vvEPA
                United States
                Environmental Protection^
                Agency       '•*<•''
                Office of Water
                Regulations and Standards
                Criteria and Standards Division
                Washington DC 20460
EPA 440/5-80-066
October 1980
                                                  C.I
Ambient
Water  Quality
Criteria for
Phenol

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       AMBIENT WATER QUALITY CRITERIA  FOR

                   PHENOL
                  Prepared  By
    U.S. ENVIRONMENTAL  PROTECTION AGENCY

  Office of Water  Regulations and Standards
       Criteria  and  Standards Division
              Washington,  D.C.

    Office of Research  and  Development
Environmental Criteria  and  Assessment Office
              Cincinnati, Ohio

        Carcinogen Assessment Group
             Washington, D.C.

    Environmental Research  Laboratories
             Corvalis, Oregon
             Duluth, Minnesota
           Gulf Breeze,  Florida
        Narragansett, Rhode  Island


        Em*'r;:~:,--:.'';ri*7.l Fro^Tion Agency
          v.'.;/',.;..,-:^ CCJ04
                   i

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                              DISCLAIMER
      This  report  has  been reviewed by the  Environmental  Criteria and
Assessment Office, U.S.  Environmental  Protection  Agency,  and approved
for publication.  Mention of trade names or commercial products does not
constitute endorsement or recommendation for use.
                          AVAILABILITY NOTICE
       This  document is  available  to the public  through the National
Technical Information Service,  (NTIS), Springfield, Virginia  22161.
                                   i

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                                FOREWORD

     Section 304 (a)(l) of  the  Clean Water Act of  1977  (P.L.  95-217),
 requires the Administrator of  the  Environmental  Protection Agency  to
 publish criteria  for  water quality accurately reflecting the  latest
 scientific knowledge on the kind and extent of all  identifiable effects
 on health  and  welfare  which  may   be  expected from  the presence  of
 pollutants in any body of  water, including ground water.  Proposed water
 quality criteria for  the  65 toxic pollutants  listed under  section  307
 (a)(l)  of the  Clean  Water Act were developed and  a  notice  of  their
 availability was published  for  public  comment  on March 15,  1979  (44  FR
 15926), July 25, 1979 (44 FR 43660), and October 1,  1979  (44 FR 56628).
 This  document   is  a  revision  of those  proposed criteria based  upon  a
 consideration  of comments received  from other Federal  Agencies,  State
 agencies,  special  interest  groups,  and  individual scientists.   The
 criteria contained in  this document replace any previously published EPA
 criteria for  the  65  pollutants.    This  criterion document  is also
 published  in satisifaction  of paragraph  11 of  the Settlement Agreement
 in Natural Resources Defense Council,  et. al. vs.  Train,  8 ERC 2120
 (D.D.C.  1976),  modified,  12 ERC 1833 (D.D.C. 1979).	

    The term "water quality criteria"  is  used in  two  sections  of the
 Clean Water Act, section 304 (a)(l)  and section  303 (c)(2).  The  term has
 a  different  program  impact  in  each  section.    In section  304, the term
 represents  a non-regulatory,  scientific assessment  of ecological ef-
 fects.  The criteria presented  in  this publication  are such scientific
 assessments.    Such water quality  criteria  associated  with  specific
 stream  uses when adopted as State water quality standards  under section
 303  become enforceable maximum acceptable levels  of  a  pollutant   in
 ambient  waters.  The water quality criteria adopted  in the State water
 quality  standards could have the same numerical limits as the criteria
 developed under section  304.  However, in many situations States may want
 to adjust water quality criteria developed  under section 304 to reflect
 local  environmental  conditions and  human  exposure  patterns  before
 incorporation  into  water  quality  standards.    It  is  not  until  their
 adoption as part of the  State water quality standards that the criteria
become regulatory.

    Guidelines   to  assist  the States in the modification  of  criteria
presented  in this  document,  in  the  development   of water  quality
standards, and  in other water-related programs of this Agency, are being
developed by EPA.
                                    STEVEN SCHATZOW
                                    Deputy Assistant Administrator
                                    Office of Water Regulations and Standards
                                   111

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                            ACKNOWLEDGEMENTS
Aquatic life Toxicology:

   William A. Brungs, ERL-Narragansett
   U.S. Environmental Protection Agency
David J. Hansen, ERL-Gulf Breeze
U.S. Environmental Protection Agency
Mammalian Toxicology and Human Health Effects:
   Rolf Hartung (author)
   University of Michigan

   John F. Risher (doc. mgr.) ECAO-Cin
   U.S. Environmental Protection Agency

   Donna Sivulka (doc. mgr.) ECAO-Cin
   U.S. Environmental Protection Agency

   Patrick Durkin
   Syracuse Research Corporation

   Vincent N. Finelli
   University of Cincinnati

   Van Kozak
   University of Wisconsin

   Steven D. Lutkenhoff, ECAO-Cin
   U.S. Environmental Protection Agency

   Alan B. Rubin
   U.S. Environmental Protection Agency
Joseph Arcos
Tulane Medical Center

Richard Carchman
Medical College of Virginia

William B. Deichman
University of Miami

David B. Faukhauser
University of Cincinnati

Frederick Hamblet, HERL
U.S. Environmental Protection Agency

Geraldine L. Krueger
University of Cincinnati

Gary Osweiler
University of Missouri

Peter Toft
Health and Welfare, Canada
Technical Support Services Staff:  D.J. Reisman, M.A. Garlough, B.L. Zwayer,
P.A. Daunt, K.S. Edwards, T.A. Scandura, A.T. Pressley, C.A. Cooper,
M.M. Denessen

Clerical Staff:  C.A. Haynes, S.J. Faehr, L.A. Wade, D. Jones, B.J. Bordicks,
B.J. Quesnell,  C. Russom, R.  Rubinstein.

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                             TABLE OF CONTENTS


                                                                   Page

Criteria Summary

Introduction                                                       A-l

Aquatic Life Toxicology                                            B-l
   Introduction                                                    B-l
   Effects                                                         B-l
      Acute Toxicology                                             B-l
      Chronic Toxicology                                           B-3
      Plant Effects                                                B-3
      Residues                                                     B-3
      Miscellaneous                                                B-3
      Summary                                                      B-4
   Criteria                                                        B-5
   References                                                      B-22

Mammalian Toxicology and Human Health Effects                      C-l
   Introduction                                                    C-l
   Exposure                                                        c-2
      Ingestion from Water                                         C-2
      Ingestion from Food                                          C-8
      Inhalation                                                   C-12
      Dermal                                                       C-15
   Pharmacokinetics                                                C-15
      Absorption                                                   C-15
      Distribution                                                 C-16
      Metabolism                                                   C-17
      Excretion                                                    C-18
   Effects                                                          C-18
      Acute, Subacute,  and Chronic Toxicity                        C-18
      Synergism and/or  Antagonism                                  C-22
      Teratogenicity and Mutagenicity                              C-22
      Carcinogenic!ty                                              C-22
   Criterion Formulation                                           C-29
      Existing  Guidelines and Standards                             C-29
      Current  Levels of Exposure                                    C-29
      Special  Groups at Risk                                        C-30
      Basis and Derivation of Criterion                             C-32
   References                                                       C-33

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                        CRITERIA DOCUMENT
                              PHENOL
CRITERIA
                           Aquatic  Life
     The available data for phenol  indicate that acute and chronic
toxicity to freshwater aquatic life occur at concentrations as low
a-ja? 10,200  and  2,560 ug/1, respectively,  and  would occur at lower
concentrations  among  species that  are  more  sensitive  than those
tested.
     The available data for phenol  indicate that toxicity to salt-
water  aquatic  life  occurs at concentrations as  low  as 5,800 ug/1
and would occur at lower concentrations  among  species that are more
sensitive than  those tested.  No data are available  concerning the
chronic toxicity of phenol to sensitive saltwater  aquatic life.
                           Human Health
     For comparison  purposes, two  approaches  were used to derive
criterion levels for phenol.   Based on available  toxicity data, for
the  protection of public  health,  the derived level is 3.5 mg/1.
Using  available  organoleptic data,  for  controlling  undesirable
taste  and  odor qualities of  ambient water, the estimated level  is
0.3  mg/1.   It  should  be  recognized  that organoleptic  data  as  a
basis  for  establishing a water quality criterion  have  limitations
and  have  no demonstrated  relationship  to potential  adverse human
health effects.
                                 VI

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                           INTRODUCTION



     Phenol  is  a large volume industrial chemical produced  almost



entirely as an intermediate for the preparation of other  chemicals.



These  include  synthetic  polymers  such  as phenolic  resins,  bis-



phenol and caprolactam plastics  intermediates,  and chlorinated and



alkylated phenols.



     Phenol,  occasionally referred  to as  "carbolic acid",   is  a



monohydroxybenzene which is a clear, colorless (light pink  when im-



purities are  present), hygroscopic,  deliquescent, crystalline  sol-



id  at  25°C„(Manufacturing Chemist Assoc.,  1964;  Kirk and Othmer,



1963; Weast,  1974).   It has  the  empirical formula CgHgO, a molecu-



lar  weight  of 94.11, a specific gravity  of  1.071 at 25°C,  and  a



vapor pressure of 0.3513 mm  Hg at  25°C .(Patty,  1963;  Manufacturing



Chemists Assoc.,  1964; Am.  Ind.  Hyg.  Assoc., 1957;  Sax,  1975).



Phenol has a  melting  point of  43°C  and a boiling point of  182°C at



760 mm Hg (Weast, 1974).



     Phenol has  a water solubility of  6.7 g/100 ml at 16°C  and is



soluble at all proportions in water at  66°C.   It is also  soluble in



relatively non-polar  solvents such as benzene, petrolatum,  and  oils



(Patty, 1963; Kirk and Othmer, 1963; Weast, 1974).



     Due to   the  electronegative  character  of the  phenyl  group,



phenol exhibits  weakly  acidic properties.   It  possesses a pKa  of



9.9 to 10.0  and  readily reacts with strong bases such  as  NaOH,  KOH,



etc., to form salts  called phenoxides  (Weast, 1974;  Kirk and  Oth-



mer, 1963).    Phenoxides exist  in highly alkaline aqueous solutions



and many, particularly the sodium and potassium salts, are readily



soluble in water.
                               A-l

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     Natural phenol  is  produced by the  distillation  of coal tar,



although  this  source constitutes  only  1  to  2  percent  of  total



phenol  production ,,(Kirk  and  Othmer,   1963).   The  cumene process



represents the  most popular  route of phenol production and involves



two basic  steps.  Cumene  is oxidized  to cumene hydroperoxide with



air  in  the  presence of  an alkali catalyst  and  is  subsequently



cleaved to phenol and acetone  with  the  aid of a sulfuric acid cata-



lyst, (Cook, 1977).  Other methods of commercial production include



the toluene  oxidation process and  the benzene sulfonation process



(Faith, et al. 1975).   In the former  process,  toluene is oxidized



to  benzoic acid  and  reduced  to phenol, using  a copper  catalyst.



The latter method involves  the  sulfonation  of  benzene to benzene-



sulfonic acid, its neutralization with sodium sulfite or  carbonate



to form sodium benzenesulfonate  and  the subsequent  reaction of this



compound with fused  caustic soda at high temperatures.  The  sodium



phenate or sodium salt is  then acidified  with  sulfur  dioxide  to



form  the  phenol  (Faith, et al.  1975) .  This  purity of  most syn-



thetic  phenols is greater than 99.5 percent,  while the purity  of



natural sources  ranges  from 80  to 82 percent and 90 to  92 percent,



depending  upon the source and  method of production.  The commercial



products  generally  contain an  impurity  which  changes the melting



point  (Spector,  1956; Stecher,  1968).



      Phenol  or phenolic wastes  also are  produced during the  coking



of  coal,   distillation  of  wood,  operation of  gas works and  oil



refineries, manufacture of  livestock dips,  as a normal constitutent



of  human  and animal  wastes,  and  microbiological decomposition  of



organic matter jBulick,  1950; Mischonsniky, 1934).
                                A-2

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     Phenol  undergoes  oxidation to a variety of products,  such  as
 the  benzenediols,  benzenetriols, and derivatives  of diphenyl and
 diphenylene  oxide, depending on  the oxidizing agent  and  conditions
 (Kirk and Othmer, 1963).  However, phenol may be biochemically hy-
 droxylated to ortho- and paradihydroxybenzenes and  readily oxidized
 to the  corresponding benzoquinones.   These  may in turn  react with
 numerous components of  industrial waters or  sewage such  as  mercap-
 tans, amines, or the -SH or -NH groups of proteins.   In the  absence
 of these  compounds,  the quinones, especially  the ortho- isomers,
 can  be  quickly  destroyed  by hydrolytic oxidizing reactions  (Stom,
 1975) .
     The hydroxyl group of phenol imparts  a  high degree of reactiv-
 ity  to  the  phenyl ring,  particularly the  ortho-  and para- posi-
 tions.  Phenol  has been shown  to be highly reactive  to chlorine  in
 dilute  aqueous  solutions  over  a  wide  pH range  (Carlson  and Caple,
 1975; Middaugh  and Davis,  1976).   The chlorination of  phenol  in
 aqueous solutions to form  2-chloro-,  4-chloro-, or  higher  chloro-
 phenols  has  been demonstrated under  conditions  similar to those
 used for disinfection of wastewater effluents (Aly,  1968; Barnhart
 and Campbell, 1972)  and represents a potential amplification of the
 organoleptic problems associated  with phenol contamination.  Syn-
 thesis of 2-chlorophenol within one hour in  aqueous  solutions con-
 taining as little as 10 mg/1 phenol and 20  mg/1 chlorine has been
 reported  (Barnhart  and Campbell, 1972).   Other studies have re-
ported  the formation of up to 1.7  ug/1 2-chlorophenol  and other
chlorinated  compounds during the chlorination  or sewage  effluents
 and power plant  cooling  waters  (Jolley, 1973; Jolley,  et al.  1975).
                               A-3

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     The photooxidation of phenol in water at alkaline pH has been
studied.   Irradiation with  a  mercury arc  lamp produced  several
intermediate compounds and p-benzosemiquinone as the final product
(Tomkiewicz, et al.  1971;  Cocivera,  et al. 1972).  Audureau, et al.
(1976)   studied  the  photooxidation of   phenol  with  ultraviolet
irradiation  (253.7  nm)  and concluded that  the  reaction initially
leads to  the formation of  a complex mixture of  tri-and tetrahy-
droxybiphenyls,  quinones  and  dihydroxybenzenes.    Aqueous  phenol
solutions irradiated with sunlight for seven days were reported to
degrade to hydroquinone and pyrocatechol  (Perel1shtein and Kaplin,
1968).    Subsequent  irradiation of pyrocatechol  with  sunlight for
seven days yielded pyrogallol.  The end products of photodecomposi-
tion were reported to be humic acids.  Conversely, similar studies
utilizing natural sunlight  as  the  source  of irradiation indicated
that phenol concentrations  in solutions of pure  water remained
unchanged after  ten days  (Wilbaut-Isebree, 1964).  However, phenol
degradation did occur in industrial sewage effluents and led  to the
conclusion  that unidentified  microorganisms,  not  sunlight,  were
responsible  for  the destruction of phenol.
     The  microbiological   degradation  of phenol  has  been  widely
studied.  Bayly, et al. (1966)  reported  the  conversion of phenol to
catechol by  Pseudomonas putida.  Neujahr  and Varga  (1970) observed
the  oxidation  of phenol by  both  intact  cells  and extracts of the
microorganism,  Trichosporon cutaneum.   Buswell  and Twomey  (1975)
and  Buswell (1975)   demonstrated  the ability of the  thermophilic
bacteria,  Bacillus  stearothermophilus,  to  catabolize  phenol.  In
these studies,  the  bacteria first converted  phenol  to  catechol and
                               A-4

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subsequently  cleaved the  aromatic  ring  to  form 2-hydroxyir,uconic



semialdehyde.  In view of the  fact that  phenol  represented  the pri-



mary carbon source provided to isolated and adapted microorganisms



in  these  studies, the  importance  or microbiological degradation



within the environment remains unclear.



