EPA-560/2-76-007 TR 76-513
INVESTIGATION OF SELECTED POTENTIAL
ENVIRONMENTAL CONTAMINANTS:
HALOALKYL PHOSPHATES
Sheldon S. Lande
Joseph Santodonato
Philip H. Howard
Dorothy Greninger
Deborah H. Christopher
Jitendra Saxena
August 1976
Final Report
Contract No. 68-01-3124
SRC No. L1255-08
Project Officer - Frank J. Letkiewicz
Prepared for:
Office of Toxic Substances
U.S. Environmental Protection Agency
Washington, D.C. 20460
Document is available to the public through the National
Technical Information Service, Springfield, Virginia 22151
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NOTICE
This report has been reviewed by the Office of Toxic Substances, EPA, and
approved for publication. Approval does not signify that the contents necessarily
reflect the views and policies of the Environmental Protection Agency, nor does
mention of trade names or commercial products constitute endorsement or
recommendation for use.
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TABLE OF CONTENTS
Page
Executive Summary xiii
I. Physical and Chemical Properties 1
A. Structure and Properties 1
1. Chemical Structure 1
2. Physical Properties 3
3. Principal Contaminants in Commercial Materials 10
B. Chemistry 13
1. Chemistry Involved in Use 13
a. Insecticides 13
b. Fire Retardants 14
2. Hydrolysis 18
a. General 18
b. Fire Retardants 22
c. Insecticides 24
3. Oxidation 27
4. Photochemistry 27
5. Other Reactions 30
II. Environmental Exposure Factors 32
A. Production/Consumption 32
1. Volume Produced 32
2. Producers, Major Distributors, Importers, Sources 34
of Imports, and Production Sites
3. Production Methods and Processes 40
a. Fire Retardants 40
b. Insecticides 41
4, Market Prices 42
5. Market Trends 43
a. Fire Retardants 43
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Table of Contents
(continued)
Page
B. Uses 46
1. Major Uses, Quantities, and Sites of Use 46
a. Fire Retardants 46
i. In Textiles 48
ii. Plastics 53
b. Insecticides 55
2. Minor Uses 57
3. Discontinued Uses 57
4. Projected Uses 57
5. Alternatives to Uses 58
a. Fire Retardants 58
i. Textiles 60
ii. Plastics 61
b. Insecticides 62
C. Environmental Contamination Potential 63
1. General 63
a. Fire Retardants 63
b. Insecticides 63
2. From Production 63
3. From Transport and Storage 64
4. From Use 64
a. Fire Retardants 64
b. Pesticides 67
5. From Disposal 67
a. Fire Retardants 67
b. Pesticides 69
6. Potential Inadvertent Production in Other Industrial 69
Sources
7. Potential Inadvertent Production in the Environment 70
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Table of Contents
(continued)
Page
D. Current Handling Practices and Control Technology 71
1. Special Handling in Use 71
a. Fire Retardants 71
b. Insecticides 71
2. Methods for Transport and Storage 72
a. Fire Retardants 72
b. Insecticides 72
3. Disposal Methods 73
a. Fire Retardants 73
b. Insecticides 73
4. Emergency Procedures 74
a. Fire Retardants 74
b. Insecticides 75
5. Current Controls 75
a. Fire Retardants 75
b. Insecticides 75
E. Monitoring and Analysis 77
1. Analysis 77
a. Pesticides 77
b. Fire Retardants 83
2. Monitoring 86
III. Health and Environmental Effects 87
A. Environmental Effects 87
1. Persistence 87
a. Biological Degradation, Organisms, and Products 87
b. Chemical Degradation in Environment 91
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Table of Contents
(continued)
Page
2. Environmental Transport 92
3. Bioaccumulation and Biomagnification 94
B. Biological Effects 96
1. Biology 96
a. Absorption, Transport, and Distribution 96
i. Tris(haloalkyl) Phosphates 96
ii. Dichlorvos 99
iii. Naled 99
b. Metabolism and Elimination 99
i. Tris(haloalkyl) Phosphates 99
ii. Dichlorvos 101
iii. Naled 104
c. Metabolic Effects 105
i. Cholinesterase Inhibition 105
ii. Alkylating Effects 108
2. Toxicity and Clinical Studies in Man 110
a. Occupational and Accidental Exposures 110
i. Tris(haloalkyl) Phosphates 110
ii. Dichlorvos 111
iii. Naled 112
b. Controlled Studies 112
i. Tris(haloalkyl) Phosphates 112
ii. Dichlorvos 118
iii. Naled 118
3. Effects on Non-Human Mammals 119
a. Acute Toxicity 119
i. Tris(haloalkyl) Phosphates 119
ii. Dichlorvos 122
iii. Naled 123
iv. 0,0-Diethyl 2-chlorovinyl Phosphate 123
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Table of Contents
(continued)
Page
b. Subacute and Chronic Toxicity 133
i. Tris(haloalkyl) Phosphates 133
ii. Dichlorvos 136
iii. Naled 137
c. Sensitization 138
d. Teratogenicity 139
i. Tris(haloalkyl) Phosphates 139
ii. Dichlorvos 139
iii. Naled 139
e. Mutagenicity 139
i. Tris(haloalkyl) Phosphates 140
ii. Dichlorvos 141
iii. Naled 142
f. Carcinogenicity 142
i. Tris(haloalkyl) Phosphates 143
ii. Dichlorvos 143
iii. Naled 144
g. Possible Synergisms 144
4. Effects on Other Vertebrates 144
a. Birds 144
b. Fish 144
i. Tris(haloalkyl) Phosphates 146
ii. Dichlorvos 147
iii. Naled 147
5. Effects on Invertebrates 153
a. Insects 153
b. Other Invertebrates 153
6. Effects on Plants 154
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Table of Contents
(continued)
7. Effects on Microorganisms 155
8. Biochemical Studies 156
a. Effects on Cell Cultures 156
b. Effects on Nucleic Acids and Protein 156
IV. Regulations and Standards 158
A. Current Regulations 158
1. Food, Drug, Pesticide Authorities 158
2. Air and Water Acts 159
3. OSHA 159
4. Transport Regulations 160
5. Consumer Product Safety Commission (CPSC) 160
B. Concensus and Similar Standards 160
1. TLV 160
2. Public Exposure Limits 161
3. Other 161
V. Summary and Conclusions 162
REFERENCES 167
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LIST OF TABLES
Number Page
1 Nomenclature of the Selected Haloalkyl Phosphates 2
2 Physical Properties of Selected Haloalkyl Phosphates 4
3 Solubilities of Selected Haloalkyl Phosphates 6
4 Compatibility of Haloalkyl Phosphate with Resins 8
5 Stability of Selected Haloalkyl Phosphates 9
6 Thermally Induced Weight Loss of Haloalkyl Phosphate Flame 9
Retardants
7 Comparative Volatility of Tris(2-chloroethyl) Phosphate and 10
Other Phosphate Plasticizers at 160°F
8 Contaminants in Commercial Haloalkyl Phosphates 12
9 Hydrolytic Stability of Tris(l,3-dichloroisopropyl) Phosphate 23
10 Hydrolytic Stability of Tris(2-chloroethyl) Phosphate in Water 23
at Various Temperatures
11 Degradation of Dichlorvos in Chehalis Clay Loam in One Day 25
12 Hydrolysis Data for Dichlorvos in Aqueous Solution 26
13 Effect of Exposure of Tris(l,3-dichloroisopropyl) Phosphate to 28
the Light of a Weather-0-Meter at 179°F
14 General Reactions of Alkyl Phosphates and Alkyl Halides 31
15 Estimated Annual Production of Haloalkyl Phosphates and 33
Related Chemicals
16 Estimated Market Share of Haloalkyl Phosphate Fire Retardants 34
17 Current Producers of Haloalkyl Phosphates 35
18 Past and Present Producers of Haloalkyl Phosphates, 1959-1975 37
19 Foreign Producers of Haloalkyl Phosphate Flame Retardants 39
20 Market Prices of Selected Haloalkyl Phosphates 43
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List of Tables
(continued)
Number Page
21 Major Markets for Plastics 45
22 Growth Projected for Polyurethane Foams 45
23 Consumption of Haloalkyl Phosphate Fire Retardants 47
24 Annual Production of Polyester and Cellulosic Acetate Fibers 50
(In Millions of Pounds)
25 Polyester and Cellulosic Acetate Textile Producers and Sites 51
of Production
26 Textile Dyers and Finishers 52
27 Consumption of Polyurethane Foams in 1973 (In Millions of Pounds) 55
28 Major Uses of Dichlorvos and Naled 56
29 Manufacturers' Suggestions of Resins and Other Materials for 59
Which Haloalkyl Phosphates Would be Useful Fire Retardants
30 Effect of Scouring on Surface Tris(2,3-dibromopropyl) Phosphate 66
31 Lower Limit of Detection for Analysis of Haloalkyl Phosphates 80
32 Summary of Analyses of Dichlorvos and Naled 81
33 Summary of Analyses Techniques for Tris(2,3-dibromopropyl) 84
Phosphate
34 Biodegradability of Tris(2,3-dibromopropyl) Phosphate (DBPP) in 90
Shake Culture Test
35 Calculated Approximate Evaporation Rates for Haloalkyl Phosphates 93
in an Air-Water System at ^25°C
36 Biomagnification Potential of Haloalkyl Phosphates 95
37 Tissue Residue Levels - ppm of Bromine in Tissue 98
38 Concentrations of Free and Conjugated 2,3-Dibromopropanol (DBP) 101
in Rat Urine as a Function of Time After Dermal Application of
Liquid DBPP on Day Zero
39 Descriptions of Tris(2,3-dibromopropyl) Phosphate-Treated 114
Fabrics
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List of Tables
(continued)
Number Page
40 Maximization Tests with Tris(2,3-dibromopropyl) Phosphate 115
41 Challenge of Subjects with Fabrics 116
42 Correlation of Surface Tris(2,3-dibromopropyl) Phosphate 117
Concentration with Sensitized Panel Response
43 Dose Response Data for Male Spartan Rats Given Acute Oral 120
Doses of Tris(2,3-dibromopropyl) Phosphate
44 Acute Oral Toxicity in Mammals 124
45 Acute Dermal Toxicity in Mammals 129
46 Acute Parenteral Toxicity in Mammals 132
47 Body Weights and Weight Gain of Rats Fed Tris(2,3-dibromopropyl) 133
Phosphate
48 Body Weight of Rats Treated with Tris(2,3-dibromopropyl) 134
Phosphate and Followed by a Recovery Period
49 Feed Consumption 134
50 Feed Efficiency 135
51 Organ Weights and Organ Weights Expressed as Percent of Body 136
Weight
52 Acute Toxicity of Dichlorvos to Birds 145
53 Fish Toxicity of Dichlorvos and Naled 148
54 Estimated 48-Hour EC Immobilization Values in yg/g for Two 154
Species of Daphnids Exposed to Dichlorvos and Naled at 60°F
and 70°F
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LIST OF FIGURES
Number Page
1 Temperature-Viscosity Relationship for Firemaster LV-T23P 5
2 A Simplified Mechanism for the Combustion of Ethane 17
3 Ultraviolet Spectrum of Dichlorvos 29
4 Absorption spectra of: (1) Methyl Iodide [CH I(g)]; 29
(2) Ethyl Iodide [C H I(g)]; (3) Methyl Bromide [CH Br(g)];
(4) Ethyl Bromide [C^BrCg)]; (5) Ethyl Chloride [C
in Alcohol Solution
5 Production Sites of Haloalkyl Phosphates 36
6 Gas Chromatographs of Tris(2,3-dibromopropyl) Phosphate 85
Reagent (a) and on Polyester (b)
7 Sites of Metabolic Cleavage of Dichlorvos 102
8 Metabolic Pathways of Dichlorvos in the Rat Based on In Vitro 103
Studies
9 The Major Pathways of l,2-Dibromo-2,2-dichloroethyl Dimethyl 106
Phosphate (Naled) Metabolism
10 Survival of Goldfish Exposed to 1 ppm of Flame Retardant 147
Compounds
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Executive Summary
I
Haloalkyl phosphate compounds are used as pesticides and fire retardants.
