FINAL DRAFT
       United States                                     ECAO-CIN-G081
       Environmental Projection                               September , 1989
       Research  and
       Development
      HEALTH  AND ENVIRONMENTAL  EFFECTS  DOCUMENT
      BUTYL BENZYL PHTHALATE
       Prepared for
       0 HCE OF SOLID WASTE AND
       E URGENCY RESPONSE
      Prepared by
      Environmental  Criteria and Assessment Office
      C  fice of  Health and Environmental  Assessment
      I  3. Environmental Protection Agency
      Cincinnati, OH  45268
                   DRAF1: DO NOT CITE OR QUOTE


                          NOTICE

   This document 1s a preliminary draft.  It has not been formally released
by the  U.S. Environmental Protection Agency and should  not at this stage be
construed to represent Agency policy.  It Is  being circulated for comments
on Us  technical accuracy and policy Implications.

                       HEADQUARTERS UBRARY
                       ENVIRONMENTAL PROTECTION AGENCY
                       WASHINGTON, D.C. 20460

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         UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
                        WASHINGTON, D.C.  20460
«*?*
                           nr,T 5 9 138G
                                                      OFFICE OF
                                                RESEARCH AND DEVELOPMENT
S'CfB JECT:
FROM:
Health and Environmental Effects Document for Butyl
Benzyl Phthalate
TO:
        H. Fatland, Ph.D.
Director
Office of Health and Environmental
  Assessment  (RD-689)

Matthew Straus
Chief, Waste Characterization Branch
Office of Solid Waste  (OS-330)
     I am forwarding  copies  of  the  Health and Environmental
Effects Document  (HEED)  for  Butyl Benzyl  Phthalate.

     The HEEDs  support  listings under  RCRA,  as well  as provide
health-related  limits and goals for emergency and remedial
actions under CERCLA.   These documents represent  scientific
summaries of the pertinent available data on the  environmental
fate and mammalian  and  aquatic  toxicity of each chemical at an
extramural effort of  about $10K.  The  attached document has been
reviewed within OHEA, by staff  in OPP  and OTS,  and by two
external scientists.

     Should you wish  to see  any of  the files related to the
development of  the  HEEDs,  please call  Chris DeRosa at
F"S:  684-7531.
Attachment

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                                  DISCLAIMER

    This report  1s  an external  draft  for  review purposes only  and  does  not
constitute  Agency  policy.   Mention of  trade names  or commercial  products
does not constitute endorsement or recommendation for use.

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                                    PREFACE
    Health and  Environmental  Effects  Documents (HEEOs) are  prepared  for  the
Office of Solid  Waste  and Emergency Response  (OSHER).  This  document series
Is Intended to support listings  under  the  Resource  Conservation and Recovery
Act  (RCRA)   as   well  as  to  provide  health-related  limits  and  goals  for
emergency  and   remedial   actions  under   the   Comprehensive  Environmental
Response,  Compensation   and   Liability   Act   (CERCLA).    Both   published
literature and   Information  obtained  for   Agency  Program  Office   files  are
evaluated  as  they  pertain  to  potential   human  health,  aquatic  life  and
environmental   effects  of  hazardous  waste  constituents.   The  literature
searched  for   In this  document  and  the   dates  searched  are  Included  In
"Appendix: Literature  Searched."  Literature  search material  Is  current  up
to 8  months   previous  to the  final draft  date listed on the  front  cover.
Final draft  document  dates  (front  cover)   reflect  the date  the document  1s
sent to the Program Officer  (OSWER).

    Several quantitative  estimates  are presented  provided  sufficient  data
are  available.    For   systemic   toxicants,   these   Include:  Reference  doses
(RfD's)  for  chronic and  subchronlc exposures  for   both  the Inhalation  and
oral exposures.   The  subchronlc or partial  lifetime RfO, Is an estimate  of
an exposure level which  would not be  expected  to cause adverse effects  when
exposure  occurs  during  a limited time Interval I.e., for an Interval  which
does not  constitute a  significant  portion  of the  llfespan.  This  type  of
exposure  estimate  has  not  been extensively used,  or rigorously  defined  as
previous  risk assessment  efforts  have  focused  primarily on lifetime exposure
scenarios.   Animal  data  used   for  subchronlc estimates  generally  reflect
exposure  durations  of 30-90  days.   The general  methodology for  estimating
subchronlc  RfO's   Is   the   same  as   traditionally   employed   for   chronic
estimates, except that subchronlc data  are  utilized  when available.

    In the case of  suspected  carcinogens,  RfD's are  not estimated.  Instead,
a  carcinogenic   potency  factor,  or   qi   (U.S.  EPA,  1980}  1s   provided.
These potency estimates  are derived for both  oral   and Inhalation exposures
where possible.   In addition, unit risk  estimates for air  and drinking water
are presented based  on Inhalation and oral  data, respectively.

    Reportable  quantities   (RQs)  based   on   both  chronic   toxlclty   and
cardnogenlclty  are derived.  The RQ  1s used to determine the  quantity  of  a
hazardous substance for   which  notification Is  required  In  the event of  a
release   as   specified   under   the  Comprehensive   Environmental   Response,
Compensation   and  Liability  Act  {CERCLA).   These two RQs (chronic  toxlclty
and carclnogenldty)  represent   two  of  six  scores  developed (the  remaining
four reflect  IgnltablHty,  reactivity,  aquatic  toxlclty,  and  acute mammalian
toxlclty).  Chemical-specific RQ's  reflect  the  lowest  of these six  primary
criteria.  The  methodology  for  chronic toxldty and cancer  based RQs  are
defined 1n U.S.  EPA, 1984 and 1986b,  respectively.
                                     Ill

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                               EXECUTIVE  SUMMARY
     Butyl benzyl  phthalate Is  a  colorless, oily,  nonvolatile,  combustible
liquid with a  slight  odor (Sax and Lewis,  1987).   It  Is  probably soluble In
most organic solvents and  Is only  sparingly soluble In water (Howard et al.,
1985).   During 1977,  between  101  and  510 million pounds  of butyl  benzyl
phthalate was  produced  In the  United States at  two locations  of  the Monsan-
to Company  (TSCAPP,  1989); as of  January 1988,  the Bridgeport,  NJ location
of this company was the  sole producer  of this  chemical (SRI, 1988).  Current
production data  were  not located.  Butyl  benzyl   phthalate  1s  produced  by
reacting  butyl  alcohol  with phthallc  anhydride  In  the presence of  an acid
catalyst  and  by  reacting  the  resulting  ester  with  benzyl  chloride  under
neutral  aqueous  or  alcoholic  solutions.   Butyl  benzyl  phthalate  Is  used
almost  exclusively  as a  plastlclzlng agent;  more  than  half  goes  Into  PVC
plastics used as flooring  materials.  Smaller amounts  of  butyl  benzyl phtha-
late are  used  In other  household  products.  Butyl  benzyl phthalate  Is also
used as a plastlclzer  for  polyvlnyl acetates, which are used as adheslves In
the packaging of food (Gledhlll et al., 1980; IARC, 1982).
     In the atmosphere,  butyl  benzyl  phthalate 1s  expected  to  exist  both In
the  vapor phase  and  In  the  partlculate  form  In the  ambient  atmosphere
(Cautreels and  van  Cauwenberghe, 1978;  Elsenrelch  et  al., 1981).   Both  dry
and wet  deposition may  be significant  atmospheric  fate  processes  for  this
compound.  Destruction by  ozone  and by direct  photolysis  are not  expected to
be  significant.   The  destruction  of vapor-phase  butyl benzyl phthalate  by
the reaction with  photochemlcally produced hydroxyl radicals  Is  expected to
be a  rapid  fate process  with  an estimated half-life  of  1.5  days (Atkinson,
1985);  however,  It  may  not  be  significant  for  the  partlculate  form.   If
                                      1v

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released to water,  the  dominant fate processes are  expected  to be mlcrobUl
degradation and bloconcentratlon  In  fish  and  aquatic organisms.  Hydrolysis,
volatilization to  the  atmosphere, oxidation and photolysis are not expected
to  be  significant  fate  processes   In  water   (Gledhlll  et a!.,   1980).   If
released to  soil,  butyl benzyl phthalate  can be strongly  adsorbed.   B1ode-
gradation 1n  soil  may  occur  under the proper  conditions.   Volatilization  of
butyl  benzyl  phthalate from  the  soil   surface  to  the atmosphere  Is  not
expected to be significant.
     Butyl  benzyl  phthalate  1s  a  nonvolatile, organic  compound  caused  by
anthropogenic  sources.   It enters  the environment  during Us  manufacture,
and  also  through   the  processing,  use  and   disposal  of  plastic  products
containing  H.   In general,  the majority  of phthalate  esters Incorporated
Into  plastic  products  are  ultimately deposited 1n landfills  (Perwak  et  al.,
1981).
     Data  were  lacking   regarding   exposure  to   butyl   benzyl   phthalate.
Occupational  exposure  to butyl  benzyl phthalate may occur  by  Inhalation  and
dermal  contact during  Its  manufacture or  formulation Into polymers.  For  the
general  population,  exposure  to  butyl  benzyl  phthalate  may  be  the  same  as
that  believed to  be  occurring for  other  phthalate  esters,  which are  also
used  as  plastlclzers.  These  routes  of  exposure   Include dermal  contact.
Inhalation  and  Ingestlon   through  drinking  water.    It  has  been  detected  In
surface  water,  groundwater,   rainwater,   Industrial  effluent  and  drinking
water.  The general population  can be exposed through  Ingestlon of contamin-
ated  water.   Sufficient data  were  not located  to  estimate the  exposure  of
the  general  population to  butyl  benzyl phthalate through Inhalation, Inges-
tlon  of food and  drinking water  and dermal  contact. Butyl benzyl phthalate

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can also  be  present In certain  foods  as  a result of migration  from plastic
packaging material.
     Butyl benzyl phthalate has  been assessed  for  acute  toxldty In at least
four  freshwater   fish  species  (Buccafusco et  al.,  1980;  EG&G,  1983a,b,c;
Gledhlll et al.,  1980; Knle et al.,  1983),  and three marine fishes (Gledhlll
et  al..  1980; Heltmuller  et  al.,  1981;  Ozretlch et al.,  1983;  Randall  et
al..  1983;  Sprlngborn  Bionomics  Inc.,  1984)    L05QS were  reported at  con-
centrations  as  low as  0.82  mg/i  In  freshwater  (EG&G,  1983a)  and  0.51
mg/8. In saltwater (Ozretlch et al., 1983).
     Acute toxldty data for  fresh  and  saltwater  Invertebrates  Indicate  that
mysld  shrimp,  M. bahla, are  slightly more sensitive than other  forms,  but
all  LCgo  values  fell  within  the  range  of 0.9-92 mg/i  (Analytical  Blochem
Labs,  1981;  Gledhlll  et al..  1980; LeBlanc,  1980;  Monsanto Co.,  1983a,b,;
Sprlngborn Life Sciences, 1988; SRI, 1981).
     Chronic toxldty of butyl benzyl phthalate has  been  assessed In fathead
minnows,  £.  promelas  and  water  fleas,  0.  magna   (Gledhlll  et  al.,  1980;
Monsanto  Co.,  1983c;  LeBlanc  et al.,  n.d.) and  In  five species  of  aquatic
flora  (Gledhlll   et  al.,  1980;  Monsanto Co.,  1983e;  Sprlngborn  Bionomics
Inc.,  1985b).  With  the  exception of one plant species  (the  bluegreen alga,
Hlcrocystls  aeruglnosa).  sensitivity  was   similar  between  tested   algal
species and  fell within the  narrow range of  0.2-1 rog/l.   M. aeruglnosa  was
considerably  more resistant,  with  a 96-hour  LC5   of 1000 mg/8, and  a  NOEC
of 560 mg/i (Gledhlll  et al.,  1980).
     Bloaccumulatlon and uptake  studies of  butyl  benzyl  phthalate with blue-
gill  sunflsh,  l^. roacrochlrus. and  English sole,  P_.  vetulus.  Indicate  that
this chemical bloaccumulates  1n  tissues of  freshwater or  marine  fauna  but Is
rapidly depurated  (Barrows et  al.,  1980;  Monsanto Co.,  1983d).   A 30-m1nute
                                      vl

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EC,Q  of  10  mg/l was  reported  for  the bacterium,  £.. putlda  (Knle et  al.
(1983).
     The lack of adequate pertinent data regarding  toxldty  of   butyl  benzyl
phthalate prevented  the development of  freshwater  or saltwater  criteria  by
the method of U.S.EPA/OWRS (1985).
     Studies  where   rats   were  orally   and   Intravenously   administered
14C-butyl    benzyl   phthalate   (Elgenberg   et   al.,  1986)   Indicate   that
gastrointestinal  absorption  Is  rapid  and  virtually  complete;  however,  at
very high doses  (2000  mg/kg), the extent of  gastrointestinal absorption  may
be reduced.  Distribution  1s  rapid and widespread,   but no  tissue appears  to
preferentially  accumulate  the  compound  or  Its  radioactive   metabolites.
Although butyl  benzyl  phthalate Is llpophlllc, accumulation 1n  fat  does  not
occur, probably because the compound 1s rapidly metabolized.
     Following  absorption,  butyl  benzyl   phthalate  undergoes  very  rapid
metabolism  and  excretion  (Elgenberg et al.,  1986).   The  principal  metabolic
pathway appears  to be  hydrolysis of the ester  linkages followed by conjuga-
tion with  glucuronlc acid.   Peak levels of  monophthalates  are  measured  In
the blood within 5 minutes of an Intravenous dose.   The  benzyl  ester linkage
appears to  be  more  labile than the butyl  ester  linkage.  There Is  evidence
that glucuronlde conjugation  becomes saturated at higher  dosages.
     Experiments with  bile duct-cannulated  rats  showed   that metabolites  of
butyl  benzyl  phthalate are excreted to  a  larger  extent   In  the  bile than  In
the urine (Elgenberg et al.,  1986); however,  In  Intact rats,  urinary excre-
tion  exceeded  fecal  excretion.  Indicating  that  substantial reabsorptlon  of
biliary excretion products occurs.  Excretion Is  very rapid  following Intra-
venous or  oral   treatment.   An overall  half-life of =6  hours  was  estimated
for removal  of  butyl benzyl  phthalate and  the  monophthalate esters  from all
tissues.
                                     vll

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     An acute  toxlclty study  Indicated that  the testes  and accessory  sex
organs appear to be Important  target organs  of  butyl  benzyl  phthalate toxlc-
Uy (Agarwal et  al.,  1985).   Exposure  of male  F344 rats  to  diets  containing
2.5 or 5.0% butyl benzyl phthalate  for  14  days  resulted In decreased weights
of  testes,   epldldymus,  seminal  vesicle  and  thymus  and  hlstopathologlcal
evidence  of  a dose-dependent  atrophy   of  the  testes,  prostate  and  seminal
vesicles  {Agarwal et  al.,  1985).   Atrophy  of the thymus  and  decreased  body
weight  were  observed  only  at  the  5.0% level.  Bone  marrow cellularlty  was
reduced at the 2.5 and 5.0% levels.
     Testlcular  degeneration  was  observed  In  male  F344  rats  fed  a  diet
containing 25,000 ppm  butyl  benzyl  phthalate for 91 days  (NTP,  1982).   Mice
fed  a  similar  diet   did  not  exhibit  signs  of  testlcular degeneration.
Atrophy of the seminiferous  tubules of the  testicles and  aspermla  were  seen
In rats fed  a  2.5%  diet for 26 weeks  (NTP,  1985).  The kidneys  of  6/15  rats
on  the 2.5%  diet  exhibited  areas  of atrophy.   In an   unpublished  90-day
toxlclty study (Honsanto, 1972), an  Increase  In liver weight  was observed In
rats  fed  diets  containing  1.0.  1.5  or   2.0%  butyl benzyl  phthalate.   No
adverse effects were observed among dogs exposed to similar doses.
     The  male  rat  appears  to  be  more sensitive  to  butyl benzyl  phthalate
toxlclty than female rats and male  and  female mice (NTP,  1982).  Groups  of 50
males fed diets  containing 6000 or  12,000  ppm butyl  benzyl phthalate experi-
enced  high  mortality within  28 weeks.  Internal  hemorrhaglng was  the  sus-
pected  cause  of  the  mortality.  Mortality  was not  seen  In  female  rats  or
male and female mice after  103 weeks exposure to these diets.
     Female  rats fed  a diet  containing  butyl  benzyl  phthalate  at a  con-
centration of  12,000 ppm demonstrated  a significantly  Increased  Incidence of

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leukemia or  lymphoma  (NTP,  1982);  however,  a high  Incidence  of tumors  In
control  rats  was  noted  (Kluwe  et  al.,  1982).   There  was  no evidence  of
cardnogenlcHy  In  mice.   Evidence suggests  that  butyl  benzyl phthalate  1s
not mutagenlc (see Table  6-3) .
     Butyl  benzyl phthalate was assigned to U.S. EPA  Group  C,  Possible Human
Carcinogen,  as   has  been  done  In  previous  evaluations  (U.S.  EPA,  1986c,
1987a,b,c).   Data  were  Inadequate  for  quantitative estimation  of  cancer
potency.   The  chemical  was  administratively  assigned to  Potency Group  2,
which resulted 1n a  LOW hazard  ranking  and  an RQ  based on  cardnogenlclty  of
100.   The  NTP (1989)  has  scheduled  butyl  benzyl  phthalate for  additional
testing 1n rats by oral administration.
     An  RfD for  subchronlc   oral  exposure  of 2  mg/kg/day was  derived  by
applying an uncertainty  factor of  100  to  the NOEL of  159  mg/kg/day  for
elevated liver weight, hematologlcal and  testlcular  effects In  the  26-week
dietary study using  male  rats  by NTP (1985).   Application  of  an  uncertainty
factor  of  1000  allowed  derivation  of  an  RfD of  0.2 mg/kg/day  for  chronic
oral exposure.   An  RQ  of  1000 for chronic  (noncancer) toxldty was  based  on
early mortality In male rats  1n the 103-week study  by  NTP  (1982).
                                      1x