     Information concerning the presence and persistence,  and fate



of phenol in the environment is incomplete or  not available.



     The widespread  use  of phenol as  an important chemical  inter-



mediate, the generation of phenolic  wastes by  industry and  agricul-



ture, and  the  toxicological  and organoleptic  properties  indicate



its importance in potential point source and nonpoint  source water



contamination.
                               A-5

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                          REFERENCES







Aly, O.M.   1968.   Separation  of phenols  in  waters  by thin-layer



chromatography.  Water Res.  2: 287.







American  Industrial Hygiene Association.   1957.   Hygienic guide



series:  Phenol.  Am. Ind. Hyg. Assoc., Detroit.







Audureau, J., et al.  1976.  Photolysis and photooxidation of phe-



nol in aqueous solutions.  Jour. Chem. Phys.  73: 614.







Barnhart, E.L. and  G.R.  Campbell.  1972.   The effect of chlorina-



tion on  selected  organic chemicals.   U.S.  Environ.  Prot.  Agency.



U.S. Government Print. Off., Washington, D.C.







Bayly,  R.C., et al.  1966.  The metabolism of cresols by a species



of Pseudomonas.  Biochem. Jour.  101: 293.







Bulick,  J.   1950.   Phenolic Waste Waters.   In;  Pub.  Health Eng.



Palivo.  30: 308   (Abst.)







Buswell, J.A.  1975.  Metabolism of phenol and cresols by Bacillus



stearothermophilus.  Jour. Bact. 17.







Buswell, J.A.  and D.G.  Twomey.  1975.   Utilization  of phenol and



cresols  by  Bacillus stearothermophilus  Strain pH 24.   Jour. Gen.



Microbiol.  87: 377.
                               A-6

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Carlson, R.M. and R. Caple.  1975.  Organo-chemical Implication of



Water Chlorination.   In; Proc. Conf. Environ. Impact Water Chlorin-



ation.  p. 73.







Cocivera, M. ,  et  al.  1972.  Electron  paramagnetic resonance and



nuclear  spin  polarization study  of  phenol  in  water.    Jour.  Am.



Chem. Soc.  94: 6598.







Cook, F.B.   1977.   Phenol business  in changing  times.   Proc. 83rd



Natl. Meet. Am. Inst. Chem. Eng.







Faith, et al.  1975.  Industrial Chemicals.  4th ed.  Interscience



Publishers, John Wiley and Sons, Inc., New York.







Jolley,  R.L.   1973.   Chlorination effects on organic constituents



in effluents from domestic sanitary sewage  treatment plants.  Ph.D.



dissertation, University of Tennessee, Knoxville.







Jolley,  R.L.,  et al.   1975.    Chlorination  of  cooling  water:   A



source  of  environmentally significant chlorine-containing organic



compounds.  Proc.  4th Natl. Symp. Radioecology.  Corvallis, Oregon.







Kirk,  R.E.  and D.F.  Othmer.    1963.   Kirk-Othmer  Encyclopedia of



Chemical Technology.  2nd  ed.  John Wiley and Sons,  Inc.,  New  York.







Manufacturing Chemists  Assoc.   1964.   Chemical safety data sheet



SD-4; Phenol.  Washington, B.C.
                               A-7

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Middaugh, D.P. and W.P.  Davis.   1976.   Impact of Chlorination Proc-
esses on Marine Ecosystems.   In; Water  quality research of the U.S.
Environ. Prot. Agency.   EPA Report No. 600/3-76-079.  Washington,
D.C.  p. 46.

Mischonsniky, S.  1934.   A study of the pollution of fish contain-
ing  waters  by  waste phenolic  waters.   14th  Congr.  Chrm.  Ind.
(Paris)  Jour. Am. Water Works Assoc.  29: 304.

Neujahr, H.Y. and J.M. Varga.   1970.  Degradation of  phenols by in-
tact  cells  and  cell-free  preparations of  Trichosporon  cutaneum.
Eur. Jour.  Biochem.  13: 37.

Patty,  F.A.   (ed.)    1963.    Industrial  Hygiene  and  Toxicology.
John Wiley and Sons, Inc., New York.

Perel'shtein, E.I.  and V.T. Kaplin.   1968.   Mechanism of the Self
Purification of Inland Surface  Waters by  the Removal  of Phenol Com-
pounds.   II.  Effect of Natural  uv Rays  on Aqueous Solutions of Phe-
nol Compounds.  Gidrokhim. Mater.  In;  Chem.  Abstr.   84: 139.

Sax,  N.I.   1975.   Dangerous  Properties of  Industrial Materials.
4th ed.   Van Nostrand Reinhold Co., New York.

Spector, W.S.   1956.  Handbook of  Toxicology.  W.B.  Saunders Co.,
Philadelphia.
                               A-8

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Stecher, P.G. (ed.)   1968.  The Merck Index.   Merck  and Co., Rahway,




New Jersey.







Stom, D.J.   1975.   Use  of  thin-layer and paper chromatography for



detection of ortho- and  para- quinones  formed in the course of phe-



nol oxidation.  Acta Hydrochim. Hydrobiol.   3: 39







Tomkiewicz,  M. ,  et  al.   1971.   Electron  paramagnetic resonance



spectra of semiquinone  intermediates observed during the photooxi-



dation of phenol in water.  Jour. Am. Chem.  Soc.   93: 7102.







Weast, R.C.  (ed.)   1974.  Handbook of Chemistry and Physics.  55th



ed.  CRC Press, Cleveland, Ohio.







Wibaut-Isebree, N.L.   1964.   Influence of light on destruction  of



phenol  in water.  Hydrobiol.   24: 540.
                                A-9

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Aquatic Life Toxicology*
                                 INTRODUCTION
    Phenol  is  predominantly  used  as  an  intermediate in  a wide  variety  of
chemical  processes.   These  processes  produce  epoxy and  phenolic  resins,
Pharmaceuticals, germicides,  fungicides,  slimicides,  herbicides,  dyes,  and a
variety of  industrially important acids.  The  phenol  molecule  easily substi-
tutes in the environment to form compounds  such  as halophenols,  which may be
more toxic than the parent molecule.   Phenol is  degraded by a  number of bac-
teria and fungi  that  may  cause slime  growths  and  may depress  dissolved oxy-
gen in the receiving waters, thus lowering water quality.
    Although an  abundance  of  data  on  the acute  toxicity of phenol  to fresh-
water fish  and  invertebrate  species is available, the chronic toxicity data
are limited to  one test with the fathead minnow.  Toxicity testing with the
same  species  by different  researchers  in  different waters  produced  LCcn
values  which  varied  widely.   This  indicates  that  parameters  such as  pH,
hardness, temperature  or  other water  quality  characteristics  may  alter the
toxicity of the compound.
    The data base for saltwater species is  much  more  limited with acute data
for three fish  and three  invertebrate  species.   No  chronic data  are avail-
able.
                                    EFFECTS
Acute Toxicity
    Toxicity  data  for  eight freshwater  invertebrate species,  including  a
*The  reader  is   referred  to  the  Guidelines  for  Deriving  Water  Quality
Criteria for the Protection of Aquatic Life  and  Its Uses in order  to better
understand  the  following   discussion  and  recommendation.    The  following
tables contain the  appropriate  data that were found  in the literature,  and
at the  bottom  of each table  are  calculations for  deriving  various  measures
of toxicity as described  in the Guidelines.
                                     B-l

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 rotifer,  a snail, cladocerans, and  copepods,  are listed  in  Table 1.   Tests
 conducted  by  Alekseyev and Antipin  (1976)  compare the  relative  sensitivity
 of  three cladoceran  species  in the  same  water using similar  test methods.
 The  LC,-0  values  range from  14,000  ug/1  for  Daphnia  longispina  to  57,000
 ug/1  for Polyphemus  pediculus.   Data in Table 1  indicate  that  a rotifer,
 Philodina  acuticornis, and  two  species of  copepods  are  among   the  least
 sensitive.  Cairns,  et al.  (1978)  tested  phenol  at different  temperatures
 and  found  little,  if  any,   effect.   LC5Q  values  were  in  the  range  from
 91,000  to 100,000  yg/1  for  Daphnia magna  and  79,000  to  93,000 ug/1  for
 Daphnia  pulex.  Anderson,  et  al.  (1948)  and Dowden  and  Bennett (1965)  found
young Daphnia magna to be about three times  more sensitive than adults.
    Acute  toxicity  data for  nine freshwater  fish  species  are included  in
Table 1.   Rainbow trout was  the most sensitive fish species tested with  an
 LC50  value of 5,020  wg/l  (McLeay,   1976).   The least sensitive species  was
the  fathead  minnow with  LC5Q  concentrations  as  high  as 67,500  ug/1  (U.S.
EPA, 1978b).  There is a wide range  of intraspecific  sensitivity in addition
to  the  wide range  of interspecific  sensitivity previously mentioned.   LC5Q
values  for rainbow  trout  varied  from 5,020  ug/1  (McLeay,  1976)   to  11,600
ug/1  (Fogels  and  Sprague,  1977).   The fathead  minnow,  a commonly used  test
species,  had  LC5Q values  that  varied from  24,000 ug/1   (Ruesink  and  Smith,
1975) to 67,500 ug/1  (U.S. EPA, 1978b).  The bluegill, another  commonly  used
test  species,  had LC5Q values  from  11,500  ug/1  (Cairns and Scheier,  1959)
to 28,116 ug/1 (Cairns, et  al. 1978).
    Only four  saltwater  species have been  tested  using standard  test  dura-
tion.   Fifty  percent  effect  levels  for  embryos  of  the  eastern  oyster  and
hard  clam  were 58,250 and  52,630 ug/1,  respectively (Table 1).   The  grass
shrimp  was much  more sensitive with an  LCgQ   of  5,800  ug/1.  The mountain
bass, a  species  endemic  to Hawaii,  provided  a  96-hour LCrQ  value of  11,000
                                     8-2

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ug/1  (Table  1).   There are too  few  data to evaluate any effect  of  environ-
mental variables on toxicity.
Chronic Toxicity
    An early life  stage test with  the  fathead  minnow (Holcombe,  et al. 1980)
produced an estimated  maximum  acceptable toxicant concentration of  1,830  to
3,570  ug/1  which  yields a  chronic value of 2,560 ug/1  and  an acute-chronic
ratio of 14 (Table 2).  Species  mean acute values and  the  acute-chronic  ra-
tio are summarized in Table 3.
      No chronic effects are available for any saltwater species.
Plant Effects
    Reynolds, et al.   (1973) conducted  a series  of  tests with an alga, Sele-
nastrum  capricornutum,  and found  at  phenol  concentrations  of  20,000  ug/1
that  growth  inhibition increased  from  12 percent to 32  percent  as  tempera-
ture  increased  from 20 to 28°C (Table  4).  Reynolds,  et  al.  (1975)  found
greater than 50 percent reduction  in cell numbers of the same alga at 20,000
ug/1  in  1.92,  2.0, and 2.26 days  at 20, 24,  and 28°C,  respectively.   Duck-
weed  was  considerately   less   sensitive  with  an   IC™ of  1,504,000  yg/1
(Blackman, et al.   1955) and 50  percent reduction in growth  at  479,400 ug/1
(Simon and Blackman, 1953).
Residues
    Table  5 contains bioconcentration  data on  phenol for goldfish.  However,
since  no  maximum  permissible tissue  concentration  is available  for phenol,
no  Final Residue Value  can be  calculated.  The bioconcentration  factors cal-
culated  for phenol  (Kobayashi,  et  al.   1976,  Kobayashi  and  Akitake,  1975)
ranged from  1.2 to 2.3.  Bioconcentration  factors this  low indicate that no
residue problem should occur from exposure to phenol.
Miscellaneous
    Birge,  et  al.   (1979)  conducted  tests  at  hardnesses  of  50 and  200 mg/1
                                      B-3

-------
as  CaC03  and  determined  4-day  LC5Q  values  for  three  species  of  fishes
after exposure  of  the entire embryo stage  and four days of the  larval  life
stage.   LC5Q  values  for  rainbow trout were  310  and 70 ug/1,  for goldfish,
840 and  340  ug/1,  and for bluegills  2,420 and 1,690  yg/1  in  soft  and  hard
water, respectively.   The  tests  indicate that hardness  may  affect the toxi-
city of phenol although related characteristics may be the factor.
    Cairns, et  al. (1978) in  tests conducted with rainbow  trout at  5,  12,
and 18°C  calculated 24-hour  LC5Q  values  of 5,600,  11,000,  and 11,300 ug/1,
respectively.    The tests  indicate that  rainbow  trout  are  about twice  as
sensitive at 5°C than at 12 and 18°C.
    Mitrovic,  et al.  (1968)  detected  gill damage  in  rainbow  trout juveniles
in 2  hours  at a concentration of 6,500  yg/1.  However, it  is difficult  to
understand the  environmental  significance  of  this because of  possible  com-
pensatory reactions in the fish.
    Histopathological  damage occurred  in  the  saltwater  clam,  Mercenaria  mer-
cenaria,   at  phenol concentrations  of  100  ug/l   and  higher  (Table  6).   No
change was observed at 10 yg/1.
    The saltwater  mountain bass  reacted  to phenol  concentrations as  low  as
2,000 ug/1,  and the  48-hour  LC5Q  for the  rainbow trout  in  saltwater  was
6,900 wg/1 (Table 6).
Summary
    The acute toxicity of phenol to  freshwater  species is expressed  over a
range of  2 to  3 orders of magnitude.   Of the  four families of invertebrate
species represented,  the  cladocerans  were the most  sensitive.  Acute  values
for fish  species  range from 67,500 ug/1  for  fathead minnows  to  5,020  ug/1
for juvenile rainbow  trout.  The  acute  value for  rainbow trout  of 5,020  ug/1
and the  value  of 5,000 ug/1 for Daphnia magna are the lowest acute  values
observed.
                                     B-4