I The four tris(haloalkyl) phosphate fire retardants, which are reviewed in de-
tail in this report, are produced and consumed in the United States in approxi-
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mately 30 million pounds per year. The three tris(chloroalkyl) phosphates are
used mostly in polyurethane foams which are additives in products which must
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meet state or Federal fire retardancy standards (e.g., furniture, automotive
• parts, and household goods). The single tris(bromoalkyl) phosphate compound
is consumed almost exclusively as a fire retardant additive for cellulose ace-
W tate and polyester fibers in textiles. Loss to the environment from production
m and consumption of tris(haloalkyl) phosphate fire retardants is unknown;
there is some evidence that the tris(bromoalkyl) phosphate may be washed from
• textiles during home laundering and it is also possible that the other tris-
(haloalkyl) phosphates are eventually released from the materials in which they
• are incorporated. One of the tris(chloroalkyl) phosphates appears on EPA's
•| list of organic chemicals detected in drinking water.
The environmental fate of the tris(haloalkyl) phosphates is unknown;
• entry into and transport through the aquatic media, however, appear to be
the most likely sources of contamination. In one study, the tris(bromoalkyl)
| phosphate produced 100% mortality in goldfish at 1 ppm in water. The major
« health effects areas of concern for the haloalkyl phosphates are related to
their potential for cholinesterase inhibition and their potential for bio-
• logical alkylation. The tris (haloalkyl) phosphates may not be potent in-
hibitors of cholinesterase enzymes since they are much less acutely toxic to
mammals than the insecticidal haloalkyl phosphates, which possess strong
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anticholinesterase activity. However, the anticholinesterase activity of the
tris(haloalkyl) phosphates has not been studied in detail. In one study, the
tris(bromoalkyl) phosphate has produced cholinesterase inhibition and severe
toxicity in fish.
Perhaps of greatest concern is the potential for mutagenic and carcino-
genic activity of the tris(haloalkyl) phosphates which may possibly result
from alkylation of biologically important molecules. Such activity seems
possible based upon known chemical and physical properties of the tris(haloalkyl)
phosphates, although it has not been demonstrated experimentally in biological
systems. Biological alkylations are often correlated with the production of
both carcinogenic and mutagenic responses. Experimental evidence has shown that
the tris(bromoalkyl) phosphate causes mutations in certain bacterial systems.
Further studies on mutagenesis and the induction of cancer in mammals by this
substance are in progress.
In summary, the tris(haloalkyl) phosphates:
(1) are produced in significant quantities
(2) have several potential sources of environmental contamination
(3) have an unknown fate in the environment
(4) may act as cholinesterase inhibitors
(5) are potentially carcinogenic and mutagenic.
Therefore, considerable experimental information must be generated before
an adequate and reliable assessment of environmental hazard for haloalkyl
phosphates is possible.
The positive results of the tris(bromoalkyl) phosphate as a mutagen in
bacterial systems is particularly significant because of the potential for
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direct human exposure. A major application for the compound is as a fire
retardant in children's sleepwear, which presents the potential for both oral
and dermal exposure. The Environmental Defense Fund has recently petitioned
the Consumer Product Safety Commission concerning regulation of the application.
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• I. Physical and Chemical Properties
A. Structure and Properties
I 1. Chemical Structure
Haloalkyl phosphates are triesters of phosphoric acid that
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have the general formula:
0
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R'O-P-OR'"
OR".
R1, R'', and R''' are alkyl groups, and at least one must contain one or more
™ halogen atoms. The haloalkyl phosphates are either fire retardants or
• pesticides. Although more technical information is available on the pesti-
cides, emphasis in this report has been placed upon the fire retardants.
• Whenever possible, analogies are drawn between information on the pesticides
and fire retardants, especially when data are unavailable for the fire
retardants.
Table 1 summarizes the names and structural formulas of the
six haloalkyl phosphates selected for study. They are usually named as
• esters of phosphoric acid. Since these names are rather tedious, common
names or acronyms will be used in this report. Four of the six haloalkyl
• phosphates are used primarily as fire retardants, and two are insecticides.
• The fire retardants are DBPP ttris(2,3-dibromopropyl) phosphate]; CEP
ttris(2-chloroethyl) phosphate]; CPP [tris(2-chloropropyl) phosphate]
• and DCPP ttris(l,3-dichloroisopropyl) phosphate]. The two insecticides are
dichlorvos [dimethyl 2,2-dichlorovinyl phosphate] and naled [dimethyl
V l,2-dibromo-2,2-dichloroethyl phosphate].
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• 2. Physical Properties
The general physical properties of the selected haloalkyl
phosphates are summarized in Table 2. The data were gathered from listings
m of properties for commercial products as well as for purified materials.
™ No physical property data for pure DBPP or DCPP were found in the literature.
B Where values are taken for commercial products, they are for the purest
grade. All have relatively low vapor pressures, high boiling points, and
1 high densities.
_ The commercially-available fire retardants are characterized
™ as essentially odorless liquids ranging in color from colorless to pale
0 yellow. The commercial pesticides are described as possessing some odor and
being essentially colorless to pale yellow or straw color.
• As commercially-available products, all the selected haloalkyl
— phosphates are viscous liquids at ambient temperatures. The viscosities are
™ important in handling the fire retardants and for some, the temperature must
ft be increased to permit their pumping in conventional manufacturing technology
(See page 72). Figure 1 depicts the temperature-viscosity relationship for
g DBPP.
_ Solubilities of the selected haloalkyl phosphates are sum-
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™ marized in Table 3. Solubility of the esters in water and water in the
ft esters decreases with increasing molecular weight. The insecticides are
somewhat soluble in aliphatic hydrocarbons, but the chloroalkyl phosphate
I fire retardants are characterized as insoluble. The esters are soluble in
aromatic hydrocarbons and in a wide range of chlorinated and oxygenated
• organic solvents.
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10,000
50 60 70
•*• TEMPERATURE (*C)
Figure 1. Temperature-Viscosity Relationship for Firemaster LV-T23P (DBPP)
(Michigan Chemical Corp., 1974b)
Reprinted with permission from Michigan Chemical Corp.
Based upon the solubility properties of DBPP, McGeehan and
Maddock (1975) concluded that it is an excellent choice for fabrics which
are to be laundered but not dry cleaned. If a DBPP-treated fabric requires
dry cleaning, a hydrocarbon solvent should be used instead of the common,
commercial chlorinated hydrocarbon dry cleaning solvents. Judging from the
listed solubility data, the above conclusion may also be extended to CEP,
CPP and DCPP. Information on the losses of DBPP from the laundering of
treated fabrics is discussed in Section II-C, p. 63.
Physical properties of haloalkyl phosphate fire retardants
must conform to the requirements of the materials to which they are added.
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• In plastics applications, desirable properties include compatibility with
the resin, thermal stability, and low volatility. Haloalkyl phosphates are
| incorporated as external additives into resins. External additives, which are
. not chemically bound to the resin, can leach, exude, or otherwise migrate
from the formulated product. The compatibility of an additive in a resin is
flj related to the ability of the resin to retain the additive. Darby and Sears
(1968) define compatibility as the ability of a resin and a plasticizer to be
I blended intimately into a homogeneous mixture with useful plastic properties.
— Table 4 lists the compatibility of three of the flame retardant haloalkyl
* phosphates with a number of commercially important resins.
fl The incompatibility of dichlorvos and polyvinyl chloride
is taken advantage of in the dichlorvos resin strip (Shell Chemical "No-Pest
• Strip"). Dichlorvos is chemically stable within the resin, but will exude
_ at a sufficient rate to maintain an insecticidally toxic atmosphere for
* several weeks (Darby and Sears, 1968).
B Thermoset plastics require that any additives that are used
be capable of withstanding the processing temperatures (Howarth et^ a^., 1973;
• Darby and Sears, 1968). Although haloalkyl phosphate flame retardants are
_ not very thermally stable (Tables 5. and 6), DBPP and DCPP are sufficiently
™ stable for use in some thermoset plastics (Howarth et^ _al_. , 1973; Darby and
• Sears, 1968).
