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                               EXECUTIVE SUMMARY

    Pure phosphlne 1s a  colorless  and odorless gas at  ambient  temperatures,
but Impurities In commercial preparations  Impart a  garlic-like  odor  that  has
been attributed  to  phosphlne  (Verstuyft,  1978).   It  Is slightly  soluble  In
water and  1s  soluble 1n ethanol,  ethyl  ether and  cuprous  chloride  (Hawley,
1981).   At least  two chemical  companies at  nine locations  1n  the  United
States manufacture this  chemical,  and  eight  additional  U.S.  companies  supply
It  to  consumers  (SRI,  1988;  Chemical  Week, 1985).   Phosphlne with  a  high
yield and  minimal diphosphlne contamination can  be  made commercially  from
the  hydrolysis  of aluminum phosphide  (Boenlg  et   al.,  1982).   The  current
U.S. production  or  Import   volume  of  this chemical 1s  not  known.   Phosphlne
1s  used  as a  grain  fumlgant.  In  the synthesis of a flame retardant, as  a
doping  agent  1n  the  semiconductor Industry,  as  a polymerization Initiator
and  as  a  condensation  catalyst (Berck,  1975;  Boenlg et al.,  1982;  Hawley,
1981).
    The  most  likely  Important process  that will  account  for  the loss  of
phosphlne  In   the  atmosphere  1s   Us  reaction with  HO  radical.   Based  on
measured rates under  simulated conditions, the lifetime of  phosphlne  In  the
troposphere that 1s due  to  this reaction  Is  estimated to be <1  day (Fritz et
al., 1982).  The fate of phosphlne In water  Is not well established.   Redox
systems  present  1n most surface  water may  oxidize phosphlne  to  phosphate.
Part of  the phosphlne In natural water may be lost as a result of reversible
and  Irreversible sorptlon;  however,   the  most significant  loss  process  1s
likely to  be volatilization.   Loss  from volatilization  may be  significant In
soils as  well.   B1ot1c  and abiotic  oxidation  and sorptlon may  account  for
partial  loss  of phosphlne  from soils  (Hilton  and Roblson, 1972;  Berck  and
Gunther, 1970).
                                      1v

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    Phosphlne at an arithmetic average concentration  of  2.2  ppb was detected
In ambient  air  samples taken -200 m  from a dlcyanamlde  manufacturing  plant
In Norway  (Vlnsjansen and  Thrane,  1978).  No  other  ambient  air  monitoring
data  on this  compound  are available.   Although  occupational exposure  of
workers  to  this compound  1n  certain Industries  1s likely,  particularly  1n
the grain  fumigating and  semiconductor  Industries, no monitoring  data from
these  or any other Industries are  available.   Monitoring data  on  the  level
of phosphlne In ambient  water,  groundwater or  drinking water  are  also  not
available.    The  levels of  phosphlne  In  various  fumigated grains  have been
reported.  In general, phosphlne levels  In  fumigated  foods decrease to  <0.01
mg/kg  14 days  following  fumigation  (Rommlnger  and  Kubel,  1972). No data
regarding the  level of  phosphlne  1n total  diet samples  are  available that
would permit estimation of exposure to this compound from food Ingestlon.
    Doudoroff and  Katz (1950) reported  that concentrations of phosphlne >3.6
ppm were toxic  to  rainbow  trout  In hard water.   An  estimated  8CF  value  of
22.1 for phosphlne  suggests that Us  bloaccumulatlon  In  aquatic organisms  Is
not significant.
    Pharmacok1net1c  data  for  phosphlne  are  limited.   Detection   of  trace
amounts  of   phosphide  1n  the  blood  and  liver,  and   detection  of  a  marked
elevated  concentration  of  aluminum  1n   the   urine   (compared  with   normal
values)  of  a man  who died  following  Ingestlon  of aluminum phosphide suggest
that absorption of  aluminum phosphide occurs  from the GI tract  (Chan et al.,
1983).   The  observation  of systemic toxlclty In  humans  exposed to phosphlne
gas In  the  ambient air (Wilson et al.,  1980)  suggests that  phosphlne  gas  1s
absorbed from  the respiratory tract.   One  author  has stated  that phosphlne
may  be  absorbed   through  broken,   but  not  through  unbroken  skin (Schoof,
1970).   Phosphlne may be metabolized to nontoxlc phosphates (OHMTAOS, 1988).

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    Two   lifetime   oral    studies   using   rats   Indicate   that   dietary
concentrations  of 
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    Warltz  and  Brown  (1975)  determined  a  4-hour  rat  LC5Q  of  11   ppm.
Treated rats had signs of respiratory  Irritation.  Fourteen days  of  repeated
exposure  to  4.0 ppm  produced  an  Inhibition  of  weight  gain,  but no  gross
pathological  effects.  Muthu  et  al.   (1980)   calculated  a  rat  Inhalation
LC5Q  of  28-33.3  ppm (42-50  mg/m3)   for  phosphlne  exposure  times  of  5.2
and 7.4  hours.   Treatment  resulted 1n  bronchlolar cellular Infiltration  and
some  edema,  but  no  morphological  changes  In  other organs.   Host  animal
Inhalation  studies  (MOller,  1940;  (dimmer,  1969; Nlkodemusz et  al.,  1981;
Muthu et  al.,  1980)  reported  clinical   or  hlstopathologlcal  evidence of  CNS
Involvement after exposure.
    Occupational  exposure   to  phosphlne   results   1n  nausea,   gastritis,
dizziness,  liver effects and   nose and throat   Irritation   (Elchler,  1934;
Harger  and Spolyar,  1958;   Torkelson  et  al.,   1966;  Wilson   et  al.,  1980;
Harano,  1984;  WHO,   1986;  Casteel  and Bailey,  1986).  Casteel  and  Bailey
.(1986)  attributed  clinical   effects In  humans   to  a nonspecific  toxicosis.
Members  of the  crew  on  a  freighter   containing phosphlne-fumlgated  grain
became  111  after  2-5 days of  exposure (Wilson  et al., 1980).   The  greatest
Incidence of Illness  occurred  1n those portions  of  the ship with the highest
exposure  concentrations (<30 ppm).   The two most severely affected  Individ-
uals  were children.  Although   one child  recovered,  the  second  died  with
congestive heart failure, myocardlal necrosis,  pulmonary edema  and damage to
the respiratory epithelium and  alveoli.
    The  odor  threshold for  phosphlne  ranges  from  0.01-2  ppm,  depending on
the  purity of  the  commercial  preparation (Pluck,  1976).    Highly  purified
phosphlne  gas   1s  odorless.    Phosphlne 1s  a   potent Inhibitor  of  State  3
(active) cellular respiration  (NakakUa et  al.,  1971; Chefurka et al., 1976).

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    Phosphlne Is most appropriately designated an EPA group 0 substance,  not
classifiable as  to human  cardnogenldty.   A subchronlc  Inhalation  RfO  of
3xlO~4  mg/ma,  was  derived  by  applying  an  uncertainty  factor  of   100  to
the NOEL  of 1  ppm 1n  rats  exposed  Intermittently  for  24  weeks  (KUmmer,
1969).   A   chronic   Inhalation   RfO  of  3xlO~s  mg/m3,   was   derived   by
applying an  additional  uncertainty  factor  of 10  (to  expand from 24-week  to
chronic exposure) to the subchronlc  rat NOEL  of 1  ppm  (KUmmer, 1969).
    A  chronic  oral RfD  of 3xlO~*  mg/kg/day was derived  from  the  NOEL  of
0.51 mg/kg/day  1n  the  2-year  dietary study using rats by Hackenberg  (1972).
This RfD 1s  currently  verified and  available on  IRIS (U.S. EPA, 1985).  The
chronic oral RfD 1s adopted as  the subchronlc RfD.
    A chronic toxldty RQ of 100  pounds was  based on  the appearance of liver
lesions In rats Intermittently exposed to 2.5 ppm phosphlne  for 24 weeks.
                                     V111

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                             TABLE OF CONTENTS

                                                                       Page
1.  INTRODUCTION	     1

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

2.  ENVIRONMENTAL FATE AND TRANSPORT	     5

    2.1.   AIR	     5
  , 2.2.   WATER	     5
    2.3.   SOIL	     6
    2.4.   SUMMARY	     7

3.  EXPOSURE	     9

    3.1.   AIR	     9
    3.2.   WATER	     9
    3.3.   FOOD	     9
    3.4.   SUMMARY	    10

4.  ENVIRONMENTAL TOXICOLOGY	    11

    4.1.   AQUATIC TOXICOLOGY 	    11

           4.1.1.   Acute Toxic Effects on Fauna	    11
           4.1.2.   Chronic Effects on Fauna	    11
           4.1.3.   Effects on Flora	    11
           4.1.4.   Effects on Bacteria 	    11

    4.2.   TERRESTRIAL TOXICOLOGY 	    12

           4.2.1.   Effects on Fauna	    12
           4.2.2.   Effects on Flora	    12

    4.3.   FIELD STUDIES	    12
    4.4.   SUMMARY	    12

5.  PHARMACOKINETCS	    13

    5.1.   ABSORPTION	    13
    5.2.   DISTRIBUTION	    14
    5.3.   METABOLISM	    14
    5.4.   EXCRETION	    14
    5.5.   SUMMARY	    14
                                     1x

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                          TABLE OF CONTENTS (cont.)

                                                                        Page
 6.   EFFECTS	    15

     6.1.    SYSTEMIC TOXICITY	    15

            6.1.1.    Inhalation Exposure 	    15
            6.1.2.    Oral  Exposure	    17
            6.1.3.    Other Relevant Information	    21

     6.2.    CARCINOGENICITY	    28

            6.2.1.    Inhalation	    28
            6.2.2.    Oral	    28
            6.2.3.    Other Relevant Information	    28

     6.3.    MUTAGENICITY	    28
     6.4.    TERATOGENICITY	    29
     6.5.    OTHER REPRODUCTIVE EFFECTS 	    29
     6.6.    SUMMARY	    29

 7.   EXISTING GUIDELINES AND STANDARDS 	    32

   .  7.1.    HUMAN	    32
     7.2.    AQUATIC	    33

 8.   RISK ASSESSMENT	    34

     8.1.    CARCINOGENICITY	    34

            8.1.1.    Inhalation	    34
            8.1.2.    Oral	    34
            8.1.3.    Other Routes	    34
            8.1.4.    Weight of Evidence	    34
            8.1.5.    Quantitative Risk Estimates 	    35

     8.2.    SYSTEMIC TOXICITY	    35

            8.2.1.    Inhalation Exposure 	    35
            8.2.2.    Oral  Exposure	    38

     8.3.    AQUATIC	    42

 9.   REPORTABLE QUANTITIES 	    43

     9.1.    BASED ON SYSTEMIC TOXICITY 	    43
     9.2.    BASED ON CARCINOGENICITY	    44

10.   REFERENCES	    46

APPENDIX A: LITERATURE SEARCHED	    57
APPENDIX B: SUMMARY TABLE  FOR PHOSPHINE	    60
APPENDIX C: DATA USED TO GENERATE DOSE/DURATION-RESPONSE GRAPH
            FOR INHALATION EXPOSURE TO PHOSPHINE 	    61

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                               LIST OF TABLES
No.                               Title                                Page
1-1     Phosphlne Producers and Suppliers 1n the United States. ...    3
6-1     Acute Inhalation Toxlclty Data for Phosphlne	   22
9-1     Phosphlne: Minimum Effective Dose (MED) and Reportable
        Quantity (RQ)	   45
                                     x1

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                             LIST  OF ABBREVIATIONS

AAS                     Atomic absorption spectrophotometry
AMP                     Adenoslne monophosphate
BCF                     Bloconcentratlon factor
BSP                     Bromosulfophthaleln
CAS                     Chemical Abstract Service
CNS                     Central nervous system
CPK                     Creatlne phosphoklnase
CS                      Composite score
EKG                     Electrocardiogram
PEL                     Frank effect level
GC                      Gas chromatography
GGPT                    Gamma glutam1c-pyruv1c transamlnase
GI                      Gastrointestinal
HEC                     Human equivalent concentration
K                       Octanol/water partition coefficient
                        Concentration lethal to 50% of recipients
                        (and all other subscripted dose levels)
   c                    Lactate dehydrogenase
LOAEL                   Lowest-observed-adverse-effect level
MED                     Minimum effective dose
MTD                     Maximum tolerated dose
NOAEL                   No-observed-adverse-effect level
NOEL                    No-observed-effect level
ppb                     Parts per billion
ppm                     Parts per million
RfO                     Reference dose
RQ                      Reportable quantity
RV.                     Dose-rating value
RVg                     Effect-rating value
SGPT                    Serum glutamlc-pyruvlc transamlnase
STEL                    Short-term exposure level
TLV                     Threshold limit value
TWA                     Time-weighted average
v/v                     Volume per volume
w/v                     Weight per volume

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                               1.  INTRODUCTION
1.1.   STRUCTURE AND CAS NUMBER
    The chemical  commonly  called phosphlne Is  also  known as  hydrogen  phos-
phide and  phosphorus  trlhydrlde.  Some of  the trade names of  this  compound
are  Celphos*.  Dellcla*  and  Phostox1n«  (U.S.  EPA,   1988a).   The  struc-
ture,  molecular  formula,  molecular  weight   and  CAS  Registry  number  for
phosphlne are as follows:
                                      H
                                    H-P-H
Molecular formula: PH.
Molecular weight: 34.00
CAS Registry number: 7803-51-2
1.2.   PHYSICAL AND CHEMICAL  PROPERTIES
    Pure phosphlne  1s  a  colorless  and odorless gas  at  ambient temperatures.
Impurities  In commercial  preparations  Impart  a  garl1c-11ke  odor   that  has
been attributed  to phosphlne  (Verstuyft,  1978).   Phosphlne becomes sponta-
neously  flammable  1n  air  1f  trace  amounts  of   dlphosphlne  (P?*^)  are
present as  an Impurity  (Ulndholz, 1983).   Phosphlne 1s  slightly soluble  1n
water and  Is  soluble  In ethanol,  ethyl  ether  and cuprous  chloride  (Hawley,
1981).  Selected physical properties  of this compound are given below:
    Melting point:              -133°C                     Ulndholz,  1983
    Boiling point:              -87.7°C                    Wlndholz,  1983
    Density:                    1.529 g/l at 0°C           Sax, 1984
    Water solubility:           0.26 vol.  (368 mg/l)        Ulndholz,  1983
                                at 20°C
    A1r odor threshold:         0.51  ppm (v/v)             Amoore and
                                                           Hautala,  1983
0132d                               -1-                              08/30/89