-------
    A fathead  minnow  early life  stage  test resulted  in  a chronic value  of
2,560 ug/1  with an acute-chronic ratio of 14.
    Bioconcentration factors  ranged  from 1.2  to 2.3  in  goldfish  in  five
days.  Factors this low  indicate that no  residue problem should occur  from
exposure to phenol.
    Only three saltwater invertebrate and  three fish  species  have  been stud-
ied  as  to  the  acute  effects  of  phenol.  LC5Q values  were observed  as  low
as 5,800 ug/1.   Histopathological damage  was  observed in  the  hard clam  at
concentrations as  low  as 100 ug/1.   A  saltwater fish  reacted  to  concentra-
tions as low as 2,000 ug/1.
                                   CRITERIA
    The available  data for phenol  indicate  that  acute and  chronic  toxicity
to  freshwater aouatic  life occur  at concentrations  as  low  as  10,200  and
2,560  ug/1,  respectively,  and   would occur  at  lower concentrations  among
species that are more sensitive than those tested.
    The available  data  for  phenol indicate that  acute  toxicity to saltwater
aouatic life  occurs at concentrations as low as 5,800 ug/1  and would occur
at  lower  concentrations  among  species  that  are more sensitive  than those
tested.  No data are  available concerning the  chronic  toxicity of phenol to
sensitive saltwater aauatic life.
                                      B-5

-------
                                                            Table  t.  Acute  values  for phenol
CD
 I
Species
Method*
LC50/EC50
(ug/l)
Species Mean
Acute Value
(ug/l) Reference
FRESHWATER SPECIES
Rot 1 f er,
Philodina acuticornls
Snail,
Physa heterostropha
Cladoceran,
Daphnla longlsplna
Cladoceran,
Daphnla magna
Cladoceran,
Daphnla magna
Cladoceran (young),
Daphnla magna
Cladoceran (adult),
Daphnla magna
Cladoceran,
Daphnla magna
Cladoceran,
Daphnla magna
Cladoceran,
Daphnia magna
Cladoceran,
Daphnla magna
C ladoceran,
Daphnla magna
Cladoceran,
Daphnla put ex
s,
s,
R.
s.
s.
s.
s.
s,
s.
s.
s,
s.
s.
u
u
u
u
u
u
u
M
M
M
M
M
U
248,000
94,000
14,000
9,600
11,800
7,000
21,000
100,000
92,000
91,000
88,000
91,200
28,000
248,000 Bulkema, et al. 1974
94,000 Patrick, et al. 1968
14,000 Alekseyev & Antipln,
1976
Kopperman, et al.
1974
U.S. EPA, 1978a
Oowden & Bennett,
1965
Oowden & Bennett,
1965
Cairns, et al. 1978
Cairns, et al. 1978
Cairns, et al. 1978
Cairns, et al. 1978
36,400 Cairns, et al. 1978
Lee, 1976

-------
                               Table I.  (Continued)
CD
 i
Species
C ladoceran,
Daphnla pulex
C ladoceran,
Daphnia pulex
C ladoceran,
Daphnla pulex
C ladoceran,
Daphnla pulex
C ladoceran,
Daphnla pulex
C ladoceran,
Daphnla pulex
C ladoceran,
Polyphemus pedlculus
Copepod,
Cyclops vernal Is
Copepod ,
Mesocyclops leukarti
Rainbow trout (juvenile).
Sal mo qairdner i
Rainbow trout (juvenile),
Sal mo galrdneri
Rainbow trout,
Salmo gairdneri
Goldfish,
Carassius auratus
Fathead minnow (adult),
Method*
S, M
s,
s,
s.
s.
R.
R,
s,
s,
R,
FT,
FT,
s,
FT,
M
M
M
M
U
U
U
U
U
M
M
U
M
LC50/EC50
ivo/n
93,000
87,800
85,000
81,000
79,000
18,000
57,000
122,000
108,000
5,020
8,900
11,600
44,490
67,500
Species Mean
Acute Value
(ug/l) Reference
Cairns, et al. 1978
Cairns, et al. 1978
Cairns, et al. 1978
Cairns, et al. 1978
Cairns, et al. 1978
58,100 Alekseyev & Antipln,
1976
57,000 Alekseyev & Antipln,
1976
122,000 Anderson, et al. 1948
108,000 Anderson, et al. 1948
McLeay, 1976
U.S. EPA, 1978b
10,200 Fogels & Sprague,
1977
44,500 Pickering &
Henderson, 1966
U.S. EPA, 1978b
                               Plmephales promelas

-------
                               Table  1.   (Continued)
03
 I
CO
Species
Fathead minnow,
Plmephales promelas
Fathead minnow,
Plmephales promelas
Fathead minnow (adult),
Plmephales promelas
Fathead minnow (adult),
Plmephales promelas
Fathead minnow,
Plmephales promelas
Fathead minnow,
Plmephales promelas
Channel catfish
(juvenl le),
Ictalurus punctatus
Flagfish,
Jordanella floridae
Mosquitoflsh,
Gambusia affinis
Guppy,
Poecilla retlculata
Guppy,
Poecilla reticulata
Bluegill,
Lepomis macrochirus
Bluegil 1 ( juveni le),
Lepomis macrochirus
Bluegi 1 1,
Method*
S, U
s, u
FT, M
FT, M
FT, M
S, U
S, U
FT, M
S. M
S, M
S, U
S, U
R, M
S, U
Species Mean
LC50/EC50 Acute Value
(liq/l) (ug/l)
34,270
32,000
36,000
24,000
28,780
32,000 36,000
16,700 16,700
36,300 36,300
26,000 26,000
31,000
39,190 34,900
13,500
19,300
13,500
Reference
Pickering 4
Henderson, 1966
Pickering &
Henderson, 1966
Ruesink & Smith,
1975
Ruesink & Smith,
1975
Phipps, et al.
Manuscript
Matt son, et al.





1976
Clemens & Sneed, 1959
Fogels & Sprague,
1977
Nunogawa, et al. 1970
Nunogawa, et al. 1970
Pickering &
Henderson, 1966
Patrick, et al. 1968
Trama, 1955
Cairns & Scheier,
                               Lepomis macrochirus
                                                                                                        1959

-------
                               Table 1.   (Continued)
03
 I
Species
B 1 ueg ! 1 1 ,
Lepomis macrochirus
Bluegil 1,
Lepomis macrochirus
B 1 ueg i 1 1 ,
Lepomis macrochirus
Mozambique mouthbrooder,
Tilapfa mossambica
Grass shrimp,
Palaemonetes pug to
Eastern oyster,
Crassostrea virgin lea
Hard clam,
Mercenaria mercenarla
Mountain bass,
Kuhlia sandv icens is

Method*
S, U
s, u
S. U
S, M
S, U
S, U
s, u
S, M
LC50/EC50
(lig/D
Species Mean
Acute Value
(lig/D
20,000
11,500
23,880 16,400
19,000 19,000
SALTWATER SPECIES
5,800
58,250
52,630
11,000
5,800
58,200
52,600
11,000
Reference
Cairns 4 Scheier,
1959
Cairns i Scheier,
1959
Pickering &
Henderson, 1966
Nunogawa, et al. 1970
Tatem, et al. 1978
Davis & Hidu, 1969
Davis & Hidu, 1969
Nunogawa, et al. 1970
                               * S =  static,  R  =  renewal,  FT = flow-through,  U = unmeasured, M = measured

-------
                                               Table 2.  Chronic values for phenol (HoIcombe, et al. 1980)

                                                                                     Limits
                                             Species
                                             Fathead minnow,
                                             Plmephales promelas
     Method*

FRESHWATER SPECIES
                          ELS
                                    1,830-
                                    3,570
                                               Chronic Value
                                                   (lig/l)
                               2,560
                                               ELS = ear Iy  I Ife stage
DO
 I
                   Acute-Chronic Ratio

                         Acute     Chronic
                         Value      Value
                         (ug/l)     (ug/l)

Fathead minnow,          36,000      2,560
Plmephales promelas
                                                                                               Ratio

                                                                                                 14

-------
                                      Table 3.  Species mean acute values and acute-chronic  ratios  for phenol
a
 i
ink*
17
16
15
14
13
12
11
10
9
8
7
6
5
4
Species
Rot 1 f er,
Phllodlna acuticornls
Copepod,
Cyclops vernal Is
Copepod,
Mesocyclops leukartf
Snail,
Physa heterostropha
C 1 adoceran ,
Oaphnla pulex
Cl adoceran,
Polyphemus pedlculus
Goldfish,
Car ass 1 us auratus
Cl adoceran,
Daphnla magna
Flagflsh,
Jordanella f lorldae
Fathead minnow,
Plmephales promelas
Guppy,
Poecll la retlculata
Mosqultof Ish,
Gambusla afflnls
Mozambique mouthbrooder,
Tllapla mossamblca
Channel catfish.
Species Mean
Acute Value
(Mfl/l)
FRESHWATER SPECIES
248,000
122,000
108,000
94,000
58,100
57,000
44,500
36,390
36,300
36,000
34,900
26,000
19,000
16,700
Acute-Chronic
Ratio
-
-
-
-
14
-
                                                  I eta Iurus punctatus

-------
                                          Table 3.   (Continued)
Cd
 I
M
to
Rank*
3
2
1
4
3
2
1
Species
Bluegill,
Lepomls macrochlrus
Cladoceran,
Daphnla lonqlspina
Rainbow trout,
Sal mo gairdneri
SALTWATER
Eastern oyster,
Crassostrea virgin lea
Hard clam,
Mercenar I a mercenar la
Mountain bass,
Kuhlla sandvlcensis
Grass shrimp,
Palaemonetes puqio

Species Mean
Acute Value

-------
                                                         Table 4.  Plant values for phenol
03
 I
M
U)
                                   Species
                                   Alga,
                                   Selenastrum caprlcornutum
                                   Alga,
                                   Selenastrum caprlcornutum
                                   Alga,
                                   Selenastrum caprlcornutum
                                   Alga,
                                   Selenastrum caprlcornutum
                                   Alga,
                                   Selenastrum caprlcornutum
                                   Alga,
                                   Selenastrum caprlcornutum
                                   Alga,
                                   Selenastrum caprlcornutum
                                   Duckweed,
                                   Lemna minor

                                   Duckweed,
                                   Lemna minor
   Effect

FRESHWATER SPECIES
 Result
 (ug/D
12$ growth
Inhibition
at 20 C

27$ growth
Inhibition
at 24 C

32$ growth
Inhibition
at 28 C

>50$ reduction
of 1-day steady
state eel I
concentrat Ion

58$ reduction
In eel I numbers
In 1.92 days
at 20 C

66$ reduction
In eel I numbers
in 2.0 days
at 24 C

60$ reduction
in eel I numbers
in 2.26 days
at 28 C

Ch I oros I s
(LC50)

50$ reduction
in growth
  20,000



  20,000



  20,000



  40,000




  20,000




  20,000




  20,000




1,504,000


  479,400
                                                                                                 Reference
Reynolds, et al.
1973
Reynolds, et al.
1973
Reynolds, et al.
1973
Reynolds, et al.
1975
Reynolds, et al.
1975
Reynolds, et al.
1975
Reynolds, et  al.
1975
Blackman, et  al.
1955

Simon  &  Blackman,
1953

-------
                                                              Table 5.  Residues for phenol

                                                                        Bioconcentration     Duration
                            Species                        Tissue            Factor           (days)      Reference
Goldfish,
Carassius auratus
Goldfish,
Carassius auratus
Goldfish,
Carassius auratus

FRESHWATER SPECIES
Whole body 2.0
Whole body 2.0
Whole body 1.2-2.3
1 Kobayashl, et al.
1976
5 Kobayashi & Akitake,
1975
5 Kobayashl & Akitake,
1975
DO
 I

-------
                                                            Table 6.   Other data for phenol
W
 I
M
01
                             Species
                             DI atom,
                             Nltzschla linear Is

                             Alga,
                             ChiorelI a pyrenaldosa
Alga,
Chi ore I la vulgar Is

Parameclum,
Chllomonas paramecium

Parameclum,
Chilomonas paramecium

Parameclum,
Chllomonas paramecium

Rotifer,
Phllodlna acutlcornis

Rotifer,
Ph11odIna acutI corn Is

Rotifer,
Philodlna acutlcornis

Rotifer,
Phllodlna acutlcornis

Rotifer,
PhI Iod i na acutIcorn Is

Annel Id,
Aeolosoma head ley I

Annelid,
Aeolosoma head ley I
FRESHWATER SPECIES
120 hrs
2 days
80 hrs
19-25 hrs
44-48 hrs
98-163 hrs
48 hrs
48 hrs
48 hrs
48 hrs
48 hrs
48 hrs
48 hrs
50$ reduction in
cell production
Comp 1 ete
destruction of
ch lorophy 1 1
20? inhibition
of growth
>50£ decrease in
growth
>50j6 decrease in
growth
>50$ decrease In
growth
LC50
LC50
LC50
LC50
LC50
LC50
LC50
                                                               Result
                                                               (ug/l)     Reference
                                                               258,000    Patrick, et al. 1968


                                                             1,500,000    Huang & Gloyna, 1968
                                                                                            470,000    Dedonder A Van
                                                                                                       Sumere, 1971

                                                                                            200,000    Cairns, et al. 1978
200,000    Cairns, et al. 1978


200,000    Cairns, et al. 1978


300,000    Cairns, et al. 1978


282,000    Cairns, et al. 1978


245,000    Cairns, et al. 1978


205,000    Cairns, et al. 1978


292,000    Cairns, et al. 1978


360,000    Cairns, et al. 1978


351,000    Cairns, et al. 1978

-------
                             Table 6.   (Continued)
03
 I
                             Species
AnnelId,
Aeolosonia  headleyi

AnnelId,
Aeolosoma  headleyi

AnnelId,
AeoIosoma  headleyi

Snail,
Limnaea stagnalIs

Snail,
NltrocrIs  sp.

Snal I,
NltrocrIs  sp.

Snail,
NltrocrIs  sp.

Snail,
NltrocrIs  sp.

Snal I,
Nltrocris  sp.