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                              TABLE  OF  CONTENTS
                                                                        Page

1.    INTRODUCTION	      1

     1.1.   STRUCTURE AND CAS NUMBER	      1
     1.2.   CHEMICAL AND PHYSICAL PROPERTIES	      1
     1.3.   PRODUCTION DATA	      2
     1.4.   USE DATA	      2
     1.5.   SUMMARY	      3

2.    ENVIRONMENTAL FATE AND TRANSPORT	      4

     2.1.   AIR	      4

            2.1.1.   Reaction with Hydroxyl Radicals	      4
            2.1.2.   Reaction with Ozone	      4
            2.1.3.   Photolysis	      4
            2.1.4.   Physical Removal Processes	      5

     2.2.   WATER	      5

            2.2.1.   Hydrolysis	      5
            2.2.2.   Oxidation	      5
            2.2.3.   Photolysis	      5
            2.2.4.   Mlcroblal Degradation	      6
            2.2.5.   81oconcentrat1on	      7
            2.2.6.   Adsorption	      7
            2.2.7.   Volatilization	      8

     2.3.   SOIL	      8

            2.3.1.   Mlcroblal Degradation	      8
            2.3.2.   Adsorption	      8
            2.3.3.   Volatilization	      9

     2.4.   SUMMARY	      9

3.    EXPOSURE	     11

     3.1.   WATER	     12
     3.2.   FOOD	     14
     3.3.   INHALATION	     14
     3.4.   DERMAL	     14
     3.5.   OTHER	     15
     3.6.   SUMMARY	     15

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                           TABLE  OF  CONTENTS  (cont.)
                                                                        Page

4.   ENVIRONMENTAL TOXICOLOGY	     16

     4.1.   AQUATIC TOXICOLOGY	     16

            4.1.1.   Acute Toxic Effects on Fauna	     16
            4.1.2.   Chronic Effects on Fauna	     16
            4.1.3.   Effects on Flora	     22
            4.1.4.   Effects of Bacteria	     22

     4.2.   TERRESTRIAL TOXICOLOGY	     22

            4.2.1.   Effects on Fauna	     22
            4.2.2.   Chronic Effects on Flora	     22

     4.3.   FIELD STUDIES	     24
     4.4    AQUATIC RISK ASSESSMENT	     24
     4.5.   SUMMARY	     27

5.   PHARMACOKINETICS	      29

     5.1.   ABSORPTION	      29
     5.2.   DISTRIBUTION	      29
     5.3.   METABOLISM	      31
     5.4.   EXCRETION	      32
     5.5.   SUMMARY	      33

6.   EFFECTS	      35

     6.1.   SYSTEMIC TOXICITY	      35

            6.1.1    Inhalation Exposures	      35
            6.1.2.   Oral Exposures	      35
            6.1.3.   Other Relevant Information	      39

     6.2.   CARCINOGENICITY	      41

            6.2.1.   Inhalation	      41
            6.2.2.   Oral	      41
            6.2.3.   Other Relevant Information	      43

     6.3.   NUTAGENICITY	      45
     6.4.   TERATOGENICITY	      45
     6.5.   OTHER REPRODUCTIVE EFFECTS	      45
     6.6.   SUMMARY	      46

7.   EXISTING GUIDELINES AND STANDARDS	      48

     7.1.   HUMAN	      48
     7.2.   AQUATIC	      48
                                      x1

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                           TABLE  OF  CONTENTS  (cont.)
                                                                        Page

8.   RISK ASSESSMENT	      49

     8.1.   CARCINOGENICITY	      49

            8.1.1.   Inhalation	      49
            8.1.2.   Oral	      49
            8.1.3.   Other Routes	      49
            8.1.4.   Weight of Evidence	      50
            8.1.5.   Quantitative Risk Assessment	      50

     8.2.   SYSTEMIC TOXICITY	      50

            8.2.1.   Inhalation Exposure	      50
            8.2.2.   Oral Exposure	      51

9.   REPORTABLE QUANTITIES	      54

     9.1.   BASED ON SYSTEMIC TOXICITY	      54
     9.2.   BASED ON CARCINOGENICITY	      56

10.  REFERENCES	      60

APPENDIX A	     A-l

APPENDIX B	     B-l

APPENDIX C	     C-l
                                      xll

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                                LIST OF TABLES
No.                                  Title                              Page
4-1        Acute ToxIcUy of Butyl Benzyl Phthalate to Aquatic Fauna..     17
4-2        Acute Toxlclty of Butyl Benzyl Phthalate to Aquatic Flora..     23
5-1        Percent of Radioactive Dose 1n Tissues or Excreta In
           Hale F344 Rats Given a Single Intravenous Dose of Ring
           Labeled "C-Butyl Benzyl Phthalate	     30
6-1        Oral LD50 Values for Butyl Benzyl  Phthalate	     40
6-2        Hematopoletlc Neoplasms In F344/N  Rats and B6C3F1 Mice Fed
           n-Butyl Benzyl Phthalate 1n the Diet for 103 Weeks	     42
6-3        Genotoxlclty Summary Table for Butyl Benzyl Phthalate	     44
9-1        Toxlclty Summary for Butyl Benzyl  Phthalate	     55
9-2        Composite Scores for Butyl Benzyl  Phthalate	     57
9-3        Butyl Benzyl Phthalate: Minimum Effective Dose (MED) and
           Reportable Quantity (RQ)	     58
                                     xlll

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                             LIST  OF  ABBREVIATIONS
ADI        Alcohol dehydrogenase
BCF        Bloconcentratlon factor
bw         Body weight
CAS        Chemical Abstract Service
CS         Composite score
ECgg       Concentration effective  to  50% of recipients  (and  all  other  sub-
           scripted concentration levels)
FEL        Frank effect level
FSH        Follicle stimulating hormone
GMAV       Genus mean acute values
GHCV       Genus mean chronic values
Koc        Soil sorptlon coefficient
Kow        Octanol/water partition coefficient
LC5Q       Concentration lethal to 50% of recipients
1059       Dose lethal to 50% of recipients
LH         Lute1n1z1ng hormone
LOAEL      Lowest-observed-adverse-effect level
MATC       Maximum allowable toxicant concentration
MCH        Mean cell hemoglobin
MCV        Mean cell volume
MCHC       Mean cell hemoglobin concentration
MEO        Minimum effective dose
NOEC       No-observed-effect concentration
NOEL       No-observed-effect level
ppb        Parts per billion
                                      xlv

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                         LIST OF  ABBREVIATIONS (cont.)
ppm          Parts per million
ppt          Parts per trillion
PVC          Polyvlnyl chloride
RfO          Reference dose
RQ           Reportable quantity
RV(j          Dose-rating value
RVe          Effect-rating value
SCAS         Semi-continuous activated sludge
SE           Standards error
UV           Ultraviolet
                                      xv

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                               1.   INTRODUCTION
1.1.   STRUCTURE AND CAS NUMBER
    Butyl benzyl phthalate 1s also known by  the  synonyms  benzyl  butyl  phtha-
late; benzyl n-butyl  phthalate; l,2-benzened1carboxcy!1c  add, butyl phenyl-
methyl ester; by  the  tradenames  Santldzer  160,  Palatlnol BB and  S1col  160;
and  the  acronym  BBP  (Chemline,  1989;  SANSS,  1989).    The  structure,   CAS
Registry number, empirical formula and molecular  weight  are as follows:
    CAS registry number:  85-68-7
    Empirical formula:  c-|gH2o04
    Molecular weight:  312.36
1.2.   CHEMICAL AND PHYSICAL PROPERTIES
    Butyl  benzyl   phthalate  Is  a  clear,  oily,  combustible  liquid  with  a
slight odor  (Sax and  Lewis,  1967).   It  Is  sparingly  soluble  In  water  (Howard
et al.,  1985).   Selected physical properties of  butyl  benzyl  phthalate  are
given below:
    Melting point:
    Boiling point:
    Density (25"C):
    Vapor pressure (25°C):
    Water solubility (25°C):
-35°C
377°C
1.119
8.25X10'6 mm Hg
2.69 mg/l
IARC, 1982
IARC, 1982
Dean, 198S
Howard et al., 1985
Howard et al.. 1985
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    Log Kow:                    5.50                     Howard et al.. 1985
    Conversion factor {25°C):   1  mg/m3 = 0.0783 ppm;
                                1  ppm = 12.76 mg/m3

1.3.   PRODUCTION DATA
    Data from the U.S.  EPA TSCA production  file (TSCAPP,  1989) Indicate that
during  1977,  between 101 and  510 million  pounds of butyl  benzyl  phthalate
was produced  In  the  United  States at  two locations  of  the Monsanto Company;
as  of  January,   1998,  the Bridgeport,  NJ  location  of  this company was  the
sole  producer of  this  chemical   In  the United  States  (SRI, 1988).   More
current production data were not located.
    Butyl benzyl phthalate  Is  produced by a  two-step reaction Involving  the
Initial formation of the mono butyl  ester  of phthallc acid by  the reaction
of  butyl  alcohol with  phthallc anhydride  using an  acid  catalyst.   The mono
ester  Is  reacted  with  benzylchlorlde  under  neutral  aqueous or  alcoholic
solutions to form the desired product (1ARC, 1982).
1.4.   USE DATA
    Butyl  benzyl phthalate  Is  used  almost  exclusively  as  a  plastlclzlng
agent.   The  major  end  use  (>50%)  for  butyl  benzyl  phthalate  Is  1n  the
synthesis  of PVC  used  as   flooring  materials.   Smaller  amounts   of  butyl
benzyl  phthalate  are  used  In  other  household  products.   Butyl  benzyl
phthalate  Is also used as   a  plastlclzer  for  polyvlnyl   acetate  emulsions,
which are used as  adheslves  In the  food  packaging Industry.  Other polymers
that can be  plastlclzed using  butyl  benzyl  phthalate Include acrylic resins,
ethyl  cellulose, polyvlnyl   formal  and  polyvlnyl  butyral  (Gledhlll et al.,
1980; IARC, 1982).
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1.5.   SUHMARY
    Butyl benzyl  phthalate  Is  a  colorless,  oily, nonvolatile,  combustible
liquid wHh a  slight  odor  (Sax and Lewis, 1987).   It  Is  probably soluble In
most organic solvents and  Is only  sparingly  soluble 1n water (Howard et al.,
1985).   During 1977,  between  101  and  510  million pounds  of butyl  benzyl
phthalate was  produced  1n  the  United States at  two locations  of  the Monsan-
to  Company  (TSCAPP,  1989); as of  January 1988, the Bridgeport,  NO  location
of  this  company was  the  sole producer  of this  chemical (SRI, 1988).   Current
production  data  were  not  located.  Butyl  benzyl   phthalate  Is  produced  by
reacting butyl alcohol  with phthalate anhydride  In the presence  of  an acid
catalyst and   by  reacting   the  resulting  ester  with  benzyl  chloride  under
neutral  aqueous   or  alcoholic  solutions.   Butyl  benzyl  phthalate   Is  used
almost  exclusively  as  a plastlclzlng agent;  more than  half  goes  Into  PVC
plastics used  as  flooring  materials.   Smaller  amounts  of  butyl  benzyl phtha-
late  are used In other  household  products.   Butyl benzyl phthalate  Is also
used as  a plastlclzer  for  polyvlnyl  acetates,  which are used as adheslves In
the packaging of food (Gledhlll et al., 1980; IARC, 1982).
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                     2.  ENVIRONMENTAL FATE AND TRANSPORT
2.1.   AIR
    Based on  the known  vapor  pressure,  8.25xlO~» mm  Hg at 25°C  (Howard  et
al., 1985), butyl benzyl phthalate  Is  expected  to  exist  both In the partlcu-
late form  and In the  vapor phase  In  the  ambient atmosphere  (Elsenrelch  et
al.. 1981).   In urban air  samples  over  Belgium,  1t was  found In  both  of
these physical states  (Cautreels and van Cauwenberghe, 1978).
2.1.1.    Reaction with  Hydroxyl  Radicals.   Using the  method  of  Atkinson
(1985),  an  estimated  rate constant  for  the vapor-phase  reaction  of  butyl
benzyl    phthalate   with   photochemlcally   produced   hydroxyl   radicals   Is
l.OSxlO11  cm3/molecule-sec.   If  an   average  atmospheric  hydroxyl  radical
concentration  1s 5x10*  molecule/cm3,  the  half-life  for  this reaction  Is
1.5 days.   Since butyl  benzyl  phthalate will also exist  In the partlculate
phase  In  the  ambient atmosphere, and  the  OH  radical  reaction  1s expected  to
be  slower with the  partlculate  form,  the actual rate  of  destruction of butyl
benzyl  phthalate through this reaction 1s expected to be  slower.
2.1.2.    Reaction with Ozone.   Butyl  benzyl phthalate  Is  not expected  to
react with ozone 1n the ambient atmosphere  (Atkinson,  1985).
2.1.3.    Photolysis.   Since  butyl  benzyl  phthalate adsorbs  UV  light  In  the
environmentally  significant  range  of  >290  nm,  It  Is a  candidate  for direct
photochemical  degradation; however,  exposure of  aqueous  solutions  of  this
compound In sealed  quartz  tubes  with  natural  sunlight showed that photochem-
ical reaction  1s not significant  (Gledhlll et al., 1980).   Therefore, photo-
chemical reaction In the atmosphere may also be  Insignificant compared with
other atmospheric removal  processes.
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2.1.4.   Physical   Removal  Processes.   Butyl  benzyl  phthalate  was found  In
the rain-dissolved phase  in  7/7  rainfalls  in  Portland,  OR,  but  not  In  gas
phase  ambient  air samples  taken  at the  same  time  (Ligocki  et al.,  1985).
These data suggest that  rain washout may be a  significant  process.   It  was
found  in  participate  matter in  indoor  air samples,  but  not  In  concurrent
samples obtained outdoors  (Weschler,  1984).   The known ability of  phthalate
esters  to  adsorb  to  particulate  matter (Weschler, 1984), combined  with  its
expected occurrence  of butyl  benzyl phthalate  partially  in  the  condensed
form  in the  ambient  atmosphere  (see Section 2.1),  suggests  that  dry deposi-
tion  may  occur for  particulate  (both adsorbed  and condensed) butyl  benzyl
phthalate.
2.2.   WATER
2.2.1.   Hydrolysis.    Pertinent  data  regarding  the  hydrolysis   of  butyl
benzyl  phthalate   were  lacking  in  the  literature  cited   in  Appendix  A;
however,  from   their  dark  photolysis  experiment,  Gledhill   et  al.  (1980)
observed  <57.  chemical degradation,  which  included hydrolysis  in  28  days.
The  authors  estimated the  half-life for hydrolysis to be  >100 days;  there-
fore, hydrolysis is not expected to be an important fate process.
2.2.2.   Oxidation.   Pertinent  data  regarding  chemical  oxidation  of butyl
benzyl phthalate in water were not located in  the  available  literature cited
in  Appendix  A.  Based on  the  dark photolysis  experiment of  Gledhill  et al.
(1980), it is not expected to be a significant  process.
2.2.3.   Photolysis.    Since  butyl  benzyl phthalate adsorbs  UV light  1n the
environmentally  significant range  of  >290  nm,  it  has  the  potential  for
direct  photochemical  degradation.   Gledhill  et  al.  (1980)  exposed  butyl
benzyl phthalate in  sealed quartz tubes  to sunlight for 28  days and observed

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<5% photodegradation.   They  estimated  the  photolysis  half-life  for  butyl
benzyl  phthalate to be  >100 days;  therefore,  this process  is  not expected to
be significant.
2.2.4.    Mkrobial  Degradation.  At an  Initial  concentration  of 1  ppm,  butyl
benzyl  phthalate was  found  to undergo *99%  primary  aerobic  degradation  in
7  days  in a river die-away study  (Saeger and Tucker,  1973).   Other  authors
(Gledhill et al., 1980) have  shown  that between >95 and 100% primary degra-
dation of  this  compound  will  occur in  7-9  days  in  natural  river and  lake
water.   The half-life  of  primary biodegradatlon In natural waters  was  esti-
mated  to  be  2-4  days;  however,  only  51-65%  of  the  compound  underwent
complete mineralization in  lake water  in 28 days  (Gledhill  et al.,  1980).
Between  92  and  99% primary  degradation  was  also observed  in  1  day  in  a
screening  test  using  a  SCAS  reactor  (Gledhill  et  al.,  1980;  Saeger  and
Tucker,  1973).   Again,   =96%  complete  mineralization  occurred  in  28  days
with the SCAS (Gledhill et  al.,  1980;  Saeger and  Tucker,  1976).   In  another
screening  study,  butyl benzyl  phthalate, at an  initial  concentration  of  5
and  10  mg/^,  was  listed   as  undergoing  100% aerobic  degradation within  7
days using  settled  domestic wastewater as microbial  inoculum (Tabak  et al.,
1981).   In  a shake  flask  test  using  an  activated  inoculum from soil  and
sewage  microorganisms  under  aerobic  conditions,  butyl   benzyl  phthalate
underwent 77.7% primary biodegradation and 43%  complete mineralization  in 28
days after a short initial  acclimation period (Sugatt et al.,  1984).
    Using sludge from municipal  digestors  of  two  different treatment  plants,
butyl  benzyl  phthalate underwent  slow anaerobic  degradation  in one  experi-
ment  and no  observable  degradation  in  the  other.   After  4  weeks,  a 24%
theoretical  methane  production  was  measured in  the  former  case,  as  opposed