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    Mater odor threshold:        0.00020 ppm (w/v)           Amoore  and
                                                           Hautala,  1983
    Log Kou:                    not available
    Chemically,  phosphlne  reacts  violently  with  oxygen  and  halogens.  It
liberates hydrogen and forms  phosphide when passed over many heated  metals.
As  a  weak  base,  It  reacts   with  halogen  adds  to  form  phosphonlum  salts
(Hlndholz, 1983).
1.3.   PRODUCTION DATA
    The producers and suppliers of phosphlne  1n the United States are listed
1n Table 1-1.
    Phosphlne with a high yield and minimal  dlphosphlne contamination can  be
made  commercially  from the  hydrolysis of  aluminum phosphide.    An electro-
lytic process  whereby nascent hydrogen  reacts  with elemental phosphorus  In
the cathode  1s  also  used  for the commercial  production of phosphlne.   It  1s
also  produced  as  a  by-product of  the  commercial  production of sodium hypo-
phosphite  (Boenlg  et  al.,  1982).   The  current  U.S. production or   Import
volume of this chemical 1s  not available.
1.4.   USE DATA
    Phosphlne  1s  used  for  grain  fumigation and  as   a  rodentlclde  (Berck,
1975).   It  1s also  used  In   the  synthesis of a  flame retardant for  cotton
fabrics  (Boenlg et   al.,  1982) and  as a  doping  agent  for  n-type semicon-
ductors,  a  polymerization  Initiator  and  a  condensation  catalyst (Hawley,
1981).
1.5.   SUMMARY
    Pure phosphlne 1s  a colorless  and  odorless gas at ambient  temperatures,
but impurities  In commercial   preparations  Impart a  garl1c-Hke odor that has
been  attributed  to  phosphlne (Verstuyft,  1978).   It  1s  slightly soluble  1n
0132d                               -2-                              03/16/89

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                                  TABLE 1-1
           Phosphlne Producers and Suppliers 1n the United States*
                        Company
                  Service
               American  Cyanamld  Co.
               Ashland Chemical Co.
               Atomerglc Chemetals  Corp.
               The Boc Group,  Inc.
               Liquid A1r Corp.
               Liquid Carbonic
               Matheson  Gas  Products,  Inc,
                 Cucamonga,  CA
                 East Rutherford, NJ
                 Gloucester, MA
                 Jollet, IL
                 La Porte, TX
                 Morrow, GA
                 Newark, CA
                 Twlnsburg Towshlp, OH
               Phoenix Research Corp.
                 La Mesa, CA
               Synthatron Corp.
               Union Carbide Corp.
                  supplier
                  supplier
                  supplier
                  supplier
                  supplier
                  supplier
                  producer
                  producer
                  supplier
                  supplier
'Source: Chemical Week,  1985;  SRI,  1988
0132d
-3-
02/14/89

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water and  1s  soluble In ethanol,  ethyl  ether and cuprous  chloride  (Hawley,
1981).   At  least  two chemical  companies at  nine locations  In the  United
States manufacture this chemical,  and eight  additional  U.S.  companies  supply
1t  to consumers  (SRI,  1988; Chemical  Week, 1985).   Phosphlne with  a  high
yield and  minimal dlphosphlne  contamination can  be  made  commercially  from
the  hydrolysis  of aluminum  phosphide  (Boenlg  et al.,  1982).  The  current
U.S.  production  or  Import  volume  of  this chemical 1s  not  known.   Phosphlne
1s  used  as a  grain  fumlgant,  In  the synthesis  of a  flame retardant,  as  a
doping  agent  for  semiconductors,  as  a  polymerization  Initiator and as  a
condensation catalyst (Berck, 1975; Boenlg et al., 1982; Hawley, 1981).
0132d                               -4-                              08/30/89

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                     2.   ENVIRONMENTAL FATE  AND  TRANSPORT
2.1.   AIR
    Limited data  are available on  the fate of phosphlne  In  air.  The  rate
constant for the  reaction  of  phosphlne with HO radical 1n the gas phase was
determined  to  be l.dxlO"11  cmVmolecule-sec  at  a  total   pressure  (argon  *
PH3)  of  10  mm Hg  and  a  temperature  of  25°C  (Fritz et al.,  1982).  The
reaction rate was found to Increase proportionately to the Increase of  total
pressure.   Based  on the  measured rate  constant  at  reduced  pressures, the
authors estimated that  the tropospherlc lifetime of  this  compound would  be
<1 day.  Also,  they  suggested  that  the reaction proceeds by H atom abstrac-
tion  and  that  the   likely  product  of  this reaction  Is   PH..   The  authors
speculated  that PH~ will  show  Uttle tendency  to  react  with  atmospheric
Op  but  may  react   with   0«,  resulting  In  the  formation   of   H-PO.   The
product  of  the  latter  compound  as  a  result  of  reaction  with  N0? and
subsequent hydrolysis 1s hypophosphorus add.   No data are available  In  the
literature regarding the reactivity of phosphlne with  other oxldants  such  as
0-, 0_, NO  1n the atmosphere.
 C   0    X
    From  the  available data  regarding the  photolysis of this  compound  at
shorter wavelengths  (Calvert and  Pitts.  1966;  Noy et  al., 1981),  It  appears
that  direct  photolysis  of  phosphlne  In  the troposphere  at wavelengths  >290
nm will not be  significant.  Partial  removal of this  compound  by atmospheric
physical processes  such  as wet and  dry deposition may be possible;  because
of Us high vapor pressure, however,  1t  Is  likely to  reenter  the atmospheric
phase by vaporization.
2.2.   WATER
    The fate of phosphlne  1n water  has  not  been well  studied.  The oxidation
of  phosphlne  by  oxldants  present  In water was  studied  by placing 1097  ppm
phosphlne with  distilled water 1n a  sealed  tube (Hilton and  Roblson,  1972).

0132d                               -5-                              08/30/89

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Less  than  1% of  phosphlne was  oxidized to  phosphate In  40 days, and  the
authors did  not  rule out  the  possibility of mlcroblal oxidation  Instead of
chemical oxidation.   The  redox  potential of  phosphlne under acidic  anoxlc
conditions and basic oxlc conditions  1n  seawater  Is  +0.195  volt  equivalent
and  +3.849  volt  equivalent, respectively (Kumar  et al.,  1985).   Therefore,
several redox systems present  1n  seawater are  capable  of  oxidizing phosphlne
under oxlc conditions and  reducing  It  under  anoxlc  conditions,  and phosphlne
may  not be  very  stable  1n most  seawaters.   In  most natural  freshwaters,
phosphlne may  not  be  very stable  because  It  Is  easily  oxidized (reducing
systems  are  not   generally   available  In   freshwater).    Hydrolysis   and
photolysis are  not  expected  to  be significant processes  for  phosphlne In
water (see Section 2.1.).
    Volatilization  1n water Is likely to be the most  Important  loss  process
for  phosphlne.   Based  on a vapor pressure of  1 atm (the  compound  1s  gaseous
at  ambient   temperatures)  and  a solubility  of 368 mg/l,  the  Henry's  Law
constant  for phosphlne  1s  estimated  (vapor   pressure/solubility)  as  0.09
atm»m3/mol.    From  the  expected  volatility  associated with various  ranges
of  Henry's Law constant (Lyman et al.,  1982),  phosphlne  1s expected  to  have
a  high volatility  from  water.   Since   phosphlne  may be lost  In soil  by
reversible  and  Irreversible  (chemlsorptlon)   sorpUon  processes  (Section
2.3.),  loss of aquatic phosphlne by sorptlon processes may also occur.
2.3.    SOIL
    The fate of phosphlne  1n  soil  placed  In  sealed  tubes was reported by
Hilton  and  Roblson  (1972).    Phosphlne  disappeared  completely  from  the
headspace gas In  three  tubes  containing  different  a1r-dr1ed  soils with  high
(12-15X),  Intermediate  (5-8%)  and low (3-5X) organic  matter  content  1n  7-18
0132d                               -6-                              08/30/89

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days.  When  the same  soils  were 100%  saturated  with water,  phosphlne  dis-
appeared completely 1n 27-40 days.  The rate  of disappearance  thus  Increased
with  the  decrease  In  moisture  content  of the soil.   The disappearance  of
phosphlne was attributed  to  Initial  sorptlon of the compound  onto  soils and
to  the  subsequent  blotlc   or   abiotic  oxidation  of  part  of  the  sorbed
compound.  In 25% water-saturated soils kept  In  contact with  phosphlne for
40  days   1n  sealed  tubes,   69,  16  and 18%  of  phosphlne was  oxidized  to
phosphate from  soils with high,  Intermediate  and  low  organic  carbon content,
respectively.   Drier conditions  resulted In more  phosphate formation because
phosphlne sorptlon  Increased with decreasing  moisture,  as more void  spaces
are  available  1n dryer  soils  (Hilton and  Roblson,  1972).  The sorptlon  of
phosphlne 1n  four  soils  was also  reported by Berck and Gunther  (1970), who
concluded that  phosphlne 1s  sorbed   to  soil  by  both  physical and  chemical
sorptlon processes.  Soils with  low  organic matter and  high mineral content
showed higher  chemlsorptlon.  In the case of chemlsorptlon,  phosphlne  will
be Irreversibly bound  In  soils and will not  be available for  volatilization.
Since  the compound  1s  gaseous at  ambient  temperatures and 1s  only slightly
soluble In water, Us loss by volatilization will  be Important  1n  most soils.
2.4.   SUMMARY
    The  most likely  Important  process  that will  account for  the loss  of
phosphlne  In the  atmosphere  1s Us  reaction with  HO radical.    Based  on
measured rates  under simulated  conditions, the lifetime of phosphlne  1n the
troposphere  that 1s due  to this  reaction 1s  estimated  to be <1 day  (Fritz et
al.,  1982).   The  fate  of phosphlne 1n water  Is not well established.   Redox
systems  present In most  surface water may  oxidize phosphlne  to  phosphate.
Part  of  the  phosphlne  1n  natural  water  may be lost as a result of reversible
and  Irreversible sorptlon;  however,   the  most significant  loss  process  1s


0132d                               -7-                              03/16/89

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likely to be volatilization.  Loss from volatilization may  be  significant  In
soils as  well.   B1ot1c and  abiotic  oxidation  and  sorptlon may account  for
partial  loss  of  phosphlne  from  soils  (Hilton  and  Roblson, 1972;  Berck  and
Gunther, 1970).
0132d                               -8-                              02/14/89

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                                 3.   EXPOSURE
3.1.   AIR
    Phosphlne  Is  likely to  be  found 1n  the ambient air  surrounding  plants
manufacturing  dlcyanamlde   from  calcium  carbide,   since  phosphlne   1s   a
by-product In  this  manufacturing  process.   Ambient air samples  taken  -200 m
from  such  a  plant  In  Norway showed  an  arithmetic average  concentration  of
2.2  ppb  with  a  maximum concentration  of 10.2  ppb  (Vlnsjansen and  Thrane,
1978).  No other  ambient air monitoring  data  for this compound were  avail-
able  1n  the  literature.   Occupational  exposure of  workers  to phosphlne  1s
very  likely  1n the  semiconductor Industry, particularly  those Involved  1n
welding and machining operations  (Verstuyft, 1978; Herget  and  Levlne,  1986),
and  to workers  In  grain fumigating operations; however, no  area or  personal
monitoring data from these Industries are available  In the  literature cited
1n  Appendix  A.  Phosphlne  was  reported  to  be present  In a  malodorous  gas
near a P-conta1n1ng carbide waste burial  site 1n Japan (Yamada  et al.,  1981).
3.2.   WATER
    Monitoring data  on  the  level of  phosphlne In water were  not  located  1n
the available literature dted 1n Appendix A.
3.3.   FOOD
    Phosphlne  residues   found on  soybeans  2-5  days  after   fumigation  and
aeration varied from less  than  the detection  limit  (0.001 ppm)  to 0.002 ppm
(Vardell  et  al.,  1973).   Phosphlne  residues  In walnuts,  hazelnuts,  Brazil
nuts, almonds, peanuts, cashews,  cocoa beans,  palm seeds,  poppy seeds, white
beans, lentils, tobacco, dried apricots,  raisins,  cinnamon,  black  pepper and
milk  powder were  below  the German acceptable  limit  of  0.01  mg/kg  In 14 days
after  fumigation,  except In  the  case of Brazil nuts,  for which  the authors
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concluded  that  phosphlne  1s  not  a  suitable  preservative  (Rommlnger  and
Kubel, 1972).   A variety of  wheat grown  In  India  and fumigated with  phos-
phlne showed  an average of  0.007-0.009 ppm  of phosphlne 1 day  after  expo-
sure; no detectable  residues  were found on the 5th  day  after  exposure.   The
authors recommended  a  minimum of 5 days storage  before  human  consumption of
wheat  treated with  phosphlne (Awasthl  et a!.,  1971).    Residue levels  of
phosphlne  1n  cartons of papayas  fumigated  at low temperature  (12.8°C)  were
0.08  ppb,  but the  concentration   dissipated  to trace  levels after  2 days of
storage.   When  the  fumigation  was  done  at  room  temperature,   the  residue
levels were 1-1.4 ppb  after  fumigation  and decreased to  0.18-0.3 ppb after 1
day of storage (Seo et al.,  1979).
3.4.   SUMMARY
    Phosphlne at an  arithmetic average  concentration of  2.2 ppb was  detected
1n  ambient  air samples taken  -200 m from a  dlcyanamlde  manufacturing  plant
In  Norway  (Vlnsjansen and Thrane, 1978).  No  other ambient air monitoring
data  on this compound  are   available.   Although  occupational   exposure  of
workers  to this compound In certain  Industries  1s  likely, particularly 1n
the  grain  fumigating  and semiconductor  Industries,  no monitoring  data  from
these or any  other  Industries are available.  Monitoring  data  on  the  level
of  phosphlne  In ambient water,  groundwater  or drinking water  are  also not
available.   The  levels of phosphlne 1n various  fumigated grains have  been
reported.  In general, phosphlne levels  In fumigated foods decrease  to  <0.01
mg/kg 1n 14  days following  fumigation  (Rommlnger and Kubel,  1972).  No  data
regarding  the level of  phosphlne 1n  total  diet  samples  are  available  that
would permit  estimation of exposure to this compound from food Ingestlon.
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                         4.   ENVIRONMENTAL TOXICOLOGY
4.1.   AQUATIC TOXICOLOGY
4.1.1.   Acute Toxic Effects  on Fauna.   Doudoroff  and  Katz  (1950)  reported
that  concentrations  of  phosphlne  >3.6 ppm  were toxic  to  rainbow  trout  In
hard water.
4.1.2.   Chronic Effects on  Fauna.
    4.1.2.1.   TOXICITY — Pertinent data  regarding the  effects  of  chronic
exposure  of  aquatic fauna  to  phosphlne  were not  located  In the  available
literature dted 1n Appendix A.
    4.1.2.2.   BIOACCUMULATION/BIOCONCENTRATION — A  measured   steady-state
BCF  value for  phosphlne was  not   found  1n  the literature.   Based on  the
regression equation, log  BCF  =  2.791  - 0.564  log  solubility  In water (Lyman
et  al.,  1982) and  a calculated water  solubility of 368 mg/i (see  Section
1.2.),  a  BCF  value of  22.1  Is  estimated  for  this  compound.   This  value
suggests  that  the  bloaccumulatlon  of phosphlne  In  aquatic  organisms  Is  not
significant.
4.1.3.   Effects on Flora.
    4.1.3.1.   TOXICITY — Pertinent  data regarding  the  toxic  effects   of
exposure  of  aquatic flora  to  phosphlne  were not  located  1n the  available
literature dted 1n Appendix A.
    4.1.3.2.   BIOCONCENTRATION —  Pertinent  data  regarding  the   bloconcen-
tratlon  potential  of  phosphlne 1n  aquatic  flora  were  not  located 1n  the
available literature dted In Appendix A.
4.1.4.   Effects  on Bacteria.   Pertinent  data  regarding   the   effects   of
exposure  of  aquatic  bacteria  to phosphlne were  not  located  1n the available
literature dted 1n Appendix A.
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4.2.   TERRESTRIAL TOXICOLOGY
4.2.1.   Effects  on  Fauna.   Pertinent   data   regarding  the  effects   of
exposure of terrestrial fauna to phosphlne 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 phosphlne were  not  located  In the available
literature cited In Appendix A.
4.3.   FIELD STUDIES
    Pertinent data  regarding  the  effects  of  phosphlne on  flora  and fauna  1n
the field were not located In the available literature dted  1n Appendix A.
4.4.   SUMMARY
    Doudoroff and Katz  (1950) reported  that  concentrations of  phosphlne >3.6
ppm were  toxic  to  rainbow  trout  In hard water.   An estimated BCF  value  of
22.1  for phosphlne  suggests  that  Us bloaccumulatlon In  aquatic  organisms  Is
not significant.
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                             5.  PHARMACOKINETICS
5.1.   ABSORPTION
    Data  regarding  the  pharmacoklnetlcs  of  phosphlne,  by  any  route  of
exposure, are limited.  Chan  et  al.  (1983) described detection  of  phosphlne
In  the  tissues  of a 27-year-old man who  died after Ingestlon of an  unknown
number of  Phostoxln* tablets  that contain aluminum phosphide as the  active
Ingredient.  GC  headspace analysis  of samples  treated by  acid to  release
phosphlne from  phosphide  revealed  measurable quantities of  phosphlne  gas  In
homogenized samples  of  blood  (0.5  ng/mi), liver  (3  ng/g) and  stomach  with
contents (3000 ng/g).  Extremely small amounts of  phosphlne  were detected  In
stomach and contents but  more was detected  In  blood  or liver when  the  sam-
ples were  not  subjected  to  acid hydrolysis.  Analysis of  blank  postmortem
samples Indicated  that  no phosphlne was formed  from putrefactive  processes.
AAS for aluminum revealed a measurable  (20-  to 200-fold)  Increase  In  urinary
aluminum content,  relative to  normal  values.   The Investigators  concluded
that aluminum phosphide had been absorbed  from the GI  tract.  Information  Is
Insufficient to assess the rate and extent of absorption.
    Phosphlne fumlgant produced systemic toxldty  and one  mortality  1n 31  of
33  members of  the  crew  and captain's family on  a  grain freighter  (Wilson  et
al., 1980) (Section  6.1.3.).   There was a  statistically significant  correla-
tion between Intoxication  and living  or working amidships or  on the  forward
deck  areas,  where   the  gas   was  leaking.   Exposure  levels  In  these  areas
ranged  from  0.5-30  ppm  (0.7-42  mg/m3).   The  results   of  the Wilson  et  al.
(1980)  study  suggest that  gaseous phosphlne  1s  absorbed  by humans;  these
results are Inadequate for estimation of rate or  extent.
    Schoof (1970)  noted  that  phosphlne can be absorbed  through  skin  wounds,
but  not  through  Intact  skin.   Data  supporting  this statement  were  not
provided.