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Low volatility of a plastic additive or coating reduces the
amount of loss during processing and final application and results in longer
retention of the desirable properties of the additive (e.g., plasticizer effect
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Table 4. Compatibility of Haloalkyl Phosphate with Resins (Stauffer Chemical Co.,
undated a,c; Guide to Plastics, Properties and Specification Charts,
1975)
Haloalkyl Phosphate
CEP
DCEP
CPP
Nylon
Pheno
Polye
Polym
Polys
Polyv
Polyv
Polyv
Polyv
Shellac
atio of resin to haloalkyl phosphate
1:1
3:1
9:1
1:1
3:1
9:1
iene-acrylonltrile rubber,
ium-high aery lonltrile content
iene-s tyrene
lose acetate
.lose acetate butyrate
.lose nitrate
lose propionate
Jose triacetate
inated rubber
Inated wax
cellulose
ene
'lie resin
thyl acrylate
ethyl methacrylate
tyrene
inyl acetate
inyl butyrate
inyl chloride
inyl chloride acetate
ac
formaldehyde
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C
I
C
C
C
1
1
C
C
C
C
C
r
c
c
c
c
1
C
c
c
c
c
c
c
c
c
r
c
c
c
c
r
c
c
c
c
c
c
c
c
c
c
c
c
c
c
c
c
C - Compatible
I - Incompatible
-------
I
I
I
I
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DCPP Pichlnrvos
Flash point *C 260 2}2 (COC) 218 (COC) 252 TM D92-52) BO(TOC)
urc point 'C Decomposes and 290 (COC) 246 (UK) 28J (ASTM D92-52)
extinguishes flame
Auto Igniti
540 390
I
• Table 5. Stability of Selected Haloalkyl Phosphates (Stauffer Chemical Co.,
1972a,b, 1973a,b,c; Michigan Chemical Corp., 1974 b; Southwest Research
• Institute, 1964; Chevron Chemical Co., 1973)
I
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•Table 6 . Thermally Induced Weight Loss of Haloalkyl Phosphate Flame Retardants&
(Great Lakes Chemical Corp., 1973a,b,c)
I
Temper ature, °C
•Percent Weight
Loss DBPP CEP DCPP
nit-m.ii decomposi nou stable to 200-250°C Stable to 150°( Will decompose slightly Dt'composts at approx-
Kaior decomposition above 130T i»atil» 2()01>C
begins at 308°l
sensitivity to sunlight Stable Stable Stable Stable Der.oonosed b,
__ ^__ sunllgfi'.
LiX - Lleveland Open Cup
IOC - Tag Open Cup
Loss
1
5
10
25
50
75
95
DBPP
215
270
285
300
310
320
120 203
187 238
206 254
230 277
249 296
261
270
3 Determined on Perkin-Elmer TGS-1 Thermobalance
(20°C/min under nitrogen)
-------
I
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and flame retardancy). Table 7 compares the evaporative loss of CEP to
that of three other common phosphate plasticizers.
Table 7. Comparative Volatility of Tris(2-chloroethyl) Phosphate and Other
Phosphate Plasticizers at 160°F (Stauffer Chemical Co., undated a)
Plasticizer
Tricresyl phosphate
Dioctyl phosphate
Tris(2-chloroethyl) phosphate
Dibutyl phosphate
o
30 g plasticizer in a petri dish
Loss of Plasticizer
at 160°F, Weight Percent
one week
0.0
0.2
0.7
7.7
two weeks
0.0
0.2
4.65
21.60
3. Principal Contaminants in Commercial Materials
Table 8 summarizes information on contaminants present in
commercial haloalkyl phosphates. The identity of the contaminants was often
not available. Shell Chemical Co. (1973a) reports that commercial dichlorvos
contains 7% of "insecticidally active, related compounds" but does not list
them. This may also apply to naled, since it is the bromine addition product
of dichlorvos. DBPP is available in two grades, "standard" and "purified";
after three hours at 135° C, the purified grade yields only 1.5% volatiles,
while the standard grade emits 7 to 11%. Michigan Chemical Corp. (1974b)
lists three volatile organic chemicals in their high purity DBPP (0.8%
volatiles after 3 hours at 135°): l,2-dibromo-3-chloropropane; 1,2,3-
10
-------
cfl r-.
"O i-l
0)
to CN
•9 '-0
a 1-1
o &,
CJ IJ
o
i-l U
to
O rH
-H ca
a o
0) -H
j= e ^-s
O O
CO r-
CD
O -
PLI
O 0)
•> JS
t-H CO •"
CO c""> T3
O l~» H
4-1 CO 0)
C 0) J3
cfl ^4 U
C CO
•H fj o
6 O
Cfl 4-1 CU
W CO C
C 0) (3
o 1-1 cu
O O H
-a
0)
e
§ s
00 00
00
CU
cfl
H
11
-------
tribromopropane; and 2,3-dibromopropanol. The low acid numbers (mg KOH/g
product required for neutralization) in the commercial products suggest that
phosphoric acid and mono- and dialkyl-phosphate esters, if present, are
minor impurities. Commercial DCPP (isopropyl isomer) does contain a high
concentration (5%) of tris(2,3-dichloro-l-propyl) phosphate (the n-propyl
isomer). If one can assume potential impurities from analogies with DBPP,
then the potential impurities in CEP, CPP and DCPP include chlorinated
alcohols and chlorinated hydrocarbons.
12
-------
B. Chemistry
1. Chemistry Involved in Use
a. Insecticides
Dichlorvos and naled are related in biological activity.
Naled, which is produced by brominating dichlorvos, reacts with natural thiols
to regenerate dichlorvos. It is suspected that regenerated dichlorvos is the
active agent in naled (Eto, 1974).
Organophosphate insecticidal activity results from a
phosphorylation reaction with an esteratic site of the enzyme cholinesterase
(ChE). Normally, ChE will remove and degrade acetylcholine (ACh) from nerve
synapses. Since phosphorylated ChE is unable to catalyze ACh degradation,
ACh accumulates and disrupts the normal operation of the nervous system
(Metcalf, 1971). The following reaction sequence describes the enzyme
0 Q
I)
(RO)9PX + EnzH r~^ (RO)9PX • EnzH (1)
k
-1
0 0
11 ko »
(RO) 0PX- EnzH _ £_>. (RO)0PEnz + HX (2)
2. i
0 0
,
(RO)2PEnz + H20 3> (RO)2POH + EnzH (3)
phosphorylation kinetics (Metcalf, 1971). The hydrolysis of the phosphoryl-
ated ChE, Reaction 3, is so slow that it requires several days. Until it is
hydrolyzed, the ChE remains inactive. There is some controversy over the site
of phosphorylation on ChE. According to Bedford and Robinson (1972), phos-
13
-------
phorylation takes place at the hydroxyl group of the serine unit, while O'Brien
(1960) and Metcalf (1971) have suggested that the reaction might occur at an
Imidazole of a histidine unit.
Insecticidal activity of the haloalkyl phosphates is
related to the P-0 bond strength and the leaving group properties of the
halogenated enol anion. Dichlorvos is typical of the phosphorylating agents
with the structure described by the P-XYZ system, where X, Y, and Z are usually
the elements H, C, N, 0, S, or halogens. Eto (1974) has described the require-
ments of the -XYZ system of a good leaving group. The P-X bond must be weak,
and Z must be strongly electron-withdrawing. In general, the phosphorus-
hetero atom bonds are strong as the result of pir-drr bonding between available
electron pairs of the hetero atom, X, and the vacant 3d orbitals of the
phosphorus atom. P-X bond strength can be weakened by PIT bonding between X
and Y. For dichlorvos, the following conjugation weakens the P-0 bond:
0 0 ,
II •• II +_
(CH30)2P-0-CH=CC12 +. v (CH30)2P-Q=CH-CC12
The chlorinated enol anion, which is the leaving group in the phosphorylation
reaction, is similarly stabilized by resonance:
0-CH=CC12 -* > 0=CH-CC1
b. Fire Retardants
Haloalkyl phosphates impart fire retardant properties to
natural and synthetic polymers. These include the natural cellulosic polymers
of wood products and fabrics (e.g.,cellulose acetates) and synthetic polymers
such as the polyolefins, polyurethanes, and polyesters (Napier and Wong, 1972;
14
-------
Pattison and Hindersinn, 1971; Lyons, 1970; Schwarz, 1973). The chemistry of
fire retardation is rather complex and only partially understood. Haloalkyl
phosphates combine the individual contributions of phosphorus compounds and
alkyl halides with the known phosphorus-halogen synergism (Pattison and
Hindersinn, 1971).
A fire retardant can suppress combustion by interfering
with any stage of the polymer combustion sequence (Pearce and Liepins, 1975;
Bostic eit al. , 1973; Hilado, 1974; Pattison and Hindersinn, 1971). This
sequence can be characterized as follows:
(1) Heating the polymer
(2) Polymer pyrolysis to yield monomeric
organic substrates
(3) Vaporization of the pyrolysis products
(4) Ignition
(5) Combustion and propagation.
It is possible that the haloalkyl phosphates contribute to retardation at
each stage.
Two mechanisms have been suggested for the haloalkyl
phosphate contribution to fire retardation in the heating (first) state:
(1) decomposition of alkyl halogen bonds in preference to polymer bonds and
(2) the formation of a surface char which subsequently insulates the polymer
from the heat source (Bostic et^ a^., 1973; Pearce and Liepins, 1975). Alkyl
halogen bonds break at lower temperature than the polymer bonds and, since
alkyl halide bond breakage is endothermic, alkyl halide pyrolysis results in
reduced energy availability for the polymer degradation. In contrast, polymer
degradation is an exothermic process and would increase the energy available
for further degradation.
15
-------
The haloalkyl phosphates improve fire resistance in the
polymer pyrolysis stage by altering the products to yield a carbonaceous char
instead of monomeric, volatile residues (Pearce and Liepins, 1975; Hilado,
1974). The char-forming reactions reduce the volatile hydrocarbon available
for combustion and also create a barrier between the flame and the polymer,
which subsequently insulates the polymer from the external heat sources
(first stage) and retards vaporization of monomeric residues (third stage).
The char results from a process called intumescence, in
which surface coke is foamed by escaping gases (Pearce and Liepins, 1975).
The char contains a large proportion of high molecular weight aromatic hydro-
carbons and phosphate (O'Mara ^t _ajL. , 1973; Napier and Wong, 1972). The
chemical reactions which alter the course of the pyrolysis and produce the
char formation are only partly understood. It appears that several reaction
sequences participate simultaneously. In one sequence, pyrolysis yields
phosphoric acid. This subsequently yields a polyphosphoric acid glaze over
the polymer surface (Schwarz, 1973). In another sequence, the alkyl halides
form olefins and hydrogen halides (Napier and Wong, 1972; Schwarz, 1973).
Polyphosphoric acid and hydrogen halide then participate by a synergistic
reaction sequence to alter the products of the polymer degradation. Appar-
ently, they induce the degrading polymer to form olefins within its chain,
rather than to degrade via chain-breaking reactions. Then the polymeric
olefins crosslink to yield the surface coke. The sequence of the coking
reaction has been partially characterized. In cellulose (polyol), the acidic
polyphosphates and hydrogen halides yield olefins by dehydrating the polymer
(Learmonth and Twaite, 1969; Schuyten £t_ al_., 1954). In synthetic polymers,
16
-------
including polyolefins and polyesters, the hydrogen halides and polyphosphoric
acids participate in olefin-forming reactions by a series of partial oxidations
and subsequent dehydrations (O'Mara et^ al. , 1973).
Hydrogen halides generated during pyrolysis interrupt
the chain reactions of hydrocarbon combustion (Pattison and Hindersinn, 1971;
Hilado, 1974). Figure 2 illustrates a simplified mechanism for the proposed
radical reaction chain. The hydrogen halides have two possible effects on the
combustion process: suffocation and flame poisoning. Suffocation is caused
by large volumes of hydrogen halides in the combustion zone which reduce the
oxygen concentration. Flame poisoning results from the halide atoms trapping
some free-radicals, in particular the hydroxy radicals (Hilado, 1974; Patti-
son and Hindersinn, 1971). Schwarz (1973) and O'Mara e± al. (1973) suggest
that the radical inhibition mechanism is most effective in the flame's
preignition zone.