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to no  significant  methane production  in  an 8-week experiment  in  the  latter
case  (Horowitz et al.,  1982).   In another anaerobic  screening  test'using  a
digester sewage sludge  inoculum,  butyl  benzyl  phthalate underwent between 30
and 75% of the theoretical methane production  in  8 weeks with  sludge  from  a
secondary digester and  75% methane  production  in 4 weeks with  sludge  from a
primary digester (Shelton and Tiedje,  1984).  A related study showed that 20
|ig/m^   butyl   benzyl   phthalate  underwent   90%  mineralization  to   CH«
within 40 days  with  primary  anaerobic sludge from  a  sewage treatment  plant
(Shelton et  al., 1984).
2.2.5.   Bioconcentration.  Based on  the  Kow value of  5.50 (Howard et  al.,
1985),  a  BCF of  8900 can be  calculated  using  the regression equation  log
BCF - 0.76  log  Kow  - 0.23  (Bysshe,  1982).   A  BCF of  663  was observed  for
butyl benzyl  in bluegills exposed  to 9.73  ppb  "C-labelled compound  for 21
days   (Gledhill  et   al.,  1980).   From  the  Kow,  Gledhill  et  al.  (1980)
calculated  a  BCF  of  510 for butyl  benzyl  phthalate.   Therefore,  this  com-
pound has a  moderate  to significant  bloaccumulation  potential   in  aquatic
organisms.
2.2.6.   Adsorption.   The  K0w of  butyl  benzyl  phthalate   (concentration  in
soil   to concentration  in water) containing  1.2-3.4% organic  matter  ranged
from  68-350  (Gledhill   et  al.,  1980).   The   experimental  Koc   for  butyl
benzyl phthalate  in  a compost soil  was 17,000 (Section 2.3.2).   These values
suggest that  butyl benzyl phthalate  should  be  sorbed at  least  moderately to
suspended particles  and  sediment, yet,  butyl  benzyl phthalate was found in
the  sediment  of the  inner harbor navigation  channel  of  Lake  Pontchartrain,
LA,  at  an  average   concentration  of  0.8 ppb  (dry weight) (McFall et  al.,
1985a); water concentrations  in  the  area  ranged from 0.1-0.3 ppb (McFall et

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al.,  1985b).   It  was  found  In  16/16  participate  samples  obtained  In  the
Hersey Estuary,  United  Kingdom, at concentrations  ranging  from 3.4-18 ng/g.
These  figures  represent   27.7-259% of  the  concentration  of  butyl  benzyl
phthalate measured  1n  the  water  (Preston  and  Al-Omran, 1986).   These  data
suggest  that  adsorption  to  sediment  and  suspended organic  matter may  be
different from adsorption to soil.
2.2.7.   Volatilization.  Butyl benzyl phthalate was  listed  as  undergoing  an
estimated zero percent  removal  during the air  stripping  process  at a sewage
treatment plant  (Petrasek  et  al., 1983).  Using the  bond method  of Hlne and
Mookerjee  (1975),  a  Henry's  Law constant  of  2.87xlO"8  l-atm/mol at  25°C
1s obtained.  Using this value, the estimated  volatilization half-life for  a
model river 1 m deep,  flowing at  1  m/sec,  with wind velocity  of  3 m/sec  1s
2254  days   (Thomas,  1982).   Volatilization  of butyl  benzyl phthalate  from
water to  the  atmosphere Is therefore  not expected to be  a  significant  fate
process.
2.3.   SOIL
2.3.1.   Mlcroblal Degradation.   In  a  biological  soil reactor, butyl  benzyl
phthalate, added as a component of  a  wood preserving sludge, underwent aero-
bic  blodegradatlon.   At an Initial  loading  of  117 mg/kg,  24  mg/kg remained
after  135  days,  corresponding   to  a half-life  of  59.2  days.    At  higher
loading concentrations,  the half-life Increased  (Klncannon and  Lin,  1985).
In  a field study  where butyl  benzyl phthalate  had entered  soil  from  the
application of spent  treatment  plant  sludge,  this  compound  was  listed by the
author as not undergoing blodegradatlon (DemirjIan  et al., 1984).
2.3.2.   Adsorption.  An experimental  K    value of  17,000 was obtained  for
butyl benzyl  phthalate  using  a  composite soil  from  Broome  County, NY (1.89%
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organic  carbon)   (Russell  and  McDuffle,  1986).   This  value suggests  that
butyl benzyl phthalate  will  be Immobile In soil  (Swann  et  al.,  1983).   In a
field study, butyl  benzyl  phthalate added as a  component  of spent treatment
                                                 _2
plant sludge  (application  rate equal  to  1.51x10   kg/ha) was soon  found  In
the  underlying soil  (3.51x10   kg/ha).   It was  also  found In  underlying
groundwater  wells  at  a concentration  ranging  from  <0.1-4 yg/l  (Dem1rj1an
et al.,  1984).   The  presence of butyl benzyl  phthalate  In these groundwater
samples may  be  due to the leaching  of  this  plastlclzer  from pipes,  drainage
tiles,  liners,  etc.,  which are  all  present  at  the experimental  site rather
than the result of spent sewage sludge.
2.3.3.   Volatilization.   The  known vapor  pressure,  8. 25x10 ~   mm  Hg  at
25°C  (Howard et  al.,  1985),  suggests  that  volatilization  from the  soil
surface to the atmosphere Is not expected to be significant.
2.4.   SUMMARY
    In  the  atmosphere,  butyl benzyl  phthalate  Is  expected  to  exist  both  In
the  vapor  phase  and  1n  the  partlculate  form  In  the  ambient  atmosphere
(Cautreels and  van Cauwenberghe, 1978;  Elsenrelch  et al.,  1981).   Both  dry
and wet  deposition may  be  significant  atmospheric  fate  processes  for  this
compound.  Destruction by ozone  and  by direct  photolysis  are not expected  to
be  significant.   The  destruction  of vapor-phase  butyl  benzyl  phthalate  by
the reaction  with  photochemical ly produced hydroxyl  radicals  1s  expected  to
be a  rapid  fate process with an estimated half-life of  1.5 days  (Atkinson,
1985);  however,  It  may not  be  significant  for  the partlculate form.   If
released  to  water,  the dominant fate processes  are expected to be mlcroblal
degradation  and  bloconcentratlon  1n  fish and  aquatic  organisms.  Hydrolysis,
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volatilization to  the  atmosphere,  oxidation and photolysis are  not  expected
to  be  significant  fate processes  in  water  (Gledhill  et  al.,  1980).   If
released  to  soil,  butyl benzyl  phthalate can be  strongly  adsorbed.   Biode-
gradation in  soil  may  occur under the  proper conditions.   Volatilization of
butyl  benzyl   phthalate from  the  soil  surface   to  the atmosphere   is  not
expected to be significant.
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                                 3.  EXPOSURE
    Butyl benzyl phthalate may  enter  the  environment  during Us manufacture,
and through  the  processing,  use and disposal of  plastic  products  containing
H.  In general, the majority of  phthalate  esters that are Incorporated Into
plastic products are ultimately deposited In landfills (Perwak et a!., 1981).
    The  National Occupational  Exposure  Survey  conducted  between 1981  and
1983 estimated  that  89,644 workers are  potentially exposed  to  butyl benzyl
phthalate  (NIOSH,  1984).   Occupational  exposure  may  result  from  Inhalation
or dermal contact during  the manufacture  of  butyl benzyl  phthalate or during
Its formulation Into polymers.
    Phthalate esters  used as plastlclzers  can  be  present  1n concentrations
up to  60% of the total  weight  of  the  PVC  plastic.  The  plastldzer Is  not
linked  by primary chemical  bonds  to  the PVC resin.   Rather,  It  Is locked
Into  the  structure of  Intermeshlng  polymer  molecules and  held by  van  der
Waals  forces.    The  result  Is   that  the  plastlclzer  Is  easily  extracted.
Plastlclzers are  responsible  for  the  odor  associated with new  plastic  toys
or flexible sheet that has been contained In a sealed package.
    Although the phthalate esters are not soluble  or  are  only  very slightly
soluble  1n  water,  they do migrate Into aqueous  solutions  placed  In  contact
with  the  plastic.   Thus  Industrial facilities  with  tank  linings, wire  and
cable  covering,  tubing  and sheet  flooring  of PVC  are  expected  to discharge
some  phthalate   esters  1n their  raw  waste.   In  addition to  their  use  as
plastlclzers, phthalate  esters  are used In  lubricating  oils  and  pesticide
carriers.   These also can  contribute  to  Industrial  discharge  of  phthalate
esters.
    Butyl  benzyl  phthalate was  detected  1n approximately  two-thirds of  the
subjects  studied In  the National  Human Adipose Tissue  Survey  (U.S.  EPA,
1986a).

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    Exposure to  butyl  benzyl  phthalate by  the  general population  may  occur
through Ingest Ion of contaminated waters.   Although  there  Is  little Informa-
tion  regarding   specific  exposure  to butyl  benzyl  phthalate,  exposure  to
phthalate esters by  the  general  population may result  from  use  1n plastlcl-
zers  (Perwak  et al.,  1981).   The resulting  routes  of exposure may  Include
Ingestlon of  food  contaminated  from  the  use of  the chemical 1n  packaging,
exposure by the  use  of plastic medical products,  such  as  tubing  and  storage
containers containing phthalate  esters as  a plastldzer, dermal  contact with
plastics containing  these compounds as plastlclzers  and Inhalation of  vapors
or partlculates  that have volatilized from plastics (Perwak et al., 1981).
3.1.   HATER
    Butyl benzyl  phthalate  has  been  found  In  surface water,  groundwater,
rainwater and   wastewater.   It  1s  not  known  to  be  a naturally  occurring
compound; It appears to be associated with Industrial activity.
    Butyl benzyl phthalate was not detected  at  the source  of  the Mississippi
River,  Lake  Itasca, MM,  but was  found  at  a  concentration  of  34 ppt  at  a
point 25 miles  below where  It meets  the  Ohio river.   The  compound was  found
at 59 ppt,  25 miles  below the dty of Memphis, TN.   It was not  found  at the
Intake  of the  Carrolton Street  water  Intake In New  Orleans  (Deleon et al.,
1986).  Butyl benzyl phthalate was  found  1n the  Influent  of  a sewage  treat-
ment  plant  1n  Philadelphia  serving  both  Industrial  and residential  sources
at a  concentration  of  40 ppb.   The  effluent from this plant  had  a measured
concentration of  100  ppb.   Two  miles  upstream  In  the Delaware  River,  the
concentration was 0.6  ppb.   The  concentration 2 miles  further upstream from
the plant was  0.3  ppb.  The  concentration of butyl  benzyl phthalate  1n the
Intake  water of Phlladephla's Torresdale water  treatment  plant  was 0.3 ppb
and the concentration  In the effluent from  this  plant was  0.1  ppb  (HHes,
1979; Sheldon and HUes, 1979).

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    Butyl  benzyl  phthalate  was  found   1n  9/31  sampling  sites  taken  from
surface waters  throughout  the  United States  during 1980-1982  at  concentra-
tions  <0.9  ng/i  (Michael  et  al.,  1984).   It  was  found  In  16/16  water
samples obtained  from the  Mersey Estuary, United Kingdom,  at concentrations
ranging  from 5.8-28.5 ng/l  (Preston  and Al-Omran,  1986).   It was  found  In
5/11 summer  samples  and 11/11  winter samples  taken from the Delaware  River
during  1976-77  at  concentrations  of  0.4-1  ppb  and  0.3  ppb,  respectively
(Sheldon and H1tes,  1978).   It was also  Identified  In  the  River  Lee,  United
Kingdom, at concentrations  >1 pg/fc (Waggott,  1981).
    In a recent review of  the  literature on  landfill sites, H was  detected,
but not quantified,  In  the leachate from 58 municipal  landfills.  (Brown and
Donnelly, 1988).  Butyl benzyl  phthalate  has been  Identified  In the leachate
from a sanitary landfill In Barcelona, Spain (Albalges et al., 1986).
    Butyl  benzyl  phthalate  has  been  quantitatively  detected  1n  drinking
water  wells  In New  York  State at a  concentration of  38 pg/a,  (Burmaster,
1982;  Kopfler  et  al.,  1977).   It has  also  been  detected  In drinking  water
from  New Orleans at concentrations  ranging from   0.08-1.8  vq/i   (Keith  et
al., 1976; Kool et al.,  1982).
    Butyl  benzyl  phthalate was  Identified  In 1454 of 30  water  samples  taken
from  Industrial effluent,  water  treatment  works  and  fjords  In   Norway  at
concentrations  >1  ng/l  (Sporstoel  et  al.,   1985).   An  analysis  of  the
STORE! data  base shows  that  butyl  benzyl phthalate  was  found  in 7.2% of 1337
effluent  samples  at  a  median concentration of  <6  yg/l  and  3.0% of  1220
surface  water   samples  at  a  median  concentration  of  <10  vg/l (Staples  et
al., 1985).
    It was  found  In  1/86 samples  In  the national urban runoff  program,  at a
concentration  of  10 vg/8,   (Cole  et  al.,   1984).   Butyl  benzyl  phthalate

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was not  found  In  the sludge of  three  publicly  owned water treatment plants;
however, It was found  1n  two  of  four  combined sludges at different plants at
concentrations  ranging from  1161-3975 ^g/l  (Feller  et  al.,  1980).   Butyl
benzyl  phthalate  was  found  In  the rainwater  In 7/7  rainfalls  In Portland,
OR,  In  1984  at  concentrations   ranging  from  20-74 ng/st  (Llgock!  et  al.,
1985).   It  has been  found  In sediment samples  In 6/31 sites  at  concentra-
tions <1.2 v»g/g dry weight (Michael et al.. 1984).
3.2.   FOOD
    Pertinent data regarding exposure  to  butyl  benzyl  phthalate In food were
not located  In  the available literature cited  In  Appendix A; however,  butyl
benzyl  phthalate  Is  used as  a  plastldzer  for adheslves approved  for  food
packaging.   The potential  for  the chemical  to migrate  from  the  packaging
material Into food Is high.
3.3.   INHALATION
    Butyl benzyl  phthalate  has been  Identified  1n the participate  form and
In  the  gas  phase  of  urban air samples  In  Belgium  (Cautreels  and van Cauwen-
berghe,  1978).    Butyl benzyl  phthalate  was  found  on   Indoor  participate
matter  at  a  concentration  of  1-20  ng/m3  but   not  on outdoor  partlculates
obtained concurrently  (Weschler,  1984).  It  was  also Identified  1n  the fly
ash from municipal  Incinerators  (Tong et  al.,  1984).  Data are  not  suffi-
cient  to predict  Inhalation  exposure of  the  general  population  to  this
compound.
3.4.   DERMAL
    Pertinent data regarding  dermal exposure to butyl benzyl  phthalate were
not located In the available literature cited In Appendix A.
6203H                                -14-                           10/17/89

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3.5.   OTHER
    Pertinent  data  regarding  other  sources  of  exposure  to  butyl  benzyl
phthalate were not located In the available literature cited In Appendix A.
3.6.   SUMMARY
    Butyl  benzyl  phthalate  Is  a nonvolatile,  organic  compound  produced  by
anthropogenic  sources.   It  enters  the environment  during  Its  manufacture,
and  also  through the  processing,  use  and  disposal  of  plastic  products
containing  H.   In  general,  the majority  of  phthalate  esters  Incorporated
Into plastic  products are  ultimately deposited In landfills  (Perwak  et al..
1981).
    Data were  lacking regarding  exposure  to  butyl  benzyl  phthalate.   Occupa-
tional exposure to butyl benzyl  phthalate  may  occur  by  Inhalation and dermal
contact  during  Us   manufacture or   formulation  Into  polymers.   For  the
general  population,  exposure to  butyl  benzyl  phthalate  may be  the  same  as
that  believed to  be occurring  for  other phthalate  esters, which are also
used  as  plastlclzers.  These  routes  of   exposure  Include dermal  contact,
Inhalation  and  Ingestlon  through drinking water.    It  has been  detected  1n
surface  water,  groundwater,  rainwater,   Industrial  effluent  and  drinking
water.  The general  population can be  exposed  through Ingestlon  of contamin-
ated  water.   Sufficient data were  not located  to estimate the  exposure  of
the general  population  to butyl  benzyl phthalate  through  Inhalation,  Inges-
tlon  of  food  and drinking water  and dermal contact. Butyl  benzyl phthalate
can also  be present   In certain  foods  as  a result of migration  from  plastic
packaging material.
6203H                                -15-                           10/17/89