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5.2.   DISTRIBUTION
    In the Chan et al.  (1983)  study  (see Section 5.1.), only trace levels of
phosphide could be  detected 1n  blood  and liver by GC.   The reported levels
were  0.5  ng/mi of  blood,  3  ng/g of  liver and 3000  ng/g  of  stomach  with
contents.  Further data regarding distribution were not located.
5.3.   METABOLISM
    Phosphlne  may be  metabolized  to  nontoxlc  phosphates   (OHMTADS,  1988),
although supporting data have not been located.  ,
5.4.   EXCRETION
    Because of Insufficient amount of  specimen,  Chan  et al.  (1983) could not
measure  levels of  phosphlne  1n  the  urine  of a  man  who died  following
Ingestlon of aluminum phosphide.
5.5.   SUMMARY
    Pharmacoklnetlc  data  for  phosphlne are  limited.   Detection of  trace
amounts  of  phosphide   1n  the  blood  and  liver  and   detection  of a  marked
elevated  concentration  of  aluminum  1n  the   urine   (compared  with  normal
values) of  a  man  who died  following  Ingestlon of aluminum phosphide suggest
that  absorption of aluminum phosphide  occurs from the GI tract  (Chan et al..
1983).  The  observation of systemic toxlclty  In humans exposed to phosphlne
gas  1n  the  ambient  air (Wilson  et al.,  1980)  suggests that  phosphlne gas 1s
absorbed  from the respiratory tract.  Schoof  (1970)  reported that phosphlne
may  be  absorbed  through  broken, but  not  through unbroken  skin.   Phosphlne
may be metabolized to nontoxlc phosphates (OHMTADS. 1988).
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                                  6.   EFFECTS
6.1.   SYSTEMIC TOXICITY
6.1.1.   Inhalation Exposure.
    6.1.1.1.   SUBCHRONIC — Klimner   (1969)    observed   the   effects   of
repeated Inhalation  exposures  to phosphlne 1n  a  series of  studies.   In  the
first  experiment,   4 female  cats  (2.1-2.95  kg)  and  10  male  Wlstar  rats
(110 g)  were  exposed  to 1  ppm  (1.4 mg/m3)  phosphlne for  6 hours/day  on
weekdays,  and 4  hours  on   Saturdays,  for 24  weeks.   At  the  end  of  the
exposure,  Kllmmer  (1969) determined  limited  urlnalysls endpolnts,  oxy- and
methemoglobln  concentrations   In   the   blood,  differential  blood  counts,
retlculocyte  counts,  liver  function  (BSP  retention)  and gross histology  of
the major  organs,  Including the brain.   Treatment had  no  adverse effects  on
any of these Indicators of toxlclty.  Control  animals  were  not mentioned.
    In  the second  experiment,  4 female cats  (2.2-3.1  kg),  4  female  guinea
pigs  (280-360 g)  and  10 male  rats  (110  g)  were  exposed  to  2.5 ppm (3.5
mg/m3)  phosphlne  on  the  same  treatment  schedule as   above.   All  animals
survived treatment.   Hematology,  BSP retention and methemoglobln concentra-
tions  were within  the normal  range  for all three species.   Cats  had  greasy
liver  Infiltrates at autopsy, and rats  had sporadic renal  epithelial  tubular
swelling with  traces of albumlnurla.   Examination  of the blood  of  the cats
revealed the  presence of an  oxyhemoglobln band,  but  blood  color  was  normal
and  methemog1ob1nem1a   was   not  present.    Guinea   pigs  had  no  apparent
treatment-related effects.   Nonspecific neuron  changes  In all  three  species
were  observed but  were  not accompanied by a positive  gllal  cell reaction,
and Kllmmer  (1969)  proposed that the changes were  a  result  of either  agonal
or  postmortem processes.   Apparently,  control  animals  were  not  Included  In
this experiment.


0132d                               -15-                             02/14/89

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    Although KHmmer (1969) did  not  consider  the rat and cat  results  at  2.5
ppm to  be  biologically significant,  cats exposed  to  5  ppm (7.0 mg/m3) 1n  a
third experiment  for eight  6-hour exposures died with  severe  hematologlcal,
kidney  and  liver  effects.  These  results  suggest that  2.5  ppm Is near  the
threshold for toxldty.  Results of  this experiment are  discussed  more fully
1n Section 6.1.3.
    MQller  (1940) exposed  two rabbits to 2.5  ppm phosphlne 4  hours/day  for
40 out  of 48 days,  and  one  rabbit  to 5 ppm  phosphlne, 4 hours/day  for  35  out
of 48 days.  Phosphlne  was  obtained  from a  gas  cylinder  and  exposure  concen-
trations  were  determined.  All  rabbits  survived exposure.   Incoordlnatlon
and drowsiness,  commonly observed at  higher  concentrations,  were minor  and
variable signs at 2.5  and  5.0  ppm.   MQller (1940) noted severe hlstopatho-
loglcal  changes   (Section  6.1.3.)  In animals  that   died  at  >10  ppm  (13.9
mg/m3),  but did  not  discuss  tissue effects  at  lower  exposure levels.   He
considered  the   toxldty   threshold  to   be   between   2.5   and  5.0  ppm.
Apparently, control  animals were not  Included  1n this  experiment.
    6.1.1.2.   CHRONIC — No  animal   data   are  available  regarding  chronic
Inhalation  exposure to  phosphlne,  and  human   data  are limited.  Long-term
exposure  to  the  chemical  results   In  gastrointestinal   upset,  jaundice,
nausea, a phosphorous odor  on the  breath, and  Increased  bone  density  without
cartilage calcification (Torkelson et al.,  1966; Harano,  1984).
    Elchler  (1934)  described  a  case of an acetylene production  worker  who
was  exposed  to   "chronically  toxic"  phosphlne  concentrations  for   several
years.  The worker  experienced episodes of  bronchitis, a painful abdomen  and
reduced hemoglobin  levels.  Within 3 years, he  was unable  to  work  because of
bronchitis,  weakness  and  dizziness;  2  years   later  a  large  gastric  ulcer
developed but bronchitis and abnormal  blood effects were no  longer present.

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Carbon monoxide, arslne  and  acetylene were considered as  etlologlc  factors,
but were  rejected  as being nontoxlc  or  present only at  low  concentrations.
Concentrations of  the above  listed  gases or of phosphlne  were  not  reported,
and It 1s  not  known  If  concentrations were monitored.   Beloskurskaya  et  al.
(1979) observed that 57  of 260 workers exposed to  phosphorus,  phosphlne  and
phosphorus  oxides  developed  chronic  toxlcologlcal  hepatitis,  characterized
by  high  blood phosphorus,  Increased  slallc  add  concentrations,  decreased
albumin,   enlarged  liver  and Impaired  liver  activity.   Berdykhodzhln  et  al.
(1974) observed  that  most  workers  exposed  chronically  to  phosphorus  and
phosphlne   vapors   had   Inflammation  of   the   nasal   cavity  and   throat.
Serologlcal  studies  Indicated  disorders  of  liver  function,  and  clinical
studies suggested  the early  stages  of neurotoxldty.  Because  none  of these
articles  or abstracts discussed actual exposure concentrations, the  data  are
not useful for quantitative risk assessment.
6.1.2.   Oral Exposure.
    6.1.2.1.   SUBCHRONIC — Kadkol  and JayaraJ (1967) exposed  two male and
two female albino  rats/treatment group for 12 weeks  to a rice diet fumigated
with  0,  1,  5  or  50 Phostoxln* tablets/metric  ton.   These  tablets  contain
aluminum phosphide.  The tablets and  rice were  mixed  In  a1r-t1ght tins for 4
days,  and  the  diet was  aerated  for  at least 2 weeks before  administration.
Actual  dietary  concentrations  of   phosphlne  were  not  ascertained.   The
Investigators  recorded  weekly  weight  gain  and food consumption,  determined
erythrocyte  counts,  blood hemoglobin  concentration and  absolute liver  and
kidney weights at  the  end  of  treatment,  and performed  hlstopathologlcal
examination,  apparently  limited to  the  liver  and  kidneys,  at  terminal
sacrifice.   Treatment  had no  effect on  any  measured  parameter.   Because
fumigation  data  on  a  variety  of  grains (Oleterlch  et  al., 1967)  Indicate


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that most phosphlne residues are dissipated after  only  48  hours  of aeration,
It  1s  unlikely that any  significant residue  remained  after the  Kadkol  and
Jayaraj (1967) procedure.
    As part of a  multlgeneratlon  study, Cabrol et al.  (1986)  administered a
prepared diet fumigated with phosphlne  to groups of  male and female Sprague-
Dawley rats.  The treated diet was  fumigated  for at  least  6 months with 2000
ppm phosphlne  In  sealed vats, and  was  aerated 48 hours before  presentation
to  the rats.   The Investigators  Indicated that the  dietary  concentration of
phosphlne residue was  -5 ppb, but  did  not state  how this  value  was  deter-
mined.   In  the  FO  generation,   4  males   and   10  females/dietary   group
received either  the  nonfumlgated  or fumigated  diet  beginning at  1  month of
age,  and  were mated  at 7  months.   Administration  of  the  respective  diets
continued throughout the lifetimes of the FQ,  F, and F_ generations.
    The  Investigators   studied  exposure  effects  In  F,   and  Fp  offspring.
Six control  and  6 treated  rats/generation  were analyzed  for  differences 1n
protein efficiency  (Increase  In  body weight/unit  protein  Ingested), hemato-
loglcal measures, and  plasma  and  urinary  constituents.   All measures  were
assessed  when  the  offspring were  2  months  old.    Data  for  F,  and  F.
offspring  were  analyzed  separately.    Sporadic  statistically  significant
treatment group  differences occurred 1n  plasma electrolyte and constituent
levels.   The  differences   usually  occurred  only  1n  either  the  F,  or  F-
generation  (but  not  both),  and did not appear to be  treatment-related.   In
addition, there  were no group  differences In  urinary  levels of  these same
constituents.  Treatment had  no  statistically  significant  effect  on hemato-
logical or protein efficiency measures.   Cabrol et al.  (1986)  concluded that
dietary phosphlne did  not  produce  a  toxic  response under  the  conditions of
the study.
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    6.1.2.2.   CHRONIC — Hackenberg  (1972)  conducted  a  2-year  study  on
groups of  30 male and  30  female adult SPF-Wlstar  rats  orally exposed  to  a
Phostox1n»-fum1gated  diet.   Thirty  control rats  of  each  sex received  the
basal diet.   The  first 2 batches  of  test  diet were prepared  by  combining  8
Phostox1n«  pellets   (8  times  the  recommended  agricultural  concentrations)
with  100  kg of  the  basal  diet  1n  hermetically  sealed  containers.   The
corresponding  Phostox1n«  concentration   was   48  g/metrlc   ton   of   diet.
Batches  3-16 were prepared  by  combining  15 pellets  with 100  kg of  basal
diet, which  corresponds to a concentration  of  90  g/metr1c ton.  The contents
of each container were  fumigated  for  48 or  72  hours,  tumbled  for  2 hours and
aerated for  1 hour.   Quantitative  analysis  of  batches  1  and 2, after  1, 5 or
8 weeks  of  storage,  Indicated  an average  residual  phosphlne level of 0.27
mg/kg  diet.  Disregarding  one  extraneous  reading,   the average  phosphlne
level  of  batches 3  through  16,  3-10 days  after aeration,  was   0.51  mg/kg
diet.  Each treated  batch of  the diet was  fed continuously  to  the  experi-
mental  rats  for  5-7  weeks.   Treated  rats  received  feed   treated  at  48
g/metMc ton for  the first 16 weeks  of  the study, and  90  g/metr1c  ton from
weeks 17-106.
    The  Investigator  evaluated  rats  weekly for  body  weight,  food  consump-
tion, physical appearance and behavior.  At 0,  2,  6,  12, 18 and 24 months of
study,  hematologlcal,   serum  biochemistry   and  urlnalysls  measurements  were
made.  For  each time  point,  Independent sets of 5 males  and 5 females/treat-
ment  group  were  analyzed  for  1) hematology,  blood  glucose and  clinical
urlnalysls  determinations,  2) SGPT and  serum  urea  concentration  determina-
tions,  and  3)  prothrombln   times.    Rats  that  died  during   the  study  and
24-month  survivors   that  were   subsequently  sacrificed were subjected  to
necropsy.    Hlstopathologlc  examination  was  performed   on >20   organs  and