Snail (adult),
Physa fontlnalis

Sna11 (juvenile),
Physa fontlnalIs

Clam,
Sphaerlum  corneum

Cladoceran,
Daphnia magna

Cladoceran (young),
Daphnia magna
                                                                                            Result
Duration
48 hrs
48 hrs
48 hrs
48 hrs
48 hrs
48 hrs
48 hrs
48 hrs
48 hrs
48 hrs
48 hrs
48 hrs
16 hrs
96 hrs
Effect
LC50
LC50
LC50
LC50
LC50
LC50
LC50
LC50
LC50
LC50
LC50
LC50
Immobi 1 ization
EC50
(ug/i)
381,000
356,000
341,000
350,000
389,000
351,000
353,000
360,000
391,000
320,000
260,000
780,000
94,000
5,000
Reference
Cairns, et al. 1978
Cairns, et al. 1978
Cairns, et al. 1978
Alekseyev 8, Antipin,
1976
Cairns, et al. 1978
Cairns, et al. 1978
Cairns, et al. 1978
Cairns, et al. 1978
Cairns, et al. 1978
Alekseyev i Antipin,
1976
Alekseyev & Antipin,
1976
Alekseyev & Antipin,
1976
Anderson, 1944
Anderson, et al. 194f

-------
                             Table 6.   (Continued)
                             Species
Effect
Result
(ufl/l)     Reference
CO
 I
Cladoceran (adult),
Paphnla magna
Conchostracan,
Lynceus brachyurus
Isopod (adult),
Asel lus aquaticus
Isopod ( juvenl le),
Asel lus aquaticus
Rainbow trout,
Sal mo galrdneri
Rainbow trout,
Salmo galrdneri
Rainbow trout,
Salmo galrdneri
Rainbow trout,
Salmo galrdneri
Rainbow trout,
Salmo gairdneri
Rainbow trout,
Salmo gairdneri
Rainbow trout (embryo),
Salmo gairdneri
Rainbow trout (embryo),
Salmo gairdneri
Rainbow trout,
Salmo galrdneri
Rainbow trout,
Salmo gairdneri
96 hrs
48 hrs
48 hrs
48 hrs
48 hrs
48 hrs
48 hrs
48 hrs
48 hrs
48 hrs
22 days
22 days
26 days
26 days
EC50
LC50
LC50
LC50
LC50
LC50
LC50
LC50
LC50
LC50
LC50 (hardness =
50 mg/l CaC03)
LC50 (hardness =
200 mg/l CaC03)
LC50 (hardness =
50 mg/l CaC03)
LC50 (hardness =
200 mg/l CaC03)
14,000
78,000
15,000
78,000
10,200
10,400
9,000
9,600
9,500
9,200
330
70
310
70
Anderson, et al. 194<
Alekseyev & Antlpln,
1976
Alekseyev & Antipln,
1976
Alekseyev & Antlpln,
1976
Alexander 4 Clarke,
1978
Alexander 4 Clarke,
1978
Alexander & Clarke,
1978
Alexander & Clarke,
1978
Alexander 4 Clarke,
1978
Alexander 4 Clarke,
1978
Birge, et al. 1979
Birge, et al. 1979
Birge, et al. 1979
Birge, et al. 1979

-------
                              Table 6.  (Continued)
to
 I
M
GO
                              Species
Duration
Effect
Result
(ug/l)     Reference
Rainbow trout (juvenile),
Sal mo gairdnerl
Rainbow trout (juvenile),
Salmo gairdneri
Rainbow trout (juvenile),
Salmo gairdneri
Rainbow trout (juvenile),
Salmo gairdnerl
Rainbow trout (yearling),
Salmo gairdnerl
Rainbow trout,
Salmo gairdneri
Rainbow trout,
Salmo gairdnerl
Rainbow trout,
Salmo gairdneri
Rainbow trout,
Salmo gairdneri
Rainbow trout (juvenile),
Salmo gairdneri
Rainbow trout,
Sa Imo gairdneri
Brook trout (juvenile),
Sa 1 ve 1 1 nus font i na 1 1 s
48 hrs
48 hrs
48 hrs
48 hrs
48 hrs
24 hrs
24 hrs
24 hrs
114 mln
2 hrs
48 hrs
24 hrs
50% morta 1 1 ty
50* mortality
50* mortality
50* mortality
50% mortality
50? mortality
50* mortality
50$ morta 1 i ty
50* mortality
Gill damage
Lowest concentra-
tion which killed
50* or more of
the test fish
Temperature selec-
tion shifted
5,400
8,000
9,800
7,500
9,400
5,600
11,000
11,300
12,200
6,500
10,000
7,500
Brown, et al. 1967b
Brown, et al. 1967b
Brown, et al. 19676
Mltrovic, et al. 1968
Brown & Da (ton, 1970
Cairns, et al. 1978
Cairns, et al. 1978
Cairns, et al. 1978
Herbert, 1962
Mitrovlc, et al. 1968
Shumway & Palensky,
1973
Miller & Ogilvie,
1975
                              Brook trout (juvenile).
                              Sal veilnus font)nails
             significantly
             downward

 24 hrs      50* mortality
                 11,700
           Miller & OgiIvie,
           1975

-------
                              Table 6.  (Continued)
                              Species
                                                           Duration
                                                                             Effect
                                                                                             Result
03
 I
Goldfish,
Carass 1 us auratus
Goldfish,
Carass 1 us auratus
Goldfish,
Carass 1 us auratus
Goldfish,
Carass 1 us auratus
Goldfish (embryo),
Carass I us auratus
Goldfish (embryo),
Carass 1 us auratus
Goldfish,
Carass 1 us auratus
Goldfish,
Carass 1 us auratus
Goldfish,
Carass 1 us auratus
Golden shiner,
Notemlgonlus crysoleueus
Golden shiner,
Notemlgonius crysoleueus
Fathead minnow (adult),
Plmephales promelas
Fathead minnow (adult),
Plmephales promelas
Fathead minnow (adult),
Plmephales promelas
8 hrs
8 hrs
24 hrs
20-30 hrs
3.5 days
3.5 days
7.5 days
7.5 days
24 hrs
24 hrs
24 hrs
24 hrs
216 hrs
122-127 hrs
LC62
LC67
50% mortal Ity
50? mortal Ity
LC50 (hardness =
50 mg/l CaC03)
LC50 (hardness =
200 mg/l CaC03)
LC50 (hardness =
50 mg/l CaC03>
LC50 (hardness =
200 mg/l CaC03)
LC50
50$ mortal Ity
50$ mortality
5Q% morta 1 i ty
Median lethal
threshold
Median lethal
threhold
• m
33,300
41,600
200,000
40,000-
100,000
1,220
390
840
340
60,000
129,000
35,000
65,340
27,000
22,000
Gersdorff, 1939
Gersdorff & Smith,
1940
Cairns, et al. 1978
Kobayashi & Akitake,
1975
Birge, et al. 1979
Blrge, et al. 1979
Blrge, et al. 1979
Birge, et al. 1979
Kobayashi , et al.
1979
Cairns, et al. 1978
Cairns, et al. 1978
Jenkins, I960
Rueslnk 4 Smith, 1975
Rueslnk & Smith, 1975

-------
                               Table 6.  (Continued)
00
 I
NJ
O
Species
Walking catfish,
Cl arias batrachus
Guppy (adult),
Poecl 1 la retlculata
Mol lies (adult),
Molllenesla latlplnna
Mol lies (adult),
Molllenesla latlplnna
B 1 ueg 1 1 1 ,
Lepomls macrochfrus
Blueglll (juvenile),
Lepomls macrochlrus
Blueglll (juvenile),
Lepomls macrochlrus
Blueglll,
Lepomls macrochlrus
Blueglll (embryo),
Lepomls macrochlrus
Blueglll (embryo),
Lepomls macrochlrus
Bluegill,
Lepomls macrochlrus
Bluegl II,
Lepomls macrochlrus
Mozambique mouthbrooder,
Tllapla mossamblca
Duration
48 hrs
30 days
25 hrs
50 hrs
25 hrs
48 hrs
48 hrs
24 hrs
2.5 days
2.5 days
6.5 days
6.5 days
1 mo
Effect
50* mortality
Increase In neuro-
secratory hormone
50* mortality
50* mortality
50* mortality
50* mortality
50* mortality
50* mortality
LC50 (hardness =
50 mg/l CaC03)
LC50 (hardness =
200 mg/l CaC03)
LC50 (hardness =
50 mg/l CaC03)
LC50 (hardness =
200 mg/l CaC03)
Manifest nemos 1-
derosls In the
Result
(M9/I)
31,500
3,120
63,000
22,000
10,000-
15,000
22,200
19,000
60,000
3,340
2,430
2,420
1,690
2,000
Reference
Mukherjee &
Bnattacharya, 1974
Matel & Flerov, 1973
Dowden & Bennett,
1965
Dowden & Bennett,
1965
Dowden & Bennett,
1965
Lammerlng & Burbank,
I960
Turnbul 1, et al. 1954
Cairns, et al. 1978
Binge, et al. 1979
Blrge, et al. 1979
Blrge, et al. 1979
Blrge, et al. 1979
Murachl, et al. 1974
                                                                          sp leen

-------
                               Table 6.   (Continued)
DO
 I
Species Duration Effect
Result
(ug/l) Reference
SALTWATER SPECIES
Hard clam (adult), 24 hrs Cellular damage 100 Fries & Tripp, 1977
Mercenarla mercenarla
Hard clam (adult), 24 hrs No cellular
Mercenarla mercenarla damaqe
10 Fries & Tripp, 1977
Mountain bass, Acute Violent reaction 20,000 Hlatt, et al. 1953
Kuhlia sandvlcensis
Mountain bass. Acute Moderate reaction 2,000 Hlatt, et al. 1953
Kuhlia sandvlcensis
Nehu, 12 hrs LC50
Stolephorus purpureus
Rainbow trout, 48 hrs LC50
Sal mo galrdnerl
510 Nunogawa, et al. 19;
6,900 Brown, et al. 1967a

-------
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                                     B-22

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 Brown,  V.M.,  et al.   1967a.   The acute toxicity  of  phenol  to rainbow trout
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Dedonder, A. and  C.F.  Van Sumere.   1971.  The effect  of  phenolics and  rela-
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                                     B-23

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Dowden,  B.F.  and H.J.  Bennett.   1965.   Toxicity of  selected chemicals  to
certain animals.  Jour.  Water Pollut.  Cont.  Fed.   37:  1308.

Fogels, A. and  J.B. Sprague.  1977.  Comparative  short-term tolerance  of  ze-
brafish, flagfish, and rainbow trout to 5 poisons  including potential  refer-
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Fries, C.R. and  M.R.  Tripp.   1977.   Cytological  damage  in Mercenaria  merce-
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um  hydrocarbons in marine  organisms  and ecosystems.   Pergamon  Press,  New
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Gersdorff, W.A.   1939.   Effect  of the  introduction  of the nitro group  into
the  phenol  molecule on  toxicity to  goldfish.    Jour.  Cell.   Comp.  Physiol.
14: 61.

Gersdorff, W.A.  and  I.E. Smith.   1940.   Effect  of introduction of  the  hal-
ogens into the phenol molecule on toxicity to goldfish.    I.   Monochlorophe-
nols.  Am. Jour. Pharm.   112: 197.

Herbert,  0.   1962.   Toxicity to  rainbow  trout of spent still liauors  from
the distillation of coal.  Ann.  Appl.  Biol.   50:  755.

Hiatt, R. W.,   et  al.  1953.   Effects  of chemicals on  a schooling  fish, Kulia
sandvicensii.   Biol. Bull.   104:  28.

Holcombe,  G.W.,  et  al.   1980.   Effects   of   phenol,  2,4-dimethylphenol,
2,4-dichloro-   phenol,   and  pentachlorophenol   on   embryo,   larval,   and
early-juvenile fathead minnows (Pimephalels  promelas).   (Manuscript).

                                     B-24

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 Huang,  J.  and E.F. Gloyna.   1968.   Effect  of organic compounds on  photosyn-
 thetic  oxygenation.   I.  Chlorophenol destruction  and  suppression of photo-
 synthetic  oxygen  production.  Water  Res.  2:  347.

 Jenkins,  C.R.   1960.   A study of  some  toxic components  in  oil  refinery ef-
 fluents.   Ph.D. Thesis.  Okla. St. Univ.

 Kobayashi,  K.  and H.  Akitake.   1975.  Metabolism  of  chlorophenols  in fish.
 IV.   Absorption  and  excretion  of  phenol  by  goldfish.   Nippon  Suisan  Gak-
 kaishi.  41: 1271.

 Kobayashi,  K.,  et al.  1976.  Studies on the metabolism of chlorophenols in
 fish:   VI.   Turnover  of absorbed phenol  in  goldfish.  Bull.  Jap.  Soc.  Sci.
 Fish.   42:  45.

 Kobayashi,  K.,  et al.  1979.  Relation between  toxicity  and accumulation of
 various chlorophenols in goldfish.  Bull.  Jap. Soc. Sci. Fish.  45: 173.

 Kopperman,  H.L.,  et  al.  1974.   Aqueous chlorination  and ozonation  studies.
 I.  Structure-toxicity  correlations  of  phenolic  compounds to  Daphnia  magna.
 Chem. Biol. Interact.   9: 245.

Lammering, M.W. and N.C.  Burbank.   1960.   The toxicity of  phenol,  o-chloro-
phenol  and  o-nitrophenol to  bluegill  sunfish.  Eng. Bull.  Purdue  Univ.  Eng.
Ext. Serv.  106: 541.
                                     B-25

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Lee, DiR.  1976.  Development of an  invertebrate  bioassay  to  screen  petrole-
um  refinery  effluents  discharged  into fresh  water.   Ph.D. Thesis.   VA.  Po-
lyt. Inst. and State Univ., Blacksburg,  Virginia.

Matei, V.E.  and B.A.  Flerov.   1973.  Effect  of  subtoxic concentrations  of
phenol on the conditioned  reflexes of Lebistes  reticulatus.   Jour.  Evol.  Bi-
ochem. Physio!.   9:  416.

Mattson,  V.R.,  et  al.  1976.   Acute toxicity of selected  organic compounds
to fathead minnows.   EPA-600/3-76-097.  U.S. Environ. Prot. Agency.

McLeay,  D.J.   1976.   Rapid method for  measuring  acute  toxicity  of pulpmill
effluents and other  toxicants to salmonid  fish at  ambient room temperature.
Jour. Fish. Res. Board  Can.   33: 1303.

Miller,  D.L.  and D.M. Ogilvie.  1975.  Temperature  selection in  brook trout
(Salve!inus  fontinalis) following exposure  to DDT,  PCB or phenol.  Bull. En-
viron. Contam.  Toxicol.  14:  545.

Mitrovic,  V.V., et  al.  1968.  Some pathological  effects  of subacute and  a-
cute  poisoning  of rainbow  trout by phenol in  hard water.  Water Res.   2:  249.