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                         4.  ENVIRONMENTAL TOXICOLOGY
4.1  AQUATIC TOXICOLOGY
4.1.1.   Acute Toxic Effects on Fauna.   Acute  toxldty  Information regarding
butyl benzyl  phthalate Is  available  for at  least four  freshwater  Inverte-
brates,  four freshwater fish, a saltwater  Invertebrate  and three marine fish
(Table  4-1).   The   48-hour LC™  ranged  from 1.64-92  mg/l for  freshwater
Invertebrates,  with  the  midge,   Chlronomus  tentans,   the  most  sensitive
species.   For  freshwater  fish,  similar  LC5Qs have  been  reported,  ranging
from  0.82-43  mg/1.   The  toxlclty  of  butyl  benzyl   phthalate  Increased
slightly  In  fathead minnows, Plmephales promelas. when  hardness (expressed
as  CaC03  content)  Increased  from 40-160  mg/l  (96-hour  LC5Q=2.1  and  5.3
mg/l, respectively) (Gledhlll et al.,  1980).
    Sensitivity to  butyl  benzyl  phthalate among  saltwater  forms was  Indica-
ted  by  LC5Qs  ranging   from  0.51-440   mg/l.    The  96-hour  LC<.   of  440
mg/l  (Heltmuller  et  al.,  1981)   for  the  sheepshead  minnow,  Cyprlnodon
varleqatus.  exceeds the  solubility  of   *2.69  mg/l  (Howard et al.,  1985)
for  butyl  benzyl  phthalate  and   may  therefore  be  Inaccurate.  All  other
LC,-n  values  for  saltwater  species  fell  within the narrow range of  0.51-3.0
mg/l.
4.1.2.   Chronic Effects on Fauna.
    4.1.2.1.   TOXICITY  -- The chronic  toxlclty  of  butyl  benzyl  phthalate
has  been   Investigated  In Daphnla   magna and Plmephales  promelas.    Chronic
exposure  for  <21  days  to  concentrations  of  1.4  and  2.4 mg/l  butyl  benzyl
phthalate  resulted In  significantly  lower  survival  and  reproduction  rates
6203H                                -16-                           08/08/89

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among  D_.  magna  compared  with   untreated  controls  (Sprlngborn  Bionomics,
1985a).   Data  yielded  the  HATC  (0.280.22<0.35  mg/l,  based  on  reduced  reproduction rate, the  most  sensitive
endpolnt  measured.   A  21-day MATC  (0.350.05).   The  MATC range  was  >0.14<0.36
mg/i.  These  data Indicate that  chronic  exposure to butyl  benzyl  phthalate
Is similarly toxic to D.  magna and P.  promelas.
    A  time-Independent  flowthrough study by  Gledhlll  et al.  (1980)  Identi-
fied a 14-day  LC   of 2.25  (95% confidence  limits  =  1.34-3.77)  mg/l.  The
lowest measured concentration  producing an  effect  after  14  days exposure was
1.06 mg/l.
    4.1.2.2.   BIOACCUMULATION/BIOCONCENTRATION   —   Barrows   et   al.(1980)
studied  the  bloconcentratlon  and  elimination  of   14C-butyl  benzyl  phthalate
In bluegUl sunflsh,  Lepomls  macrochlrus. using a closed system designed to
deliver   a  measured   sublethal   concentration    of   compound   (9.73*2.02
ng/l).   Following  the 28-day exposure  period,   fish   were   transferred  to
untreated  water  for  7  days of depuration and  analyzed  to estimate  half-life
of     tissue     residues.      Five    fish     were    analyzed    at     each
l)203H                                -20-                           10/17/89

-------
sampling interval during  exposure  and depuration..  The authors calculated  a
BCF of  663  based on  "C determinations  and  a half-life  in  tissues of  <1
day.
    Monsanto Co.  (1983d)  conducted a bioconcentration study of butyl  benzyl
phthalate  with  bluegill   sunfish,  L.  macrochlrus.    The  rate  and  extent  of
"C  residues  were   measured  in  121  bluegills exposed  continuously  to  a
measured  concentration  of  2.22  \iq/t  "C-butyl   benzyl   phthalate  during
a  17-day  definitive exposure  period (a duration predetermined to  be suffi-
cient time for steady-state to be reached).  Six fish were  collected  at  each
of  nine sampling times.   Three  were analyzed as whole fish,  and  the muscle
and visceral contents  were measured In the other three.    During  the uptake
portion  of  the   study,   the  average  exposure  was  2.96  yg/^  (range  «
2.30-4.19  yg/*>,  yielding a  wholefish  BCF  of  187.65,    a   muscle  BCF  of
28.54 and  a viscera BCF  of 1693.25.  Most of  the  "C-residue was  contained
in  the  visceral  contents   (either adsorbed on  food  or in metabolized form).
This  observed   BCF   is considerably  lower  than that  predicted  from  octa-
nol/water  partition  coefficient  data, reported by  the  authors as  510.   The
authors  suggested that the  discrepancy between BCF values from  this  study
and that of  Barrows  et al.  (1980)  and EG&G (1983a,b,c) of  663 may  be due to
the greater  impurities in the test  compound in the  latter  studies, which may
have  been  adsorbed  and  metabolized  more  readily   than  the purer  compound.
Purities of  compounds  were not reported by  either  of these researchers; the
compound  tested  by  Monsanto Co.   (1983d)  was  identified by  trade  name,
Santicizer  160.
    Boese  (1984)  examined  uptake  efficiency of  the gills of English sole,
Parophrys  vetulus.  and   determined  that,  at  concentrations ranging  from
20-250  jig/*, mean uptake  was 42.51  (SE = 2.5).  The  log Kow was 5.8.
6203H                                 -21-                           07/24/89

-------
    These data Indicate that butyl benzyl phthalate has  a  moderate potential
to accumulate, but is depurated rapidly.
4.1.3.   Effects on Flora.
    4.1.3.1.   TOXICITY  —  The  available data  concerning effects  of  butyl
benzyl phthalate on  aquatic plants  are summarized in Table 4-2.   The lowest
reported   96-hour   LC50  1s   0.4  mg/^  in  the  freshwater   green  alga,
Selenastrum  capricornutum  (Gledhill   et  al.,   1980).     Except   for   one
freshwater  species,  toxicity   to  aquatic flora  was within a narrow  range of
0.2-1.0   mg/^.    The   blue-green   alga,    Microcystis   aeruginosa.    was
considerably  more  resistant   to  this  chemical  (96-hour  LC50-1000  mg/^>
(Gledhill et al.,  1980).   The  algae  were slightly  more sensitive  to  butyl
benzyl phthalate  than  were  freshwater fauna, and were at an equal risk  level
with marine fauna.
    4.1.3.2.   BIOCONCENTRATION
    Pertinent data regarding  the  bioconcentration potential of  butyl  benzyl.
phthalate  in aquatic  flora  were  not  located   in  the   available  literature
cited in Appendix A.
4.1.4.   Effects  on  Bacteria.   Knie   et  al. (1983)  tested  the  effects  of
butyl benzyl phthalate on the  bacterium,  Pseudomonas  putida and  identified a
30-minute EC10 of 10 mg/^.
4.2.   TERRESTRIAL TOXICOLOGY
4.2.1.   Effects on  Fauna.  Pertinent data  regarding the effects of exposure
of  terrestrial  fauna  to butyl  benzyl  phthalate were  not located  in  the
available literature cited in  Appendix A.
4.2.2.   Effects on Flora.   Pertinent data regarding  the effects of exposure
of  terrestrial  flora to flora were not  located  in  the  available literature
cited in Appendix A.
6203H                                _22-                           07/24/89

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4.3.   FIELD STUDIES
    Pertinent data  regarding  the  effects of butyl benzyl  phthalate  on flora
and fauna In the  field were  not  located In the available literature cited 1n
Appendix A.
4.4.   AQUATIC RISK ASSESSMENT
    The lack of  data  regarding the effects of  exposure  of aquatic fauna and
flora  to  butyl  benzyl phthalate  prevented the  development of  a  freshwater
criterion by  the  method  of  U.S.  EPA/OWRS (1986)  (Figure  4-1).   Available
data Indicate that  acute  toxic effects  can occur  at  concentrations as low as
0.82 mg/s.  and that chronic  effects  can occur at  concentrations  as  low as
0.22  mg/a.  In  fish  and  0.4  mg/i   In  algae.    Bloconcentratlon   studies
Indicate that butyl benzyl  phthalate accumulates In  freshwater  fauna (range
= 28.54-663), but  that  1t depurates rapidly (half-life  <1  day).  Additional
data required  for  the  development of  a  fresh  water criterion Include  the
results  of   acute  assays  with  a  benthlc crustacean,  a  nonarthropod  and
nonchordate species, and  an  Insect or  species  from  a phylum not represented
previously.
    The lack of  data  regarding the effects of  exposure  of aquatic fauna and
flora  to  butyl   benzyl  phthalate  prevented  the  development  of a  saltwater
criterion by  the  method  of  U.S.  EPA/OWRS (1986)  (Figure  4-2).   Available
data Indicate that  acute  toxic effects  can occur  at  concentrations as low as
0.51  In  marine  fish.   Additional  data  required for the development of  a
saltwater criterion Include  the  results of acute assays with  a nonarthropod
and  nonchordate  species,  and  two  additional  nonchordate  species.   The
development  of  a  saltwater  criterion  will  also require  data  from  chronic
toxldty tests with two  species  of  fauna and at least  one bloconcentratlon
study.


6203H                                -24-                           08/08/89

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                                                  TEST TYPE
Family
#1
Chordate (Salmonid-fish)
#2
Chordate (warmwater fish)
13
Chordate (fish or amphibian)
#4
Crustacean (planktonic)
#5
Crustacean (benthic)
#6
Insectan
#7
non-Arthropod/ -Chordate
#8
New Insectan or phylum
representative
#9
algae
GMAVa
(mg/L)
1.64b
2.27C
8.55d
3.7e
i
NA
2.4*
NA
NA
xxxxxxxxxxxx
xxxxxxxxxxxx
GMCVa
(mg/L)
NA
0.22?
NA
0.63h
NA
NA
NA
NA
0.4i
BCFa
NA
NA
188
NA
NA
NA
NA
NA
NA
         #10                     XXXXXXXXXXXX
  Vascular plant              XXXXXXXXXXXX        NA           NA
aNA«Not   available;    "Mean   96-hour   LC,0   for   rainbow   trout,   Sal mo
^airdneri;  °Mean  96-hour  LCSO  for  fathead  minnows,  Pimephales  promelas:
 Mean  96-hour  LCso  for  bluegill   sunfish,  Lepomis  macrochlrus:  e48-hour
EC50  for  the  water  flea,   Daphnia  magna;  'Mean  48-hour  LC50  for  the
midge, Chironomus  tentans:  930-day  chronic  value for  the  fathead  minnow,
Pimephales  promelas:'Tl-day  chronic  value  for  the  water flea,  Daphnia
Maijna; '96-hour LC50  for the  green  alga, Selenastrum caprlcornutum.

                                 FIGURE  4-1

    Organization Chart for Listing GMAVs, GMCVs  and BCFs  Required  to Derive
Numerical Water  Quality  Criterua by  the Method  of U.S.  EPA/ONRS  (1986)  For
the  Protection  of Freshwater  Aquatic  Life  from Exposure  to  Butyl  Benzyl
Phthalate                                                                 y
6203H                               _25_                           07/24/89

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TEST TYPE
Family
11
Chordate
#2
Chordate
#3
non- Arthropod/ -Chordate
14
Crustacean (Mysid/Panaeid)
#5
non-Chordate
#6
non-Chordate
#7
non-Chordate
#8
other
#9
algae
#10
Vascular plant
GMAVa
(mg/L)
1.43b
0.51C
NA
0.99d
NA
NA
NA
NA
xxxxxxxxxxxx
xxxxxxxxxxxx
xxxxxxxxxxxx
xxxxxxxxxxxx
GMCVa
(mg/L)
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
BCFa
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
aNA=Not    available;    "Mean    96-hour    LC50    for   sheepshead   minnows,
Cyprinodon   variegatus:   c96-hour  LC50   for  silver   perch,   Cymatogaster
aggregata: "Mean 96-hour LC50 for the mysid shrimp, Mysidopsis bahla.

                                 FIGURE 4-2

    Organization Chart for  Listing  GMAVs, GMCVs  and  BCFs  Required to Derive
Numerical Nater Quality  Criteria by the  Method of U.S. EPA/ONRS  (1986)  for
the  Protection of Saltwater  Aquatic  Life  From Exposure  to  Butyl  Benzyl
Phthlate
6203H
                                     -26-
07/24/89

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4.5.   SUMMARY
    Butyl  benzyl phthalate  has  been  assessed for acute  toxicity  in  at least
four  freshwater  fish  species   (Buccafusco  et  al.,   1981;  EG&G,  1983a,b,c;
Gledhill et al.,  1980;  Knie et al.,  1983)  and  three  marine fishes (Gledhill
et  al.,  1980; Heitmuller  et  al., 1981;  Ozretlch et  al.,  1983; Randall  et
al.,  1983;  Springborn Bionomics  Inc.,  1984)    LD50s  were  reported  at  con-
centrations as  low  as 0.82 mg/^  in  freshwater  (EG&G,  1983a)  fish  and  0.51
mg/* in saltwater fish (Ozretlch et al., 1983).
    Acute toxicity  data  for fresh and saltwater  invertebrates  Indicate  that
mysid  shrimp,  M.  balm,  are  slightly more  sensitive than other  forms, but
all  LC50   values   fell   within  the   range   of  0.9-92   mg/£  (Analytical
Biochemistry  Labs,  1981;  Gledhill  et al., 1980; LeBlanc, 1980; Monsanto Co.,
1983a,b,; Springborn  Life Sciences, 1988; SRI,  1981).
    Chronic toxicity  of  butyl  benzyl  phthalate  has been assessed  in fathead
minnows, P.  promelas, and  water  fleas,  D.  magna  (Gledhill  et  al.,   1980;
Monsanto Co.,  1983c; LeBlanc  et  al.,  n.d.)  and in  five  species  of aquatic
flora  (Gledhill  et  al.,  1980;  Monsanto  Co.,   1983e;   Springborn  Bionomics
Inc.,  1985a).   With the  exception of one plant  species  (the blue-green  alga,
Microcvstis  aeruginosa).   sensitivity   was   similar   between   tested   algal
species  and fell  within  the  narrow  range of 0.2-1 mg/£.   M.  aeruginosa was
considerably  more  resistant,  with  a 96-hour  LC50  of  1000 mg/^ and  a  NOEC
of  560  mg/^ (Gledhill et al.,  1980).
    Bioaccumulation  and  uptake studies  of butyl  benzyl  phthalate  with  blue-
gill  sunfish,  L.  macrochirus.  and English  sole,  P.   yetulus,  indicate  that
this chemical  bioaccumulates in tissues  of freshwater or marine fauna, but is
6203H                                -27-                           07/24/89

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rapidly depurated (Barrows et  al.,  1980;  Monsanto Co.,  1983d).   A  30-minute
£C,0 of  10  mg/^ was  reported for  the  bacterium,  P.  putlda  (Knle et  al.
(1983).
    The lack of  data  regarding toxiclty of  butyl  benzyl phthalate  prevented
the development  of  freshwater  or  saltwater  criteria by  the  method of  U.S.
EPA/OWRS (1986).
 6203H                                 -28-                            07/24/89

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                             5.  PHARHACOKINETICS
5.1.   ABSORPTION
    Excretion data  Indicate  that butyl benzyl phthalate  Is  readily absorbed
from the  gastrointestinal  tract 1n  rats.   Elgenberg et al.  (1986)  adminis-
tered ring-labeled  14C-butyl  benzyl  phthalate  In ethanol/Emulphor at  2,  20
or  200 mg/kg, or  at 2000 mg/kg  (neat) orally to  male  F344  rats  and measured
the percent of radioactive dose  excreted  1n  urine and  feces.   Between 61 and
74% of  the dose  was  excreted  1n  the urine  and  between 13  and 19%  In the
feces at  2-200 mg/kg  In 24 hours.   Elgenberg et  al.  (1986)  also showed that
butyl  benzyl  phthalate  undergoes  extensive  enterohepatlc  clrcu-  latlon
(Section 5.4), suggesting that absorption exceeded  the minimal  estl- mate of
61-74% based  on  urinary excretion.  In rats  treated at  2000  mg/kg,  16.6% of
the dose  was  excreted 1n the  urine  and  64.9% In the  feces within  24 hours.
The Investigators did not determine  1f the  Increased fecal  excretion at 2000
mg/kg  represented  Incomplete  absorption  of  the  administered  compound  or
Incomplete reabsorptlon of products of biliary excretion.
5.2.   DISTRIBUTION
    Elgenberg et  al.  (1986) examined the tissue distribution  of  radioacti-
vity 1n  male F344  rats dosed  In  the tall  vein  with  20 mg/kg  ring-labeled
14C-butyl  benzyl  phthalate.   The  results  are  presented  In  Table  5-1.
Butyl benzyl  phthalate  was  rapidly  distributed  to tissues  and eliminated.
The  highest  concentration  of  radioactivity  (as  % of  total   dose)  at  30
minutes was  found  In  the  small  Intestine  followed by muscle,  skin,  blood,
liver,   fat and  kidney.   Smaller  amounts  were  found In  the   brain,  lung,
spleen  and  testes.   Although  butyl  benzyl  phthalate  Is   llpophlllc,  the
Investigators noted  that radioactivity was not sequestered  In  fat,  probably
because the compound 1s rapidly metabolized.