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tissues from rats  that  died during the study  and  from 5 rats/sex sacrificed
at termination.  At terminal  sacrifice, Hackenberg (1972)  weighed the liver,
heart,  spleen,  thyroid, kidneys  and  adrenals of  exposed and  control  rats.
the only  treatment group difference was a  slight,  statistically nonsignifi-
cant Increase In weight gain 1n test females.
    Cabrol  Telle  et  al.  (1985)   conducted  a  chronic  dietary  study  where
Sprague-Dawley rats were exposed  to an  average residual  phosphlne level of 5
ppb (0.005  ppm).   The  experimental rat  chow diet was  fumigated continually
for at  least  6 months  with  phosphlne  pellets, and was  aerated for  48 hours
before  feeding.   Control rats  received  the nonfumlgated  basal  diet.  There
were  no differences  In  the average phosphorus  content between  control  and
experimental  diets.    The   Investigators   did  not   Indicate  whether  they
estimated or  actually  measured  residual  phosphlne levels;  however, results
from  field  and  laboratory  studies  (Dleterlch  et  al.,  1967)  Involving  a
variety  of  agricultural  products suggest  that  prolonged  fumigation  and
aeration eliminate virtually all phosphlne residues.
    Groups  of  30  rats/sex  were  Initiated  on each  diet  as weanlings,  and
maintained  on  the  same diet for  1-2 years.   The Investigators  evaluated the
clinical condition  of the  rats, and measured  body weights and  food consump-
tion.   Routine  hematology,   urlnalysls   and  blood   chemistry  tests  were
performed.  After  1  year,  19-20 rats  of each  sex/group were sacrificed, and
the remaining  survivors were sacrificed after 2 years.   Comprehensive gross
and  microscopic  pathology  was  conducted   on  all  rats  sacrificed   after  2
years,  and  on  -10  rats/group  sacrificed  after 1  year.   Cabrol Telle et al.
(1985)  determined  fresh  weights of  most major  organs, and assayed for spleen
and  thymus   Iron  content.   Water,  ash,  llpld  and   nitrogen   content  were
determined  from samples of carcass homogenate.
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    Females  treated  for  1  year  had  Increased  Incidence  of  degenerative
thymlc  pigmentation  spots  and  zones  of   lysis.   The  Incidence  of  these
lesions was  not markedly  elevated  In  females  treated  for  2  years, nor  In
treated males. Treated females  sacrificed  at 1 or 2 years  had statistically
significantly  Increased  relative  thymus   weights  compared   to   controls.
Certain other  hlstopathologlcal changes.  Including  duodenal  congestion  and
ulcerous and necrotlc zones In  the colon,  tended  to  occur  more frequently 1n
treated rats after 1 but not after 2  years of  exposure.   Cabrol Telle et  al.
(1985)  did  not  consider  any  of  these   effects  biologically  significant.
Although there were  sporadic  statistically  significant differences  In  other
endpolnts,  none were consistently treatment-related.
6.1.3.   Other Relevant Information.   Table 6-1 lists results of  represen-
tative animal studies on the acute effects  of  Inhalation  phosphlne  exposure.
KHmmer (1969)  showed  that repeated   exposure  to  5.0 ppm was  lethal  for  all
cats, rats and  guinea  pigs after 24-45 hours  of total exposure.  Cats  had a
trace  of  albumlnurla,  anemia  and  oxyhemogloblnemla.  These  endpolnts were
not  evaluated  1n rats or  guinea pigs.  At  necropsy,  all three species  had
pulmonary  edema  and  bronchial  petechlal  hemorrhage, with  unspecified  liver
and  kidney  damage.  Treated   cats  and guinea  pigs  had  neuropathologlcal
changes without  an  accompanying gllal cell  reaction.  The  study pathologist
proposed that  these changes  were  a  result of either  agonal  or  postmortem
processes.  Treated rats, however, had  distinct  damage to  the dentate nucleus
cells with a positive gllal reaction.   KHmmer  (1969) did not  expose rabbits
to  5.0  ppm,  but  observed  death and  overt clinical  signs,  Including tonlc-
clonlc  convulsions,  at >10.0  ppm.   Generally, time  to  death  was  Inversely
related to exposure concentration for  all tested species.
0132d                               -21-                             08/30/89

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                                                          TABLE 6-1
                                         Acute  Inhalation Toxlclty  Data for Phosphlne
o
M.J
CO
Species No. /Sex
Cat 3/F
3/F
3/F
3/F
Exposure Conditions
5 ppm
10 ppro
25 ppro
54 ppm
(7 mg/m3)
(14 mg/m3
(348 mg/m
(75 mg/m3
for 8x6 hours
) for 3x8
3) for 8.5
) for 6.5
hours
hours
hours
all
all
45
all
all
Effects
dead
In
dead In
minutes
dead
dead
In
In
45
12
8.
6
hours
hours
5 hours
hours
Reference
Kllmmer,
Kllmmer,
Kllmmer,
Kllmmer,
1969
1969
1969
1969
ro
N>
i
         Rat
o
CO
CO
o
00
ID
 3/F

 3/F

10/H
10/H
10/H

10/H

10/H
10/H

 6/H
120 ppm (167 mg/m3) for 130
minutes
167 ppm (232 mg/m3) for 100
minutes
5 ppm for 8x6 hours
10 ppro for 3x8 hours
25 ppm for 8.5 hours

54 ppm for 6.5 hours

120 ppm for 130 minutes
140 ppm (195 mg/m3) for 110
minutes
167 ppm for 100 minutes
25 minutes
all dead In 130 minutes
all dead In 75 minutes
all dead In 45 hours
all dead In 18 hours
all dead In 8 hours
20 minutes
all dead In 4 hours
30 minutes
all dead In 123 minutes
all dead In 110 minutes
all dead In 75 minutes
Kllmmer, 1969

Kllmmer. 1969
Kllmmer. 1969
Kllmmer. 1969
Kllmmer. 1969

Kllmmer, 1969

Kllmmer, 1969
Kllmmer. 1969
Kllmmer. 1969

-------
                                                      TABL'EJM'fcont.)
f\»
          Species
No./Sex
      Exposure Conditions
        Effects
  Reference
         Rat
         Rabbit
to
         Guinea pig
o
00
u
o
CO
  6/F

  6/N

  6/N
  3/F
  3/F
  2/F
  2/NR

  4/NR
  3/NR
  3/NR
  3/F
  3/F

  2/NR
28-33.3 ppm (42-50 rog/ma) for
5.2 and 7.4 hours, respectively
11 ppm (15 mg/ma) for 4 hours
                                     4.0 ppm (5.7 rog/ma),  4 hours/
                                     day for 12 days
10 ppm for 3x8 hours
120 ppm for 130 minutes
167 ppm for 100 minutes
8.3 ppm (11.6 mg/ma),  4 hours/
day
10 ppm. 4 hours/day
25 ppm for 1-2 hours
25 ppm for 4 hours
5 ppm for 8x6 hours
54 ppm for 6.5 hours

25 ppm for 4 hours
"50
"50
no mortality or gross
pathological effects;
reduced rate of body
weight gain
all dead In 16.5 hours
all dead In 130 minutes
both dead In 98 minutes
both dead In 5 days

all dead In 14 days
0/3 dead
3/3 dead
all dead In 32 hours
all dead In 5 hours
20 minutes
both dead
Huthu et al.,
1980
War Hz and
Brown. 1975
Warltz and
Brown. 1975
Kllmmer. 1969
Kllmmer. 1969
Kllmmer. 1969
Huller. 1940

Muller, 1940
Huller, 1940
Huller, 1940
Kllmmer. 1969
Kllmmer. 1969
Huller, 1940
         NR = Not reported

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    Mflller  (1940)  observed  that  exposure  to >8.3  ppm (11.6  mg/m3)  for  4
hours/day was fatal  to  all  treated  rabbits.  Clinical  signs of  Intoxication
at  the  highest  concentrations  Included  paralysis,  dyspnea and  convulsions.
Pathological findings Included  frank hyperemla In almost all organs.  Includ-
ing the brain.  The  heart was usually dilated and flaccid,  and the lungs  had
hemorrhaglc  edema  and  thromboses.   Data from  the  10.0  ppm  group  revealed
tracheal  hyperemla,  fatty  liver,  renal  tubular swelling  and  necrosis,  and
Iron deposits In  the spleen.   Nlkodemusz et  al. (1981)  Indicated  that  voles
fumigated with  a  commercial phosphlne preparation  (Polytanol)  had pulmonary
hyperemla and cerebral edema.  Exposure  levels were  not reported.
    Several  Investigators  (Warltz  and  Brown, 1975;  Muthu  et  al.,  1980)  did
not find  extensive  tissue damage In phosphlne-exposed rats.   In  the  former
study, groups of six  male  rats  received  either  single or  12-day exposures to
phosphlne  from  a gas cylinder  for  4  hours/day.   The single  exposure  IC™
was 11  ppm  (15 mg/m3).  Treated rats  had  signs of  respiratory Irritation,
Including  red  ears,  salivation,  lacHmatlon and dyspnea,  but  no compound-
related hlstopathologlc lesions were observed In a  set of  -18  major tissues.
Weight gain  was decreased  during repeated exposures;  however,  no hlstopatho-
loglcal  effects  were  seen  In  two rats  sacrificed  14 days  after  single
exposure  to 20 ppm  (27.8  mg/m3),  three rats  sacrificed  Immediately  after
repeated  exposure  to 4.0  ppm (5.7  mg/m3)  or three rats sacrificed 14  days
after  repeated  exposure  to 4.1   mg/m3  phosphlne.   Huthu  et  al.  (1980)
exposed  six female   rats/concentration  to  phosphlne  generated  from aluminum
phosphide  pellets,  and  measured  exposure  levels   1n a "Phosphlne  Detector
Tube."   Exposure  times were   4,  6 or  8  hours.    Based   on  two  different
experiments,  the  LC^s were  28-33.3 ppm  (42 and  50 mg/m3)   for  calculated
exposure  times  of  5.2  and 7.4  hours.    The  corresponding  LCg5s were 68  and

0132d                               -24-                             08/30/89

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50 mg/m3  (6.2 and  8.8 hours,  respectively),  emphasizing  the steepness  of
the  concentration-response  curve.    Treated  rats  had  polyurla,   dyspnea,
paralysis, transient  body  weight decrease,  slightly  Increased  lung  weights,
perlbronchlolar cellular  Infiltration and  some  edema,  but  no  morphological
changes 1n the liver, kidney, lung,  heart or spleen.
    Oehme (1970)  stated  that cats and  dogs are more resistant to oral  zinc
phosphide than rats  and  rabbits, because the former  species  are  only Inter-
mittent HC1  secreters,  resulting In  a  slower  liberation of phosphlne  gas.
No empirical  data were provided to support this  statement.
    Early effects of acute phosphlne  Intoxication  In  man  Include  pain In the
diaphragm,  nausea,   vomiting,  excitement  and  a  phosphorous  smell  on  the
breath  (Torkelson et  al.,  1966; WHO,  1986;  Marano,  1984;  Schoof,  1970;
Casteel and  Bailey,   1986).   With exposure  to  higher  concentrations,  weak-
ness,  bronchitis, edema,  dyspnea,   convulsions  and  death  can occur.   The
effects of  chronic  exposure 1n  humans  mimic those  of  chronic  phosphorous
Intoxication:  gastroenteritis and Jaundice  (Marano,  1984;  Torkelson et  al.,
1966).  In  a  review of the oral toxlclty  of   zinc  phosphide, Casteel  and
Bailey (1986) attributed these effects  to  direct damage to blood  vessels and
erythrocyte  membranes   mediated  by   the  liberation    of   phosphlne   gas.
Clinically, this  toxicosis 1s  expressed  by cardiovascular failure,  pulmonary
congestion,  hemorrhage,  and hypoxla,  renal and  hepatic congestion,  renal
necrosis and gastroenteritis.
    Highly purified  phosphlne, which  can be obtained  by molecular  sieving or
GC  of the  commercially  prepared gas,  Is  odorless  (Pluck,  1976).   Since
commercial phosphlne 1s  always  a mixture  of gases,  Pluck  (1976)  determined
odor  thresholds for  four preparations.  The thresholds for technical  aluminum
phosphide,  phosphonlum  Iodide,   Phostox1n«, and  purified  Phostoxln*  were


0132d                               -25-                             08/30/89

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0.1-0.2, 2, 0.01-0.02  and  1-2 ppm, respectively.  Amoore  and  Hautala (1983)
determined the  geometric  mean air  odor  threshold for phosphlne  as  0.51  ppm
(0.7 mg/m3), based on a review of the available literature.
    Phosphlne  1s  a  potent  Inhibitor   of  State  3  (active  mltochondrlal)
cellular  respiration  released  by  AMP,   calcium and  the uncoupling agent,
2,4-d1n1trophenol  (Nakaklta  et  a!.,  1971).   Chefurka  et al.  (1976)  found
that  this  Inhibition occurs  at  the level of  cytochrome  oxldase.   In Intact
mitochondria,  State  4 respiration was  much  less   sensitive to  phosphlne
action.    Sonlcatlon   of   the  mitochondria!  preparation  to  disrupt  the
Integrity  of  the  mltochondrlal  membrane  Increased  the Inhibitory effect
because of Increased phosphlne permeability through the mltochondrlal matrix.
    In   an  early  occupational   study,   Jones   et  al.    (1964)    reported
gastrointestinal, cardloresplratory and  CNS symptoms  In  67 men employed In a
seaboard  grain  shipping  terminal  that was  fumigated   with  phosphlne  In
1960-1961.  Exposures  were  roughly  quantified  as ranging from 0-35 ppm (0-50
mg/m3),  but  generally  averaged  <10 ppm  (14  mg/m3).   Symptoms   appeared
from  almost  Immediately  to 2 days  after  the  workers  reported a particularly
strong  gas  odor.   The  use  of  respirators  appeared to  be  Ineffective  In
reducing  the  frequency of  symptoms, and  there appeared  to be no tendency to
develop tolerance to repeated exposures.
    Results  from two occupational  exposure studies  revealed that short-term
Inhalation  exposure to  phosphlne gas can  be fatal.   Wilson et  al. (1980)
reported  that  31 of 33 members  of  the  crew and captain's family  on a grain
freighter  became 111  after  being exposed to  fumes  from phosphlne-fumlgated
grain  for 2-5  days.   The  two  Individuals affected  most severely  were  the
captain's  children.   One  child,  nearly  5,   had  vomiting,  headache  and
0132d                               -26-                             08/30/89