CH^CH^OOH
/N3 2
o
ii
0^
CH CH + 'OH
CH3CH3—r^ CH3cv
+ r
2\ H2 \ 09^
~X HO- ^-^ H 0 + H' *-^ «OH
0+' +
HO- H
2 2
Figure 2. A Simplified Mechanism for the Combustion of Ethane
(Pattison and Hindersinn, 1971)
17
-------
2. Hydrolysis
a. General
Hydrolysis and related reactions of haloalkyl phosphates
can proceed by either bimolecular (4) or monomolecular (5) reaction kinetics.
While the rate of the former is proportional to the concentrations of both
haloalkyl phosphate and the nucleophile (e.g. hydroxide), the rate of the
latter is proportional only to the concentration of the haloalkyl phosphate.
kl
X: + RY - .- - »- RX + Y: (4)
k1 + -
RY , ' - ' R + Y
k-l
1 (5)
R++x- fast . RX
Hydrolysis and related reactions can proceed at one of
several sites in haloalkyl phosphates: (1) at the phosphorus atom, (2) at
any of the three alkyl carbons of the P-O-C portion of the molecule, or
(3) at the alkyl carbon atom attached to the halogen. For reactions at
carbon atoms, monomolecular kinetics correspond with an S.,1 mechanism, in which
a carbonium ion is formed (See reaction (6) , where X is either halide (Br or
Cl~) or phosphate [ (RO) P(0)0~] ) .
I I
-C-X - »- -C+ + X (6)
I I
Bimolecular kinetics fit an S 2 mechanism, in which the
nucleophile attaches to the carbon as the bond to the leaving group is broken
[see (7)].
N:+ -C-X - 1- N --- C --- X - o- C-N + X: (7)
18
-------
Hydrolysis and related ionic reactions shift from S 2
to SI mechanism in the following order of alkyl groups: methyl, primary
alkyl, secondary alkyl, and tertiary alkyl. Addition of alkyl groups to the
C-X carbon atom will stabilize carbonium ions formed in the Si mechanism and
N
at the same time cause steric hindrance for the S ,2 transition state (Cram
N
and Hammond, 1964; Bedford and Robinson, 1972). Although the phosphorus
atom reacts by similar mechanisms, the chemistry of the phosphorus and carbon
atoms are not identical (Hudson, 1965; Fest and Schmidt, 1973).
Alkyl phosphates have the polarity illustrated by (8).
Hydrolysis and related ionic reactions generally proceed by nucleophilic
0
R0\" C8>
^P-O-C (8)
RO 6+ 6- 6+
attack at the phosphorus or carbon atom. Protonation (or complex formation
with Lewis acids) at an oxygen (either the carbonyl or the C-O-P) can catalyze
the reaction (Eto, 1974). The preference for reaction at the phosphorus or
carbon atom has been explained by application of the Pearson theory of "hard"
and "soft" acids and bases (Pearson and Songstad, 1967; Bedford and Robinson,
1972; Fest and Schmidt, 1973). The ions are characterized by the size of
their charge densities: highly charged, relatively compact ions are "hard"
and less densely charged are "soft." Hard acids prefer reaction with hard
bases, and soft acids prefer reaction with soft bases. In phosphate esters,
the phosphorus atom is a hard acid site and the carbon atom is a soft acid
site. While hard bases such as hydroxide, ammonia, and alkoxide ion prefer
reaction at phosphorus, soft bases such as water, alkyl amines, and mercaptides
19
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1
t
I
*• (RS ) prefer reaction at carbon (Fest and Schmidt, 1973). The Pearson theory
• can aid in predicting whether a substrate will react in a biological system
as a phosphorylating agent or an alkylating agent. For example, dichlorvos
• reacts as a phosphorylating agent (9) with enzyme serinyl groups (hard bases),
while glutathione residues (soft bases) prefer alkylation (10) (Bedford and
« Robinson, 1972; Rowlands, 1967).
«o o
II II
I
I
(CH.O)nPOCH=CCl0 > (CH.O)0POCH0R + OCH=CC10 (9)
32*2 322 2
f^
RCH00~
2
m. ^ 0 0
v y^ 11 _ ii
• RCH2S CH3OP(OCH3)OCH=CC12 > OP(OCH )OCH=CC12 + RCH2SCH3 (10)
V Trialkyl phosphate hydrolysis rate and mechanism are
generally pH dependent. In hydrolysis, rate minima occur at approximately
pH 1 and pH 8, and a rate maximum appears between pH 4 and 5 (Kosolapoff,
4Hr 1950). In alkaline conditions, hydrolysis takes place by bimolecular
kinetics. Hydroxide ion (a hard base) attacks at phosphorus (a hard acid
• site) and forms a trigonal bipyramid intermediate (11) (Hudson, 1965; Fest
RO 0 RO 0 0
H0~ + P-OR > HO P OR > RO- + HO-P-OR (11)
/ I I
f. RO OR OR
and Schmidt, 1973). This yields a secondary phosphate ester, which under
• basic conditions forms the anion, (RO)?P(0)0~. The secondary phosphate ester
does not hydrolyze unless it is exposed to "drastic" alkaline conditions
g (Kosolapoff, 1950; Cherbuliez, 1973).
20
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1
I
• When trialkyl phosphates are hydrolyzed in mildly
_ acidic or neutral conditions, the reaction proceeds by water attacking at a
carbon atom. The reaction is aided by protonation at C-O-P oxygen, according
t
_
I
to Fest and Schmidt (1973). With methyl esters, hydrolysis and related
reactions are bimolecular (S,,2), but with increasingly larger alkyl groups,
I the mechanism shifts toward S 1 character (Bedford and Robinson, 1972). The
N
_ reaction sequence for a methyl ester is described by (12). Secondary and
HO 6+HHHO 0
«.."^V I H .. \/ I II .11
H-0: CH30-P(OR)2 > H-0 C Q-P(OR)2 -> CH3OH2+ + (HO)P(OR)2 (12)
JM H + H H 5+
primary phosphate esters hydrolyze, although more slowly, to ultimately
• yield phosphoric acid. In strong aqueous acid the attack of water at phos-
• phorus competes with reaction at carbon (Fest and Schmidt, 1973).
_• +0 0
I
t
t
mechanisms (Cram and Hammond, 1964; Bedford and Robinson, 1972). Bromine
B and chlorine atoms are soft bases and are better leaving groups than phosphate.
RO-P(OR)2 > H2OP(OR)2 + ROH (13)
A
H H
Alkyl halides hydrolyze slowly both by S>rl and SIT
N N
In addition to substitution reactions, alkyl halides can eliminate the ele-
ments of HX in alkaline solutions to yield olefins. Elimination proceeds by
bimolecular kinetics or an E-2 mechanism which is illustrated by (14) .
21
-------
H A
\ "^ \ /
B: .C-C C=C + BH + X: C=C (14)
'I \
Preference for elimination increases with increase in base strength and in
the following order of alkyl halide: primary < secondary < tertiary (Cram and
Hammond, 1964).
b. Fire Retardants
Tris(haloalkyl) phosphates hydrolyze at the P-O-C
function rather than at the alkyl halide bond (Cherbuliez, 1973). Technical
information for the commercial products describes their hydrolysis under
neutral conditions as slow (Tenneco Chemicals, undated; Jones et al., 1946;
Michigan Chemical Corp., 1962; Stauffer Chemical Co., undated a,b,c,d).
Tables 9 and 10 record the changes in acid number
(mg KOH/g of ester required to neutralize the solution) for DCPP and CEP,
respectively. Hydrolysis products are not identified. The change in acid
number for aqueous DBPP held at 75°C for 24 hours is also reported as
insignificant (Tenneco Chemicals, undated).
22
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f
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f
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Table 9. Hydrolytic Stability of Tris(l,3-dichloroisopropyl) Phosphate
(Stauffer Chemical Co., undated c)
(a)
Temperature, °C
25
70
100
Time , Days
178
178
1
Acid Number (mg
Initial
0.1
0.1
0.1
KOH/g of ester)
Final
0.5
0.5
0.5
(a) 5% Aqueous Mixture of DCPP
Table 10. Hydrolytic Stability of Tris(2-chloroethyl) Phosphate in Water
at Various Temperatures (Stauffer Chemical Co., undated a)
Concentration
of ester in watt
Temperature
Time , days
Original
1
30
178
Acid number (ing
5%
25°C 70°C Reflux
0.031 0.031 0.031
0.038 0.597 6.0
0 075 0 68"} -
OOfifi C. flf.<^
KOH/g of e
25°C
0.031
0.038
OTIS
n ^m
ster )
95%
70°C Reflux
0.031 0.031
0.597 18.0
OfiQ O
23
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In acidic or basic solution, the triesters apparently
hydrolyze somewhat more rapidly than under neutral conditions. Moderate
hydrolysis is reported for the hydrolysis of CPP, DCPP, or DBPP in aqueous
base (Stauffer Chemical Co., 1972b, 1973a,b). It is reported that DBPP
dehydrohalogenates at elevated temperatures in strong aqueous alkali, but its
products are not reported (Michigan Chemical Corp., 1962; Tenneco Chemicals,
Inc., undated). Product literature (Stauffer Chemical Co., 1972a,b, 1973a,b)
also reports that all four tris(haloalkyl) phosphates hydrolyze in aqueous
acid. Their hydrolyses are described as "non-violent."
c. Insecticides
Naled and dichlorvos are both hydrolyzed rapidly under
ambient environmental conditions. Studies with sterilized water, sediment,
and soil indicate that biochemical hydrolysis from microbial action is much
faster than that from purely chemical reactions (Getzin and Rosefield, 1968).
Table 11 compares the degradation of dichlorvos in sterile soil (autoclaved)
and normal soil (Getzin and Rosefield, 1968). Degradation is primarily by
hydrolysis (Goring et al., 1975).
24
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I
I
« Table 11. Degradation of Dichlorvos in Chehalis Clay Loam in One Day
(Getzin and Rosefield, 1968)
1
Soil Percent Dichlorvos Degraded
I
I
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I
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I
Nonsterile 99
Autoclaved 17
Irradiated 88
Dichlorvos hydrolyzes in aqueous acid by a mechanism
other than those listed for the other selected haloalkyl phosphates. The
reaction proceeds according to (15) ; the phosphorus oxygen-bond of the vinyl
0 00
til + II + II
(CH.,0) POCH=CC1 + H - >• (CH_0) POCHCHC1- - >• (CH.,0)0POH + CHC10CHO (15)
J / L 5 i ,. 2. + J L 2.