6203H                                -29-                           08/08/89

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                                                                    08/08/89

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    Levels of radioactivity  In  blood,  liver, kidney, muscle,  skin  and small
Intestine were characterized  by a blexponentlal decay curve with  an Initial
half-life of <30 minutes  and a terminal half-life  of  4.5-7.3  hours.  Levels
1n fat,  brain,  lung,  testes  and  spleen were described  by  a  monoexponentlal
decay curve with a half-life of 0.45-3.4 hours.
    14C-Monophthalate, a  metabolite of  butyl  benzyl phthalate, was rapidly
formed  and  distributed   to   blood  (=10%  of dose),  liver  (=3.5%),  muscle
(=4%)  and kidney  (=1%)  after  Intravenous  administration of butyl  benzyl
phthalate (Elgenberg et al.,  1986}.  Peak  blood levels  of monophthalate were
observed  5 minutes  after  dosing  and  decayed 1n a  blexponentlal manner with
an Initial phase  half-life of  13 minutes  and a terminal phase  half-life of
5.9  hours.   The  elimination  of  monophthalate  from the  liver,  kidney  and
small  Intestine also  followed  a  blexponentlal  decay,  with  half-lives  of
10-30 minutes and 5.5-6.8  hours for  Initial  and terminal phases,  respective-
ly.   Parent  butyl  benzyl  phthalate was eliminated  from blood and  fat  in a
monoexponentlal manner  (half-lives of  10 minutes and  1.1  hours,  respective-
ly), whereas levels In the  kidney,  muscle,  skin and small Intestine followed
a  blexponentlal  decay curve with  Initial  and  terminal  half-lives of  9-26
minutes and 2.3-7.4 hours, respectively.
5.3.   METABOLISM
    Elgenberg  et  al.  (1986)   Investigated  the metabolism  of butyl  benzyl
phthalate  In male  F344 rats  24 hours  after  oral  treatment  with ring-labeled
"C-butyl  benzyl   phthalate  at  2,  20  or  200 mg/kg.   The  major  urinary
metabolites  of  14C-butyl  benzyl  phthalate  were  monophthalate  (22-42%  of
the  dose),  monophthalate  glucuronlde  (14-21% of the dose) and unidentified
metabolites.   The  Investigators   noted  that   the  monophthalate  fraction
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consisted of  nearly three  times more  monobutyl .phthalate  than  monobenzyl
phthalate, but offered  no  explanation  for the preferential  hydrolysis of the
benzyl ester linkage.  They also  noted  that  there was a  notable  decrease  in
the  ratio  of conjugated  to  free  monophalate  at  200  rag/kg  compared  with
either  of  the  lower  doses,   suggesting   that   the  glucuronide  conjugation
pathway  may have  become  saturated  at the  higher  dose.  Monophthalate  was
rapidly  formed  following  intravenous  administration  of  20  mg/kg  t4C-butyl
benzyl  phthalate;  peak  blood  levels  of monophthalate were observed 5 minutes
after dosing.
    Large  quantities  of  glucuronides  of monobutyl  phthalate  (26% of  the
dose) and monobenzyl phthalate (13% of the dose) as well  as  trace amounts  of
free  monobenzyl  phthalate  and  monobutyl  phthalate and  unidentified metabo-
lites (speculated  by the authors to be phthalic  acid  and oxidation products
of  monobutyl  phthalate) were  detected  in the  bile of  bile duct-cannulated
rats  4  hours  after intravenous administration  of 20 mg/kg  "C-butyl  benzyl
phthalate  (Eigenberg et  al.,  1986).   No parent  compound  appeared  in  the
bile.  Monobutyl phthalate has been identified as a toxic metabolite and has
been  shown to cause testicular atrophy (Eigenberg et al., 1986).
5.4.    EXCRETION
    Four  hours  after   intravenous  administration  of   20  mg/kg   14C-butyl
benzyl  phthalate,  55% of the  dose of radioactivity was  excreted  in the bile
and  34%  in  the  urine  of bile duct-cannulated  rats,  representing 89% of the
administered  dose  (Eigenberg  et  al.,  1986).   In identically  treated Intact
rats,  urinary excretion accounted for 74.2% and  fecal excretion  for  19.5% of
the dose  after 24  hours, representing 93.7% of  the  dose.
6203H                                -32-                           07/24/89

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    These data  also  indicate  that  substantial  enterohepatic  recirculation
occurred because the  extent  of fecal excretion in Intact  rats  was less than
the extent of  biliary excretion in bile duct-cannulated rats.   The  observa-
tion that urinary  excretion  in intact rats exceeded  that 1n bile duct-cannu-
lated  rats  suggests  that  considerable absorption  of  biliary  metabolites
occurred.
    Rapid excretion of  l4C-butyl  benzyl phthalate equivalents  was  found  at
all doses  (2,  20, 200  and  2000 mg/kg)  in  rats treated  orally  (Eigenberg  et
al.,  1986).   Urinary  and fecal  excretion  represented  75-86%  of  the  dose
after  24 hours and  92-98% after  96  hours.   The  Investigators  estimated  an
overall half-life of  6  hours  for  butyl  benzyl  phthalate and  for the monoph-
thalate esters 1n all tissues of rats.
5.5.   SUMMARY
    Studies  in rats  with orally  and  intravenously  administered '"C-butyl
benzyl  phthalate  (Eigenberg et  al., 1986)  indicate that gastrointestinal.
absorption  is  rapid  and  virtually  complete;   however,  at  very  high  doses
(2000  mg/kg),  the  extent of  gastrointestinal  absorption may   be  reduced.
Distribution is  rapid and widespread, but no tissue appears to preferential-
ly  accumulate  the  compound or  its radioactive metabolites.   Although  butyl
benzyl  phthalate  is  lipophilk, accumulation in fat does  not occur, probably
because  the compound  is rapidly metabolized.
    Following  absorption,   butyl   benzyl   phthalate  undergoes   very  rapid
metabolism and  excretion  (Eigenberg et al., 1986).   The principal  metabolic
pathway  appears  to be hydrolysis  of  the ester  linkages  followed  by conjuga-
tion  with  glucuronic  acid.   Peak levels  of monophthalates  are measured   in
6203H                                -33-                            07/24/89

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the blood within 5 minutes of an intravenous dose..  The  benzyl  ester  linkage
appears  to  be  more  labile  than  the  butyl  ester linkage.   There  is -evidence
that glucuronide conjugation becomes  saturated at higher dosages.
    Experiments  with bile  duct-cannulated  rats  showed that metabolites  of
butyl benzyl phthalate  are  excreted  to a larger extent 1n the bllt  than  in
the urine (Eigenberg et al., 1986);  however,  in  Intact rats,  urinary excre-
tion exceeded  fecal  excretion,   Indicating  that substantial reabsorption  of
biliary  excretion  products  occurs.   Excretion Is very rapid following intra-
venous or oral  treatment.  An  overall  half-life of  =6 hours  was  estimated
for removal  of  butyl benzyl phthalate and  the  monophthalate  esters  from all
tissues.
6203H                                -34-                           07/24/89

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                                  6.   EFFECTS
6.1.   SYSTEHIC TOXICITY
6.1.1.   Inhalation Exposures.
    6.1.1.1.   SUBCHRONIC —  Pertinent  data  regarding the toxlclty of  butyl
benzyl  phthalate  following   subchronlc  Inhalation  exposure  of  animals  or
humans were not located 1n the available literature cited In Appendix A.
    6.1.1.2.     CHRONIC  --  Pertinent data regarding  the  toxlclty  of  butyl
benzyl phthalate  following  chronic Inhalation exposure  of animals  or humans
were not located In the available literature cited In Appendix A.
6.1.2.   Oral Exposures.
    6.1.2.1.   SUBCHRONIC  --  Krauskopf  (1973) briefly reported the  results
of a 90-day unpublished toxlclty  study  on  dogs and rats  performed by Monsan-
to  (1972).   The numbers,  strains and  sexes  of  the  rats  and dogs  were  not
specified.  Rats  were fed diets  containing 0, 0.25,  0.5,  1.0, 1.5  or 2.0%
butyl benzyl  phthalate.   Assuming a  factor  of  0.05  kg  food/kg bw/day  (U.S.
EPA,  1980),  doses  can  be  estimated  at   0,  125,  250,  500, 750  or  1000
mg/kg/day.  Dogs  were dosed  with capsules containing  butyl  benzyl  phthalate
In amounts of 0,  1.0,  2.0 or  5.0% In the  diet.   Dose data were not  provided;
doses of  0,  250,  500 or  1250  mg/kg/day can be estimated by  assuming a food
factor of 0.025 kg  food/kg bw/day.   An  Increase  In liver weight was observed
In  rats  fed diets containing  1.0,  1.5  and 2.0% butyl benzyl  phthalate.   No
hlstopathologlcal changes were  found, but  the extent  of  the  examination  was
not  specified.   A  slight reduction  In growth  rate  was  noted  at  the  two
highest dietary concentrations.   No  hematologlcal  or  uMnalysls effects were
seen In rats  exposed  to butyl  benzyl  phthalate.   No  adverse  effects (deaths,
weight  gain,   hematology,   urlnalysls,  liver  and   kidney   function)   were
observed among treated dogs.

6203H                                -35-                            10/17/89

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    In an  unpublished  report,  NTP  (1985) sponsored  a  toxlclty  study  using
groups of  15  male F344  rats.   Rats were  treated  with  0, 0.03,  0.09,  0.28,
0.83 or 2.50% butyl benzyl phthalate  In  the  diet  for  26 weeks.   In addition,
groups of  15  male rats  were  fed diets containing butyl  benzyl  phthalate  at
0, 0.03,  0.28  or 2.50% of the  diet for  10 weeks  In  a  fertility experiment.
The dietary  levels of 0,  0.03, 0.09, 0.28,  0.83  and  2.50%  corresponded  to
doses of  0,  17, 51, 159,  470  and 2875 mg/kg/day  (U.S. EPA,  1987a,b).   Food
consumption and  body  weight  gain  were  significantly depressed  at 2.50%  In
the diet  throughout the  26-  and 10-week  studies.  No deaths  attributable  to
butyl benzyl phthalate  toxUUy were  noted.   Among  rats fed the  2.50% diet
that  survived  for  26  weeks,  11/11  had small testes.    Soft testes  were seen
In  5/11  rats,  while  1/11  had  a   small  prostate  and  seminal   vesicle.   No
grossly observable effects on  male  reproductive  organs were  found  In  the
other treated groups  fed for  26 weeks or  In  rats  exposed for only 10 weeks.
The  kidneys  of  six  rats  In  the  high-dose 26-week group  exhibited  focal
cortical areas  of 1nfarct-l1ke atrophy.
    Several organ  weights  and organ/body  weight  ratios were altered  In  the
high-dose  groups,  compared with  controls,  but the Investigators  attributed
many  of these  changes  to reduced food Intake  and  suggested  that organ/brain
weight ratios  may  more  nearly  reflect the effects of  the chemical.   Organ/
brain weight alterations attributed to the test  compound  Included reductions
In  heart,  kidney,  liver,  lungs, prostate,  seminal   vesicle  and  testes  for
rats  In  the  10-week group, and  reductions In heart, kidney, lungs,  seminal
vesicles  and  testes for rats  In the  26-week group.    Hematologlcal  effects
attributed  to   treatment were  seen In  both high-dose  groups   and  Included
reduced   hematocrlt,  blood hemoglobin concentration, red cell   mass  and  red
6203H                                -36-                           08/08/89

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cell count.   There was also  evidence of  Increased  polkllocytosls and  ply-
chromasla as  well  as  Increased  HCH, MCV  and MCHC,  which  the  Investigators
attributed to an Increased but compensated  turnover  of  red  cells.   Compound-
related  hlstopathologUal  lesions  observed  1n  both  high-dose  groups  were
limited  to atrophy  of  the  seminiferous  tubules and  aspermla  In  the epldldy-
mus.   Complete  hlstopathologlcal  examination  was  performed on  controls  and
high-dose rats; examination was  limited  to reproductive organs  In  the  other
dose groups.   The   Investigators concluded  that  no adverse effects  occurred
1n rats  fed the 0.83% diet.
    In evaluating these data, however, U.S. EPA  (1987a,b) noted  some  changes
1n  the  rats  fed the 0.83% diet  that may have been  compound-related.   These
Included  significantly Increased  absolute liver  weight,   liver/body  weight
ratio and  I1ver/bra1n  weight  ratio.  U.S.  EPA (1986b, 1987a,b) also  stated
that absolute liver weight and the  liver/body weight  ratio  were  significant-
ly  Increased In the group  on  the 2.5% diet.   Liver weights  In the  2.5% group
were decreased, compared with controls, probably because of the  reduced  food
Intake  observed 1n  this  group.    U.S.  EPA  (1987a,b)  also  reported  minor
changes  In some of  the  red cell  Indices at some  of the sample times through-
out the  study.   U.S.  EPA  (1986c)  considered  the 0.83% level to represent  a
LOAEL and the 0.28% diet to represent a  NOEL In this  study.
    NTP  (1982)  evaluated   the subchronlc  toxlclty  of butyl benzyl  phthalate
In  groups  of  10 F344  rats  of each  sex.   Rats  were  fed diets containing 0,
1600,  3100,  6300,  12,500  or 25,000  ppm  [0, 80,  155,  315,   625  or  1250
mg/kg/day, assuming  a  food factor  of 0.05 kg  food/kg  bw  (U.S. EPA,  1980)]
for 91  days.
6203H                                -37-   *                       10/17/89

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    Observations were  limited  to  clinical  signs,  necropsy and  Mstopatho-
loglcal examination of unspecified  tissues.   Depressed  weight  gain (28% when
compared with  controls)   and  testlcular degeneration were observed  In  male
rats  fed  the  25,000  ppm  diet.   No butyl  benzyl phthalate-related  effects
were  observed   In  female  rats  or  In  rats  of  either  sex  at  lower  dietary
levels.  In  the same study,  groups  of  10 B6C3F1  mice  of each sex were fed
diets  containing  0,  1600,  3100,  6300,  12,500 or  25,000 ppm [(0, 208,  403,
819,  1625  or 3250 mg/kg/day,  assuming  a  food factor of 0.13 kg  food/kg  bw
(U.S.  EPA,  1980)]  for 91  days.  Height  gain was depressed  by  >10%  1n all
groups of male  mice and  In female mice  fed diets containing 12,500 or 25,000
ppm.  No other butyl benzyl phthalate-related effects were observed In mice.
    6.1.2.2.   CHRONIC —  Groups of  50 male and 50  female F344 rats  and
B6C3F1  mice were  fed  diets  containing 0,  6000 or  12,000 ppm butyl  benzyl
phthalate  for   28  weeks   (male  treated rats only)  or   103  weeks (mice and
female  rats)  (NTP, 1982).  Assuming that  a  rat consumes  food equivalent  to
5% of  Us body  weight/day,  6000 and 12,000 ppm are equivalent  to  300  and 600
mg/kg/day doses.   The  equivalent doses for  mice are 780  and  1560 mg/kg/day
assuming  that  a  mouse   consumes   food   equivalent  to  13%  of  Us  body
weight/day.   Rats  and mice  were  examined  for  mortality,  changes   In  body
weight and  food consumption,  clinical signs  of  toxlclty and gross and micro-
scopic pathology.  At  week 28, only 15/50 (30%)  of  the high-dose group male
rats  remained   alive  and  deaths  were  occurring among  low-dose   group  male
rats.   Because of the  high  early mortality  In  treated  male   rats,  these
groups  were  terminated  at  29-30   weeks  without  hlstopathologlcal  examina-
tion.   Internal hemorrhage  was observed   at necropsy  of  the  decedents  and
Implicated  as  the  cause  of  the Increased mortality.   Body weights of dosed
6203H                                -38-                           08/08/89

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rats of  both sexes  were  slightly  reduced  when compared  to  controls.   Food
consumption was  slightly  decreased  (70-80% that of controls)  In  female rats
treated  with  butyl  benzyl  phthalate.   The only  other  effects  observed  In
treated  rats  were hepatomegaly and splenomegaly  In high-dose females,  which
appeared to be  related  to an  Increased Incidence of  mononuclear cell leukem-
ia  also reported In  this  group.   Compound-related  effects  1n mice  were
limited  to a  dose-related decrease  In  mean  body weights  of males and females
that was observed throughout  the study.   Data  on food consumption  In mice
were not provided.
6.1.3.   Other Relevant Information
    Table  6-1 summarizes data on  acute oral  LD5Q  values for butyl  benzyl
phthalate.    The  rat appears  to be  slightly  more  sensitive  to the  acute
toxlclty  of  butyl  benzyl  phthalate  than  the  mouse.   Rats  and  mice  are
considerably  more sensitive  than  the  guinea  pig.   Agarwal  et  al.  (1985)
evaluated the toxlclty  of butyl  benzyl  phthalate In  a  14-day study of groups
of 10 male F344  rats fed  diets containing 0, 0.625,  1.25,  2.50 or 5.0% butyl
benzyl  phthalate.   Based on   data  provided  by  Agarwal  et  al.  (1985),  the
approximate rates  of food consumption for  each  dose group were 60 g food/kg
bw/day  (0.625 and  1.23%), 75  g food/kg bw/day (2.5%)  and 44 g food/kg bw/day
(5.0%).  Using  these data,  the dietary  levels  of  0.625,  1.25,  2.50  and 5.0%
butyl  benzyl  phthalate  correspond  to  dosages  of 375.  750,  1875 and  2000
mg/kg/day.   Increases  In  relative liver and kidney weights  were  observed  In
all  treated  groups.   Regeneration of  the proximal tubule of  the kidney was
observed  In  some   rats  In  all  treated  groups.   Body  weight  gain  was
significantly  reduced by 2.5 and  5%  butyl  benzyl  phthalate  1n the  diet.
Food consumption was slightly reduced at the 2.5% concentration and markedly
6203H                                -39-                           08/08/89