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fatigue, and,  based on an  abnormal EKG,  myocardlal  Injury; her  subjective
and objective  clinical  signs  returned  to normal  within  18 hours  of  treat-
ment.   The  second  child,  a  2-year-old,  died  with congestive heart failure,
pulmonary  edema,  pleural  effusion, an   enlarged  spleen  and  aspiration  of
gastrointestinal  contents.    Microscopic  examination  Indicated  focal  myo-
cardlal necrosis,  Inflamed  heart valves,  desquamated  respiratory  epithelium
and  thickened   alveoli.   The  most  common signs  and  symptoms  among  crew
members  were   fatigue,  nausea,   headache and   dizziness.   Clinical   tests
revealed occult urinary blood,  b1Urub1nur1a,  Increases  In SGPT,  GGPT  and
LDH,.,   myocardlal   Injury   and  elevated  CPK  levels.   All  crew  members
recovered  eventually.   Phosphlne concentrations,  measured  4 days  after  the
first  report  of  Illness,  were  highest   (20-30  ppm,  or  27-42  mg/m3)  1n  a
void  space  located amidships. Substantial  phosphlne levels (7.5-10 ppm,  or
10.5-13.9 mg/m3)  occurred  on  the  forward deck, and  levels  of  0.5  ppm (0.7
mg/m3)  were measured   In  the  children's  living quarters  amidships.   The
Investigators  observed  a strong correlation   between  amidships  and  forward
deck exposure,  and Illness.
    In a second occupational  study,  a 16-year-old  worker  died after repeated
exposures  1n  an  acetylene   production  process  (Harger  and Spolyar,  1958).
The subject, who had no known history of previous Illness, had  been employed
for 1  month when  he  began  to have blackouts.   In  another  2 weeks,  he was
found  dead  near   the  generator  hopper.   The  only remarkable  finding  at
autopsy was  acute  pulmonary edema.  The  Investigators determined  that phos-
phlne  concentrations above  the  hopper were variable,  but may have averaged
-8  ppm (11.2  mg/m3)  at breathing level.  Under  unfavorable conditions  of
air movement  or  Increased  frequency of dally  hopper  fillings,  the  actual
concentrations may have been greater.

0132d                               -27-                             08/30/89

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6.2.   CARCINOGENICITY
6.2.1.   Inhalation.  Pertinent data regarding  the  carclnogenklty of phos-
phlne after Inhalation exposure were not  located  1n  the  available literature
cited In Appendix A.
6.2.2.   Oral.   Details  of  two  lifetime dietary  exposure  studies  In  rats
were described In Section  6.1.2.2.  Hackenberg  (1972)  exposed  30  rats/sex to
diets containing  average  phosphlne concentrations of 0.27 mg/kg  food  (weeks
1-16) and  0.51  mg/kg food (weeks  17-106).   Extensive  hlstopathologlc  exami-
nations were  performed  on all rats  that died during the  experiment,  and on
5/sex/group sacrificed  at termination.   Hackenberg  (1972) also examined all
tissues that macroscoplcally appeared neoplastlc, and  did  bone marrow smears
on  5  rats/sex In each  treatment  group.   Dietary treatment  had no effect on
tumor  Incidence.   Cabrol  Telle et al.  (1985) treated 30  rats of both sexes
with  -5 ppb  dietary phosphlne for  <2  years.  After  1  year,  19-20  treated
rats/sex were sacrificed  for  gross examination,  and  hlstopathologlc examina-
tion  was  performed  on  ~10  rats/sex/group.   The  Investigators  conducted
similar examination  of  10 male and 10 female  rats  sacrificed  after 2 years.
Comparable numbers  of control rats were sacrificed  at  each time point.  No
tumors  occurred  In  any group of  rats sacrificed after  1  year.   Although a
number  of  tumors occurred 1n  treated  and control groups  at termination, no
significant differences 1n Incidence were observed.
6.2.3.   Other   Relevant   Information.   Pertinent   data    regarding   other
relevant  carcinogenic  Information  regarding  phosphlne  exposure were  not
located 1n the available literature cited 1n Appendix A.
6.3.   HUTAGENICITY
    Pertinent data  regarding the mutagenldty of phosphlne  were  not  located
1n the available literature cited  1n Appendix A.


0132d                               -28-                             08/30/89

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6.4.   TERATOGENICITY
    Pertinent data  regarding the  developmental  toxlclty  of  phosphlne  were
not located In the available literature cited In  Appendix A.
6.5.   OTHER REPRODUCTIVE EFFECTS
    Cabrol  et  al.  (1986)  conducted a  3-generat1on  study 1n  Sprague-Dawley
rats  exposed  to   a  phosphlne-fumlgated  diet.   Dietary  preparation   was
described  previously  In  Section 6.1.2.2.  (Cabrol  Telle  et al.,  1985).   FQ
rats  (10  females  and 4  males/group)  received either  control  or  phosphlne-
fumlgated  diet (5  ppb phosphlne) beginning  at 1 month of age.  At 7  months
the rats  were  mated.   The resulting F,  generation was mated  at 2 months  to
produce  the F~  generation.   The  Investigators  measured various endpolnts
of maternal  and  developmental  toxlclty  Including 1) number of  gravid/number
of  mated  dams,  2) number  of  Hveborn  Utters/number   of  gravid females,
3) 6-day  pups/live  pups  at birth,  4) 21-day  live  pups/6-day  live pups,  and
5) sex  ratio for both  the FQ and  F,  generation.    Treatment  had no  effect
on any of the measured variables.
6.6.   SUMMARY
    Two  lifetime  oral studies 1n  rats  Indicate  that  dietary  concentrations
of <0.51  mg/kg food/day  have no significant toxic effect  (Hackenberg,  1972;
Cabrol  Telle et  al., 1985).   Residual   phosphlne  levels,  however, were  not
measured  In  the  latter  study.   Phosphlne  was  not  carcinogenic   In  two
lifetime  dietary exposure  studies 1n rats  (Hackenberg, 1972; Cabrol Telle et
al.,  1985), but  the MTD  had not  been  reached and  these studies  are  not
adequate  to evaluate the  carclnogenlclty of oral exposure  to phosphlne  In
rats.   Data regarding the genotoxlclty  or teratogenldty of  phosphlne  were
not located In the  available literature.  Rats exposed  to 0.005  ppm  dietary
phosphlne  had no  Impairment  In  reproductive  function  and  no  consistent


0132d                               -29-                             08/30/89

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effect on  protein  efficiency,  hematology or plasma and  urinary  constituents
1n  either  the FQ  or the  FI  offspring  of a  multlgeneratlon study  (Cabrol
et al.. 1986).
    Kadkol  and  Jayaraj  (1967)  reported  no effects  on growth,  erythrocyte
levels, hemoglobin content, liver  and  kidney weights or hlstopathology  In  a
12-week dietary  study  1n rats exposed  to <50 Phostox1n«  tablets/metric  ton
of  a  rice diet.   Because  these  Investigators  used a  lengthy postfumlgatlon
aeration  procedure.  It  Is unlikely  that  significant  amounts of  phosphlne
residue remained In the experimental diet (Dleterkh et al.,  1967).
    Subchronlc exposure  Inhalation studies  In rats,  cats,  guinea pigs  and
rabbits  (Kllmmer,   1969;   Mullen,  1940)  Indicated a  steep,  concentration-
response curve.  KHmmer (1969) showed  that  6-hour  dally exposure to  2.5 ppm
produced  minor  hepatic,  renal  and hematologlcal  changes.   Exposure  to  5.0
ppm resulted  In more severe blood  and  tissue effects.   All  tested rats,  cats
and guinea  pigs  died within  45 hours of  total exposure  to 5.0 ppm.   Rabbits
exposed to  2.5 or  5.0 ppm  for  4  hours/day had slight signs of Incoordlnatlon
after 35-40 days (MGller, 1940).
    Warltz  and  Brown  (1975)  determined  a   4-hour  rat  LC5Q  of  11  ppm.
Treated rats  had signs of  respiratory  Irritation.   Fourteen  days  of repeated
exposure  to  4.0 ppm produced an  Inhibition  of  weight gain,  but no  gross
pathological  effects.    Muthu  et  al.  (1980)  calculated  a  rat  Inhalation
LCg-  of  28-33.3  ppm  (42-50  mg/m3)   for  phosphlne  exposure  times  of  5.2
and 7.4  hours.   Treatment  resulted In  bronchlolar  cellular  Infiltration and
some  edema,  but  no  morphological changes  In  other   organs.   Host  animal
Inhalation  studies  (MGller,  1940;  Kllmmer, 1969;  Nlkodemusz et al.,  1981;
Muthu  et  al., 1980) reported clinical  or hlstopathologlcal   evidence  of  CNS
Involvement after exposure.


0132d                               -30-                             08/30/89

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    Occupational exposure to  phosphlne  results In nausea, gastritis,  dizzi-
ness, liver  effects  and nose  and throat  Irritation  (Elchler,  1934;  Harger
and  Spolyar,  1958;  Torkelson  et  al.,  1966;  Wilson  et  al.,  1980;  Harano,
1984; MHO,  1986;  Casteel   and Bailey,  1986).   Casteel  and  Bailey  (1986)
attributed clinical  effects  In humans  to  a nonspecific  toxicosis.   Members
of the  crew  on a  freighter containing  phosphlne-fumlgated  grain became  111
after 2-5 days of  exposure  (Wilson et al.,  1980).  The  greatest  Incidence of
Illness   occurred  1n those  portions  of  the ship with  the  highest  exposure
concentrations  (<30  ppm).   The two most  severely affected Individuals  were
children.  Although  one child recovered,  the second  died  with  congestive
heart  failure,  myocardlal  necrosis,   pulmonary  edema  and  damage  to  the
respiratory epithelium and  alveoli.
    The  odor  threshold for phosphlne  ranges from 0.01-2 ppm,  depending  on
the  purity  of  the  commercial preparation  (Fluck,   1976).  Highly  purified
phosphlne  gas  1s  odorless.   Phosphlne Is  a potent  Inhibitor   of  State  3
(active) cellular respiration  (NakakUa  et al., 1971;  Chefurka et  al.,  1976).
0132d                               -31-                             08/30/89

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                    7.   EXISTING GUIDELINES AND STANDARDS
7.1.   HUMAN
    ACGIH  (1986)  recommended  a  TWA-TLV  of 0.3  ppm  (0.4  mg/m3)  for  phos-
phlne,  with a  STEL  of 1.0  ppm  (-1.0 mg/m3).   These  values  were  subse-
quently adopted  (ACGIH,  1987).   The TLV was based on  observations  (Jones  et
al., 1964) of diarrhea,  vomiting, chest  tightness, headache  and  dizziness  In
workers  Intermittently   exposed  to  35  ppm, but  averaging  <10  ppm In  most
cases.  Cumulative  toxlclty did not  develop.   The  OSHA (1985) standard  1s
also  0.4  mg/m3.   The U.S.  EPA  (1985)  RfD 1s 3xlO~4  mg/kg/day, based  on  a
NOEL  of  0.026  mg/kg/day  In a  2-year  dietary  study  1n rats  (Hackenberg,
1972).   The  FAO/WHO  (1967,  1968,  1970,   1972)  phosphlne  maximum  residue
limits  are 0.1  mg/kg for  raw cereals,  and 0.01 mg/kg  for flour and  other
milled  cereal products,  breakfast cereals  and  dried  foodstuffs.  The regula-
tion  requires that  the  finished  food be aerated  before  being  offered  to the
consumer,  and  that  the aluminum  phosphide-containing  formulation  or  Us
unreacted  residues  not   come  Into  contact with  any  finished  food  (FAO/WHO,
1978).  In practice,  the 0.1  ppm  hydrogen phosphide  residue  1n raw cereal,
after  cleaning  and  milling, yields a  residue  1n consumable grains  of  <0.01
ppm.   The U.S.  EPA  (1977,  1978) established  residue  tolerances of 0.1  ppm
phosphlne  on raw grains,  dried nuts,  beans,  and  seed and pod vegetables,
resulting  from   aluminum or  magnesium phosphide  fumigation.    An  amendment
(U.S.  EPA, 1983a)  to this  rule established  residue tolerances of  0.01  ppm
for  avocados,  bananas,   Chinese  cabbage,  dtrus  dtron, eggplants,  endive,
grapefruit,  kumquats,  lemons, lettuce,  limes, mangoes,  mushrooms,  oranges,
papayas,  peppers,  persimmons, pimentos,  plantains,  salsify tops,  tangelos,
tangerines  and  tomatoes.    The  U.S.   EPA  (1983b)   established  a  residue
tolerance  of 0.01  ppm  for  all  agricultural  commodities   after  preharvest

0132d                               -32-                             02/14/89

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treatment of  pest  burrows with  magnesium or  aluminum  phosphide.  The  0.01
ppm residue tolerance was later extended to sweet potatoes (U.S.  EPA,  1987).
    U.S.  EPA  (1988b) Indicated  a  final  RQ  for phosphlne  of  100, based  on
1gn1tab1l1ty and acute toxlclty.
7.2.   AQUATIC
    Guidelines  and  standards  for  the  protection  of  aquatic  life  from
exposure  to phosphlne were  not located In the  available  literature  dted  In
Appendix A.
0132d                               -33-                             03/16/89

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                             8.  RISK ASSESSMENT
8.1.   CARCINOGENICITY
8.1.1.   Inhalation.   Pertinent data  regarding human or  animal cardnogen-
Vclty after Inhalation exposure to  phosphlne  were not located  In the avail-
able literature dted In  Appendix  A.
8.1.2.   Oral.  No human data  were  located  regarding the cardnogenlclty of
phosphlne after oral  exposure.  Hackenberg (1972) exposed rats  of both sexes
to  dietary  phosphlne at  0.27  mg/kg diet  for  16 weeks, and  0.51  mg/kg diet
for 90 weeks.  Tissues from all rats  that died  during the study and at least
5  treated  rats/sex killed at  termination were examined macroscoplcally and
microscopically for neoplasms.  There were no differences In  tumor  Incidence
between  controls  and treated  rats.  Cabrol  Telle  et al.  (1985)  treated 20
rats/sex with  -5  ppb (0.005  ppm)  dietary phosphlne for  1 year, and 10 rats/
sex  for  2  years. Treatment  had no  effect  on the  Incidence of  gross  or
palpable tumors.   These  studies  are Inadequate to predict the  cardnogenlc-
Ity  of  phosphlne  to  rats.    Adverse  effects were  not observed  In  either
study, Indicating  that the MTD had not been reached.  In  the  Cabrol Telle et
al.  (1985)   study,  only  one  dose  level  was  evaluated  and  too  few  rats
remained  after  the  Interim  sacrifice  for   potential  low  excess  tumor
Incidences to achieve statistical  significance.
8.1.3.   Other  Routes.   Pertinent  data  regarding  the cardnogenlclty  In
humans or animals  after  phosphlne exposure  by other routes were not  located
In the available literature cited  In Appendix  A.
8.1.4.   Weight of Evidence.   Data  were not  located  regarding the cardno-
genlclty of phosphlne In humans and the data  regarding  evidence for cardno-
genlclty In  animals  are  Inadequate.  Phosphlne  Is  not  scheduled  for cancer
testing by the NTP (1988).  According to the  U.S.  EPA (1986a) guidelines for

