-------
-------
-------
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
-------
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).
-------
Two lifetime oral studies using rats Indicate that dietary
concentrations of
-------
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).
-------
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
-------
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
-------
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
-------
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
-------
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
-------
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
-------
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
-------
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
-------
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
-------
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
0132d -9- 08/30/89
-------
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.
0132d -10- 08/30/89
-------
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.
0132d -11- 02/14/89
-------
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.
0132d -12- 02/14/89
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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.
0132d -13- 08/30/89
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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).
0132d -14- 08/30/89
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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.
0132d -16- 08/30/89
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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
0132d -17- 08/30/89
-------
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.
0132d -18- 08/30/89
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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
0132d -19- 08/30/89
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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.
0132d -20- 08/30/89
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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
-------
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
-------
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
0132d -45- 02/14/89
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10. REFERENCES
ACGIH (American Conference of Governmental Industrial Hyg1en1sts). 1986.
Documentation of the Threshold Limit Values and Biological Exposure Indices,
5th ed. Cincinnati, OH. p. 482.
ACGIH (American Conference of Governmental Industrial Hygenlsts). 1987.
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Cincinnati, OH. p. 30.
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.
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poisoning. Tr. Nil Kraev. Patol. KazSSR. 36: 25-30. (CA 92/202790t)
Berck, B. 1975. Analysis of fumlgants and fumlgant residues. J.
Chromatogr. Sd. 13: 256-267.
0132d -46- 02/14/89
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Berck, B. and F.A. Gunther. 1970. Rapid determination of sorptlon affinity
of phosphlne by fumigation within a gas chromatographlc column. J. Agrlc.
Food Chem. 18: 148-153.
Berdykhodzhln, M.T., R.K. Tulebaev and A.F. Krlkunov. 1974. Evaluation of
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Boenlg, I.A., M.M. Crutchfleld and C.W. Heutsch. 1982. Phosphlnes and
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Cabrol, A.M., G. De Saint Blanquat and R. Derache. 1986. Reproduction 1n
the rat fed a phosphlne-fumlgated diet. H1crob1ol. Aliments, Nutr. 4(4):
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. .
0132d -47- 03/16/89
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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
-------
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
-------
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
-------
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
-------
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
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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
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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-
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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
0132d
-62-
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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
0132d
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