested  maximum air  concentration  and  rationale  for  not  estimating  acceptable  Intakes.
           uncertainty  factor  of  10  was applied  to  convert  from  subchronlc  to chronic  exposure;  assumed:
        worker  breathes  10 m3  of  air during working hours  for 5 days/week.
       ND  -  Not derived

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