0132d                               -34-                             08/30/89

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carcinogenic risk assessment,  phosphlne should be  assigned  to EPA Group  D,
not classifiable as  to carclnogenldty 1n humans.
8.1.5.   Quantitative Risk  Estimates.   Data were  Inadequate  for  estimating
the  carcinogenic  potency of  phosphlne  to  humans  after  oral  or  Inhalation
exposure.
8.2.   SYSTEMIC TOXICITY
8.2.1.   Inhalation  Exposure.
    8.2.1.1.   LESS   THAN  LIFETIME EXPOSURES ~ A  subchronlc  NOEL  of 1  ppm
(1.4  mg/m3)  for Inhalation exposure  to phosphlne  was  determined In  4  cats
and 10 rats  (KHmmer, 1969).  This exposure concentration  was  administered 6
hours/day on weekdays  and 4 hours/day  on  Saturdays for 24  weeks.  Treatment
had  no  effect  on  urinary measures,  oxy- or  methemoglobln   content   of  the
blood,  differential  blood  counts,  retlculocyte  counts,  liver  function  or
hlstopathology  of  major  organs,  Including the  brain.   Six  cats,  6  guinea
pigs  and  10 rats were exposed to 2.5  ppm (3.5 mg/m3) on  the  same  treatment
schedule.   At  this  concentration, cats  had greasy liver  Infiltrates  and  an
oxyhemoglobln band  In  the blood.  Rats  had  sporadic renal  tubular  swelling
and  album1nur1a, and  guinea  pigs  showed no apparent   effects.   Repeated
6-hour  exposures  at 5  ppm (7.0  mg/m3) produced  death within  45 hours  In
all  treated  cats, rats  and  guinea pigs.  MQller (1940)  observed  two  rabbits
exposed  to  2.5  ppm  phosphlne vapors 4  hours/day for 40 of 48 days,  and one
rabbit exposed  to 5.0  ppm 4 hours/day  for 35  of 48  days.   All three  rabbits
showed  minor  Incoordlnatlon and  drowsiness,  but  no  other toxic  signs.   At
>10.0  ppm,  all  exposed  rabbits  died.   Hlstologlcal   analysis  revealed
generalized edema and hyperemla, and pulmonary thrombosis.
    Warltz  and  Brown (1975)  reported  decreased weight gain  and  respiratory
Irritation  1n  rats  exposed 4  hours/day for 12 days  to 4.0 ppm  (5.7 mg/m3)
phosphlne.  Treatment had no effect on gross hlstopathology.

0132d                               -35-                             08/30/89

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    Commercial  seamen  exposed  for  2-5  days  to  phosphlne-fumlgated  grain
developed fatigue,  nausea,  headache, occult urinary  blood, liver and  serum
enzyme  changes   and  myocardlal  Injury  (Wilson   et  al.,  1980).   Phosphlne
exposure  levels  on  the  ship  ranged  from  0.5-3.0  ppm  (0.7-42  mg/m3).
Harger and Spolyar (1958) described a case  of  an  acetylene production worker
who died after a 6-week  occupational exposure  to  phosphlne vapors.   Although
exposure levels  were difficult to  assess,  the Investigators  estimated  mean
concentrations to be >8 ppm (11.2 mg/m3).
    The  human  studies  did not quantify  exposure  concentrations  sufficiently
to be considered for risk assessment.   The  only animal  studies of sufficient
duration to  be considered  for  risk assessment were  the  studies by  KHmmer
(1969) using  cats,  rats  and guinea pigs and by Muller  (1940)  using rabbits.
Apparently,  neither  study  used  control  animals, and  1t  Is  doubtful  that
either  study should  be  considered  adequate  for  derivation  of  an  RfD  for
subchronlc Inhalation  exposure.   The KHmmer  (1969) study has an advantage,
however, In  that 1t  used three species and a longer duration  of  exposure.
In the  Kllmmer  (1969)  study,  guinea pigs appeared  to  be less  sensitive than
cats and rats, both of which appeared to be equally sensitive.
    If  an  RfO  were  calculated from  the KHmmer   (1969)  study,-U would  be
most  reasonable  to  base  It  on  rats,  because   cats   and rats  were  more
sensitive  than  guinea pigs and  because a  greater  number of  rats  than  cats
were  used  In  the  experiment,  making  the  rat  data more  reliable.   The  rat
NOEL  of  1  ppm  (1.4  mg/m3)  6  hours/day  on  5 days/week and  4  hours/day  on 1
day/week  (34/168 hours/week)   can  be expanded to a  continuous  exposure  of
0.28  mg/m3.   A  subchronlc  Inhalation RfD  can be derived for a vapor  that
causes  systemic effects.   In  the  absence  of  data  to  the contrary,  1t  Is
assumed  that   equilibrium  conditions   had been  established  during  each

0132d                               -36-                             08/30/89

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exposure period and that the ratio of  the  blood/gas  partition  coefficient 1n
animals  to  humans  1s  1.   The HEC  1s  therefore  0.28  mg/m3.  Applying  an
uncertainty factor  of  100  (10 to  reflect  the uncertainties associated  with
estimation  of  an  HEC  from  animal  exposure data  and  10  for  Intrahuman
variation  1n  sensitivity)  and  a  modifying  factor of  10  to  reflect  severe
limitations of  the key  study results  1n  an  RfD  for  subchronlc  Inhalation
exposure  of  2.8xlO"4  mg/m3,  which   may  be  rounded  to   3xlO~4   mg/m3.
An additional uncertainty factor to reflect deficiencies of  the  data  base Is
not applied  because U.S.  EPA  (1988b)  noted  that the efficacy and  safety of
phosphlne has been  established by a long history of  use.   Confidence  1n  this
RfD Is low.
    8.2.1.2.   CHRONIC  EXPOSURES  — No animal   data  regarding  the  chronic
Inhalation effects  of  phosphlne  are available.  In  humans,  exposure  results
In gastrointestinal  upset,  jaundice,   headache  and dizziness, and  Increased
bone  density  (Torkelson et  al.,  1966;  Marano,  1984;  Jones  et al.,  1964).
Elchler  (1934) observed weakness, bronchitis and a gastric  ulcer  1n a worker
exposed  for  5  years   to  phosphlne   vapors.    Other  occupational exposure
studies  (Beloskurskaya  et  al., 1979;  Berdykhodzhln  et al., 1974)  described
diverse  effects,   Including  disorders  of  liver  function,  high blood  phos-
phorus  levels,  possible neurotoxldty  and respiratory  Irritation.   Occupa-
tional exposure levels were not sufficiently well  quantified  to  permit these
studies  to be used  1n risk assessment.
    If  an RfD  were derived  for  chronic  Inhalation exposure,  H could  be
derived  from  the  subchronlc  RfD of  2.8xlO~4  mg/m3  based  on  the  6-month
study  using rats  by KHmmer  (1969).  Application of  an  uncertainty factor of
10 to  expand  from 24 weeks  to  chronic  exposure results  1n an RfD for  chronic
Inhalation  exposure  of 2.8xlO~s  mg/m3,  which may be  rounded   to  3xlO~5


0132d                               -37-                             04/25/89

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rog/m3.   Confidence  In  the  RfD  Is   low  (see  Section 8.2.1.1.)-   A  dose/
duration-response graph for  Inhalation exposure generated using  the  method-
ology  of  Crockett et  al. (1985)  and the  computer software  by Durkln  and
Meylan  (1988)  1s presented  1n Figure 8-1.  .The data  used  are  compiled  1n
Appendix C.   The ordlnate of  this  graph  1s labeled a  scaled  concentration.
This  variable Is  estimated  by adjusting  the  experimental concentration  to
continuous  exposure  (1f   necessary)   and  applying  the  body  weight  ratio
correction  transform 1n  the  same  manner  that  a human equivalent  dosage  1s
estimated from an experimental dosage 1n oral studies using animals.
    The adverse  effects  line  Is  defined  by the Inhalation  LC5Q In  rats  of
15  mg/m3  (WarHz  and  Brown,  1975),  the  LOAEL  of 5.7 mg/m3  1n the  12-day
rat  study  associated  with  reduced  rate  of  body  weight  gain   (WarHz  and
Brown,  1975),  and the  LOAEL of 3.5  mg/m3  1n  the  24-week study using  rats
associated  with  kidney effects  (Kllmmer,  1969).  The  NOEL  that lies  above
the  adverse  effects  line 1s  for effects  1n  guinea  pigs (Kllmmer,  1969),
which  suggests  that guinea  pigs  are  more  resistant than the other  species
tested, and results  In  a  small  region of  contradiction.   The  NOEL at  the far
right  on  the  graph Is  1.4 mg/m3  In  rats  exposed for 24 weeks.   This  1s  the
data point  that  was  used  to  derive  the RfD  for Inhalation exposure.  The RfD
for  subchronlc  exposure  1s  ~4  orders of  magnitude below  the  scaled  concen-
tration for this data point.
8.2.2.   Oral Exposure.
    8.2.2.1.   LESS  THAN  LIFETIME EXPOSURES —  In  a  12-week  dietary  study,
groups  of  two  rats/sex  received rice diets  fumigated  with  0,  1, 5 or  50
Phostoxln®  tablets/metric ton  (Kadkol  and  Jayaraj,  1967).   The diets  were
aerated for >2 weeks before  administration  to  the  rats and the Investigators
did   not   report  actual   residue   levels.    No  treatment-related  effects

0132d                               -38-                             03/16/89

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occurred.   Because of  the  long aeration  procedure.  1t  1s  unlikely  that
measurable  amounts of  phosphlne remained  1n  the  diet  (Dleterlch et  al.,
1967).  These data are therefore not useful  1n quantitative risk assessment.
    Cabrol et al.  (1986)  treated male  and female rats with 5 ppb (0.005 ppm)
dietary  phosphlne  as  part of a  multlgeneratlon study.   Only  one  dose level
was studied and  the precise  rationale  behind  the selection of the 5 ppb dose
level  was  not  stated  by the  authors.   FQ,  F, and F-  rats were  exposed
throughout  their  lifetimes.   A small  sample  size of 4 males  and  10 females
composed  the  FQ generation.   Rats  of  the latter two generations  were stud-
led  at  2 months  of age  for protein  efficiency,  hematology and  plasma  and
urinary  constituents.   Treatment had  no consistent  effect  on any  of these
endpolnts.  This  free-standing  NOEL 1s  ~2  orders of magnitude  lower  than a
dietary  NOEL of  0,51  ppm  generated  In  a  2-year study (Hackenberg, 1972),  and
Is  not appropriate for  RfD  derivation.   The  RfD of 3xlO"4  mg/kg/day deri-
ved from the chronic  study  (Section 8.2.2.2.)  Is sufficiently protective  for
subchronlc  exposures  and Is  adopted as  the  subchronlc oral  RfD for  the
purposes of this document.
    8.2.2.2.   CHRONIC  EXPOSURE — In  a  2-year  study,  Hackenberg  (1972)
exposed  30  rats/sex to a Phostox1n-fum1gated  diet.   Thirty control rats/sex
were  also  used.  Analytically determined residue levels  averaged  0.27 mg/kg
diet  during  the first 16 weeks, and 0.51 mg/kg diet  during the remaining 90
weeks.   Rats  were evaluated at  0,  2,  6, 12,  18 and 24  months  on study  for
hematologlcal,  serologlcal  and  urlnalysls measures.   At  terminal  sacrifice,
Hackenberg  (1972)  weighed six  organs/rat and  performed gross hlstopathology.
Microscopic  pathology was done  on  all  rats  that died during the treatment
and  five rats/sex 1n both groups.   There were  no  treatment-related effects
on any endpolnt.

0132d                               -40-                             08/30/89

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    Cabrol Telle et  al.  (1985) treated  30  rats/sex with a reported  dietary
phosphlne  level  of  5  ppb  (0.005  ppm).   Approximately  20  rats/sex  were
sacrificed after 1 year, and  10 rats/sex were sacrificed after 2 years,  for
comprehensive  hlstopathology  and  measurement  of  organ  weights.   Treatment
did  not  affect appearance,  behavior,  body weights,  hematology, urlnalysls
Iron content or  carcass  water, I1p1d  or  nitrogen content.   Females  treated
for  1  but not  2  years had  a slightly  Increased  Incidence of  degenerative
thymus pigmentation  spots  and Increased zones of  lysis,  and females  sacri-
ficed at  both  1  and  2 years had elevated thymus  weights.   H1stopatholog1cal
changes  1n  the thymus did  not occur  1n  treated  females  sacrificed after  2
years or  1n  treated  males, and effects  on  the thymus are not considered  to
be compound-related.
    Because  the  dose  of  residual  phosphlne  used by  Hackenberg  (1972)  was
higher than  the dose used  by Cabrol  Telle et  al.  (1985), the former  experi-
ment  Identifies  the  higher  NOEL  and  1s more appropriate  for  quantitative
risk assessment.  Assuming  an average dietary concentration throughout  most
of  the  Hackenberg  (1972)  study  of 0.51 mg/kg diet,  and  assuming  that  rats
consume  the  equivalent of  5%  of  their body weight dally (U.S. EPA,  1986b),
the average dietary  dose Is estimated  at  0.026 mg/kg/day.   Application of an
uncertainty  factor   of  100  (10 for   Interspecles  and  10  for   Intraspedes
extrapolation)  results  In  a  chronic  oral RfD of  3x10~4  mg/kg/day, or  0.02
mg/day for a 70 kg human.
    Confidence In the  RfD  Is  low  to medium because It  was  based on  a free-
standing  NOEL,  and   because  of limitations  of the data base.  Although  the
toxldty  data  base Is  limited, the efficiency and  safety of  fumigation with
phosphlne appear  to  be well  established  (U.S. EPA,  1985)  and 1t may  not be
0132d                               -41-                             08/30/89

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necessary to  apply  an additional uncertainty  factor  to reflect  the  limita-
tions of  the data  base.   This  analysis  and RfD  are consistent with  those
currently available on IRIS (U.S. EPA, 1985).
    The only  oral  data considered  for generation  of dose/duration-response
graphs were  the NOEL  of  0.026 mg/kg/day  1n  the 2-year study  by Hackenberg
(1972) and  the  NOAEL of  0.00025 mg/kg/day  In  the  1- to  2-year  study  by
Cabrol et al. (1986) and  Cabrol  Telle et al.  (1985)  (Appendix C).   Because
no  adverse   effects  were  associated  with   oral  exposure  to  phosphlne,
dose/duration-response graphs could not be generated.
8.3.   AQUATIC
    No data   were  available  regarding  the  effects  of  exposure of  aquatic
fauna  and  flora  to  phosphlne.  precluding  the  development  of  either  a
freshwater or saltwater criterion by the method of U.S. EPA/OMRS (1986).
0132d                               -42-                             08/30/89