4B" group breaks after olefin protonation (Eto, 1974; Fest and Schmidt, 1973).
Hydrolysis products are dichloroacetaldehyde and dimethylphosphate, which
• can subsequently hydrolyze (Lewis and Geldart, 1966; Shell Chemical Co.,
1973a) . Biochemical hydrolysis of dichlorvos yields desmethyl dichlorvos
• and methanol (Eto, 1974) and, therefore, since biochemical hydrolysis seems
• to be an important hydrolytic pathway, desmethyl dichlorvos would be an
expected environmental degradation product.
Table 12 lists hydrolysis half-lives for aqueous
dichlorvos at different temperatures and pH values. The half-life decreases
rapidly when the pH is changed from slightly-acid to neutral solution. While
a two unit pH change from 7 to 9.1 (at 38°C) decreased the half-life by less than
25
-------
a factor of two, a change from 5.4 to 7 increased the half-life by a factor
of ten (Attfield and Webster, 1966). The half-life is relatively constant
in the range of pH 1 to 5 (Muhlmann and Schrader, 1957).
Table 12. Hydrolysis Data for Dichlorvos in Aqueous Solution
Series Temperature °C
Variable pH (a) ' 38
38
38
38
38
38
Variable pH (b) 70
70
70
70
70
70
70
70
Variable Temperature (b) 0
10
20
30
40
50
60
70
PH
1.1
5.4
6
7
8
9.1
1.
2.
3.
4.
5.
6.
7.
8.
1-5
1-5
1-5
1-5
1-5
1-5
1-5
1-5
Half-life
60 hours
77
35
7.7
5
4.5
2.3 hours
3.4
3.4
3.0
2.8
1.4
0.45
—
1030 days
240
61.5
17.3
5.8
1.66
0.88
0.164
(a) Attfield and Webster, 1966
(b) Muhlmann and Schrader, 1957
Naled appears to hydrolyze more slowly than dichlorvos.
Eto (1974) reports that it hydrolyzes completely within two days (at room
temperature) to yield bromodichloroacetaldehyde, dimethyl phosphate, and
26
-------
hydrogen bromide. Information on commercial naled (Chevron Chemical Co.,
1970) states that naled hydrolyzes at 10% per day under neutral or slightly
acidic conditions.
3. Oxidation
The literature contains no specific information on the oxi-
dation of tris(haloalkyl) phosphates. According to the manufacturers'
literature (Stauffer Chemical Co., 1972a,b, 1973a,b; Tenneco Chemicals,
undated), they are stable under usual environmental conditions.
Dichlorvos can be oxidized at its double bond. The addition
of bromine to dichlorvos to yield naled is an oxidation reaction (Eto, 1974).
Other chemical reactants are expected to oxidize the dichlorvos double bond
in typical reactions (Cram and Hammond, 1964). However, dichlorvos is more
rapidly degraded in soil by hydrolysis than by oxidation (Goring et al.,
1975).
4. Photochemistry
There is no specific information on the photochemistry of
the haloalkyl phosphates. Available information does suggest that some
photochemical degradation occurs. Eto (1974) notes that, in the presence of
moisture, ultraviolet irradiation will cause hydrolysis of phosphate esters.
Manufacturers' data (Chevron Chemical Co., 1970) states that naled is
degraded by sunlight and should be stored either in brown glass or in light-
proof packing. However, it is not clear from the available information
whether the degradation is caused by photolysis of the naled or by reactions
involving impurities in the commercial product. Mitchell (1961) investi-
gated the possibility that irradiation at 253.7 nm degrades dichlorvos, but
the results were inconclusive.
27
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I
t
• Technical bulletins (Stauffer Chemical Co., undated a,b,
c,d) report that the commercial tris(haloalkyl) phosphates are stable to
* sunlight but might exhibit some instability in some resins, i.e., polyesters,
• acrylics, and urethane. Table 13 records changes in acid number for commer-
cial DCPP exposed to sunlight.
I
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f
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Table 13. Effect of Exposure of Tris(l,3-dichloroisopropyl) Phosphate to
the Light of a Weather-0-Meter at 179°F (Stauffer Chemical Co.,
undated c)
After 1100 Hours
Initial Exposure
Color, Gardner-Holdt 1 6^
Acid Number, Mg KOH/g 0.1 25
0 Figures 3 and 4 record the ultraviolet spectra of dichlorvos
^ and alkyl halides, respectively. Dichlorvos does not absorb light wave-
lengths above 260 nm. Maxima for the alkyl halides appear at approximately
• 173 nm for chlorides and 203 nm for bromides; extinction coefficients increase
with increasing halogen content (Calvert and Pitts, 1966). No ultraviolet
|| spectra were found for simple trialkyl phosphates or the remaining haloalkyl
^ phosphates. Since sunlight cuts off below 290 nm, the available data suggest
that direct excitation of the haloalkyl phosphates is quite unlikely.
28
-------
u.u
2
4
6
LiJ
Z 8
£ 1.0
§ 12
1.4
1.6
1 8
i n
/
/
/
x^
5=^
Concentration 0.1 A/ml
Solvent methanol
Cell Path 1 mm
Manufacturer Shell Chemical Co
Quality 99%
180 200 220 240 260 280 300
WAVELENGTH (MILLIMICRONS)
320
340
360
Figure 3. Ultraviolet Spectrum of Dichlorvos (Gore et al., 1971)
1800
2200
2600 3000
Wavelength, A
3400
Figure 4. Absorption Spectra of: (1) Methyl Iodide [CH I(g)]; (2) Ethyl
Iodide tC H I(g)]; (3) Methyl Bromide [CHJBr(g)]; (4) Ethyl
Bromide [C H Br(g)]; (5) Ethyl Chloride [C H Cl] in Alcohol
Solution (Calvert and Pitts, 1966)
Reprinted with permission from John Wiley & Sons, Inc.
29
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• 5. Other Reactions
— Other reactions of haloalkyl phosphates are expected to
* resemble those of alkyl halides and alkyl phosphates. Their general
9 reactions are summarized in Table 14. The ionic reactions will proceed by
the mechanisms described in the "Hydrolysis" discussion (Section I-B-2, p. 18),
M Haloalkyl phosphate reactions with amines are important to commercial fire
retardant use in that they are not compatible with amine curing agents
™ (Great Lakes Chemical Corp., 1973a,b,c).
ft Eto (1974) reports that mercaptides will react with the
vinylidene chlorines of dichlorvos to yield the dimercapto compound (16).
I
10 0
II II
2RS + (CH30)2POCH = CC12 - > (CH30)2POCH=C(SR)2 + 2C1~ (16)
Both naled and dichlorvos will react with iron but not
If with stainless steel (Chevron Chemical Co., 1970; Shell Chemical Co., 1973a) .
t
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30
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•Table 14. General Reactions of Alkyl Phosphates and Alkyl Halides (Cram and
Hammond, 1964; Fest and Schmidt, 1973; Bebikh et^ al^, 1974; Eto,
1974; Kosolapoff, 1950; Bedford and Robinson, 1972)
I
I
A. Alkyl Halides (X = Cl or Br)
I
I
1. Substitution
RX + Y: >• RY + X°
w Y = water; alcohols; thiols; amines; iodide; hydride
(e.g. LiALH,); nitrile; organometallics; other
• nucleophiles
2. Elimination (with strong bases)
I
B. Alkyl Phosphates
^, Base x s
CH - CX - >• C = C ( + HX)
' ^
1. Substitution
a. At phosphorus - "hard" bases: X = alkoxide; ammonia
0 0
// ' (~\
(R'O) P OR + X: > (R'O) P X + RO
b. At carbon - "soft" bases: X - alcohol; secondary amines
0 0
(R'O) P OR + X: >- (R'O) P 0® + RX
2. Reaction with phosphorus oxychloride
I
I/ //
CR'Ol P OR + X: >• CRT)1) P
I
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1
I
(RO) PO + pOCl - >• (RO) P(0)C1 + (RO)P(0)C1
-------
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V II- Environmental Exposure Factors
^ A. Production/Consumption
1. Volume Produced
V Table 15 summarizes production data for selected haloalkyl
phosphates. Information on non-halogenated organophosphates has been
( included for comparison.
^ The available data for the haloalkyl phosphates used as fire
retardants refer mainly to the four selected: DBPP, DCPP, CEP, and CPP.
• Some of the reported quantities might include other haloalkyl phosphates
and the related haloalkyl phosphonates.
j| Table 16 reports the approximate market shares of the indi-
A vidual esters. Calculations are based on industry estimates (Stauffer
Chemical Co., 1975; Tenneco Chemicals, Inc., 1975; Great Lakes Chemical
V Corp., 1975; Michigan Chemical Corp., 1975). The 30 million pounds include
approximately three million pounds of haloalkyl phosphonates. Industrial
| sources contacted in this study generally rated DBPP as the highest-volume
^ estey of the four haloalkyl phosphates. Its estimated annual production
ranged from eight million pounds (Stauffer Chemical Co., 1975) to eleven
V million pounds (Tenneco Chemicals, Inc., 1975). While this study has ranked
the three chlorinated esters in the relative order DCPP>CEP>CPP, the indus-
| trial sources have suggested that production patterns fluctuate and that the
x
•order might vary in other years.
I
Both naled and dichlorvos are produced in approximately
*
• equivalent volumes. Production of each is estimated at three million
pounds.
I
32
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t
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t
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t
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Table 15. Estimated Annual Production of Haloalkyl Phosphates and
Related Chemicals
Production in Thousands of Pounds
Fire Retardants Insecticides
Haloalkyl Phosphates
1964
1965
1966
1967
1968
1969 9,500(a)
1970
1971
1972 15,000(a)
1973 24,000(a)
1974 24,600(b)
1975 24, 000-30, 200(c,d,e)
Dichlorvos Naled
260(f)
912(g)
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t
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Table 16. Estimated Market Share of Haloalkyl Phosphate Fire Retardants
Annual Production,
In Thousands of
Fire Retardant Percent of Market Pounds
Tris (2,3-dibromopropyl) phosphate 30-40 9,000-12,000
Tris (1,3-dichloropropyl) phosphate 20-33.3 6,000-10,000
Tris (2-chloroethyl) phosphate 10-33.3 3,000-10,000
Tris (2-chloropropyl) phosphate 10 3,000
Halogenated Phosphonates 10 3,000
Total 2A,000-38,000
(a) From personal contact with producers.