Mukherjee,  S. and S.  Bhattacharya.   1974.   Effect  of some industrial pollu-
tants on  fish   brain  chloinesterase activity.   Environ.  Physio!.   Biochem.
4:  226.

Murachi, S., et al.   1974.   Relation of hemosiderosis  in fish spleen to the
waste from  chemical  plants.  Hiroshima   Daigahu  Suichikusan  Gakubu  Kiyo.
 13: 207.
                                      B-26

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 Nunogawa, J.N., et  al.   1970.  The  relative  toxicities  of selected chemicals
 to  several  species of  tropical  fish.  Adv.  Water Pollut.  Res.,  Proc.  5th
 Int. Conf.

 Patrick, R., et al.   1968.   The relative sensitivity of  diatoms,  snails and
 fish to twenty common  constituents  of industrial wastes.  Prog.   Fish-Cult.
 30: 137.

 Phipps,  6.L., et  al.   The acute  toxicity  phenol and substituted  phenols  to
 the fathead  minnow.  (Manuscript).

 Pickering,  Q.H.  and  C.  Henderson.  1966.  Acute toxicity of some  important
 petrochemicals to  fish.   Jour.  Water Pollut.  Control. Fed.  38:   1419.

 Reynolds,  J.H.,  et al.   1973.  Continuous  flow kinetic  model to predict the
 effects  of temperature  on the toxicity of oil refinery waste to algae.   Eng.
 Bull.  Purdue  Univ.  Eng.  Ext.  Ser.  142: 259.

 Reynolds,  J.H., et al.   1975.  Effects of temperature on  oil refinery waste
 toxicity.  Jour. Water  Pollut.  Control Fed.  47:  2674.

 Ruesink, R.G.  and  L.L.  Smith,  Jr.  1975.  The relationship  of  the  96-hour
 LCgg  to  the  lethal  threshold concentration of  hexavalent  chromium,  phenol,
 and sodium pentachlorophenate for  fathead minnows (Pimephales promelas Raf i-
 nesaue).  Trans.  Am. Fish. Soc.  3: 567.

Shumway,  D.L. and J.R. Palensky.   1973.  Impairment of the  flavor of  fish by
water pollutants.   EPA-R3-73-010.   U.S. Environ. Prot.  Agency.
                                     B-27

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Simon, E.W.  and  G.E.  Blackman.   1953.   Studies  in the principles  of  phyto-
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to estuarine crustacean.  Estuarine Coastal  Mar.  Sci.   6:  365.

Trama, F.B.  1955.  The acute toxicity of phenol to the common  bluegill  (Le-
pomis macrochirus Rafinesoue).  Notulae Naturae.   269: 1.

Turnbull, H., et  al.   1954.   Toxicity of various  refinery materials to fresh
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U.S.  EPA.   1978a.  In-depth  studies  on  health and environmental  impacts of
selected water pollutants.  Contract  No.  68-01-4646.

U.S.  EPA.    1978b.   Effects of aoueous  effluents  from  in situ  fossil  fuel
processing technologies on  aauatic systems.  Contract No.  77-C-04-3913.
                                      B-28

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 Mammalian Toxicology and Human Health Effects
                            INTRODUCTION
      Phenol  is  a high-volume industrial  chemical  which is widely
 used as  an  intermediate  in the  manufacture of  other chemicals.
 Phenol is also produced by  biological processes  and is  a by-product
 of combustion and some industrial processes.
      Phenol  exists  at  25°C as  a clear,  colorless,  hygroscopic,
 deliquescent, crystalline solid which may  become  slightly pink in
 color as a result of impurities (Lederman and Poffenberger, 1968).
 The chemical and physical characteristics  of phenol are presented
 in Table 1.
      Phenol has a long history of  industrial and  medical  use.   In
 1867, Lister reported  on the use  of phenol sprays for disinfecting
 operating rooms.   Today its medicinal  uses are limited  to  a  few
 mouth,  throat,  and skin medications.  The  industrial capacity  for
 the production  of  phenol  in the  United States was  2,885 x  106
 pounds  per  year  in  1975  (Anonymous,  1975);  about 90 percent of  the
 phenol  produced that year  was  used in the  production  of  phenolic
 resins,  caprolactam, bisphenol-A,  alkylphenols,  and  adipic acid
 (Chemical Profiles, 1972).  Phenol is highly soluble in  water under
 ambient conditions.
     It  should  be noted that analytical  data for phenol should  be
 interpreted with caution. Many spectrophotometric  tests, specific-
ally  those  following   the  methodologies  presented  by Deichmann
 (1942)  are positive for  phenol as  well as  a  spectrum of  substituted
phenol compounds  (Am.  Pub.  Health  Assoc.,  1971; Ettinger, et al.
1951; Smith, 1976).
                               C-l

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                           TABLE 1
           Chemical and Physical Properties of Phenol*
Formula:
Molecular weight:
PKa:
Melting point:
Boiling point:
Vapor pressure @ 25°C
Specific gravity: solid @ 25°C
                  liquid @ 25°C
Relative vapor density: (air = 1.0)
Solubility:  (X = mole fraction)
     Phenol  in water: -log X =
     0.375 log(66 - T) + 1.15.
     Water in phenol: -log X =
     -0.62 log(66 - T) + 0.99
Color:

Odor:
Flashpoint:  open cup
             closed cup
Ignition temperature:
Light sensitivity:

Saturated vapor concentration  (25°C)
C6H5OH
94.11
9.9
40-41°C
181.75°C
0.35 mm Hg
1.071
1.049
3.24
Also soluble in ether,
alcohol, acetic acid,
glycerol, liquid sul-
fur dioxide, benzene.
Colorless to light
pink solid
Sweet; threshold = Ippm
85°C
79°C
715°C
Darkens on exposure
to light
461 ppm
*Source: NIOSH, 1976
                                C-2

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      The National Organic  Monitoring Survey  (U.S.  EPA,  1977)  re-
 ported finding unspecified  concentrations  of phenol  in 2 out of 110
 raw water supplies.   The  survey  found no phenol in any finished wa-
 ter supplies.   The National Commission on Water Quality (1975)  re-
 ported from U.S. Geological Survey  data  that  the annual mean con-
 centration of  phenol in the lower Mississippi  River was 1.5 yg/1,
 with a maximum of 6.7 yg/1 and  a minimum  of 0.0  yg/1.   The Inter-
 national Joint Commission  (1978) reported finding  <0.5 to 5 yg/1
 phenol in the  Detroit river between  1972  and  1977.
      Phenol is also produced endogenously  in the mammalian intesti-
 nal  tract  through  the  microbial   metabolism  of  1-tyrosine  and
 p-hydroxybenzoic acid (Harborne, 1964).   In addition,  exposures to
 benzene  (Docter and Zielhuis,  1967)  and  the  ingestion  of  certain
 drugs (Fishbeck,  et al. 1975)  can lead  to  increased  phenol  produc-
 tion and  excretion.
                             EXPOSURE
 Ingestion  from Water
      As  noted  previously,  during the National Organic  Monitoring
 Survey (U.S. EPA, 1977), phenol was found in only 2 of 110 raw water
 supplies  analyzed by gas-liquid chromatography and mass spectro-
metry;  however,  in  the  two  instances  in  which  the  presence  of
phenol was  detected,  no  quantification  was made.   No phenol  was
found in finished water  supplies. The National  Commission on Water
Quality (1975)  reported an annual mean concentration  of 1.5  yg/1 of
phenol in raw  water from  the lower Mississippi  River.   At a water
intake of 2 liters per day,  this  would result in a phenol intake of
3 yg/person/day.
                               C-3

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     A 1974 train derailment in southern Wisconsin resulted  in sig-
nificant groundwater  contamination by  phenol  (Delfino  and Dube,
1976; Baker, et al. 1978).  Most families in the area of the spill
continued drinking  their  well water until  it became unpalatable.
The maximum concentration of phenol in  the contaminated water actu-
ally  ingested  by the 39  victims is uncertain.    The  first tests
revealed phenol concentrations of 0.21  to 3.2  mg/1 in nearby wells.
Concentrations in  the well  water eventually  reached a  maximum of
1,130 mg/1.   Baker, et  al.   (1978) estimated exposures of 10 to
240 mg/person/day in the highest exposure group.  Medical histories
taken six months after  the spill showed  a statistically significant
increase in reported cases  of diarrhea, mouth  sores,  dark urine,
and burning of the mouth.  Laboratory tests done at  this same time
for  serum  glutamic oxalacetic  transaminase   (SCOT),  bilirubin,
creatinine, uric acid,  glucose, and cholesterol showed no signifi-
cant  abnormalities.  Six  months after  each group's initial expo-
sure, urinary free and  conjugated phenol levels  were 11.97 mg/1 for
the study group  and 11.56 mg/1 for the  control group,  indicating
that the metabolism of  dietary constituents, rather than the inges-
tion of contaminated water, contributed  to the phenol found in the
urine at that time.
     Prior  to  1900,  phenol  was frequently  ingested  to commit sui-
cide  (von Oettingen, 1949).   Reported lethal doses in  man ranged
from 4.8 to 128.0 grams  [National Institute  for  Occupational Safety
Health  (NIOSH), 1976j.
                               C-4

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 Ingestion from Food
      Free and conjugated  phenol  are  normal constituents of animal
 matter (Table 2) .  They  are  most likely formed  in  the intestinal
 tract by  microbial  metabolism of  1-tyrosine  and p-hydroxybenzoic
 acid  (von Oettingen, 1949; Harborne,  1964).   There  are  no market
 basket surveys of free and conjugated  phenol  to allow an estimate
 of the daily  dietary  intake of phenol.  Lustre and Issenberg (1970)
 have reported finding 7 mg phenol/kg  in  smoked  summer sausage and
 28.6 mg/kg in smoked  pork belly.
      Four medicinal preparations  which could  be expected  to  con-
 tribute  to the  ingestion  of  phenol are  presently  on  the  market.
 They are  Cepastat® Mouthwash and  Cepastai® Lozenges,  containing
 1.45 percent  phenol;  Chloraseptic® Mouthwash,  containing  1.4  per-
 cent phenol;  and Chloraseptic® Lozenges, containing  32.5  mg  total
 phenol (free  phenol and sodium phenolate) per  lozenge with a  total
 manufacturer's  recommended dose  of up to  eight lozenges per  day
 (Huff, 1978).  Because there  is no  control  over  the  intake of  non-
 prescription  drugs,  some  individuals  may consume  considerably
 higher doses.
      The  taste and odor of phenol,  and  particularly  of some of  its
 derivatives,  are  noticeable  at   relatively  low   concentrations
 (Table 3) .
      In  a study conducted at the  Mellon Institute   in Pittsburg,
 Pennsylvania, by  Hoak (1957), a  panel  of 2 or  4 persons sniffed
 samples of  pure  phenolic  compounds in  odor-free water, which  had
 been  heated to 30  to  60°C.   A flask of plain  odor-free water  was
provided for comparison.   The  various  samples were placed  in random
                               C-5

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Tissue
                           TABLE 2

             Phenol  Content  of  Normal  Rabbit Tissues*
                            (6 animals)
                         Free
Phenol (mg/kg)

  Conjugated
Total
Blood
CNS
Kidney
Lung
Liver
Muscle
G.I. Tract (includ-
ing contents)
Heart, spleen, thymus,
testes, adrenals
Urine (24 hr. vol.)
Feces (24 hr.)
0-0.7
0
0-1.0
0-2.3
0-0.9
0-1.6
0-3.0
0-0.3
0-3.9
0.4-5.3
0-0.5
0-1.8
0-0.5
0-3.4
1.1-5.5
0-1.8
0-2.3
0-1.0
11.5-100.0
1.4-8.0
0-0.7
0-1.8
0-1.4
0-3.4
1.1-6.2
0-3.4
0-4.4
0-1.0
11.5-100.0
1.8-11.7
*Source: Deichmann, 1944.
                               C-6

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                             TABLE 3

          Taste and Odor Thresholds for Phenol in Water



Taste     Odor             Temperature          Reference
mg/1      mg/1                  °C


>1.0     >1.0               ca.24          Burttschell,
                                               et al. 1959

  °-3       4-0               20-22          Dietz and Traud,
                                               1978

 60                             -            Campbell, et al.
                                               1958

           10-0                  30          Hoak, 1957

            5-°                  60          Hoak, 1957

  1.0       1.0                 -            Veldrye, 1972
                               C-7

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order before the  test persons,  and  the  flask with the lowest per-
ceptible odor  was noted by each  individual sniffer.   The lowest
concentration detected was considered to be the threshold.  Of the
chemicals  tested, chlorinated  phenols  were  the compounds  most
easily detected.   The odor  thresholds reported for phenol were 10
yg/1 at 30°C and  5 ug/1 at 60°C.  Hoak  (1957) speculated that odor
should be  expected to  become  more  noticeable  as temperature in-
creases; however, in evaluating  phenol and  a series  of chloro-
phenols and  cresols,  it was found  that some compounds had higher
odor thresholds at 30°C, while others were  higher at 60°c.
     Burttschell,  et  al.  (1959)  made  dilutions  of  phenolic com-
pounds in carbon-filtered tap water  and used a panel  of  from 4 to  6
persons to evaluate odor and taste.   Tests  were carried  out at room
temperature, which the  investigator  estimated  to be 25°C.   If  a
panel  member's response  was  doubtful,  the sample was considered
negative.  The geometric means (>-1,000 yg/1 for odor and  taste) of
the  panel  responses were  used  as  the  organoleptic thresholds.  The
data presented did not  indicate a range of  responses.
     Campbell,  et al.   (1958)  studied the   taste  thresholds of six
odor-producing chemicals  including phenol.   Solutions of the chemi-
cals were  prepared using redistilled water.   Panels  of  21 to  22
experienced  judges participated  in  different organoleptic tests  of
the  triangle type.  Concentrations of chemicals chosen for the tri-
angle  tests  were  such  that the  odd sample would be  identified  by
more than  35, but less than 100 percent of  the judges.  Samples were
served in  25 ml  portions, and  the judges were asked  only to  iden-
                                C-8