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                           9.  REPORTABLE QUANTITIES
9.1.   BASED ON SYSTEMIC TOXICITY
    Information  on  the  systemic  toxldty  of  phosphlne  was  reviewed  1n
Chapter  6.   The only  data even  marginally adequate  for  RQ derivation  are
from  KHmmer  (1969).   In that  study,   four  cats  exposed  to  2.5  ppm  (3.5
mg/m3)  phosphlne,  6  hours/day  on  weekdays and  4  hours/day  on Saturdays,
for 24  weeks  had greasy  liver  Infiltrates  and oxyhemogloblnemla.  Ten  rats
exposed  on  the  same  schedule had  sporadic renal  tubular  swelling.   These
effects  were  more  severe at  5.0  ppm (7.0 mg/m3),  and  all  exposed rats  and
cats  died  within 45  hours  of total  exposure.   The hlstopathologlc  effects
observed In  both rats  and  cats  at  2.5  ppm are assigned an  RV  of  5.   The
mortality observed  In both species  at  5 ppm  Is  considered an acute  effect
and  1s   not  considered  1n  derivation  of  a CS based  on  chronic  toxldty.
Because  only  four  cats  were  exposed, a CS 1s derived only  for  the  effect In
rats.
    The  exposure  concentration  of  7.0  mg/m3  1s   multiplied  by  34  hours
exposure/week (168 hours) to  estimate a  continuous  exposure  concentration of
1.4 mg/m3.   Multiplication  of the  estimated continuous exposure concentra-
tion  of 1.4  mg/m3  by  the  reference  Inhalation  value  for  rats  of  0.223
ms/day  and  dividing  by  the  rat  reference body  weight  of  0.35  kg  (only
starting body weights  were   reported  by the  Investigators)  results  In  an
estimated dosage of  0.89 mg/kg/day.   Multiplication of this  dosage  by  the
cube  root  of the  ratio of the  rat  body weight  (0.35  kg)  to  the  reference
human  body  weight (70  kg) and  dividing by an uncertainty  factor  of  3 to
expand  to  chronic exposure  results  In  an  equivalent  human  dosage  of  0.05
mg/kg/day,  which corresponds  to an MED  of 3.5  mg/day for  a  70 kg human.   The
0132d                               -43-                             02/14/89

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MED  corresponds  to an  RVd of  4.7.   The  CS,  the  product of  RVd and  RVe,
Is 23.5.  which  corresponds to an  RQ  of  100.  These values are  presented  1n
Table 9-1.
9.2.   BASED ON CARCINOGENICTY
    Details regarding  oncogenldty after  lifetime  oral  exposure  1n  rodents
were  provided  1n Section  6.2.1.   There  are no  animal Inhalation  or  dermal
studies,  and  no  human  data  could  be located  1n  the available  literature.
Hackenberg  (1972)  treated  30  rats/sex to one dose of  dietary  phosphlne,  and
sacrificed  5 rats/sex for  gross and microscopic  analysis  of  neoplastlc sites
and  bone  marrow after  2  years.   Cabrol  Telle et  al.   (1985)  exposed  20
rats/sex  to 0.005 ppm dietary  phosphlne for 1  year,  and 10 rats/sex  for  2
years.   Neither  study  found an Increased  Incidence  of neoplasms  In  treated
rats,  relative  to controls.   For  the reasons  described  In Section  8.1.4.,
neither  study 1s  adequate  for  determination  of  the  carcinogenic  potential  of
phosphlne.   Phosphlne  has  been  assigned  to  EPA Group D.   Estimation of  a
potency  factor and hazard ranking 1s not  possible for EPA  Group D substances.
0132d                               -44-                             03/16/89

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                                  TABLE 9-1
                                  PHOSPHINE
          Minimum Effective Dose (MED) and Reportable Quantity (RQ)

Route:                  Inhalation
Dose*:                  0.66 mg/day
Effect:                 greasy liver  Infiltrates
Reference:              KHmmer,  1969
RVd:                    5.8
RVe:                    5
Composite Score:         29
RQ:                     100

*Equ1valent human dose
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                               10.  REFERENCES

ACGIH  (American  Conference  of  Governmental  Industrial Hyg1en1sts).   1986.
Documentation of the Threshold Limit  Values  and  Biological  Exposure Indices,
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ACGIH  (American  Conference  of  Governmental Industrial  Hygenlsts).   1987.
Threshold  Limit   Values  and  Biological  Exposure  Indices  for  1987-1988.
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Amoore, J.E. and E. Hautala.  1983.   Odor  as an  aid to chemical safety: Odor
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Awasthl,  H.D.,  S.  M1sra,  S.   Verma,  S.  Handa  and  R.S.  Dewan.   1971.
Phosphlne  residues  from "Celphos"  fumigated wheat grains  Var.  Kalyan  Sona.
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Beloskurskaya,   G.I.,   Y.G.   Paraskevopulos  and   O.E.   Shlyglna.    1979.
Clinical-functional state  of the  liver  1n patients with chronic  phosphorus
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Berck,  B.    1975.    Analysis   of  fumlgants  and   fumlgant  residues.   J.
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Berck, B. and F.A. Gunther.  1970.  Rapid determination of  sorptlon affinity
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Berdykhodzhln,  M.T., R.K.  Tulebaev  and  A.F.  Krlkunov.  1974.  Evaluation  of
the health  status  of workers  at  a phosphorus  plant.   Zdravookhr. Kaz.   7:
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Boenlg,  I.A.,  M.M.  Crutchfleld  and  C.W.  Heutsch.   1982.   Phosphlnes  and
phosphlne  derivatives.    In.:   K1rk-0thmer  Encycolopedla  of  Chemical   Tech-
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Cabrol, A.M., G.  De Saint Blanquat and  R.  Derache.   1986.   Reproduction  1n
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241-246.

Cabrol  Telle,  A.M.,  G.  De Saint  Blanquat,  R.  Derache,  E.  Hollande,  B.
Perlquet  and  J.P.  Thouvenot.   1985.   Nutritional  and lexicological effects
of long-term  Ingestlon  of phosphlne-fumlgated diet by  the rat.    Food  Chem.
Toxlcol.  23(11): 1001-1010.

Calvert,  J.G.  and  J.N.  PHts   Jr.   1966.   Photochemistry.   John  Wiley  and
Sons, Inc., New York.  p. 204.

Casteel,  S.W. and E.M. Bailey  Jr.   1986.  A  review of zinc phosphide poison-
Ing.  Vet. Human Toxlcol.  28(2):  151-154.   .
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Chan,  L.T.F.,  R.J.  Crowley,  D.  DelHou  and  R.  Geyer.   1983.   Phosphlne
analysis In  postmortem  specimens  following Ingestlon of aluminum  phosphide.
J. Anal. Toxlcol.  7(4): 165-167.

Chefurka, W.,  K.P.  Kashl and  E.J.  Bond.  1976.   Th  effect of  phosphlne  on
electron transport In mitochondria.   Pestle.  Blochem.  Physlol.   6(1):  65-84.

Chemical Week.   1985.   Buyer's  Guide  1986.    HcGraw  H111  Inc.,  New  York.
p. 459.

Crockett, P.M.,  B.  K1l1an,  K.S.  Crump  and   R.P.  Howe.    1985.   Descriptive
Methods  for  Using  Data  from Dissimilar  Experiments  to Locate  a No-Adverse-
Toxic-Effects Region In the  Dose-Duration  Plane.   Prepared by  K.S.  Crump  and
Company, Inc.,  under Contract  No.  68-01-6807 for  Environmental  Criteria  and
Assessment Office, U.S.  EPA, Cincinnati,  OH.

D1eter1ch,  H.H.,  G.  Mayr,  K. H1ld,  J.B. Sullivan  and  J.  Murphy.   1967.
Hydrogen  phosphide  as   a  fumlgant   for   foods,   feeds  and  processed  food
products.  Res. Rev.  19: 135-149.

Doudoroff,  P.  and  M.   Katz.   1950.   Critical  review of  literature on  the
toxldty  of Industrial  wastes and   their  components  to   fish.   Sew.  Ind.
Wastes.  22: 1432-1458.

Durkln,  P.  and  W.  Meylan.  1988.   Users Guide  for  D2PLOT:  A Program  for
Dose/Duration  Graphs.    Prepared   by Chemical  Hazard  Assessment  Division,
Syracuse Research  Corporation, under  Contract No.  68-C8-0004  for  Environ-
mental Criteria and Assessment Office, U.S. EPA, Cincinnati, OH.
0132d                               -48-                             04/25/89

-------
Elchler,  0.   1934.   Phosphlne  poisoning:  Chronic,  occupational?   Sammlung
von Verglftungsfaellen.   5:  23-26.   (Taken from NIOSH/00136718)

FAO/WHO   (Food  and   Agriculture   Organization/World   Health  Organization).
1967.   Evaluation  of Some  Pesticide  Residue   In  Food.   FAQ,  Rome,  Italy.
FAO: PL/CP/15.  WHO Food Add./67.32.   (Cited 1n FAO/WHO,  1978)

FAO/WHO (Food and  Agriculture Organlztlon/World Health Organization).   1968.
1967 Evaluation of  Some  Pesticide  Residues In  Food.  FAO, Rome,  Italy.   FAO
PL: 1967/1967/M/ll.  WHO Food Add./68.30.   (Cited  1n  FAO/WHO,  1978)

FAO/WHO   (Food  and   Agriculture   Organization/World   Health  Organization).
1970.   1969  Evaluations  of Some  Pesticide Residues  In Food.   FAO,  Rome,
Italy.  FAO PL:  1969/H/17/1.  WHO Food Add./70.38.   (Cited 1n  FAO/WHO,  1978)

FAO/WHO   (Food  and   Agriculture   Organization/World   Health  Organization).
1972.   1971  Evaluations  of  Some  Pesticide Residues  1n  Food.  WHO,  Geneva,
Switzerland.    AGP:  1971/M/9/1.    WHO  Pesticide   Residues  Series,   No.   1.
p. 1-2, 289-295, 323-328.

FAO/WHO   (Food  and   Agriculture   Organization/World   Health  Organization).
1978.   Pesticide  Residues  In Food:  Index and  Summary   of Report  of  Joint
Meetings  of   FAO  and WHO  Expert  Bodies  on   Pesticide  Residues  1965-1978.
Rome, Italy,   p. 5, 7, 28, 38-40.

Fluck,  E.  1976.   The odor  of  threshold  phosphlne.   J.  A1r  Pollut.  Control
Assoc.  26(8): 795.

0132d                               -49-                             03/16/89

-------
Fritz. B., K. Lorenz, U. Stelnert and  R.  Zellner.   1982.   Laboratory  kinetic
Investigations  of   the  tropospherlc   oxidation   of  selected   Industrial
emissions.  Comm.  Eur.  Communities,  (Rep.) EUR.   EUR 7624.   p.  192-202.

Hackenberg,  U.  1972.   Chronic  Ingest Ion  by rats  of  standard diet  treated
with aluminum phosphide.  Toxlcol.  Appl.  Pharmacol.   23(1):  147-158.

Harger,  R.N.  and  L.H. Spolyar.   1958.   Toxldty  of  phosphlne,   with  a
possible fatality from  this poison.  Am.  Med. Assoc.  Arch.  Ind.  Health.   18:
497-504.

Hawley,  G.G.   1981.   The  Condensed  Chemical  Dictionary,  10th  ed.    Van
Nostrand Relnhold  Co.,  New York.  p. 808.

Herget,  W.F. and  S.P.  Levlne.  1986.   Fourier  transform Infrared  (FTIR)
spectroscopy for monitoring semiconductor  process gas  emissions.   Appl.  Ind.
Hyg.  1(2): 110-112.

Hilton, H.W. and  H.H.  Roblson.   1972.   Fate of  zinc  phosphide  and phosphlne
In the soil-water  environment.  J.  Agrlc. Food Chem.  20(6): 1209-1213.

Jones, A.T.. R.C. Jones and E.O. Longley.   1964.   Environmental  and  clinical
aspects of bulk wheat  fumigation with  aluminum  phosphide.   Ind.  Hyg.  J.   25:
376-379.

Kadkol, S.B.  and  P. Jayaraj.   1967.   Effect of phosphlne  fumigated  rice on
the  growth  of  albino  rats.   Reports  Central  Food  Technol.  Res.   Inst.,
Mysore, Vol. 2.  p.  6-7.
0132d                               -50-                             03/16/89

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KHmmer,  O.R.   1969.   Contribution  to  the  study  of  action  of  phosphlne
(PH.).   On  the question  of  so-called  chronic phosphlne  poisoning.   Arch.
Toxlcol.  24(2):  164-187.

Kumar, M.D., K. Somasundar and A. Rajendran.  1985.  Stability of phosphorus
species 1n seawater.   Indian J.  Mar.  Sd.   14(l):20-23.

Lyman,  W.J.,  W.F.  Reehl and  D.H.  Rosenblatt.  1982.   Handbook  of  Chemical
Property  Estimation  Methods.   Environmental  Behavior  of  Organic Compounds.
McGraw-Hill  Book  Co., New York.   p. 5-4-5-5,  5-10-5-11,  15-16.

Marano,  D.E.   1984.   Chemical  fumlgants   1n the  grain-handling  Industry.
Health Haz.  Occup.  Environ.   7(3): 76-82.

MQller,   U.    1940.     Uber  phosphorwasserstoffverglftung   (Tlerversuche).
Report  I. Acute and  subacute  Intoxication.   Naunyn-Schmledeberg's Arch. Exp.
Pathol. Pharmakol.   95:  184-193.

Muthu,  M.,  M.K.  KrlshnakumaM, Muralldhara  and  S.K.  Majumder.   1980.    A
study  on  the  acute Inhalation  toxldty of  phosphlne  to albino rats.  Bull.
Environ. Contam.  Toxlcol.   24(3): 404-410.

NakakUa, H,  Y.  Katsumata and  T. Ozawa.   1971.   The  effect of phosphlne on
respiration of rat  liver mitochondria.   J.  Blochem.  69: 589-593.

Nlkodemusz, E.,  G.  Nechay  and  R.   Imre.   1981.   H1stopatholog1cal  changes
resulting by  some  pesticides In the common  vole  (Mlcrotus arvalls).  Acta.
Vet. Acd. Sd. Hung.   29(3): 317-326.  (Taken from B1ol. Abstr.  10830)

0132d                               -51-                            03/16/89

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Noy, N., M.  Podolak  and  A.  Bar-Nun.  1981.  Photochemistry  of  phosphlne  and
Jupiter's great red spot.  J.  Geophys.  Res.  86(C12):  11985-11988.

NTP (National Toxicology Program).  1988.  Management  Status  Report  produced
from NTP  Chemtrack System.    Data  received up to  May  6,  1988.  NTP,  NIEHS,
Research Triangle Park, NC.

Oehme,   F.W.    1970.   Species  differences:  The basis  for  and  Importance  of
comparative toxicology.  CUn. Toxlcol.   3(1):  5-10.