(b) Annual Production = 30,000 X Percent of Market
100
2. Producers, Major Distributors, Importers, Sources of
Imports, and Production Sites
• Table 17 lists current producers of the selected haloalkyl
phosphates; production sites are mapped in Figure 5. Table 18 summarizes
• current historical information on producers which was gathered from the
f Directory of Chemical Producers (SRI, 1974, 1975), U.S. International Trade
Commission (USITC, 1959-1974) reports, and personal contact with the manu-
• facturers. Some differences were noticed in information gathered from each
source. The final list of current producers (Table 17) was based upon
• personal contact with producers. A few apparent errors in the Directory of
fl Chemical Producers (SRI, 1974, 1975) are worthy of note. While SRI reports
that Chevron Chemical Co. is the sole producer of naled, sources contacted
£ at both Chevron Chemical Co. (1975) and Shell Chemical Co. (1975) have stated
that Shell Chemical Co. is the sole manufacturer and Chevron Chemical Co.
34
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Table 17. Current Producers of
Company
Shell Chemical Co.
Agricultural Div.
Stauffer Chemical Co.
Specialty Chemical Div.
Dow Chemical Co.
Great Lakes Chem. Corp.
Nease Chemical Co., Inc.
Northwest Indust., Inc.
Michigan Chem. Corp. ,
Subsidiary
Tenneco Chemicals, Inc.
White Chemical Corp.
*3
Haloalkyl Phosphates
Production Site
Denver , Col . 7
Mobile, Ala. J
Gallipolis Ferry, W.Va.
Midland, Mich.
El Dorado, Ark.
State College, Pa.
St. Louis, Mich.
Fords, N.J.
Bayonne , N.J.
Haloalkyl
Phosphates
Produced
Jhaled
[dichlorvos
DCPP
CPP
CEP
DBPP
DBPP
DBPP
DBPP
DBPP
DBPP
(a) From SRI (1974, 1975), USITC (1974)
and personal communication
with producers.
35
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B (Ortho Division) is its major formulator and distributor. SRI (1974, 1975)
— lists Stauffer Chemical Co. as a manufacturer of tris(2,3-dichloro-n-propyl)
' phosphate; Stauffer Chemical Co.(1975), however, reports that its product
B consists of 95% tris(l,3-dichloroisopropyl) phosphate and a small quantity
of the isomeric tris(2,3-dichloro-n-propyl) phosphate. Although SRI (1974,
I 1975) lists Michigan Chemical Corp. as a manufacturer of tris(l-bromo-3-
_ chloroisopropyl) phosphate, Michigan Chemical Corp. (1975) states that it
™ does not manufacture the ester.
B Relatively few companies now manufacture haloalkyl phosphates.
Shell Chemical Co. is the sole producer of both dichlorvos and naled. Until
• Montrose Chemical Co. lost a patent dispute with Shell Chemical Co. in 1963,
^ they were also a producer (Montrose Chemical Co., 1975). Stauffer Chemical
™ Co. is the only current producer of tris(chloroalkyl) phosphates. Three
B current producers of DBPP reported that they either have withdrawn or will
withdraw from the market by the end of 1975: White Chemical Corp., Dow
• Chemical Co., and Nease Chemical Co. Three producers of DBPP remain: Michi-
_ gan Chemical Corp., Great Lakes Chemical Corp., and Tenneco Chemicals, Inc.
' Table 19 lists foreign producers of haloalkyl phosphates.
A Several esters other than the four haloalkyl phosphates selected for this
study are available from foreign producers (Kuryla, 1973). No information
I is available on amounts imported into the U.S. (TSUS, 1969, 1971). Some
CPP may have been formerly imported from ICI (U.K.)(Stauffer Chemical Co.,
™ 1975).
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Table 19. Foreign Producers of Haloalkyl Phosphate Flame Retardants
(Kuryla, 1973)
Haloalkyl Phosphate
Tris(2,3-dibromopropyl) phosphate
Tris(2-chloropropyl) phosphate
C1CH
N
CH-0 , PO
BrCH
(BrCH CHBrCH 0),
Z LA
Trls (2 , 3-dichloro-n-propyl) phosphate
Tri(3-chloro-n-propyl) phosphate
Tris(1-chloroisopropyl) phosphate
0
II
39
Producer
Nippon Oils (Japan)
Kalk (W. Germany)
Bromine Compounds (Israel)
Berk (U.K.)
Billant (France)
Daihachi (Japan)
British Celanese (U.K.)
Bayer (W. Germany)
SUC Ugine Kuhlman (France)
Teijin Chemical (Japan)
Daihachi (Japan)
Daihachi (Japan)
Nippon Oils (Japan)
SUC Ugine Kuhlman (France)
Nippon Oils (Japan)
British Celanese (U.K.)
Daihachi (Japan)
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•
I
3. Production Methods and Processes
a. Fire Retardants
The tris(haloalkyl) phosphate fire retardants are
prepared by reaction of the appropriate alcohol and phosphorus oxychloride in
JB
the presence of a tertiary amine base, such as pyridine (Reaction 1) or by
reaction of the appropriate epoxide and phosphorus oxyhalide in the presence of
an acid catalyst such as phosphorus trichloride, aluminum trichloride, zir-
conium chloride, or titanium chloride (Reaction 2) (Kosolapoff, 1950; Cher-
buliez, 1973; van Wazer, 1961). When alcohols react with phosphorus oxy-
H
chloride, alkyl chloride formation competes with ester production. Formation of
™ +~
RCH2OH + POC13 + B: solvent > (RCH20) PO + 3BHC1 (1)
I /°\
R9 - CH + POX CatalySS (RCHXCH 0) PO (2)
H J Z J
alkyl chlorides can be held to relatively small amounts in reactions using
• primary alcohols, but their production from reactions using secondary alcohols
• cannot be held to low levels (van Wazer, 1961). For economic reasons,
reactions between epoxides and phosphorus oxychloride (Reaction 2) are
• preferred for preparing tris(chloroalkyl) phosphates. CEP, CPP, and DCPP are
prepared commercially by reaction of ethylene oxide, propylene oxide, and
• epichlorohydrin, respectively, with phosphorus oxychloride. Since epibromo-
• hydrin and phosphorus oxybromide are relatively expensive, DBPP is seldom
prepared from these starting materials (Samuel et al. , 1958; Great Lakes
I Chemical Corp., 1975), but is produced commercially from 2,3-dibromopropanol
and phosphorus oxychloride, Reaction 1 (Tenneco Chemicals, Inc., 1975). Van
40
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I Wazer (1961, 1968) has described some of the pertinent commercial aspects of
processes based on Reactions 1 and 2.
iB In production processes based upon Reaction 1, phosphorus
• oxychloride is added to primary alcohol at temperatures from 0° to 20°C. Van
Wazer (1961) reports that a 24-hour digestion is required in the absence of a
• catalyst or some method for removing liberated hydrogen chloride. Techniques
for removing hydrogen chloride include addition of bases, such as tertiary
• amines, or stripping by means of inert gas or reduced pressure. Phosphorus
• trichloride is an effective catalyst. In the product purification step, the
reaction mixture is neutralized, washed, and stripped of excess alcohol by
• distillation. The ester is distilled in vacuo. Reported yields range from
85 to 95%.
• Van Wazer (1961) describes the production of CEP from
• ethylene oxide and phosphorus oxychloride as a very exothermic process. The
process is carried out in a closed reactor. Liquid ethylene oxide is fed into
• phosphorus oxychloride under a slight positive pressure of an inert gas; this
reduces the hazard of explosive decomposition of ethylene oxide. The rate of
•J epoxide addition is described as sufficient to allow the reactor cooling
M system to dissipate the high heat generated by the reaction. The ethylene
oxide is reportedly added in slight excess. After excess epoxide is removed
• by evacuation of the reactor, the haloalkyl phosphate is purified by washing.
Van Wazer (1961) reports that the commercial product is usually not distilled.
• b. Insecticides
m Dichlorvos is produced commercially from chloral and
trimethyl phosphate, Reaction 3 (Sittig, 1967; Tedder et^ al., 1975; Shell
• Chemical Co., 1975). According to Sittig (1967) the two starting materials
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(CH30)2P(0)(OCH=CC12) + CH3C1 (3)
temperatures of 10 to 150 C. The preferred molar ratio for chloral and tri-
• are reacted in a stirred, jacketed kettle of conventional design maintained at
I
I
methyl phosphate reportedly is between 1:2 and 2:1. Sittig (1967) reports
that the reaction does not require catalysts. Product recovery steps include
dilution with water, washing with benzene, and extraction into chloroform.
• The chloroform is then stripped in vacuo.
Naled is prepared commercially by brominating dichlorvos
| in the presence of ultraviolet irradiation (Casida et^ al., 1962; Sittig, 1967;
mL Eto, 1974). Sittig (1967) describes the reactor as a Pfaudler glass-lined
kettle with baffles. It is jacketed for heating and cooling and contains a
water-cooled, quartz mercury vapor light source, which is installed within an
immersion well. The best yields are achieved by brominating in the temperature
range of 0° to 30°C and by adding the bromine slowly (10 to 11 hours) to a
solution of dichlorvos. While carbon tetrachloride is the preferred solvent,
other inert polar organic solvents could be used. Sittig (1967) reports
(50 mm Hg) at a maximum temperature of 80 C. The recovered product is 90 to
• that product work-up consists of stripping solvent and excess bromine in vacuo
I
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93% naled. It represents essentially a quantitative yield based on dichlorvos.
4. Market Prices
Table 20 lists market prices of haloalkyl phosphates. The
• prices of the fire retardants have been increasing over the past three to
four years. Shell Chemical Co. (1975) stated that the price drop for dichlorvos
1§ results from the upcoming expiration of its patent, which will increase market
competition.
42
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• Table 20. Market Prices of Selected Haloalkyl Phosphates
• Price in dollars per pound'
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•
Dichlorvos
Naled
Tris (2 , 3-dibromopropyl)
phosphate
Tris (2-chloroethyl)
phosphate
Tris (2-chloropropyl)
phosphate
Tris (1, 3-dichloroisopropyl)
phosphate
1973 1974
4.25
1.90 to 1.95
0.75
0.49 0.49
0.54 to 0.67
0.65 0.70
1975
4.50
2.75
0.86
0.55
0.67
1976
3.30
2.30
0.94 to 0
0.67
0.67
0.74
o
Prices quoted by the producers
$0.94 by tanker; $0.96 for truckload; $0.98 for less than truckload
5. Market Trends
• a. Fire Retardants
The growth rate for halogenated phosphate fire retardants
is projected to exceed 20% annually into the 1980's (Nobles, 1974; Schongar
m and Zengierki, 1975). Major influences which will expand the market are the
general growth of plastics and synthetic fibers and an increase in the number
• of products covered by Federal flammability standards. Total fire retardant
growth is expected to increase most dramatically in home furnishings and
| transportation.