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 tify the  odd  sample.  When 50 percent of the judges correctly sepa-
 rated the samples in a  given  triangle test, the  concentration of
 compound  used  in that  test was  considered to  be  the  threshold
 level.   Although a number of judges were  able  to  detect  the pres-
 ence of phenol at a  concentration of 14 mg/1,  a threshold level of
 60  mg/1 was  reported based  upon the experimental methodology used.
      Dietz  and Traud (1978)  used a panel  composed  of 9  to 12 per-
 sons of both  sexes and  various  age  groups  to test  the organoleptic
 detection thresholds for 126 phenolic  compounds.   To test for odor
 thresholds,  200 ml  samples  of  the  different  test  concentrations
 were placed  in  stoppered   odor-free   glass  bottles,  shaken  for
 approximately five minutes,  and sniffed at room temperature (20 to
 22  C).  For each test, water without the phenolic additive was used
 as  a background sample.  The odor tests took place  in several indi-
 vidual  rooms  in  which  phenols and  other  substances with  intense
 odors  had not been  used previously.   Geometric  mean values  were
 used to determine threshold levels.  To determine  taste  threshold
 concentrations of selected phenolic compounds,  a panel of  four test
 individuals  tasted  water  samples  containing   various  amounts  of
 phenolic  additives.    As  a point   of  comparison,  water  without
 phenolic  additives  was  tasted  first.    Samples  with increasing
 phenolic  concentrations  were then  tested.  Between samples,  the
 mouth was rinsed with the comparison water  and  the  test person  ate
 several bites of  dry  white  bread to "neutralize" the taste.  Geo-
metric mean detection level values for  both tests provided  thresh-
old  levels of phenol of  0.3 mg/1 for taste  and  4.0 mg/1 for  odor.
                               C-9

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     None  of  the  four  organoleptic  studies  described,  however,
indicated whether  the  determined threshold  levels  made  the water
undesirable or unfit for consumption.
     A bioconcentration factor (BCF) relates the concentrations of
a chemical in aquatic animals to the concentration  in the water in
which they live.   The  steady-state BCFs for  a lipid-soluble com-
pound in the tissues of various aquatic animals seem to be propor-
tional to  the percent  lipid in the  tissue.   Thus,  the per capita
ingestion of a lipid-soluble chemical can be estimated  from the per
capita consumption of fish and  shellfish, the weighted average per-
cent lipids of consumed fish and shellfish,  and a steady-state BCF
for the chemical.
     Data from a recent survey on fish and  shellfish consumption  in
the United States were  analyzed by SRI  International (U.S. EPA,
1980a).  These data  were  used  to estimate  that the  per capita con-
sumption  of  freshwater  and estuarine  fish and  shellfish in the
United  States is  6.5  g/day (Stephan,  1980).   In  addition,  these
data were used with data on the fat content of the edible portion  of
the  same  species  to estimate  that the  weighted  average  percent
lipids  for consumed  freshwater and  estuarine fish and  shellfish  is
3.0 percent.
     Measured  BCFs  of  1.2 to 2.3  were obtained with goldfish  by
Kobayashi, et al.  (1976)  and Kobayashi and Akitake  (1975), but per-
cent  lipids was not measured.   The equation  "Log  BCF =  (0.85  Log
P)  -  0.70" can be  used  (Veith, et al. 1979) to estimate the BCF for
aquatic organisms  that contain about  7.6 percent  lipids (Veith,
 1980)  from the octanol/water partition coefficient (P) .   Based  on
                               C-10

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 an average measured log P value  of  1.48  (Hansch and Leo, 1979), the
 steady-state BCF for phenol is estimated to be 3.6.  An adjustment
 factor of 3.0/7.6 = 0.395  can be used  to adjust  the estimated BCF
 from the 7.6 percent lipids on  which the equation is based to the
 3.0 percent lipids  that  is the  weighted average  for consumed fish
 and shellfish.   Thus, the  weighted average  BCF for  phenol and the
 edible portion of  all  freshwater  and estuarine  aquatic organisms
 consumed by Americans is calculated to  be 3.6 x  0.395 = 1.4.
 Inhalation
      The  inhalation  of phenol  vapors  appears to be  largely re-
 stricted to the occupational environment.   Phenol vapor  is effi-
 ciently absorbed from  the  lungs.   Piotrowski  (1971)  administered
 phenol vapors to human volunteers wearing masks to minimize the ef-
 fect of skin absorption.   The phenol concentrations  ranged from  6
 to 20  mg/m .  Piotrowski  (1971)  found that the retention of phenol
 averaged 80  percent  at  the  beginning of  the  exposure  but decreased
 to an  average  retention of  70 percent after eight hours  of  expo-
 sure.   He  did not report  any adverse effects in his  subjects after
 the  exposures to phenol vapor.
     Ohtsuji and Ikeda  (1972) found up to 12.5 mg/m3  of phenol va-
 pors in  bakelite factories.  They  reported no adverse  effects  but
 confirmed  that phenol was efficiently absorbed through  the lungs.
     The present threshold limit  value  (TLV)  for phenol  is  20 mg/m3
 as a  time-weighted  average  (TWA) with  a ceiling value  of  60 mg/m3
 (NIOSH, 1976).
Dermal
     The primary site of phenol absorption in industrial exposures
 is the skin.  The skin is a major route of entry for phenol vapor,

                              C-ll

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phenol  solutions,  liquid  phenol,  or solid  phenol.   Piotrowski
(1971)  determined  that  the  rate  of absorption  of  phenol  vapor
through the skin was  similar  to that through  the respiratory tract.
Aqueous phenol  solutions (1  percent  w/v)  readily penetrate human
skin  (Roberts,  et al.   1977).   As  the  phenol  concentration  in-
creases, the permeability coefficient also  increases.  At very high
concentrations  of  phenol in  water,  the  resulting skin damage  re-
tards the absorption of  phenol  (Deichmann and Keplinger, 1963).
      In addition  to  exposures from occupational  sources, a number
of medicinal preparations can be  sources of dermally  absorbed phe-
nol.  A partial census of phenol-containing preparations for skin
                                           (R)
application  is  as  follows:  Campho-Phenique—' liquid  - 4.75 percent
phenol, powder - 2 percent; Calamine lotion, 1 percent phenol;
ointment or liquid, 1 percent phenol; Panscoi-' ointment,  1  percent
phenol; Benadex^ ointment,  1 percent phenol; Kip for  Burns-' oint-
ment,  0.5 percent phenol;  Noxzema Medicated  Cream-',  0.5  percent
phenol;  Tanuror^ ointment,  0.75 percent phenol; Dri  ToxeiW cream,
 1  percent  phenol;  Peterson's ointment-^,  2.5  percent  phenol.   The
 quantities  of  these drugs used are not under control.   In addition,
 some  feminine hygiene products  and  hemorrhoidal products  contain
 phenol  (Huff,  1978; Am.   Pharm.  Assoc.  1977).
                       PHARMACOKINETICS
 Absorption
      Phenol is readily absorbed  by all routes of entry.  Absorption
 is rapid,  as  illustrated by  the fact that acutely toxic  doses of
 phenol  can produce symptoms  within  minutes of  administration,  re-
 gardless of the route of administration.
                               C-12

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     As  noted earlier in this document, Piotrowski  (1971)  exposed
 human  volunteers  in  climate-controlled  inhalation chambers  to phe-
 nol  administered  through face masks to eliminate  the  influence  of
 dermal exposure.   He found  that, initially, an average  of  80 per-
 cent of  the phenol was  retained  in  the lungs.  The percentage  of
 retained phenol dropped during the experiment, so that after 6 to 8
 hours  an  average  of  only 70 percent of the  inhaled phenol  was re-
 tained in  the lungs.   Subsequently,  Piotrowski (1971) exposed his
 volunteers  for 6 to 8 hours to various phenol concentrations in the
 exposure chamber atmosphere, while permitting them to  breathe clean
 air  through the  face masks.  He  found  that phenol vapor could  be
 readily absorbed  through the  intact  skin  and that normal clothing
 provided little or no protective effect.  He found that the  rate  of
 dermal absorption of phenol vapor could be  represented by the for-
 mula A=(0.35)C,  where A  equals  the amount  of phenol absorbed  in
 mg/hr, and C  is the phenol concentration in  mg/m  .
     When the data presented by Ohtsuji and Ikeda  (1972)  (see Inha-
 lation section) are recalculated utilizing  the efficiency of inha-
 lation data  and  the  skin absorption  coefficient  reported  by  Pio-
 trowski,  the  figures presented may be confirmed.
Distribution
     Phenol  is rapidly  distributed  to all tissues in  animals  that
 have been poisoned with the  compound.  Within 15 minutes  of  an oral
dose,  the  highest  concentrations are  found  in the liver, followed
by  heart,  kidneys,  lungs,  blood,  and muscle  (Deichmann,  1944)
 (Table 4).  As time  progresses,  concentrations become fairly  uni-
form and  start to decrease as the body begins to clear the  phenol;
                               C-13

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                               TABLE 4

    Distribution of Phenol in the Organs of Rabbits After an
                     Oral Dose of 0.5 g/kg
Tissue
Phenol
Died
after
15 min.
Died
after
82 min.
Concentration of
Liver


Blood


Kidneys


Lungs


Heart,
Thymus,
Testes,
Spleen
Brain &
Cord

Muscle


Urine


Exhaled
air

Free
Conjugated
Total**
Free
Conjugated
Total
Free
Conjugated
Total
Free
Conjugated
Total
Free
Conjugated
Total
Free
Conjugated
Total
Free
Conjugated
Total
Free
Conjugated
Total
Free
Conjugated
Total
63.7
0.9
64.6
30.8
0.9
31.7
35.3
0.8
36.1
34.2
1.8
36.0
53.0
0.6
53.6
31.3
0.5
31.8
19.0
0
19.0

no sample

0

0
22.4
4.2
26.6
22.4
5.3
27.7
13.4
7.4
20.8
20.8
4.7
25.5
21.0
2.3
23.3



8.2
0.5
8.7
0.5
14.0
14.5
0.1*

0.1
Killed
after
2 hrs.
Phenol in
3.4
3.2
6.6
5.8
8.0
13.8
4.8
22.8
27.6
5.4
6.7
12.1
6.8
5.7
12.5
6.8
0.7
7.5
9.2
1.1
10.3

no sample

0.7*

0.7
Killed
after
2k hrs.
mg/100 g
13.5
6.0
19.5
11.3
10.2
21.5
11.2
12.9
24.1
12.2
5.1
17.3
14.0
5.1
19.1
10.4
0.3
10.7
12.0
0.8
12.8
11.6
52.0
63.6
0.1*

0.1
Killed
after
6 hrs.
tissue
0.5
9.4
9.9
6.5
9.8
16.3
2.6
30.0
32.6
1.5
3.0
4.5
7.5
7.7
15.2
2.5
0.4
2.9
10.1
1.4
11.5
11.0
12.3
23.3
0.2*

0.2
 aSource: Adapted from Deichmann, 1944.
 *Phenol in total air exhaled.
**Total phenol obtained by summation of free and conjugated fractions,
                               C-14

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 the  concentrations  of  total phenol in the kidney remain relatively
 constant  for the first  six hours after  oral dosing.  In  rabbits,
 roughly  77 percent  of the  administered  dose  is  excreted  in  the
 urine during the first 24 hours, and about 20 percent is completely
 metabolized.   In summary,  the distribution  of phenol  presents  a
 rapid absorption phase,  followed  by  rapid generalized distribution
 to  all  organ systems,  followed by relatively  rapid  metabolism  and
 excretion.
     The  data of Piotrowski (1971)  similarly indicate a rapid rate
 of clearance of  phenol in man, even though his  study  did  not pro-
 vide distributional  data  for  various  organs.
 Metabolism
     Free  and conjugated phenol appear to be  normal  trace consti-
 tuents of the  human body  and have also  been  found  in  other mam-
 malian species  (Harborne,  1964).   Values reported for  phenol con-
 centrations in normal human blood  differ markedly among various  in-
 vestigators.  Ruedemann and Deichmann  (1953)  reported  normal blood
 values to  be 1.5 mg/1  for  free phenol and 3.5 mg/1 for  conjugated
 phenol.   In a  brief  list  of "normal" human  blood  values,  NIOSH
 (1976)  cites  ranges for  free phenol  of  from none  or  traces to
 40 mg/1 and  lists conjugated phenol concentrations ranging  from  1
 to 20 mg/1.   The  variability appears  to be  due  in  part to  the
 specificity of the  analytical method used to  detect phenol  (Ikeda
 and Ohtsuji, 1969)  and to  the amount  of  dietary protein which  in-
creases urinary  phenol  excretion (Folin and Denis,  1915).  More  re-
cent values  determined by  gas-liquid  chromatography  are  0.04  to
0.56  mg/1 for free phenol,  1.06 to 5.18 mg/1  for  conjugated phenols
                              C-15

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(Dirmikis  and  Darbre, 1974),  and 2  to 18 mg/1  for  total phenol
(Van Haaften and Sie, 1965).
     The urinary excretion  of  phenol can be increased above back-
ground levels by exposure to agents which are normally metabolized
to  phenol,  such as  benzene or  phenylsalicylate  (Kociba, et al.
1976).  The urinary excretion levels of phenol in a worker exposed
to phenylsalicylate  ranged  from  150  to 1,371 mg/1.   The ingestion
of manufacturer's  recommended  dosages  of  Pepto-BismoiS' (contains
phenylsalicylate)  resulted  in  peak   urinary  phenol  levels  of
260 mg/1 in a human volunteer  (Fishbeck, et  al.  1975).  The normal
background concentration for urinary phenol in this series was 1.5
to 5 mg/1, as detected by gas chromatography.  After the ingestion
of eight doses of Chloraseptic**' lozenges at the recommended dosing
schedule,  the   total  urinary   phenol  concentration  peaked  at
270 mg/1,  and  the  free  phenol  concentration  peaked  at   10 mg/1.
When dogs were fed 125 mg  phenylsalicylate/kg  body  weight/day for
41  days,  the  peak  urinary phenol concentration was 6,144 mg/1.
This  treatment  was not  associated with any reported  ill  effects
(Kociba, et al.  1976).
     The metabolism of exogenous phenol has been most clearly pre-
sented by Deichmann and Keplinger  (1963) for a lethal oral dose of
0.5 g/kg body  weight in  rabbits and  for  a  sublethal oral  dose of
0.3 g/kg body weight  in  rabbits.   These studies are summarized in
Figures 1 and 2.
     There are  some  species differences in the metabolism of phe-
nol.  Capel, et  al.  (1972)  reported  that man,  rat,  mouse,  jerboa,
gerbil,  hamster,  lemming,  and  guinea  pig  excreted  four  major
                               C-16

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                              Rabbit
                            Oral Dose
                            0.5 g/kg.
Oxidized in
body to C02
and water
plus traces of
1,4-dihydroxy-
benzene and
orthodihy-
droxybenzene
Excreted
in urine
 X
Remaining
in carcass
Exhaled
in air
                                                     Trace
Excreted
in feces
              37%
           Excreted as
           free phenol
                  63%
                   Excreted as
                conjugated phenol
                             FIGURE  1

   Fate of a Lethal Oral Dose of  Phenol Analyzed  Over  5  Hours

              Source:  Deichmann and Keplinger, 1963
                               C-17

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          23%
  ^-
Oxidized in
body to C02
and water
plus traces of
1,4-dihydroxy-
benzene and
orthodihy-
droxybenzene
Excreted
in urine
                              Rabbit
                            Oral Dose
                             0.3  g/kg
                         Trace \ 1%
Remaining   Exhaled   Excreted
in carcass   in air   in feces
                    48%

               Excreted as
               free phenol
                   50%
             Conjugated
               with
            sulfuric acid
                        52%

                      Excreted as
                    conjugated phenol
                     30%
                  Conjugated
                    with
               glucuronic acid
                          20%
                       Conjugated
                          with
                       other acids
                            FIGURE  2

 Fate of a Sublethal Oral Dose  of Phenol Analyzed  over  24  Hours

              Source:  Deichmann and Keplinger, 1963
                              C-18

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metabolites: sulfate and  glucuronic  acid conjugates of phenol and



of 1,4-dihydroxybenzene.  The  squirrel monkey and the capuchin mon-



key excreted phenyl glucuronide, 1,4-dihydroxybenzene glucuronide,



and phenyl  sulphate.   The  ferret,  dog,  hedgehog,  and  rabbit ex-



creted  phenyl  sulfate,  1,4-dihydroxybenzene  sulfate,  and phenyl



glucuronide.  The  rhesus  monkey, fruit  bat,  and  chicken excreted



phenyl sulfate and phenyl glucuronide but not 1,4-dihydroxybenzene



conjugates.  The  cat  appeared to excrete only  phenyl  sulfate and



1,4-dihydroxybenzene  sulfate,  and  the  pig was found  to excrete



phenylglucuronide  as  its major  metabolite  of phenol.   The doses



used  in  this study  were relatively  low.   Miller,  et al.  (1976)



demonstrated that  the  cat was  sensitive  to  phenol;  in addition to



sulfate  conjugates,  free 1,4-dihydroxybenzene  was  found  to  be a



major metabolite, possibly accounting for the toxicity observed in



the  cat.   The authors also noted that  the metabolic  pattern was



dose dependent.   Oehme and Davis  (1970)  found that with the excep-



tion  of  cats,  the  rate of phenylglucuronide  excretion  increased



progressively with the dose,  so  that  at  high  doses phenylglucuro-



nide formation predominated over phenyl sulfate formation.