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                                   TABLE  6-1



                  Oral  1050 Values  for  Butyl  Benzyl  Phthalate
  Species                           1050                  Reference
Rat/F344                           2330                   NTP, 1982



Male mouse/B6C3Fl                  6160                   NTP, 1982



Female mouse/B6C3Fl                4170                   NTP, 1982



Guinea pig                        13750                   NIOSH, 1989
6270H                                 -40-                          08/08/89

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reduced at  the  554 concentration  In  the diet.  Significant  decreases  In the
relative weights of the  testes,  epIcMdymus,  seminal  vesicles and thymus were
observed 1n rats  fed  2.5 and 5%  In  the diet.  H1stopatholog1cal examination
revealed  a  dose-dependent  atrophy   of  the  testls,  prostate  and  seminal
vesicles  at 2.5  and  5.0%.   Atrophy   of  the  epldldymus,   characterized  by
necrosis  of the  tubular  epithelium  and  accompanied  by   the  presence  of
Immature  spermatogenlc  cells,   was   reported  In  rats  fed  the  5%  diet.
Increased circulating levels of  FSH  and LH  were reported In rats fed the 2.5
and  5.0%  diets  and  decreased  circulating  levels  of  testosterone  were
reported 1n  rats  fed the  5.0%  diet.   Atrophy of the  thymus  was  observed  at
5%  1n  the  diet.  Although the  circulating  components of blood  and clotting
times   (prothrombln   time,  activated  partial   thromboplastln   time)   were
unaffected, bone marrow cellularlty was reduced at 2.5  and  5.0%.
6.2.   CARCINOGENICITY
6.2.1.   Inhalation.  Pertinent  data  regarding the  carclnogenlclty of  butyl
benzyl  phthalate  following  Inhalation  exposures were  not  located In  the
available literature cited 1n Appendix A.
6.2.2. Oral.   In  the   NTP   (1982)   chronic  dietary  study  (see  Section
6.1.2.2),  the  carcinogenic  potential  of orally  administered butyl   benzyl
phthalate  to  rats  and  mice  was  evaluated.   Hale  rats  were not  evaluated
because early mortality  (not related  to  cancer)  resulted  In  termination  of
these  groups  after   29-30 weeks  of  treatment.   Statistically  significant
Increases  1n  the Incidences  of  tumors 1n  female  rats were  limited   to  an
Increase 1n mononuclear  cell  leukemia or lymphoma at  the high-dose level  of
12,000  ppm In   the  diet  (Table  6-2).   The  time  until the  first  observable
tumor  was   the  same  (83  weeks]   In  both  the high-dose  group  and 1n  the
untreated  controls.    No  butyl  benzyl  phthalate-lnduced   Increases  In  the
Incidence  of  tumors  were found  In  mice   of either  sex   (Table  6-2).   A

6203H                                -41-                           09/11/89

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6275H
-42-
08/08/89

-------
dose-related  decrease  In  the   Incidence  of  lymphoraas  and  leukemlas  was
reported In male mice.  NTP  (1982)  concluded  that  butyl  benzyl phthalate was
"probably carcinogenic  for  female  F344 rats."  The NTP  (1989) has  scheduled
butyl benzyl phthalate for additional testing In rats  by oral administration.
    In a separate  report,  Kluwe et al. (1982) concluded  that  the results of
the  NTP  study  provide only  equivocal evidence  of  butyl   benzyl  phthalate
carclnogenlclty In female F344  rats  because of  the  considerable variation In
the background  Incidence  of  myelomonocytlc  leukemia In F344 rats.  Also,  the
form  of  leukemia  In  the  treated rats  was  the same as  that  occurring natur-
ally  In these  rats.   Evidence  for  the  carclnogenlclty   of  butyl  benzyl
phthalate 1n mice  was not found.  Following an evaluation of  the NTP (1982)
data,  IARC  (1982)  concluded that  the data  were  Inadequate  to assess  the
carclnogenlclty of butyl benzyl  phthalate to  animals.   The NTP (1989) report
noted, however,  that  additional study of butyl benzyl  phthalate metabolites
(n-butanol  and benzyl  alchol) was Important.
6.2.3.   Other Relevant Information.
    Thelss  et al.  (1977) examined  the  carclnogenlclty  of  butyl benzyl phtha-
late  In  the strain A  mouse  lung tumor  assay  following Intraperltoneal admin-
istration.   Three  groups  of  20  male A/St mice  (6-8 weeks old) were adminis-
tered 160,  400  or  800 mg/kg (3  times  weekly  during 8  weeks) In trlcaprylln.
Controls were  Injected with trlcaprylln.   Twenty-four weeks after  the first
Injection,   the  mice  were killed and  examined for  lung  tumors.   No signifi-
cant  difference  In the  Incidence  of  lung  tumors  was  found between control
and  treated  rats.   IARC  (1982) noted that  the negative result  reported In
this  study  cannot  be  taken  as   evidence  of  the noncarclnogenlclty  of butyl
benzyl phthalate.
6203H                                -4-3-                           10/17/89

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6.3.   MUTAGENICITY
    Studies  that  examined  the mutagenlcUy  of  butyl  benzyl  phthalate  are
summarized  In  Table 6-3.   In  jjt vitro  studies,  butyl benzyl  phthalate  was
notmutagenlc 1n Salmonella  typh1mur1um (Zelger  et a!.,  1982;  Kozumbo et al.,
1982; NTP,  1982;  Anonymous, 1977).   Butyl  benzyl phthalate  did  not produce
forward  mutations   In  mouse  lymphoma L5178Y  cells  (Anonymous,  1977).   In
sister chromatld and  chromosome aberration assays  (NTP,  1982),  butyl  benzyl
phthalate produced negative results.
6.4.   TERATOGENICITY
    Pertinent  data  regarding  the  teratogenldty  of  butyl benzyl  phthalate
were not located In the available literature cited 1n Appendix A.
6.5.   OTHER REPRODUCTIVE EFFECTS
    In the  14-day  dietary  study by Agarwal et  al.  (1985)  In  which  male rats
were  fed  diets  containing  0, 0.625,   1.25,  2.50  or  5.054  butyl  benzyl
phthalate,  gross,  hlstopathologlcal  and  endocrlnologlcal  evidence  of  damage
to  the  reproductive tract  was  reported at  2.5  and 5.054 In the diet but  not
at  0.625  or  1.2554  In  the diet  (see  Section  6.1.3).   Fertility was  not
evaluated.
    In the  10-week  NTP (1985)  study  In male  rats fed diets containing butyl
benzyl phthalate at 0, 0.3, 0.28  or  2.5%  (see Section 6.1.2.1),  atrophy of
the  seminiferous  tubules  of  the  testicles and  aspermla  were seen  In rats
treated  orally with  2875  mg/kg/day  butyl  benzyl  phthalate  In  their  diet.
The  pregnancy  rate was 0/30  for  unexposed females mated with  males fed  the
2.554  diet.   There  was no effect on  fertility in rats fed  the  0.03 or 0.2854
diets.
6203H                                -45-                           09/11/89

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6.6.   SUMMARY
    An  acute  toxlclty  study  Indicated  that  the  testes  and accessory  sex
organs appear to be  Important  target  organs  of butyl  benzyl  phthalate toxlc-
lty (Agarwal et  al..  1985).   Exposure of male  F344 rats  to  diets containing
2.5 or  5.0% butyl benzyl  phthalate  for  14  days resulted In decreased weights
of  testes,  epldldymus,   seminal  vesicle  and  thymus  and  hlstopathologlcal
evidence  of  a dose-dependent  atrophy  of  the  testes,  prostate  and  seminal
vesicles  {Agarwal et al., 1985).   Atrophy  of the thymus  and decreased body
weight  were  observed  only  at  the  5.OX level.  Bone  marrow  cellularlty  was
reduced at the 2.5 and 5.0% levels.
    Testlcular  degeneration   was  observed   In  male  F344 rats   fed  a  diet
containing 25,000 ppm  butyl  benzyl  phthalate  for 91  days  (NTP,  1982).   Mice
fed  a  similar   diet  did not exhibit  signs  of  testlcular  degeneration.
Atrophy of the  seminiferous  tubules of the  testicles and  aspermla were seen
In  rats fed  a  2.5% diet  for 26 weeks  (NTP,  1985).  The  kidneys  of 6/15 rats
on  the 2.5%  diet  exhibited  areas  of atrophy.   In an  unpublished  90-day
toxlclty  study (Monsanto, 1972), an  Increase 1n liver weight was observed In
rats  fed   diets  containing  1.0.  1.5  or   2.0% butyl benzyl phthalate.   No
adverse effects were observed among dogs exposed to similar doses.
    The male rat  appears to  be more  sensitive  to  butyl  benzyl  phthalate
toxlclty  than female rats and  male  and  female mice (NTP, 1982). Groups of 50
males  fed  diets  containing 6000 or  12,000  ppm butyl  benzyl phthalate experi-
enced  high early mortality within  28 weeks.  Internal  hemorrhaglng  was  the
suspected  cause  of  the mortality.   Mortality was not seen In female rats or
male and  female mice after 103 weeks exposure to these diets.
    Female rats  fed  a  diet containing butyl  benzyl  phthalate at a concentra-
tion  of  12,000   ppm  demonstrated  a  significantly  Increased   Incidence  of
leukemia  or  lymphoma  (NTP,  1982);  however, a  high  Incidence  of  tumors  In
6203H                                -46-                           09/11/89

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control  rats  was  noted  {Kluwe  et al.,  1982).   There  was  no  evidence of
carc1nogen1c1ty  1n  mice.   Evidence suggests  that  butyl  benzyl phthalate Is
not mutagenU  (see Table  6-3)  .
6203H                                -47-                           09/11/89

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                     7.   EXISTING  GUIDELINES AND  STANDARDS
7.1.   HUMAN
    Pertinent guidelines and standards,  Including  EPA  ambient  water  and air
quality criteria, drinking water  standards,  FAO/WHO  ADIs,  EPA  or  FDA toler-
ances  for  raw agricultural  commodities  or foods, and  ACGIH, NIOSH  or  OSHA
occupational  exposure  limits were  not  located  In  the available  literature
cited  In Appendix A.  Butyl  benzyl  phthalate  1s  subject to the  provisions of
Title  III,  section  313,  of the Superfund Amendments and ReauthoMzatlon Act
of 1986 (U.S. EPA, 1987).
7.2.   AQUATIC
    Guidelines and  standards for  the  protection  of  aquatic  life  from  expo-
sure to butyl  benzyl phthalate were not located  1n  the available  literature
cited  In Appendix A.
6203H                                -48-                           10/17/89

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                              8.   RISK  ASSESSHENT
8.1.   CARCINOGENICITY
8.1.1.   Inhalation.  Pertinent data regarding  the cardnogenlclty of  butyl
benzyl phthalate to animals or humans  following  Inhalation  exposure were not
located 1n the available literature cited In Appendix A.
8.1.2.   Oral.  NTP (1982)  reported  a  statistically significant  Increase  In
mononuclear cell leukemia  or  lymphoma  1n female F344  rats  that were treated
with  butyl  benzyl  phthalate  1n  the diet at  a  concentration of  12,000 ppm.
The tumor  Incidence was  7/49  for controls, 7/49 In  the low group {6000 ppm}
and 19/50  1n  the  high group.   Because of high early mortality  In male rats,
the data  were Insufficient for analysis  of carcinogenic potential  of butyl
benzyl phthalate  1n this sex.  Groups of  50  male  and  50 female  B6C3F1 mice
fed a  diet containing 0,  6000 or 12,000 ppm butyl  benzyl  phthalate  did not
show  an   Increased  Incidence  of  tumors  when compared  with controls  (NTP,
1982).   NTP  (1982)   concluded  that  butyl   benzyl  phthalate  was  "probably
carcinogenic  for female  F344  rats;"  however.  U.S.  EPA (1987c)  noted that the
tumors occurring In the  treated  female rats were  hlstopathologlcally similar
to  those   occurring  In  the  controls  and   further  noted that  there  was  no
reduction  In  time  to  first tumor 1n the treated groups.  It should be noted
that  the   NTP (1989)   has  scheduled butyl  benzyl  phthalate for  additional
testing In rats by oral administration.
8.1.3.   Other  Routes.  Thelss   et  al.  (1977)  evaluated  the  carcinogenic
potential  of  butyl  benzyl  phthalate  In  mice  following  IntrapeMtoneal
administration.  Three groups of  20 male  A/St  mice were  administered 160,
400 or 800 mg/kg  bw butyl  benzyl phthalate (3 times weekly during 8 weeks).
The mice  were  killed  24 weeks  after  the  first  Injection  and examined  for
lung  tumors.   No  significant  differences   In the   Incidence  of  lung  tumors
were found between control  and treated rats.
6203H                             •   -49-                           09/11/89

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8.1.4.   Weight of  Evidence.   Data were not  located  regarding  the  carclno-
genlclty  of  butyl  benzyl  phthalate to  humans.  The  oral  study of  butyl
benzyl  phthalate  In  female  F344  rats  (NTP,  1982}  provides suggestive  but
limited evidence for  the  carclnogenlclty of butyl  benzyl  phthalate In female
rats.   IARC  (1982)  concluded  that  the  available data  did not  present  a
compelling basis  upon which  to model  the cardnogenldty  of   butyl  benzyl
phthalate  to  rats  and  mice.   Using  the Guidelines  for  Carcinogen  Risk
Assessment (U.S.  EPA, 1986d),  the  U.S.  EPA  (1987a)  assigned   butyl  benzyl
phthalate  to   U.S.   EPA  Group   C   —  possible  human   carcinogen.   This
classification Is verified and available on IRIS (U.S.  EPA,  1987c).
8.1.5.   Quantitative Risk Estlmeates.
    8.1.5.1.    INHALATION  —  The  lack  of  adequate   carclnogenlclty  data
precludes quantitative estimation  of carcinogenic risk for  Inhalation expo-
sure to butyl benzyl phthalate.
    8.1.5.2.    ORAL  --  NTP  (1982)  reported  leukemia   or  lymphoma  In 7/49
control,  7/49  low-group  and  19/50  high-group  female   rats  1n   the  103-week
dietary study  1n female  rats.   NTP (1982)  concluded  that  butyl  benzyl phtha-
late  was  "probably carcinogenic"  for  female  rats  1n  this   study.  U.S.  EPA
(1987a,b,c)  concluded that  the leukemia data  In female rats were  Inadequate
for  quantitative estimates  of  cancer  potency; therefore,  no   estimates  of
cancer potency are derived 1n this evaluation.
8.2.   SYSTEMIC TOXICITY
8.2.1.   Inhalation  Exposure.   Pertinent   data  regarding  the   tox1c1ty   of
Inhalation exposure  to  butyl  benzyl  phthalate  were not  located,  precluding
derivation of RfD values for Inhalation exposure.
6203H                                -50-                           10/17/89

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8.2.2.   Oral Exposure.
    8.2.1.1.   LESS  THAN  LIFETIME  EXPOSURES  (SUBCHRONIC)  —  In  an  unpub-
lished  90-day study  \n  rats   (Monsanto,  1972),  Krauskopf  (1973)  reported
elevated liver weights  In rats  fed  a diet  containing  1.0% (500 mg/kg/day),
but not  1n rats  fed  a diet  containing 0.5%  (250  mg/kg/day).  In  the  same
report, no  effects were  reported  In dogs  fed given capsules  equivalent  to
5.0%  1n  the  diet  (1250  mg/kg/day)  for  90  days.   These  studies were  too
briefly reported  for  adequate  evaluation  and are not considered further  for
risk assessment.
    NTP (1982)  evaluated  the  subchronlc  toxlclty of butyl  benzyl  phthalate
In groups  of  10  F344  rats  of  each  sex fed  diets containing  0,  1600,  3100,
6300,   12,500  or  25,000 ppm butyl  benzyl  phthalate  (estimated  dosages  of  0,
80, 155, 315, 625  or  1250 mg/kg/day) for  91  days.  Depressed weight gain  and
testlcular  degeneration were observed In  male rats  fed  1250 mg/kg/day  butyl
benzyl phthalate.   No butyl benzyl  phthalate-related effects  were observed
1n female  rats.    In  the  same  study,  groups of  10  B6C3F1  mice of  each  sex
were  fed diets containing the  same  concentrations of butyl  benzyl  phthalate
(estimated  dosages of 0,  208,  403.  819, 1625 or  3250 mg/kg/day) for 91  days.
Weight gain was  depressed by >10%  1n all  groups of male mice  and  In  female
mice  fed  1625  or  3250  mg/kg/day  butyl  benzyl   phthalate.   No other  butyl
benzyl phthalate-related effects were observed 1n mice.
    In  an   unpublished  study  (NTP,  1985),  male F344  rats  were   fed  diets
containing  butyl   benzyl  phthalate  at  0, 0.03,  0.09,   0.28,  0.83 or  2.50%
(estimated  doses  of 0, 17,  51, 159,  470 or  2875  mg/kg/day)  for  26  weeks.
Other   groups  were  fed  diets  containing  0,  0.03,  0.28 or  2.50%  (estimated
doses   of 0, 17,   159 or 2875 mg/kg/day) for  10  weeks to evaluate  fertility.
6203H                                -51-                           09/11/89