• , Haloalkyl phosphate fire retardants are consumed primarily
in polyurethane foams and in cellulosic acetate and polyester fabrics. While
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I DBPP is principally used in fabrics, its use in polyurethane foam appears to be
M small but still significant. The chloroalkyl phosphates are predominantly
used in polyurethane foams (See "Major Uses," p> 46). New markets could
fl result from haloalkyl phosphate promotion as additives for other resins (See
"Projected Uses," p. 37). Raw material shortages could reduce haloalkyl
p phosphate growth rate.
. DBPP consumption will probably grow most rapidly in
' polyester fabrics. Annual growth of cellulosic acetate fibers is forecast
• at 1.8%, compared to 8.8% for polyester in wearing apparel and 6.7% in home
furnishings (Wallace, 1971, 1974). Polyester single-knit fabrics, which
| include that used in children's sleepwear, are forecasted to increase at 12%
— annually, reaching 437 million pounds in 1979 from 221 million pounds in 1973
(Wallace, 1974). No alternative additive has been suggested as a viable
fl economic competitor to DBPP in the polyester market. In polyurethane foams,
DBPP has lost some ground to competitors such as bromopropanol (Monsanto,
g 1975; Stauffer Chemical Co., 1975). The newly-marketed chloroalkyl phosphate —
^ tetrakis(2-chloroethyl)ethylene diphosphate — could put additional pressure on
™ DBPP's market in polyurethane foams (Olin, 1976).
• Growth of chloroalkyl phosphates. will probably be
greatest in polyurethane foams used in furniture, transportation, and house-
| hold goods (See "Major Uses," p. 46). Tables 21 and 22 summarize
_ projected growth for all plastics and for polyurethane foams, respectively.
* Haloalkyl phosphates are not used as fire retardants for construction
fl materials. No alternatives to chloroalkyl phosphates in urethane foams were
suggested as economic competitors in the near future.
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1
1
1
VI
1
•
1
1
1
•
1
1
•
1
1
1
Table 21. Major
Markets for Plastics (Schongar and Zengierski, 1975)
Percent Projected
Market Size Fire- Growth of
(1973) in Retarded Fire-Retarded Plastics,
Millions of Pounds (1973) Percent Annually
Building & Construction 5,154 10 13-15
Electrical/Electronic 1,638 22.5 10-12
Transportation
Furnishings
Packaging
Housewares
Appliances
Other
Table 22. Growth
Transportation
Furniture
Construction
Refrigerators and
Freezers
1,551 20 17
1,095 15 17-20
5,830 1
1,363"!
938j 1-2 10
6,831 1
24,400 6.2
Projected for Polyurethane Foams (Frey, 1974b)
Rigid Foam Flexible Foam
Projected Market Projected Market
(1978) Percent (1978) Percent
in Annual in Annual
Millions of Pounds Growth Millions of Pounds Growth
74-81 8-10 515-616 8-12
79-103 12-18 561-616 7-9
320-378 18-22
121-132 10-12
Industrial Insulation 35-42 12-16
1
•
*
1
1
Bedding
Carpet Underlay
Textile Laminate
Miscellaneous
154-169 7-9
123 8-10
25 0
38-44 7-10 119 7
45
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B. Uses
• 1. Major Uses, Quantities, and Sites of Use
• a. Fire Retardants
The only important uses of DBPP, CEP, CPP, and DCPP are as
• fire retardant additives to plastics and synthetic textiles. The compounds are
only used in plastics and textiles which must pass flammability standards.
• Many alternative fire retardant additives and techniques compete with these
• chemicals (See "Alternatives to Use," p. 58). An additive is selected
to fit many criteria, including cost, effectiveness in fire retardation, sta-
• bility to withstand the conditions of processing and use, and effects on per-
formance and esthetics of the material (Drake, 1966).
• Table 23 summarizes information on the consumption of DBPP,
• CEP, CPP, and DCPP. The information was gathered from available literature
sources and from contacts with industry. Although available information dis-
• cusses general properties and uses of haloalkyl phosphate fire retardants,
no literature or industry source describes, either qualitatively or quanti-
• tatively, the overall consumption of haloalkyl phosphates. However, more in-
• formation is expected soon, since the National Fire Retardant Chemical
Association (1975) is now assembling marketing data and expects to have in-
• formation available sometime after July, 1976.
Literature and industrial sources concur on the major
| markets for the selected haloalkyl phosphates, but some disagreement exists
M on minor market segments. The dominant markets for haloalkyl phosphates are
polyester and cellulosic acetate (This term is used for cellulose acetate and
• cellulose triacetate) fabrics and polyurethane foam. The markets for individual
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46
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47
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chloroalkyl phosphates are similar to each other but substantially different
I from the DBPP market. Polyurethane foam (rigid and flexible) dominates consump-
tion of chloroalkyl phosphates, while their consumption in the textiles industry
I is minor. Although the consensus of industry is that consumption in textiles is
• small, there exists some disagreement over whether or not chloroalkyl phosphate
use is, in fact, insignificant (Stauffer Chemical Co., 1975; Hooker Chemicals and
• Plastics Corp., 1975; Frey, 1974a). In contrast, DBPP consumption in cellulosic
acetate and polyester fabrics is larger than its consumption in plastics (Tenneco
| Chemicals Inc., 1975; Stauffer Chemical Co., 1975). Polyurethane foam is the pre-
_ dominant consumer of DBPP, among its plastic applications. One industry source
(Great Lakes Chemical Corp., 1975) has estimated that about two-thirds of the
I DBPP is consumed by the textiles.
i. In Textiles
| As noted earlier, DBPP is primarily used for polyester
_ and cellulosic acetate fabrics. It was suggested that the ratio of its consump-
* tion in polyester to cellulosic acetate is about 2:1 (Great Lakes Chemical Corp.,
I 1975). Some use of DBPP and the chloroalkyl phosphates in acrylic fabrics has
also been mentioned (Hooker Chemicals and Plastics Corp., 1975; Frey, 1974a).
Jj DBPP or chloroalkyl phosphate fire retardants can be
added to textiles by the producer or the dyer and finisher. Addition by dyers
• and finishers appears to be more common. Cellulosic acetate can be treated
• during fiber spinning (Drake, 1971; Stauffer Chemical Co., 1975; FMC Corp., 1975).
DBPP is usually added at 6 to 10% to the spinning dope and diffused through the
• fiber by the heat and pressure of the spinning (McGeehan and Haddock, 1975;
Williams, 1974). Polyester fibers cannot be fire retarded by this technique,
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48
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since their spinning temperatures exceed those at which DBPP is stable. Either
the producer or the textile finisher can fire retard polyester and cellulosic
acetate fabrics with a topical application of DBPP. Pad-dry techniques seem to
be the most common method. DBPP is padded onto the fabric from organic solvents
or aqueous emulsions (3 to 10% DBPP), squeezed through padded rollers to remove
excess solvent, and then dried quickly. Residues are removed by scouring (Williams,
1974; McGeehan and Maddock, 1975; Drake, 1971). DBPP can also be applied during
batch dying by vapor emulsion (Williams, 1974; McGeehan and Maddock, 1975).
Consumption data on polyester and cellulosic acetate
fibers in fabric production are summarized in Table 24. Fiber producers and
their production sites and capacities are listed in Table 25. Non-textile uses
of the fibers do not consume haloalkyl phosphates (e.g., polyester cord for tires
and cellulose acetate for cigarette filters). Fabric dyers and finishers are
summarized in Table 26.
Children's sleepwear (sizes 0 to 6X) is perhaps the
largest market for fabrics fire retarded with DBPP (McGeehan and Maddock, 1975;
Great Lakes Chemical Corp., 1975; Stauffer Chemical Co., 1975). Fabrics for
children's sleepwear are predominantly single knits. Wallace (1971, 1974) has
estimated single knit fabric consumption at 155.3 million pounds of cellulosic
acetates (1970) and 221.0 million pounds of polyester (1973). There is no infor-
mation on the quantities of haloalkyl phosphates consumed in children's sleepwear.
Smaller amounts of the haloalkyl phosphates are consumed in draperies and up-
holstery fabrics (Michigan Chemical Corp., 1975).
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Table 24 . Annual Production of Polyester and Cellulosic Acetate Fibers
(In Millions of Pounds) (Wallace, 1971, 1974)
Acetate
(Textile)
Polyester Fibers Fibers
(1973) (1970)
Production
Domestic shipments
Imports
Domestic Consumption
Apparel
Knit fabrics
Woven fabrics
Home Furnishings
Carpets and rugs
Bedsheets and cases
Draperies and curtains
Blankets
Upholstery
Other
Industrial and other areas
3,016.1 498.9
2,978.0 479.1
135.2 3.2
3,113.2 482.3
1,977.6
1,164.4 253.8
813.2 218.6 (a)
516.3
194.8
190.1
60.1
49.9
7.9
13.5
619.3 9.9
(a) Includes 2.1 million pounds in blankets
50
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Table 25. Polyester and Cellulosic Acetate Textile Producers and Sites
of Production (Wallace, 1971, 1974; SRI, 1975)
Producer and Site
Akzona Inc .
American Enka, Dlv.
Central, S.C.
Lowland, Tenn.
Allied Chemical Corp.
Fibers Dlv.
Columbia, S.C.
Beauknit Corp.
Fibers Dlv.
EliEabethtown, Tenn.
Dow Badishe Co .
Anderson, S.C.
Celanese Corp.
Celanese Fibers Co.
Cumberland, Md.
Narrows, Va .
Roikhill, S.C.
Rome , Ga .
E.I. duPont deNemours 6. Co.
Textile Fibers Dept.
Camden, S.C.
Chattanooga, Tenn.
Kinston, N.C.
Old Hickory, Tenn.
Waynesboro, Va.
Wilmington, N.C.
Eastman Kodak Co.
Carolina Eastman Co. Div.
Columbia, S.C.
Tennessee Eastman Co., Dlv.
Kingsport, Tenn.
Fiber Industries Inc.
Salisbury, N.C.
Shelby, N.C.
Greenville, S.C.
Palmetto, S.C.
FMC Corp.
American Viscose Div.
Meadville, Pa.
Fiber Div.
Lewiston, Pa.
Front Royal, Va .
Hoechst Fibers Inc.
Spartanburg, S.C.
Monsanto Co.
Monsanto Textile Co.
Decatur, Ala.
Guntersvllle, Ala.
Phillips Petroleum Co.
Phillips Fibers Corp.
Rocky Mount, N.C.
Fibers International Corp.
Guayama , P . R .
Rohm and Haas Co .
Fibers Div.
Fayetteville, N.C.
Texfi Industries, Inr .
Fibers Div.
Asheboro, N.C.
New Bern, N.C.