     In man, the rate  of  absorption,  metabolism,  and excretion of



phenol is relatively rapid.  Pietrowski  (1971) noted that absorbed



phenol  was  almost completely  metabolized  and  excreted  within



24 hours in inhalation experiments near the TLV.



Excretion



     In man  and  all  mammals that have been  tested,  nearly all of



the phenol and  its metabolites are excreted  in  the urine.  Only mi-



nor  amounts  are  excreted in  air and in the  feces  (Deichmann and
                               C-19

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Keplinger,  1963).   Piotrowski  (1971)  studied the  excretion  of
phenol  in  human  volunteers  who had been exposed to phenol  through
inhalation  or  skin absorption.  He  found  that the human body  be-
haved  almost like  a  single  compartment  with respect  to  phenol
absorption  and clearance, with an  excretion  rate constant of K=0.2
hr   .   This corresponds  to  a  half-life of approximately 3.5 hours
(Figures 3  and 4).  The half-life  is defined as
                            M, - °-693  •
                            '      K
     Twenty-four  hours after  administering  300 mg phenol/kg body
weight  orally  to rabbits,  Deichmann  (1944)  reported finding less
than 1 percent of the  administered dose  in the  feces.
                            EFFECTS
Acute, Subacute, and Chronic Toxicity
     Regardless  of  the route  of administration,  the signs  and/or
symptoms of acute toxicity in  man and experimental  animals are sim-
ilar.  The predominant acute action of a toxic dose  in man  appears
to be on the central nervous system,  leading  to sudden collapse  and
unconsciousness.  In some  mammalian species,  these  effects are pre-
ceeded by muscular twitchings  and severe convulsions.  Mukhitov  (as
cited in the 1976 NIOSH Criteria Document on Phenol) reported that
three humans experienced  an increased  sensitivity to  light  after
six  5-minute  exposures to  vapor   containing  0.0155 mg  phenol/m3.
Four additional subjects responded through the formation of  condi-
tioned cortical reflexes after 15-second exposures  to 0.024  mg/m3,
and  3  out  of  4  subjects responded  after 15-second  exposures  to
0.0155 mg/m .  The  significance of these findings  is questionable
and unknown.
                               C-20

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                        EXPOSURE TO
                       PHENOL VAPOUR
                                                      120
         16  20 24   4   8
          Time of day (hr)
12  16  20  24
8
                           FIGURE 3

     Concentrations and excretion  rates  of  phenol  in  urine  in  a

subject exposed to  phenol vapor  in a concentration of 18.3 mg/m3 by
inhalation.

Source: Piotrowski, 1971
                            C-21

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  1.2-i
      0    2   4   6    8   10  12   14  16   18  20  22  24
      Hours from start of exposure
                          FIGURE 4
 Excretion Rate  of  "Excess" Phenol in Relation to  Absorption.
Means + S.D.  Dotted Line - Theoretical Curve for K=0.2 Hour"
                   Source: Piotrowski, 1971
                            C-22

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     After the absorption of an acutely toxic dose, the heart rate

first increases and then becomes  slow and  irregular.  After an ini-

tial rise, the blood pressure falls significantly.  Salivation may

be evident.   There  is  usually a slight fall  in  body temperature,

and  a  marked  depression  in  respiration occurs.    Death  may occur

within minutes of the acute  exposure and is usually due to respira-

tory arrest (Deichmann  and  Keplinger,  1963;  Sollmann,  1957).  The

approximate lethal doses  (LD5Q)  for phenol  in various  species ex-

posed by several different routes are listed  in Table 5.  It  can be

noted that most of  the data fall within  one order  of magnitude.  The

cat  appears to  be  the most  sensitive species, which seems to be a

consequence of  its metabolism of phenol.  It  is difficult to esti-

mate  the  LE>5Q  for  oral exposure  to phenol  for  man,  even  though

phenol has a long history of use  in suicidal  attempts.  A series of

human data is  presented in Table  6. Dosages  were calculated  assum-

ing  a bodyweight of 70 kg.

     When the data in Tables 5 and 6 are compared, it becomes evi-

dent that man is not  unusually sensitive to  the acute  effects of

phenol when compared to other mammalian species.

     Deichmann  and Keplinger  (1963) describe the following  patho-

logical changes  associated with acute exposures  to phenol:

     The  pathological  changes produced by  phenol in animals
     vary with the route of  absorption,  vehicle employed, con-
     centration, and duration  of exposure.   Local damages  to
     the  skin  include  eczema,  inflammation, discoloration,
     papillomas, necrosis,  sloughing,  and gangrene.   Follow-
     ing  oral ingestion,  the mucous membranes  of the throat
     and  esophagus may  show swelling,  corrosions, and necro-
     ses, with hemorrhage and serious infiltration of the sur-
     rounding areas.  In a severe  intoxication,  the lungs may
     show  hyperemia,    infarcts,   bronchopneumonia,  purulent
     bronchitis,  and  hyperplasia  of  the  peribronchial  tis-
     sues.  There can be myocardial degeneration  and necrosis.
                             C-23

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                          TABLE 5
       The Acute Toxicity of Phenol3 to Nonhuman Mammals
Species
Cat
Cat
Dog
Guinea
Pig
Mouse
Rabbit
Rabbit
Rabbit
Rabbit
Rabbit
Rat
Rat
Rat
Rat
Rat
Rat
Route
Subcut.
Oral
Oral
Subcut.
Subcut.
I.V.
Subcut.
Oral
Oral
I. P.
Subcut.
Oral
Oral
I. P.
Dermal
Dermal
LD50
(gAg)
0.09
0.1
0.5
0.68
0.3
0.18
0.5-0.6
0.6
0.4-0.6
0.5-0.6
0.45
0.53
0.34 (20% emuls.)
0.25 (In olive oil)
2.5
0.67
Reference
Tollens, 1905
Macht, 1915
Macht, 1915
Duplay & Cazin, 1891
Tollens, 1905
Deichmann & Wither up,
Tauber, 1895; Tollens
Clarke & Brown, 1906
Deichmann & Witherup,
Deichmann & Witherup,
Deichmann & Witherup,
Deichmann & Witherup,
Deichmann & Witherup,






1944
, 1905

1944
1944
1944
1944
1944
Farquharson, et al. 1958
Deichmann & Witherup,
Conning & Hayes, 1970
1944

In dilute aqueous solution, unless noted otherwise.
                           C-24

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                           TABLE 6



              Oral Toxicity of Phenol in Humans
Total Dose
(g)
5
10-20
15
15
25-30
50
53
Estimated*
(g/kg)
0.07
0.14-0.29
0.21
0.21
0.36-0.43
0.71
0.75
Effect
Survived
Died
Survived
Died
Died
Survived
Survived
Reference
Willhard, 1886
Stajduhar-Caric
Model, 1889
Kronlein, 1873
Geill, 1888
Geill, 1888
Bennett, et al.


, 1968




1950
*assuming a 70 kg bodyweight.
                            C-25

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     The 'hepatic  cells may  be enlarged, pale,  and coarsely
     granular with  swollen,  fragmented,  and pyknotic nuclei.
     Prolonged administration of phenol may cause parenchyma-
     tous nephritis, hyperemia of the glomerular and cortical
     regions,  cloudy  swelling, edema  of the  convoluted tu-
     bules, and degenerative changes of the glomeruli.  Blood
     cells  become  hyaline,  vacuolated, or  filled  with gran-
     ules.  Muscle fibers show marked striation.


     In addition to the above-mentioned effects, the urine is usu-

ally dark or "smoky"  in  appearance, probably due to oxidation prod-

ucts of phenol.  The urine may darken further upon standing  (Soll-

mann, 1957).

     The symptoms  reported  by  humans who had consumed phenol-con-

taminated groundwater  for  approximately one month  (Baker,  et al.

1978) are summarized in Table 7.   The daily  dose of phenol consumed

was estimated to be 10 to 240 mg.

     Deichmann  and Oesper  (1940)  administered phenol  to  rats  in

their drinking water for 12 months at 0, 800, 1,200, 1,600, 2,000,

and  2,400  mg/1  concentrations.   This  corresponded  to  an average

daily  intake  of 0, 21,  30,  49,  56,  and 55 mg,  respectively,   of

phenol per  rat based on actual water consumption data.  At the end

of the experiment, there were no significant differences in tissue

phenol  levels between  the  control  and  experimental rats.   The

weight gain of the rats  at the  two highest dose  levels  was de-

pressed.   A daily  oral  dose of 56 mg/rat is approximately 30 per-

cent of the single oral dose required to kill a  large proportion  of

rats  in a  short  time.    An additional  indication of  the rapid

metabolism  of  phenol  is the fact that  the  rats  that ingested the
                               C-26

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                             TABLE 7

    Symptom Distribution of  Cases  and  Controls  After  Ingestion
              of Well Water Contaminated by Phenol*
Symptom
Vomiting
Diarrhea
Headache
Skin rash
Mouth sores
Paresthesia or numbness
Abdominal pain
Dizziness
Dark urine
Burning with urination"1"
Fever
Back pain
Burning mouth
Shortness of breath
Percentage of
Study Group
(N = 39)
15.4
41.0**
23.1
35.9
48.7**
13.2
23.1
21.1
17.9
10.3
15.4
20.5
23.1**
10.3
Individuals
Control Group
(N = 119)
13.9
13.5
16.1
22.6
12.6
8.4
11.8
9.3
3.4
10.0
10.9
11.0
6.8
6.7
 *Source: Baker, et al.  1978.
**Significantly greater  than controls, P
-------
highest  daily  amount administered  in  this test  consumed,  over a
1-year  period,  the  equivalence  of  approximately  120  LD50  oral
doses.
     Heller and Pursell (1938)  fed phenol to rats  in  their drinking
water over  several  generations.   The  results  of  their  experiment
are listed  in Table 8.
     In  an  unpublished  study by Dow Chemical Company  (1976) , rats
were fed by gavage 20 daily  doses of  0.1 g phenol/kg body weight.
These rats showed slight liver  and kidney effects,  while  rats which
received 20 daily  doses of  0.05  or 0.01 g phenol/kg  body weight
demonstrated none  of those  effects.    In a subsequent  series of
tests,  rats received 135  doses  of 0.1  or 0.05 g phenol/kg  body
weight  by  gavage over a 6-month  period.   The growth  of the rats
receiving the phenol was comparable to that of the controls.  Very
slight liver changes and slight to moderate kidney  damage were seen
in the  rats which  had  received  0.1 g  phenol/kg.   The  feeding of
0.05 g phenol/kg resulted only in slight kidney damage.
     In  a  41-day feeding  study,  Kociba, et al.  (1976)  fed 125 mg
phenylsalicylate/kg/day to beagle dogs.  Since phenylsalicylate is
metabolized to  phenol,  this resulted in urinary phenol levels up to
6,144 mg/1.  This high level  of phenol  excretion was  not  associated
with any discernible ill effects  in the  dogs.   Repeated exposures
to phenol  at  high concentrations  have resulted  in  chronic liver
damage in man  (Merliss,  1972).
                               C-28

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o
I
to
vo
                                               TABLE 8



                              The Effect of Phenol Solutions Upon  Rats*
Phenol
Drinking
Solutions
mg/1
100
500
1,000
3,000
5,000
7,000
8,000
10,000
12,000

Growth

Normal
Normal
Normal
Normal
Normal
Below normal
Fair
Retarded
Retarded

Reproduction

5 generations
5 generations
5 generations
3 generations
3 generations
2 generations
2 generations
Retarded
None

Comments

Splendid condition
Appearance good
Food & water intake satisfactory
General appearance good
General appearance good
Stunted growth in young
Many young died
Young not cared for
Old died in hot weather
        *Source: Heller and Pursell, 1938

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 Synergism and/or Antagonism
      No significant evidence could  be  found  to support the occur-
 rence of synergistic or antagonistic actions of  phenol with other
 compounds in mammals.
      Challis (1973) reported that phenol  could react rapidly with
 nitrites in vitro to produce p-nitrosophenol.
 Teratogenicity
      The work by  Heller  and Pursell  (1938),  which  has  been dis-
 cussed previously,  demonstrated no significant effects of phenol on
 reproduction in  rats receiving  100  to 5,000 mg  phenol/1  in their
 drinking water over 3  to 5 generations.  This  study,  however,  was
 not designed specifically  as  a  teratogenicity study.
 Mutagenicity
      Demerec,  et al.  (1951)  reported  that  phenol produced  back-
 mutations  in E.  coli ranging from streptomycin dependence  to non-
 dependence.  Significant back-mutations occurred at 0.1 to 0.2 per-
 cent  phenol  concentrations.   However,  at these concentrations  the
 survival  of  bacteria was  only 0.5 to 1.7 percent.  Dickey,  et  al.
 (1949) found phenol to  be  nonmutagenic  in Neurospora.  Hadorn  and
 Niggli  (1946) found phenol mutagenic in Drosophila after  exposing
 the gonads of Drosophila to phenol in vitro.
     The  existing  information  on the  mutagenicity  of  phenol  is
 equivocal  and needs to be  re-examined  through  the  use of  better
 established methodologies.
Carcinogenicity
     Boutwell and Bosch (1959) tested the tumor promoting  activity
of phenolic  compounds  in  various strains of mice.   Mice that  had
                               C-30