OHMTAOS  (011  and  Hazardous  Materials  Technical  Assistance  Data  System).
1988.  On-Hne: 5/16/88.

OSHA (Occupational  Safety and  Health  Administration).  1985.   Occupational
Standards Permissible Exposure Limits.   29 CFR 1910.1000.   p. 655,  657.

Rommlnger, K. and  D.  Kubel.   1972.  Residue dynamics  of phosphlne In  foods.
Ernaehrungsforschung.  16(4):  595-603.   (CA 78:83001k)

Sax, N.I.  1984.   Dangerous Properties of  Industrial Materials,  6th  ed.   Van
Nostrand Relnhold Co., New York.  p. 2211.

Schoof, H.F.  1970.   Z1nc phosphide as a  rodentlclde.   Pest  Control.   38(5):
38, 42-44.
0132d                               -52-                             03/16/89

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Seo,  S.T.,  E.K.  Akamlne,  T.T.S.  Goo,  E.J.  Harris and  C.Y.L.  Lee.   1979.
Oriental  and  Mediterranean   fruit   flies:  Fumigation  of  papaya,  avocado,
tomato, bell pepper, eggplant, and banana with  phosphlne.   J.  Econ.  Entomol.
72(3): 354-359.

SRI  (Stanford  Research Institute).  1988.   Directory of  Chemical  Producers
United States of America.   SRI International,  Menlo Park,  CA.   p.  848.

Torkelson, T.R., H.R. Hoyle and V.K. Rowe.  1966.   Tox1colog1cal  hazards  and
properties of  commonly used  space,  structural  and certain other  fumlgants.
Pest Control.  34(7): 13-18,  42,  44,  46,  48,  50.

U.S.  EPA.   1977.   Tolerances  and Exemptions  from Tolerances for  Pesticide
Chemicals  1n   or   on  Raw   Agricultural  Commodities.    Federal   Register.
42(204): 56113-56115.

U.S.  EPA.   1978.   Tolerances  and Exemptions  from Tolerances for  Pesticide
Chemicals  1n   or   on  Raw   Agricultural  Commodities.    Federal   Register.
43(231): 56042-56043.

U.S.  EPA.   1980.   Guidelines and  Methodology  Used  1n  the  Preparation  of
Health  Effects  Assessment  Chapters of  the  Consent  Decree  Water  Criteria
Documents.  Federal Register.  45(231):  79347-79357.

U.S.  EPA.   1983a.  Tolerances and  Exemptions from Tolerances for  Pesticide
Chemicals  In  or  on  Raw  Agricultural   Commodities;  Magnesium  Phosphide.
Federal Register.  48(13): 2323-2324.


0132d                               -53-                             03/16/89

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U.S. EPA.   1983b.   Tolerances and  Exemptions  from Tolerances  for  Pesticide
Chemicals  In  or on  Raw Agricultural  Commodities;  Certain Pesticide  Chemi-
cals.  Federal Register.  48(189):  44205-44206.

U.S. EPA.   1984.   Methodology  and  Guidelines for Ranking Chemicals  Based  on
Chronic Toxldty Data.   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.

U.S. EPA.   1985.   Integrated Risk  Information System  (IRIS).   Reference Dose
(RfD)  for  Oral  Exposure for  Phosphlne. Online.   (Verification  date  8/19/85.)
Office  of  Health  and  Environmental Assessment,  Environmental  Criteria  and
Assessment Office,  Cincinnati,  OH.

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

U.S. EPA.   19865.   Reference  Values  for Risk  Assessment.   Prepared  by  the
Office  of  Health  and  Environmental Assessment,*Environmental  Criteria  and
Assessment Office, Cincinnati, OH  for  the Office  of  Solid  Waste,  Washington,
DC.

U.S.  EPA.   1987.   Pesticide  Tolerances  for  Certain  Pesticide  Chemicals.
Federal Register.  52(38): 5768-5769.

U.S. EPA.   1988a.   SANSS  (Structure  and Nomenclature Search System).   Data
Base.  On-line: May 13, 1988.
0132d                               -54-                             04/25/89

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U.S. EPA.   1988b.   Integrated  Risk Information System (IRIS):  Chemical  file
for  Phosphlne.   Online.   Office  of  Health  and  Environmental  Assessment,
Environmental Criteria and Assessment Office,  Cincinnati,  OH.

U.S. EPA/OHRS  (Office of  Mater Regulations  and  Standards).    1986.   Guide-
lines for  Deriving Numerical Water  Quality Criteria  for  the  Protection  of
Aquatic Organisms and Their Uses.   U.S. EPA, Washington,  DC.   p. 22-58,  98.

Vardell, H.H.,  A.  Cagle  and  E. Cooper.   1973.   Phosphlne residues on  soy-
beans fumigated with aluminum phosphide.  J. Econ.  Entomol. 66(3):  800-801.

Verstuyft,   A.W.   1978.   Sampling  and  analytical  methods  for  phosphlne -  A
review.  J. Am. Ind. Hyg. Assoc.  39(6): 431-437.

Vlnsjansen, A. and  K.E.  Thrane.   1978.  Gas-chromatograph1c determination  of
phosphlne 1n ambient air.  Analyst.  103(1233):  1195-1198.

War Hz,  R.S.  and R.M.  Brown.   1975.   Acute  and  subacute Inhalation  toxic-
Hies of phosphlne, phenylphosphlne and trlphenylphosphlne.    Am.  Ind.  Hyg.
Assoc. 0.  36(6): 452-458.

WHO  (World  Health Organization).  1986.   Diseases  caused by  phosphorus  and
Its  toxic  compounds.   Iri:  Early  Detection of  Occupational   Diseases.   WHO,
Geneva,  Switzerland,  p. 53-62.
0132d                               -55-                             04/25/89

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Wilson,  R.,  F.H.   Love joy,   R.J.   Jaeger,   P.L.   LandMgan.   1980.   Acute
phosphlne poisoning  aboard  a grain  freighter.   Epldemlologlc,  clinical and
pathological findings.   J.  Am. Med.  Assoc.   244(2):  148-150.

Wlndholz, M.,  Ed.   1983.  The  Merck Index.  An  Encyclopedia  of Chemicals,
Drugs, and Blologlcals,  10th  ed.  Merck  and  Co.,  Inc., Rahway, NJ.  p. 1058.

Yamada,  K.,  J. Fukuyama and H. Atsuhlro.   1981.   A malodorous  gas  from a
waste burial site.   Selkatsu  E1se1.   25(2):  78-79.   [CA 95(20):174513w]
0132d                               -56-                            03/16/89

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                                  APPENDIX A

                             LITERATURE SEARCHED



    This  HEED  1s  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)
              HSDB
              SCISEARCH
              Federal Research  1n Progress


These  searches  were  conducted   1n  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  Hyglenlsts).
    1987.  TLVs:  Threshold  Limit  Values for Chemical Substances  1n  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.  p. 2879-3816.
0132d                               -57-                             02/14/89

-------
    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.   p.  3817-5112.

    Grayson,  M. and  D. Eckroth,  Ed.   1978-1984.  Klrk-Othmer  Encyclo-
    pedia  of  Chemical Technology, 3rd ed.  John Wiley and  Sons,  NY.   23
    Volumes.

    Hamilton,  A. and H.L. Hardy.  1974.   Industrial Toxicology,  3rd  ed.
    Publishing Sciences Group, Inc.,  Littleton,  MA.   575 p.

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

    Jaber, H.M.,  W.R.  Mabey,  A.T.  L1eu,  T.W.  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.    SRI   International,   Menlo
    Park,  CA.

    NTP (National Toxicology  Program).   1987.  Toxicology  Research  and
    Testing  Program.   Chemicals  on  Standard  Protocol.   Management
    Status.

    Ouellette,  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.  Menlo Park,  CA.

    U.S.  EPA.   1986.  Report  on Status  Report  1n  the Special  Review
    Program,   Registration   Standards  Program  and   the  Data  Call   In
    Programs.    Registration  Standards and  the Data Call   1n  Programs.
    Office of Pesticide Programs,  Washington, DC.

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

    Verschueren, K.   1983.   Handbook of  Environmental  Data  on  Organic
    Chemicals, 2nd ed.   Van  Nostrand  Relnhold Co., NY.

    Wlndholz,  M.,  Ed.  1983.   The Merck Index,  10th  ed.   Merck and Co.,
    Inc.,  Rahway,  NJ.

    Worthing,  C.R.  and S.B.  Walker,  Ed.   1983.  The Pesticide  Manual.
    British Crop Protection  Council.   695  p.
0132d                               -58-                             02/14/89

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    In addition,  approximately 30  compendia of aquatic  toxlclty data  were

reviewed, Including the following:


    Battelle's  Columbus  Laboratories.   1971.   Mater  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. Flnley.   1980.  Handbook  of  Acute  Toxlclty
    of  Chemicals  to  F1sh and  Aquatic   Invertebrates.   Summaries  of
    Toxlclty  Tests  Conducted  at  Columbia  National  Fisheries  Research
    Laboratory.   1965-1978.    U.S.  Dept.  Interior,  Fish  and  Wildlife
    Serv. Res. Publ. 137,  Washington,  DC.

    McKee, J.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.

    Plmental, 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.
0132d                               -59-                             02/14/89

-------
o
_^


IV)
o
 I
                                                                               APPENDIX B



                                                                      Sunmary Table for  Phosphlne
Species
Inhalation Exposure
Subchronlc rat
Chronic rat
Carclnogenlclty ID
Oral Exposure
Subchronlc rat
Chronic rat
Carclnogenlclty ID
RE PORTABLE QUANTITIES
Based on chronic toxtclty:
Based on Carclnogenlclty:
Exposure Effect RfO or qi*

1 ppn (1.4 «g/««) NOEL for renal effects 3xlO"« ng/m»
Intermittently on
6 days (34 hours)/
week
1 ppn (1.4 mq/m*) NOEL for renal effects 3xlO"» ng/m»
Intermittently on
6 days (34 hours)/
week
ID ID 10

0.51 ag/kg diet (0.026 NOEL 3xlO"« mg/kg/day
•g/kg bw/day) for 2
years
0.51 ng/kg/dlet (0.026 NOEL 3xlO"« ng/kg/day
•g/kg bw/day) for 2
years
ID ID ID

100
ID
Reference

Kilmer, 1969
Kilmer, 1969
NA

Hackenberg. 1972
Hackenberg, 1972
NA

Kilmer. 1969
NA
           ID c Insufficient data; NA = not applicable
 en


 CO

-------
                                  APPENDIX C

            Data Used to Generate Dose/Duration-Response Graph for
                       Inhalation Exposure to Phosphlne
Chemical Name:
CAS Number:
Document Title:
Document Number;
Document Date:
Document Type:
Phosphlne
7803-51-2
Health and Environmental Effects Document on Phosphlne
SRC-TR-88-177
1/23/89
HEED
RECORD #1:








Comment:
Citation:
RECORD #2:








Species: Cats
Sex: Female
Effect: NOAEL
Route: Inhalation
Number Exposed: 4
Number Responses: NR
Type of Effect: TOXSL
Site of Effect: LIVER
Severity Effect: 4
Dose:
Duration Exposure:
Duration Observation

4
NR
ENZYM
BLOOD
4
1 ppm (1.4 mg/m3) 34 hours/week for 24 weeks. No
KHmmer, 1969
Species: Cats
Sex: Female
Effect: LOAEL
Route: Inhalation
Number Exposed: 4
Number Responses: NR
Type of Effect: TOXSL
SHe of Effect: LIVER
Severity Effect: 4

Dose:
Duration Exposure:
Duration Observation

4
NR
ENZYM
BLOOD
4 .
0.283
24.0 weeks
: 24.0 weeks






controls.
•
0.708
24.0 weeks
: 24.0 weeks






Comment:       2.5  ppm  (3.5  mg/m3)  (see  previous  record)
               Infiltration, oxyhemoglobln band In blood.

Citation:      KHmmer, 1969
                                              Greasy  liver
0132d
                  -61-
04/25/89

-------
RECORD #3:
Comment:

Citation:
Species:
Sex:
Effect:
Route:
Rats
Male
NOEL
Inhalation
Dose:
Duration Exposure:
Duration Observation:
Number Exposed:      10
Number Responses:    NR
Type of Effect:      DEGEN
SHe of Effect:      KIDNY
Severity Effect:    4

1 ppm (1.4 mg/m3)  34 hours/week  for  24  weeks,

KHmmer, 1969
0.283
24.0 weeks
24.0 weeks
                                    No  controls,
RECORD #4:



Species:
Sex:
Effect:
Route:
Rats
Male
LOAEL
Inhalation
Dose:
Duration
Duration


Exposure:
Observation:

0.708
24.0 weeks
24.0 weeks

Comment:


Citation:
Number Exposed:     10
Number Responses:   NR
Type of Effect:     DEGEN
SHe of Effect:     KIDNY
Severity Effect:    4

2.5  ppm  (3.5  mg/m3),  see
lesions and albumlnurea.

KHmmer. 1969
                   previous  record.    M1ld  kidney
RECORD #5:



Species:
Sex:
Effect:
Route:
Guinea pigs
Female
NOEL
Inhalation
Dose:
Duration
Duration


Exposure:
Observation:

0.708
24.0 weeks
24.0 weeks

Comment:
Citation:
Number Exposed:
Number Responses:
Type of Effect:
SHe of Effect:
Severity Effect:

2.5  ppm   (3.5   mg/m3)   34  hours/week  for  24  weeks.    No
effects, no controls; Guinea pigs  less  sensitive  than  cats  or
rats.

KHmmer, 1969
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RECORD #6:
Comment:


Citation:
Species:
Sex:
Effect:
Route:
Rabbits
NR
LOAEL
Inhalation
Dose:                  0.486
Duration Exposure:     48.0 days
Duration Observation:   48.0 days
Number Exposed:     2
Number Responses:    NR
Type of Effect:     FUNS
SHe of Effect:     CNS
Severity Effect:     6

2.5  ppm  (3.5  mg/m3)  4  hours/day  for  40  of  48  days;   no
controls.  Incoord1nat1on and drowsiness.

Muller, 1940
RECORD #7:








Comment:
Citation:
RECORD #8:








Species: Rats
Sex: Both
Effect: PEL
Route: Inhalation
Number Exposed: 6
Number Responses: NR
Type of Effect: DEATH
Site of Effect: BODY
Severity Effect: 9
11 ppm (15 mg/m3): 4-hour L
WarUz and Brown, 1975
Species: Rats
Sex: Male
Effect: LOAEL
Route: Inhalation
Number Exposed: 6
Number Responses: NR
Type of Effect: WGTDC
Site of Effect: BODY
Severity Effect: 4
Dose: 2.500
Duration Exposure: 1.0 days
Duration Observation: 1.0 days






C50-

Dose: 0.950
Duration Exposure: 12.0 days
Duration Observation: 12.0 days






Comment:       4.0 ppm  (5.7 mg/m3) 4  hours/day for  12  days.  No  mortality
               or gross path, effects;  reduced rate of body weight  gain.

Citation:      VlarUz and Brown, 1975
NR = Not reported
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