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Reduced  food  consumption and body  weight  gain, testlcular  atrophy,  steril-
ity,  kidney  lesions  and   hematologlcal   effects   were   reported  at  2875
mg/kg/day.  Significant  Increases In absolute  liver  weight  as  well as In the
liver/body  weight  and  liver/brain weight  rations  were  reported  at  470
rag/kg/day.  This was considered a LOAEL by  U.S. EPA (1986c).
    Doses that may  serve as  the  basis  of an RfD for subchronlc oral exposure
Include  the  NOEL  of 0.2854  1n  the diet (159 mg/kg/day)  In male mice  1n the
26-week  toxlclty  and  10-week fertility study  by NTP (1985) and the  NOEL  of
12,500 ppm  In the  diet  (625 mg/kg/day)  In the  91-day  study  In rats  by NTP
(1982).   The  NOEL of  159 mg/kg/day In the NTP  (1985)  study appears  a  more
reasonable  selection  because  the NTP (1985)  study was more  comprehensive.
The NTP  study was  more  completely  reported and evaluated  reduced fertility
In  male   rats,  a  known  toxic  effect  of  the   chemical.   The  NOAEL  of  159
mg/kg/day (rec #1)  Is  divided by an uncertainty factor of  100 (10 to extra-
polate from animals to humans and  10  to protect more  sensitive Individuals)
to estimate an RfD  of  1.59  mg/kg/day,  which  1s rounded  to  2 mg/kg/day.  This
RfD  Is  In  agreement  with   previous  Agency evaluations   (U.S.  EPA,  1986c,
1987a.b).
    Confidence 1n  the  key study  Is medium.   A 14-day dietary  study  In  rats
(Agarwal   et  al.,  1985) reported  elevated  relative kidney  weights  and a low
Incidence of  hlstopathologUal observations  Indicative  of  mild kidney damage
and repair at 0.625% In  the  diet (375  mg/kg/day),  suggesting that  the kidney
may be the  most sensitive organ In rats;  however, the NTP  (1985)  study did
not  report  elevated kidney  weights at  any level  <2.5% of  the  diet  (2875
mg/kg/day).    Hlstopathologlcal  examination of   the  kidney  was  restricted  to
controls   and  high-group  rats.    Degenerative  lesions  were  observed  In  the
kidneys of high-group rats.

6203H                                -52-                           10/17/89

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    Confidence  \n  the  data base  1s  medium.   NOAELs were  not  Identified for
reduced body weight gain  1n male  mice  In  the NTP (1982) subchronlc study nor
for mild  kidney effects  In rats  In  the 14-day Agarwal et  al.  (1985) study.
The developmental  toxlclty and reproductive toxlclty  of  butyl  benzyl phtha-
late  In  female rats  has  not  been  evaluated.   Confidence  In  the RfD  Is
medium.   The RfD  will not  protect against  butyl   benzyl  phthalate-lnduced
cardnogenlclty.
    8.2.2.2.     CHRONIC  EXPOSURES  —  NTP  (1982)  evaluated  the  chronic
toxlclty  of  butyl  benzyl   phthalate  1n  male and female F344 rats  and 86C3F1
male  and  female mice  fed diets  containing  0, 6000  or 12000  ppm.   Reduced
body weights were  reported  In  mice  of  both  sexes  throughout the study.   This
study  Identified male  rats as  the most  sensitive group.   Male  rats  were
exposed  for  only   28  weeks  because  of  high early  mortality,  apparently
attributable to  Internal  hemorrhaglng.  In  contrast  to the NTP (1982) study,
no  butyl  benzyl phthalate-related  deaths  were found  In  male  F344  rats fed
diets containing <25,000  ppm (2875 mg/kg/day)  for 26 weeks (NTP, 1985).   The
reason  for   the discrepancy  between  the  two NTP  studies Is not  readily
apparent.
    NTP   (1985)  determined  a  NOEL   for   testlcular   and  kidney  effects,
decreased body  weight  and hematologlcal effects  In male rats,  and  It  Is  an
acceptable basis for  an  RfD for  chronic  oral exposure.  A chronic  oral RfD
of  0.2  mg/kg/day for butyl benzyl  phthalate can be derived by dividing the
subchronlc oral  RfD by  an additional uncertainty  factor of 10  to expand  from
subchronlc  to  chronic  exposure.    Confidence  In  this  RfD 1s medium  (see
Section 8.2.2.1).
6203H                                -53-                           09/11/89

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                           9.   REPORTABLE  QUANTITIES
9.1.   BASED ON SYSTEMIC TOXICITY
    The  toxlclty  of butyl  benzyl  phthalate was  discussed In Chapter  6  and
dose-response  data considered  for  CS derivation  are  summarized  In  Table
9-1.   In a  chronic toxlclty  study,  a  dose-related  and significant  early
mortality from  unexplained hemorrhaglng was observed  1n male F344  rats  fed
diets  containing  6000  or  12,000 ppm  (300  and 600  mg/kg/day)  for  28  weeks
(NIP,  1982).   The study was originally  Intended  to continue for  103 weeks.
In  this  same  study,  female  rats  fed the  12,000  ppm  diet  for  103  weeks
exhibited reduced  body weights, hepatomegaly and  spenomegaly.   Reduced body
weights were also  observed at  6000 ppm;  reduced  food  consumption  was repor-
ted  at both dietary  levels.    Since  the toxlcologlcal  significance of  the
reduced body weight In  the presence  of  reduced  food  consumption  Is uncertain
and  the hepatomegaly  and  splenomegaly were  limited  to  rats  that  also  had
leukemia, these effects are not  Included  1n  Table 9-1.    Mice of  both  sexes
fed  these diets  for   103  weeks  had  decreased body  weights throughout  the
study  (NTP,  1982).  Data for female mice are presented 1n Table  9-1.
    NTP  (1982)  found  testlcular  degeneration and  depressed weight  gain  In
male F-344  rats  fed a  diet containing  25,000  ppm for 91  days.  In  the same
study,  reduced body  weight  gain  was  reported   In  male  mice  fed a  diet
containing 1600  ppm for  91  days.  NTP  (1985)  reported   reduced body weight
gain and  severe  testlcular effects  1n male rats  fed  a diet  containing  2.50%
for 26 weeks.  This treatment  resulted  In  total  sterility In male  rats  after
only 10  weeks.   In the 26-week study, a  diet  containing 0.83 was  associated
with  Increased  absolute  and   relative  liver  weight.  The  unpublished  sub-
chronic study by Monsanto  (1972) was Inadequately reported for  evaluation.
6203H                                -54-                           09/11/89

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    Effects  compiled  In  Table 9-1  Include mortality,  reduced body  weight
gain or  body weight,  testlcular degeneration, sterility  and  Increased liver
weight.  Table 9-2 presents CSs and  RQs  derived  for  the lowest human equiva-
lent dosages associated with each of  the effects  compiled 1n  Table 9-1.  The
highest CS calculated, 17, was  associated with mortality  In rats (NTP, 1982)
and selected as most  stringently representing the  chronic toxldty of  butyl
benzyl phthalate.  The CS of 17 and  Its  corresponding RQ  of 1000 are presen-
ted 1n Table 9-3.  Both  the CS of  17 and the RQ  of 1000 reported here  are In
agreement with  the CS and  RQ  values  (17 and  1000,   respectively}  for  butyl
benzyl phthalate derived  previously by the U.S.  EPA (1987a).
9.2.   BASED ON CARCINOGENICITY
    The carclnogenlclty  of  butyl benzyl  phthalate was discussed  In  Chapter
6.  NTP  (1982)  reported  a statistically significant  Increase  In mononuclear
cell  leukemia  or  lymphoma In  the  high group of  female F344 rats  that were
fed  diets  containing  6000 or 12,000  ppm  butyl  benzyl  phthalate.   Early
mortality precluded  evaluation of carclnogenlclty 1n the male  rats.   There
was no evidence of  a  carcinogenic  response  1n mice  fed the same diets.  The
NTP  (1989)  has scheduled butyl  benzyl  phthalate  for additional  testing  In
rats by oral administration.
    A  high  Incidence  of  leukemia  In controls,  no reduction  In the time  to
tumor In treated rats compared  with  controls and  the fact that the tumors In
the treated rats were hlstologlcally  Identical to  those In controls prompted
U.S. EPA  (1986c,  1987a,b,c)  to consider  the data  In the   female rats  as  not
providing  a  compelling  basis   for  quantitative   cancer   potency  estimation.
Butyl  benzyl  phthalate  was assigned  to  U.S. EPA  Group C  --  possible  human
carcinogen.  Because  there  Is  no quantitative risk  assessment,  butyl  benzyl
6203H                                -56-                           10/17/89

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                                  TABLE 9-3
                            Butyl Benzyl  Phthalate
           Minimum  Effective Dose (MED) and Reportable Quantity  (RQ)
Route:
Species/Sex:
Dose3:
Duration:
Effect:
RVd:
RVe:
CS:
RQ:
Reference:
oral
rat/male
4.93
28 weeks
Increased mortality 1n male rats
1.7
10
17
1000
NTP, 1982
Equivalent human dose
6267H
                       -58-
09/11/89

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phthalate  can  be  administratively assigned  to Potency  Group  2.   Group  C
chemicals assigned to  Potency  Group 2 are given a  low  hazard ranking,  which
corresponds to an RQ of 100.
6203H                                -59-                           09/11/89

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6203H                                -63-                           09/11/89

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6203H                                -64-                           09/11/89

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6203H                                -65-                           09/11/89

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6203H            •                    -67-                           09/11/89

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6203H                                -69-                           09/11/89

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6203H                                -70-                           09/11/89

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6203H                                -72-                           09/11/89

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Group,  Office  of  Health  and Environmental  Assessment  for   the  Office  of
Emergency and Remedial Response,  Washington, DC.

U.S. EPA.  1986c.  Drinking Water Criteria  Document  for  Phthallc  Acid Esters
(PAE)s.   Prepared  by  the  Office  of  Health  and  Environmental  Assessment,
Environmental Criteria and Assessment Office,  Cincinnati, OH  for  the Office
of Drinking Water,  Washington, DC.  External Review Draft.

U.S.  EPA.   1986d.    Guidelines   for  Carcinogen  Risk  Assessment.   Federal
Register.  51(185);  33992-34003.

U.S.  EPA.   1987a.   Health and  Environmental  Effects  Profile for  Phthallc
Acid  Alkyl,  Aryl and  Alkyl/Aryl  Esters.   Prepared  by  the Office of Health
and  Environmental Assessment,  Environmental Criteria and  Assessment  Office,
Cincinnati,  OH  for   the   Office  of  Solid  Waste  and  Emergency  Response,
Washington, DC.  EPA/600/X-87/384.  NTIS PB89-120158/AS.

U.S.  EPA.    1987b.   Health  Effects  Assessment for  Selected  Phthallc  Acid
Esters.   Prepared  by  the  Office  of  Health  and  Environmental  Assessment,
Environmental Criteria and Assessment Office,  Cincinnati, OH  for  the Office
of Emergency and Remedial  Response,  Washington, DC.   EPA/600/8-88/053.   NTIS
PB88-178934.

6203H       .                         -73-                           10/17/89

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U.S. EPA.  1987c.  Integrated Risk  Information  System (IRIS).   Risk Estimate
for  CarclnogenlcHy  for  Butylbenzylphthalate.   Online.   (Verification  date
8/26/87).   Office  of  Health   and  Environmental  Assessment,  Environmental
Criteria and Assessment Office,  Cincinnati, OH.

U.S.  EPA.    1987d.   Statement  of  Policy  and  Guidance Regarding  Petitions
Under   Section   313   of   Title  III   of  the   Superfund  Amendments   and
ReauthoMzatlon Act of 1986.  Federal  Register.   52(23): 3479.

U.S.  EPA/OHRS   (U.S.   Environmental   Protection  Agency  Office   of   Water
Regulations  and   Standards).    1986.    Guidelines   for  Deriving   Numerical
National Hater Quality  Criteria for the Protection of  Aquatic  Organisms  and
Their Uses.  U.S. EPA, Washington, DC.   p. 22-58, 98.   NTIS PB85-227049/XAB.

Waggott,  A.    1981.    Trace organic  substances  1n  the  River  Lee  (Great
Britain).  Chem.  Water Reuse.  2: 55-99.

Weschler,  C.J.    1984.    Indoor-outdoor  relationships  for  nonpolar  organic
constituents of aerosol particles.  Environ.  Scl. Techno!.   18(9):  648-652.

Zelger,   E.,  S.  Haworth,  S. Speck,  K.   Hortelmans.   1982.  Phthalate  ester
testing  In  the  National  Toxicology Program's environmental mutagenesls  test
development program.   Environ.  Health  Perspect.   44:  99-101.
6203H                                -74-                           10/17/89

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                                  APPENDIX A

    This  HEED  Is  based  on  data  Identified  by  computerized  literature

searches of the following:

                   CHEMLINE
                   TSCATS
                   CASR online (U.S.  EPA Chemical Activities  Status  Report)
                   TOXLINE
                   TOXLIT
                   TOXLIT 65
                   RTECS
                   OHM TADS
                   STORET
                   SRC Environmental  Fate Data Bases
                   SANSS
                   AQUIRE
                   TSCAPP
                   NTIS
                   Federal  Register
                   CAS ONLINE (Chemistry and Aquatic)
                   HSOB
                   SCISEARCH
                   Federal  Research In Progress
These  searches  were  conducted  In  May,  1988,  and  the  following  secondary

sources were reviewed:
       ACGIH  (American  Conference  of  Governmental  Industrial  Hyglenlsts).
       1986.   Documentation  of  the  Threshold  Limit  Values  and  Biological
       Exposure Indices.  5th ed.   Cincinnati,  OH.

       ACGIH  (American  Conference  of  Governmental  Industrial  HyglenUts).
       1987.   TLVs:  Threshold Limit  Values  for Chemical  Substances In  the
       Work   Environment   adopted   by  ACGIH   with   Intended   Changes   for
       1987-1988.  Cincinnati, OH.   114 p.

       Clayton,  G.D.  and  F.E.   Clayton,   Ed.    1981.    Patty's  Industrial
       Hygiene and Toxicology.  3rd rev. ed.  Vol. 2A.   John  Wiley and  Sons,
       NY.  2878 p.

       Clayton,  G.D.  and  F.E.   Clayton,   Ed.    1981.    Patty's  Industrial
       Hygiene and Toxicology.  3rd rev. ed.  Vol. 2B.   John  WHey and  Sons,
       NY.  2879-3816 p.

       Clayton,  G.D.  and  F.E.   Clayton,   Ed.    1982.    Patty's  Industrial
       Hygiene and Toxicology.  3rd rev. ed.  Vol. 2C.   John  Wiley and  Sons,
       NY.  3817-5112 p.
6203H                                A-l                             08/08/89

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       Grayson, M.  and 0.  Eckroth,  Ed.   1978-84.   Klrk-Othmer  Encyclopedia
       of Chemical Technology, 3rd ed.   John Wiley and Sons,  NY.   23 Volumes.

       Hamilton,  A.  and  H.L.  Hardy.    1974.    Industrial  Toxicology.   3rd
       edition.  Publishing Sciences Group,  Inc.,  HA.  575 p.

       IARC (International  Agency  for  Research on Cancer).   IARC  Monographs
       on the Evaluation of Carcinogenic Risk  of  Chemicals  to  Humans.   IARC,
       Lyons,  France: WHO.

       Jaber,   H.H.,  W.R.  Mabey,  A.T.  Lieu,  T.U. Chou  and H.L.  Johnson.
       1984.    Data   acquisition   for   environmental  transport  and   fate
       screening  for  compounds  of  Interest to  the   Office  of Solid  Waste.
       EPA-600/6-84-010.   (NTIS  PB84-243906)  Menlo  Park,  CA:  SRI  Inter-
       national.

       NTP  (National  Toxicology  Program).   1988.   Toxicology Research  and
       Testing Program.  Chemicals on Standard  Protocol.   Management Status.

       Quellette,   R.P.  and  J.A.  King.   1977.   Chemical   Week   Pesticide
       Register.  McGraw-Hill  Book Co.,  NY.

       Sax, I.N.   1984.   Dangerous  Properties of  Industrial Materials.   6th
       ed.  Van Nostrand Relnhold Co.,  NY.

       SRI  (Stanford  Research  Institute).    1987.    Directory  of  Chemical
       Producers.   Stanford, CA.

       U.S. EPA.   1986.   Report  on Status  Report  In   the  Special  Review
       Program,   Registration   Standards   Program  and   the   Data   Call   In
       Programs.   Registration  Standards  and  the  Data  Call  In  Programs.
       Office of Pesticide Programs, Washington,  DC.