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been  exposed  to  a  single  dose  of  the  initiator  9,10-dimethyl-
1,2-benzanthracene (DMBA)  by skin  painting were given repeated der-
mal applications  of  selected phenols.   In  one  experiment in this
series, following initiation with DMBA and promotion by croton oil
through skin  painting,  mice which  had been  specially  inbred for
sensitivity to  develop  tumors  received  a  single  application  of
75 ug DMBA to the shaved skin.   This  was  followed  one week later by
twice-weekly dermal applications of 2.5 mg phenol (as a 10 percent
solution in benzene)  for 42 consecutive weeks.  The mice receiving
this dosage of phenol exhibited severe skin damage, decreased body
weight, and increased mortality.  After 13 weeks,  22 out of 23 mice
had developed papillomas, and 73 percent had developed carcinomas.
In a group of mice which  were  treated with  DMBA only, 3 out of 21
survivors exhibited papillomas after 42 weeks.  In a group exposed
to twice-weekly skin paintings with 10 percent phenol alone, 5 out
of 14  survivors  (36  percent)  had papillomas after  52  weeks.   The
skin  painting  with phenol  was  continued until the  72nd  week,  at
which  time one fibrosarcoma was diagnosed.   Other strains of mice
(Holtzman, CAFlf and C3H)  also produced papillomas after initiation
with DMBA and subsequent skin painting with 10 percent phenol, but
the  incidence was  lower.    The  same  schedule  of  application  of
1.25 mg phenol twice-weekly to Rusch's special breed of Sutter mice
resulted  in  a lower  incidence  of papillomas and carcinomas.   No
carcimomas occurred  in  the  standard breeds of mice when exposed to
phenol  without  pretreatment with  DMBA.   Tests with  a 20 percent
phenol  solution   (5 mg/mouse)  caused  a  number  of  deaths  due  to
systemic toxicity.
                               C-31

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      Salaman  and Glendenning  (1957) reported that "S" strain albino
 mice  showed strong promoting activity for tumor formation after in-
 itiation with 0.3 mg DMBA followed by repeated skin applications of
 20  percent phenol.   Twenty  percent phenol solutions produced  sig-
 nificant damage  to the skin and were weakly carcinogenic  when ap-
 plied alone.   Phenol in a  5  percent  solution  had a moderate  pro-
 moting  effect,  but was not carcinogenic without previous  initia-
 tion.
      Van Duuren, et al.  (1971)  found  phenol  (3 mg/mouse,  3  x/week)
 to  have only  slight  promoting activity in ICR/Ha Swiss mice after
 initiation with benzo(a)pyrene  (BaP).    In subsequent  experiments,
 Van Duuren, et al.  (1973)  demonstrated  that phenol  is not cocar-
 cinogenic since, when  it  is repeatedly applied together with  BaP,
 tumorigenesis is inhibited  slightly.   This partial  inhibitory  ef-
 fect  in cocarcinogenesis experiments  was  subsequently  confirmed by
 Van Duuren and Goldschmidt  (1976).
      In conclusion, phenol appears to have tumor-promoting  activity
 in many strains of mice when  repeatedly applied to the shaved  skin
 after  initiation with  known carcinogens.  The tumor-promoting  ac-
 tivity is highest at  dose  levels of phenol which have some  scleros-
 ing activity, but  also  occurs in sensitive strains at phenol  con-
 centrations which do not produce obvious skin  damage.   Phenol  has
 no cocarcinogenic  activity  when repeatedly applied  simultaneously
 with BaP to mouse skin, but it reduces the incidence of tumor  for-
mation slightly.   When  applied repeatedly to  the skin of a  special-
 ly bred strain of Sutter mice, phenol  exhibits carcinogenic activi-
 ty, especially at  concentrations which produce repeated skin  dam-
                               :-32

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age.   Phenol has not  been  found to  be  carcinogenic when applied
alone to the skin of standard strains of mice.
     While the existing qualitative data derived from skin painting
in one sensitive strain of  mice  provide suspicion for a weak car-
cinogenic response to phenol, the protocol was  found,  in agreement
with NIOSH (1976), to be inappropriate and inadequate  for the pur-
pose of judging phenol to be a carcinogen in  ingested  water.
                               C-33

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                     CRITERION FORMULATION
 Existing Guidelines and Standards
      In 1974,  the Federal standard for phenol  in  air  in the work-
 place was 19 mg/m3 or 5 ppm as a time-weighted average (39 FR 125).
 This  coincided with the recommendation of  the  American  Conference
 of  Governmental Industrial  Hygienists  (1977).    The NIOSH  (1976)
 criterion  for  a recommended  standard for occupational exposure to
 phenol  is  20 mg/m3  in air  as a time-weighted average  (TWA)  for up
 to  a  10-hour work day  and  a  40-hour work  week,  with  a  ceiling con-
 centration of  60 mg/m3  for any  15-minute  period.
      The  U.S.   EPA   interim  drinking  water  limit  for  phenol  is
 0.001 mg/1, which is largely an aesthetic  standard based  on the ob-
 jectionable  taste  and odor  produced  by  chlorinated phenols;  this
 limit is  identical  to the 1962  U.S.  PHS  Drinking Water  Standard.
 In  response  to a  phenol spill in southern Wisconsin, the  U.S.  EPA
 proposed on November 26, 1974 a local emergency standard of  0.1 mg
 phenol/1  as  being  temporarily  acceptable  for  human consumption
 (Baker, et al.  1978).
 Current Levels of Exposure
     The National Organic  Monitoring Survey  (U.S.  EPA,  1977)  re-
 ported finding  unspecified  concentrations  of phenol in  2  out  of 110
 raw water supplies.   The survey found  no phenol  in  any  finished wa-
 ter supplies.  The National Commission on Water Quality  (1975)  re-
ported  that  the  annual mean phenol  concentration  in  the  lower
Mississippi River  was 1.5 ug/1 in  1973, with a maximum of 6.7  yg/1.
Endogenously produced phenols in man occur  at significantly  higher
concentration than this.
                               C-34

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     Occupational exposures  at a  threshold limit  value  (TLV)  of
20 mg/m3 TWA would result  in  the  absorption of  105 mg phenol from
the  inspired  air,  assuming   moderate  to  low  activity  (7  m  air
breathed per eight hours)  and an  absorption efficiency of 75 per-
cent.   During  heavier activity  (equivalent to  20  m   inspired in
eight hours),  the  absorption would  rise  to 300 mg phenol  for an
8-hour shift.   The additional skin absorption would be expected to
substantially increase these quantities.
Special Groups at Risk
     In 1976, NIOSH estimated the number  of people who may be ex-
posed to phenol  to be  10,000.   This  reflects the number of people
who are employed in the production of phenol, its formulation into
products, or the distribution of concentrated phenol products.  In
addition, an  uncertain but  probably large number  of  people will
have intermittent contact with phenol as components of medications
or in the workplace as chemists, pharmacists, biomedical personnel,
and other occupations.
Basis and Derivation of Criterion
     Heller and Pursell (1938) reported no significant effects in  a
multi-generation feeding  study in rats at  100,  500,  and 1,000 mg
phenol/1 of drinking  water  for five generations and  at 3,000 and
5,000 mg/1 for three generations.   Assuming a daily  water  intake of
30 ml and  an  average  body weight of  300  grams, these rats  would
have received  doses  of 10, 50, 100,  300,  and  500 mg/kg/day.  The
upper range approaches a  single LDcn dose per  day.  Deichmann and
Oesper (1940)  reported no  significant effects in  rats  receiving 21,
30,  49,  56,  and 55 mg/day in their  drinking water for 12 months.
                               C-35

-------
However, neither of these studies reported detailed pathological or
biochemical  studies,  but  relied mainly on the weights and  general
appearance of  the  animals for evaluation.  In a more  recent  study
(Dow  Chem.  Co.,  1976), 135 dosings  by gavage over  six  months  at
100 mg phenol/kg/dose resulted  in some liver and kidney damage.   At
50 mg/kg/dose, however, the exposure resulted  in  only slight kidney
damage.  It must be borne in mind that in the  first two studies  the
phenol was incorporated into  the drinking water, so  that the  daily
dose was taken gradually.  In the Dow  study,  the phenol was admin-
istered in a single slug.   A  500-fold uncertainty factor applied to
the 50 mg/kg  exposure in  the Dow study would provide  an estimated
acceptable level of 0.1 mg/kg/day for  man.
     The 500-fold  uncertainty factor was selected for a number  of
reasons.   In the case of  phenol,  a great  deal  of  information  on
human exposure exists. Long-term animal data are  available as  well;
however, the detail in these studies is very  incomplete.  Shorter-
term studies of sufficient detail provide the lowest dose level  in
animal studies for  which  an adverse  effect was seen.   It was judged
that the existing  data did not  fully satisfy the  requirements  for
the use  of a  100X  uncertainty  factor,  but were  better  than  the
requirements for a  1,OOOX uncertainty factor  [National Academy  of
Sciences (NAS), 1977].  Consequently,  an intermediate 500X uncer-
tainty factor was selected.
     When one  examines  through  use  of  the  Stokinger and Woodward
model (1958)  the amount of phenol absorbed  through inhalation near
the TLV of  20 mg/m   for occupational exposures, one finds that with
a  breathing rate of 10 m3/8-hour day and 75 percent absorption, a
                               C-36

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70 kg man would absorb approximately  2.14 mg/kg body weight/working


day, assuming no skin  absorption.  The  use of the Stokinger-Wood-


ward model  may be applicable  to estimate  acceptable  intake from


water.

     It has been established that phenol is absorbed  rapidly by all


routes and is subsequently rapidly distributed.   If a 10-fold safe-

ty  factor  is  applied  to the projected doses absorbed from  inhala-

tion at  the TLV  (which already incorporates some safety  factors) ,


then  the  projected acceptable level  would be 0.2 mg/kg/day.  The

estimate from animal data is 0.1  mg/kg/day.  On the basis  of chron-

ic  toxicity data in animals and man,  an estimated acceptable daily


intake for phenol in man should be 0.1 mg/kg/day  or 7.0 mg/man, as-

suming a  70  kg  body  weight.  Therefore, assuming 100 percent gas-

trointestinal absorption of phenol,  the consumption of 2  liters  of


water daily  and  6.5  g of contaminated fish having a bioconcentra-

tion  factor  of  1.4 would result  in  a maximum permissible  concen-


tration of 3.5 mg/1 for  the ingested  water.

     The equation for calculating the criterion  for  the phenol con-

tent of water given an  Acceptable Daily Intake  (ADI) is

                    2X  +  (0.0065)  (BCF)  (X)  = ADI
where
               2   = amount  of  drinking  water, I/day


               X   = phenol  concentration in water, mg/1

          0.0065   = amount  of  fish consumed,  kg/day

             BCF   = bioconcentration  factor,  mg  phenol/kg fish
                    per  mg  phenol/1  water


             ADI   = limit on daily exposure for  a 70 kg person

                    2X  +  (0.0065)  (1.4)X = 7.0 mg/day

                    X  = 3.5 mg/1
                               C-37

-------
     This water duality criterion is in the ranae  of  reported taste
and odor threshold values for phenol listed in Table  2.   It must be
noted that this value has been derived for unchlorinated phenol.
     It is recoqnized that when ambient water containinq this con-
centration of  phenol is chlorinated,  various chlorinated phenols
mav be  produced in  sufficient  quantities to  produce obiectional
taste and odors (see Introduction).   Therefore,  while the criterion
for ambient water is 3.5 mq phenol/1, the possible consequences of
chlorination treatment of such water mav have to be  considered for
specific local conditions.  In those cases where siqnificant chlo-
rination of  ambient water is practiced,  reference  is made to the
water quality  criteria  for  2-chlorophenol  (U.S.  EPA,  1980b)  and
2,4-dichlorophenol  (U.S. EPA, 1980c).
     In summary, based on the use of chronic toxicoloqic test data
for rats and  an uncertainty factor of 500,  the criterion  for phenol
correspondinq  to   the  calculated   acceptable   daily  intake  of
0.1 mq/kq is 3.5 mq/1.  Drinkinq water contributes >• 99 percent of
the assumed exposure, while  eatinq  contaminated fish products ac-
counts for -=c 1 percent.   The criterion  level could alternatively be
expressed as 769 mq/1  if  exposure is assumed  to  be  from the con-
sumption of fish and shellfish products alone.
     Since the  odor and taste detection  threshold   concentrations
for  phenol  are  well  below  the toxicitv-based  criterion  level
derived above,  the  ambient  water  quality  criterion is  based  on
orqanoleptic data.   It should be emphasized that this criterion is
based on aesthetic  quality  rather than health  effects.  However, to
the extent that this criterion is derived  from the chronic toxicity
                               C-38

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study of Dow Chemical Co.  (1976),  it  is  also likely to be protec-
tive of human health.
     The data of Hoak (1957);  Burttschell,  et al.  (1959); and Dietz
and Traud (1978)  all  indicate  that  low mg concentrations of phenols
in water are capable  of  producing a discernable  odor.  Burttschell,
et al.  (1959)  and  Dietz and Traud  (1978)  further  observed  a dis-
tinct flavor alteration of water at low and  sub-mg levels, respec-
tively, of  this  chemical.   Although 9 of  21 tasters  in the Camp-
bell, et al. (1958)  study detected the presence  of  phenols in water
at  14  mg/1  (the  lowest tested  concentration  reported),  a  taste
threshold of 60 mg/1  was determined based on  the methodology of the
experiment.  The data from these studies,  in particular the Burtt-
schell, et  al.  (1959) and  Dietz and Traud  (1978)  experiments, are
considered to be reasonably mutually supportive  [i.e., Hoak (1957),
10 mg/1  for  odor;  Burttschell,  et al.  (1959), >.1.0 mg/1 for odor
and taste; and Dietz  and Traud (1978), 4 mg/1 for odor and 0.3 mg/1
for taste].
     Therefore, based on the prevention of  undesirable organoleptic
qualities,  the  criterion level  for phenol in  water  is 0.3  mg/1.
This level  should  be low  enough to prevent objectionable organo-
leptic characteristics  for most people and still  below animal no-
effect concentrations determined in laboratory animals.   As more
substantive  and  reliable data  become  available in  the future,   a
criterion level  based  on human  health effects  may be more confi-
dently postulated.
                               C-39

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