       USITC   (United   States   International    Trade  Commission).    1986.
       Synthetic  Organic  Chemicals.   U.S.  Production  and  Sales, 1985,  USITC
       Publication 1892.  Washington, DC.

       Verschueren,  K.   1963.   Handbook of  Environmental  Data  on  Organic
       Chemicals.   2nd edition.  Van Nostrand Relnhold Co., NY.

       Worthing,  C.R.  and  S.B. Walker,  Ed.   1983.   The Pesticide  Manual.
       British Crop Protection Council.   695 p.

       Wlndholz,  M.  Ed.   1983.  The Merck  Index.  10th  ed.   Merck  and  Co.,
       Inc., Rahway, NJ.
6203H                                A-2                            08/08/89

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    In  addition,  approximately  30  compendia of  aquatic  toxlcity data  were

reviewed, Including the following:


       Battelle's Columbus Laboratories.  1971.  Water Quality  Criteria  Data
       Book.   Volume  3.   Effects  of  Chemicals on  Aquatic  Life.   Selected
       Data from  the  Literature through  1968.  Prepared  for  the U.S.  EPA
       under Contract  No. 68-01-0007.  Washington,  DC.

       Johnson, W.W. and  M.T.  Finley.   1980.  Handbook of Acute  Toxicity of
       Chemicals to Fish and Aquatic  Invertebrates.   Summaries  of  Toxicity
       Tests  Conducted  at Columbia  National Fisheries Research  Laboratory.
       1965-1978.   United States  Dept.  Interior,  Fish and  Wildlife  Serv.
       Res. Publ. 137, Washington,  DC.

       HcKee,  O.E.  and  H.W.  Wolf.   1963.   Water Quality Criteria.   2nd ed.
       Prepared for the  Resources  Agency of California, State  Water  Quality
       Control Board.   Publ. No. 3-A.

       Pimental, D.   1971.  Ecological  Effects  of Pesticides  on Non-Target
       Species.  Prepared for the U.S.   EPA, Washington, DC.   PB-269605.

       Schneider,  B.A.   1979.    Toxicology  Handbook.   Mammalian  and  Aquatic
       Data.   Book  1:  Toxicology  Data.  Office of  Pesticide Programs,  U.S.
       EPA, Washington, DC.  EPA 540/9-79-003.  NTIS PB 80-196876.
 6203H                                 A-3                              7/24/89

-------


















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-------
                                APPENDIX C
               DOSE/DURATION RESPONSE GRAPHS FOR EXPOSURE TO
                            BUTYLBENZYLPHTHALATE
C.I.   DISCUSSION
    Dose/duration-response   graphs   for  oral   exposure  to  butyl   benzyl
phthalate   generated  by  the method  of Crockett  et  al.  (1985)  using  the
computer software  by  Durkln  and  Meylan (1988)  developed  under  contract  to
ECAO-Cincinnati  are  presented In  Figure  C-l.   Data  used  to generate  this
graph are  presented in Section C.2.   In  the generation of  this  figure,  all
responses are classified as adverse (FEL,  A£L or LOAEL)  or  non-adverse (NOEL
or  NOAEL) for  plotting.   For oral exposure, the ordinate expresses dosage as
human equivalent dose.  The  animal  dosage  in mg/kg/day  1s  multiplied  by  the
cube root of  the ratio of the animal:human body weight  to adjust for species
differences  in  basal  metabolic  rate (Mantel and  Schneiderman,   1975).   The
result  is   then  multiplied  by  70  kg,  the  reference  human  body  weight,  to
express the human equivalent dose as mg/day for a 70 kg  human.
    The  Boundary for Adverse  Effects  (solid  line)  Is  drawn  by identifying
the lowest  adverse  effect dose  or concentration at  the  shortest duration of
exposure at  which  an  adverse effect occurred.   From this  point, an infinite
line  is  extended upward parallel   to the  dose  axis.   The  starting  point is
then  connected  to  the lowest  adverse effect  dose  or  concentration  at  the
next  longer  duration  of  exposure  that  has   an  adverse   effect  dose  or
concentration  equal  to or  lower than  the  previous  one.   This  process is
continued  to the  lowest  adverse effect  dose  or  concentration.   From this
point,  a line  is  extended to the right parallel  to the duration axis.  The
Region of Adverse Effects  lies above the Adverse Effects Boundary.

6286H                                  C-l                            07/24/89

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    Using the  envelope  method,  the  Boundary for No Adverse  Effects  (dashed
line)  is drawn  by  Identifying  the  highest  no  adverse  effects  dose  or
concentration.    From  this  point,  a  line  parallel  to  the  duration axis  is
extended to  the  dose or  concentration  axis.    The  starting  point  is  then
connected to the next  lower or equal no adverse  effect dose or concentration
at  a longer duration  of  exposure.    When  this  process  can  no  longer  be
continued,  a  line  is dropped  parallel  to  the  dose or  concentration axis  to
the duration axis.   The No  Adverse  Effects  Region  lies below  the  No  Adverse
Effects  Boundary.   At  either  ends  of the  graph  between the  Adverse  Effects
and  No Adverse  Effects  boundaries  are Regions  of Ambiguity.   The area (if
any)  resulting  from  intersection  of  the  Adverse  Effects  and  No  Adverse
Effects boundaries  is defined as the Region of  Contradiction.
    In the censored data  method, all no adverse  effect points located in the
Region of  Contradiction  are  dropped from consideration and the  No  Adverse
Effect boundary  is  redrawn  so that it does not intersect the Adverse Effects
boundary and no  Region of Contradiction is  generated.   This  method  results
in the most conservative  definition of the  No Adverse Effects region.
    Figure C-l  presents  the  dose/duration-response  graph  for  oral  exposure
drawn by the envelope method.   The  Adverse  Effects Boundary  is  defined  by
LD50 values  in  rats  (rec  #16) and mice  (rec #18),  a  LOAEL for mild  kidney
lesions  in rats  in  a 14-day  study  (rec  #15) and a LOAEL for reduced rate of
body weight  gain in mice  (rec  #11).   The  No  Adverse  Effects Boundary  is
defined  by a  NOAEL (rec  #5)  for   mortality, hematology,   liver  and  kidney
function, weight gain and urinalysis in dogs, a  NOAEL  (rec  #8) for decreased
body weight  in female rats and  a  NOAEL (rec  #1)  for  atrophy of  the testis
and kidneys, decreased body weight  and hematology in  rats.   Record  #1   (NTP,

6286H                                 C-2                           07/24/89

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1985) served  as  the  basis  for the  determination of the  RfD  for  subchronic
and chronic oral  exposure.  The presence of a LOAEL of 208 mg/kg/day  in mice
(rec #11)  below  the  NOEL of  159  mg/kg/day  in  rats (rec #1)  that  served as
the basis for  the  RfD values  reflects  the  impact  of the  cube  root of  the
body weight  ratio conversion  on  species with quite different body weights.
The  relatively   large   Region  of   Contradiction  reflects  the   apparent
insensitivity  of  dogs (rec  #5),  the reduces sensitivity  of  female compared
with male rats (rec  #8)  and the effect  of the much  smaller   body  weight of
mice (rec #11) as  well  as the general diversity of the data base.   Data were
insufficient to generate a graph by the censored data method.
C.2  DATA USED TO GENERATE DOSE/DURATION-RESPONSE GRAPHS
C.2.1.    ORAL EXPOSURE
Chemical Name:
CAS Number:
Document Title:
Document Number:
Document Date:
Document Type:
RECORD #1:
n-Butyl benzyl phthalate
85-68-7
Health and Environmental Effects Document  on   Butyl  Benzyl
Phthalate
pending
pending
HEED
Species: Rats
Sex: Male
Effect: NOEL
Route : Food
Number Exposed:
Number Responses:
Type of Effect:
Site of Effect:
Severity Effect:




15
NR
ATROP
TESTE
6
Dose: 159.000
Duration Exposure: 26.0
Duration Observation: 26

15 15 15
NR NR NR
ATROP HGTDC ENZYM
KIDNY BODY BLOOD
6 4 1

weeks
.0 weeks






               Comment:   Range: 0. 0.03, 0.09, 0.28, 0.83, 2.50% (0, 17,
                          51,  159, 470, 2875 mg/kg/day). See rec #2, 3 for
                          effects.
               Citation:  NTP, 1985
6286H
                    C-3
07/24/89

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RECORD #2:
Species:
Sex:
Effect:
Route:
Rats
Male
LOAEL
Food
        Dose:  470.000
        Duration Exposure:  26.0 weeks
        Duration Observation:  26.0 weeks
               Number Exposed:
               Number Responses:
               Type of Effect:
               Site of Effect:
               Severity Effect:
15
NR
ATROP
TESTE
6
15
NR
ATROP
KIDNY
6
15
NR
WGTDC
BODY
4
15
NR
ENZYM
BLOOD
I
               Comment:   Doses: See rec#1.  Increased liver weight, altered
                          hematological parameters. Testicular atrophy, hem-
                          atologic changes,  kidney lesions at 2875 mg/kg/day
               Citation:  NTP, 1985
RECORD #3:
Species:
Sex:
Effect:
Route:
Rats
N.S.
LOAEL
Food
  Dose:  500.000
Duration Exposure: 90.0 days
Duration Observation:  90.0 days
               Number Exposed:     NR
               Number Responses:   NR
               Type of Effect:     WGTIN
               Site of Effect:     LIVER
               Severity Effect:    4
               Comment:  Doses: 0, 125, 250, 500, 750 or 1000 mg/kg/day <0,
                          0.25, 0.5, 1.0, 1.5, 2.0% in diet).  Reduced
                          growth rate at 1.5, 2.0%.
               Citation:  Monsanto, 1972
6286H
                       C-4
                                          07/24/89

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RECORD #4:
Species:
Sex:
Effect:
Route:
Rats
N.S.
NOEL
Food
Dose: 250.000
Duration Exposure: 90.0 days
Duration Observation: 90.0 days
               Number Exposed:     NR
               Number Responses:   NR
               Type of Effect:     WGTIN
               Site of Effect:     LIVER
               Severity Effect:    4
               Comment:   See previous record.
               Citation:  Monsanto, 1972
RECORD #5:



Species:
Sex:
Effect:
Route:
Dogs
N.S.
NOEL
Food
Dose: 1250.000
Duration Exposure: 90.
Duration Observation:


0 days
90.0 days

               Number Exposed:
               Number Responses:
               Type of Effect:
               Site of Effect:
               Severity Effect:
NR
NR
MORTL
N.S.
10
NR
NR
ENZYM
BLOOD
1
NR
NR
' ENZYM
KIDNY
1
NR
NR
WGTIN
BODY
4
               Comment:   Doses: 0, 250, 500 or 1250 mg/kg/day (0, 1.0, 2.0,
                          5.0%).
               Citation:  Monsanto, 1982
6286H
                       C-5
                                          07/24/89

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RECORD #6:
Species:
Sex:
Effect:
Route:
Rats
Male
LOAEL
Food
Dose: 1250.000
Duration Exposure: 91.0 days
Duration Observation: 91.0 days
               Number Exposed:      10      10
               Number Responses:    NR      NR
               Type of Effect:      DEGEN   HGTDC
               Site of Effect:      TESTE   BODY
               Severity Effect:     6       4
               Comment:    Doses:  Ot 80, 155, 315, 625 or 1250 mg/kg/day (0,
                          1600, 3100, 6300, 12500, 25000 ppm).
               Citation:   NTP, 1982
RECORD #7:



Species:
Sex:
Effect:
Route:
Rats
Male
NOEL
Food
Dose: 625.000
Duration Exposure: 91
Duration Observation:


.0 days
91 .0 days

               Number Exposed:     10      10
               Number Responses:   NR      NR
               Type of Effect:     DEGEN   WGTNS
               Site of Effect:     TESTE   BODY
               Severity Effect:    6       4
               Comment:   See previous record.
               Citation:  NTP, 1982
6286H
                       C-6
                                           07/24/89

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RECORD #8:
Species:
Sex:
Effect:
Route:
Rats
Female
NOEL
Food
Oose: 1250.000
Duration Exposure: 91.0 days
Duration Observation: 91.0 days
               Number Exposed:      10
               Number Responses:    NR
               Type of Effect:      WGTDC
               Site of Effect:      BODY
               Severity Effect:     4
               Comment:  Doses:  See rec#6.   Unlike male
                          depressed weight  gain was not
                          rats.
                                         rats ,
                                         observed in female
               Citation:  NTP, 1982
RECORD #9:



Species:
Sex:
Effect:
Route:
Mice
Female
LOAEL
Food
Dose: 1625.000
Duration Exposure: 91
Duration Observation:


.0 days
91.0 days

               Number Exposed:     10
               Number Responses:   NR
               Type of Effect:     WGTDC
               Site of Effect:     BODY
               Severity Effect:    4
               Comment:   Doses: 0, 208, 403, 819, 1625 or 3250 mg/kg/day
                          (0, 1600, 3100, 6300, 12500, 25000 ppm).
               Citation:  NTP, 1982
6286H
                       C-7
                                          07/24/89

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RECORD #10:
Species:
Sex:
Effect:
Route:
Mice
Female
NOEL
Food
Dose: 819.000
Duration Exposure: 91.0 days
Duration Observation: 91.0 days
               Number Exposed:     10
               Number Responses:   NR
               Type of Effect:     WGTDC
               Site of Effect:     BODY
               Severity Effect:    4
               Comment:   See previous record,
               Citation:  NTP, 1982
RECORD #1 1 :



Species:
Sex:
Effect:
Route :
Mice
Male
LOAEL
Food
Dose: 208.000
Duration Exposure: 91
Duration Observation:


.0 days
91 .0 days

               Number Exposed:     10
               Number Responses:   NR
               Type of Effect:     WGTDC
               Site of Effect:     BODY
               Severity Effect:    4
               Comment:   See rec # 9 for dosages,
               Citation:  NTP, 1982
6286H
                        C-8
                                           07/24/89

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RECORD #12:
Species:
Sex:
Effect:
Route:
Rats
Male
PEL
Food
Dose: 300.000
Duration Exposure: 28.0 weeks
Duration Observation: 28.0 weeks
               Number Exposed:      50      50
               Number Responses:    NR      NR
               Type of Effect:      DEATH   WGTDC
               Site of Effect:      N.S.     BODY
               Severity Effect:     10      4
               Comment:    Doses 0, 300 & 600 mg/kg/day (0,  6000,  12000 ppm)
                          Males terminated because of early mortality.
               Citation:   NTP,  1982
RECORD #1 3 :



Species:
Sex:
Effect:
Route:
Rats
Female
LOAEL
Food
Dose: 300.000
Duration Exposure: 103.0 weeks
Duration Observation: 103.0 weeks

               Number Exposed:     50
               Number Responses:   NR
               Type of Effect:     WGTDC
               Site of Effect:     BODY
               Severity Effect:    4
               Comment:   Doses: See previous record.  Body weight was
                          decreased in female rats. Also, food consumption
                          was slightly decreased <70-80% that of controls).
               Citation:  NTP, 1982
6286H
                       C-9
                                          07/24/89

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RECORD #14:
Species:
Sex:
Effect:
Route:
Mice
Both
LOAEL
Food
Dose: 780.000
Duration Exposure: 103.0 weeks
Duration Observation: 103.0 weeks
               Number Exposed:     50
               Number Responses:   NR
               Type of Effect:     HGTDC
               Site of Effect:     BODY
               Severity Effect:    4
               Comment:   Doses: 0, 780 & 1560 mg/kg/day (0, 6000, 12000
                          ppm).
               Citation:  NTP, 1982
RECORD #15:



Species:
Sex:
Effect:
Route:
Rats
Male
LOAEL
Food
Dose: 375.000
Duration Exposure: 14
Duration Observation:


.0 days
14.0 days

               Number Exposed:     10      10
               Number Responses:   NR      NR
               Type of Effect:     WGTIN   DEGEN
               Site of Effect:     KIDNY   KIDNY
               Severity Effect:    4       6
               Comment:   Doses: 375, 750, 1875 & 2000 mg/kg/day (0, 0.625,
                          1.25, 2.50, 5.0%).  Mild regenerative lesions In
                          kidney.
               Citation:  Agarwal et a!., 1985
6286H
                       C-10
                                           07/24/89

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RECORD #16:
Species:
Sex:
Effect:
Route:
Rats
Both
PEL
Gavage
Dose: 2330.000
Duration Exposure: 1.0 days
Duration Observation: 1.0 days
               Number Exposed:     5
               Number Responses:   NR
               Type of Effect:     DEATH
               Site of Effect:     N.S.
               Severity Effect:    10
               Comment:   LDSO value for male and female rats. The
                          vehicle  was corn oil.
               Citation:  NTP, 1982
RECORD #17:


Species:
Sex:
Effect:
Route:
Mice
Male
PEL
Gavage
                                           Dose: 6160.000
                                           Duration Exposure: 1.0 days
                                           Duration Observation: 1.0 days
               Number Exposed:     5
               Number Responses:   NR
               Type of Effect:     DEATH
               Site of Effect:     N.S.
               Severity Effect:    10
               Comment:   LD50 value.  The vehicle was corn oil
               Citation:  NTP,  1982
6286H
                        C-ll
                                           07/24/89

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6286H                                 C-12                          07/24/89

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