Total
Annual Capacity (1974)
In Millions of Pounds
Cellulose Acetate
and
Polyester Triacetate
125
X
X
(a)
6 w
X
15
X
57
X
327
X
X
X
X
1040 55
X
X
X
X
X
X
310 90
X
X X
595
X
X
X
X
95 85
X
X
X
225
X
155
X
X
70
X
X
65
X
30
X
X
2788 557
(a) Experimental plant
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Table 26 . Textile Dyers and Finishers (McGeehan and Haddock, 1975)
MANUFACTURER
1. Burlington Mills
2. Collins and Aikman
3. Cone Mills
4. Dan River
5. Deering Milliken Corporation
6. Fieldcrest
7. Graniteville Company
8. Guilford Mills
9. M. Lowenstein and Sons
10. Reeves Brothers
11. Riegel Textile Corporation
12. Russell Corporation
13. Springs Mills
14. J. P. Stevens and Company
15. United Merchants and Manufacturers
16. United Piece Dye Works
17. West Point Pepperell
SITE
Greensboro, North Carolina
New York, New York
Greensboro, North Carolina
Danville, Virginia
Spartanburg, South Carolina
Eden, North Carolina
Graniteville, South Carolina
Greensboro, North Carolina
New York, New York
New York, New York
New York, New York
Alexander City, Alabama
Fort Mill, South Carolina
Garfield, New Jersey
New York, New York
Hightstown, New Jersey
West Point, Georgia
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Durability of the DBPP treated fabrics is one of the
most important factors in its selection as an additive for polyester and cellu-
losic acetate fabrics. Children's sleepwear is required to meet flammability
standards after 50 machine washes with subsequent 30 minute drying (McGeehan
and Haddock, 1975). This washing and drying is considered to be representative
of the treatment encountered during the lifetime of the product. A fire-
retarded textile's ability to pass flammability standards throughout the life-
time of laundering and use (e.g., contact with urine, sweat, and water) is
defined as its durability (Drake, 1966). Fabrics treated with additives such
as alumina and borate salts are non-durable and may not be used in sleepwear.
These inorganic fire retardants are acceptable in rugs and carpets from which
they will not normally leach.
Other important factors in the choice of DBPP as a fire
retardant for polyester and cellulosic fabrics include its favorable effects
on the fiber properties and esthetic qualities of the woven fabrics. The risk
of unfavorable health effects to humans, such as contact dermatitis, was
reported to be comparatively low based upon tests on treated fabrics (McGeehan
and Haddock, 1975; Morrow ^t _al^. , 1975).
ii. Plastics
Polyurethane foams are the dominant plastic to which
haloalkyl phosphate fire retardants are added (Frey, 1974a; Stauffer Chemical
Co., 1975). Addition to polyurethane foams is considered to dominate the
consumption of DCPP, CPP and CEP and is also the major use of DBPP among
plastics (Tenneco Chemicals, Inc., 1975; Stauffer Chemical Co., 1975; Great
Lakes Chemical Corp., 1975). The haloalkyl phosphates are added to both rigid
53
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and flexible foams. Consumption in flexible foams appears to be greater than
in rigid foams (Howarth, et al., 1973; Hooker Chemicals and Plastics Corp.,
1975; Levek and Williams, 1975-76). Small amounts of DBPP are reported as
an additive for polystyrene foam (Levek and Williams, 1975-76; Great Lakes
Chemical Corp., 1975). Information on haloalkyl phosphate use in other plastics
is inconclusive.
Howarth and coworkers (1973) estimate that fire
retarded polyurethane requires the following approximate combinations (by
weight) of phosphorus and halogen: 0.5% phosphorus and 4-7% bromine or
1% phosphorus and 10-15% chlorine. This corresponds to about 10% DBPP
(Tenneco Chemicals Inc., 1975) or 15% of a chloroalkyl phosphate in the product.
While it is reported that fire retardants can be added to the finished foam,
haloalkyl phosphates are almost always added before the foam is blown
(Skochdopole, 1966; Hooker Chemicals and Plastics Corp., 1975; Olin Corp.,
1976). Following the addition of the haloalkyl phosphates, the polyurethane
is blown and cured at approximately 200 to 300°F (100°-150°C) (Frey, 1974b;
Olin, 1976; Bayha and Loh, 1975).
Table 27 describes the polyurethane foam market.
No quantitative information is available on distribution of foams treated
with haloalkyl phosphates. Flexible foams are principally used for cush-
ioning. Uses of cushioning treated with haloalkyl phosphates include auto-
motive and aircraft interiors, institutional bedding, cushions, and uphol-
stered furniture (Frey, 1974b; Schongar and Zengierski, 1975; Michigan
Chemical Corp., 1975; Howarth et. ^1., 1973). Rigid foams have a consider-
able number of applications, including insulation, furniture, automobile
interior parts, and water flotation devices. Haloalkyl phosphates are not
54
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added to rigid foams used for building insulation; these foams use less
expensive fire retardants (Great Lakes Chemical Corp., 1975; Stauffer
Chemical Co., 1975).
Table 27. Consumption of Polyurethane Foams in 1973 (In Millions of Pounds)
(Wallace, 1974)
Furniture
Transportation
Bedding
Carpet Underlay
Textile Laminates
Packaging
Refrigerators and Freezers
Construction
Flotation
Miscellaneous
Total
Flexible
400
350
110
f\
80a
25
20
65
1050
Rigid
55
50
75
140
10
17
367
o
An additional 100 million pounds of "bonded" polyurethane foam
carpet underlays are estimated to have been produced from scrap
foam.
b. Insecticides
Naled and dichlorvos are consumed only as pesticides.
While they are primarily insecticides, they are also used as miticides and
anthelmintics. Table 28 lists their most important uses. They are used
where low toxicity and short residual times are desired.
Most dichlorvos is formulated into resin strips (popu-
larly known under its Shell Chemical Co. trademark, "No-Pest Strip"). Shell
Chemical Co. (1975) estimated that about 80% of dichlorvos goes into the
resin strips. They are primarily consumed as household items. Dichlorvos
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is also formulated into aerosol sprays for use in households and by pest
control operators (exterminators). Von Rumker e_t _al. (1974) ranked dichlorvos
as one of three active ingredients most frequently used by pest control
operators. Aerosol formulations of dichlorvos are the most popular among
pest control operators. The largest consumption of naled appears to be by
public health programs; it is primarily used for mosquito and fly control.
Von Rumker e^ al. (1974) reported naled consumption of 412,000 pounds (active
ingredients) in a survey they conducted among state (35 responding) and
municipal (22 responding) agencies. Public health programs in the southern
United States are estimated to be the heaviest users (Chevron Chemical Co.,
1975). Other relatively important uses for naled are crop and ornamental
plant spraying. Naled is particularly important as a preharvest spray for
vegetables (Berg, 1976; Chevron Chemical Co., 1975).
Table 28. Major Uses of Dichlorvos and Naled (Berg, 1976; Shell
Chemical Co., 1975; Chevron Chemical Co., 1975)
DICHLORVOS
PVO Resin Strips ("No-Pest Strip")
Households
Pest Control Operators (exterminators)
Animal Barns
Other Uses
Aerosol Sprays
Households
Pest Control Operators (exterminators)
Anthelmitics for Swine, Horses, and Dogs
Flea Collars
NALED
Public Health Spray Programs (fly and mosquito control)
Preharvest Crop Spray (usually vegetables)
Plant Sprays
Animal Barns
Flea Collars
56
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2. Minor Uses
Dichlorvos and naled are used only as pesticides (Shell
Chemical Co., 1975; Chevron Chemical Co., 1975).
Little, if any, of the DBPP, CEP, GPP, and DCPP is consumed
other than as additives for imparting fire retardancy to plastics and tex-
tiles. Possible minor uses have been mentioned, but they were not confirmed
as current uses. These include use as automobile fuel and oil additives
and flotation agents in uranium ore refining (Kolka, 1958; van Wazer, 1968).
3. Discontinued Uses
Reports of production and use of tris(bromochloroisopropyl)
phosphate have been noted in available literature (Levek and Williams, 1975-
76; SRI, 1974, 1975). However, industry sources (Stauffer Chemical Co.,
1975; Michigan Chemical Corp., 1975) stated that its manufacture and use has
been discontinued since it is not economically competitive with other fire
retardants.
DBPP was formerly used as a fire retardant additive for viscous
rayon fiber (Drake, 1971). Since DBPP treated rayon was not durable in
laundering (about five launderings removed the fire retardancy), its use has
ceased (FMC, 1976).
4. Projected Uses
Projected uses of DBPP, CEP, CPP, and DCPP include new appli-
cations as fire retardant additives in plastics and synthetic fibers. The
new uses are of two types: new products of fibers and plastics which are
now treated with the haloalkyl phosphates and new markets for haloalkyl
phosphates among resins which do not currently use them as fire retardants.
As the flammability regulations and standards are expanded, new products will
57
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I
be treated with fire retardants to meet requirements. These products include
• children's sleepwear (sized 7 to 14), blankets, furniture, and automotive
interiors (Howarth et al^. , 1973; McGeehan and Maddock, 1975; Modern Plastics,
| 1973). An important market for fire-retarded plastic materials will be
_ created by substitution of plastics for metal parts in automobiles (Modern
* Plastics, 1973; Frey, 1974b) .
V Haloalkyl phosphate producers are promoting their use in
resins in which they are not now being consumed in significant quantities.
| The fire retardant formulators suggest that the haloalkyl phosphates could
^ be effective with the resins and other materials listed in Table 29. From
personal contact with producers, it appears that they are promoting new
A formulations of the chloroalkyl phosphates, but they are reluctant" to discuss
these potential markets or their proprietary formulations because of compe-
• tition within the fire retardant industry.
— Olin Corp. (1976) began marketing of tetrakis(2-chloroethyl)
™ ethylene diphosphate (CEEP) in 1975. It is being promoted primarily as an
A additive for flexible polyurethane foams. No information was available on
last year's sales or projected growth. The product is currently manufactured
• at pilot plant scale by another company for Olin exclusively. Olin Corp.,
_ which hold patents on CEEP, does plan to start its own production but has
™ not specified when.
t
5. Alternatives to Use
a. Fire Retardants
V Current regulatory actions in certain applications seem
committed to textiles and plastic products which are not fire hazards. It
1
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iH tfl
co -H
O T3
r-( (1)
to a
EC O
r-\
X O
o c.
.M 01
-C C
3 C
W
O W
IH a
•H
CO 4J
tH CO
CO cfl
•H .H
-------
appears unlikely that flammability standards will be relaxed. Thus, if a
fire retardant haloalkyl phosphate has an adverse health or environmental
effect, the products to which it is added will require an alternative
fire retardation method or may be removed from the market. Substitute
products could be produced that do not need fire retardant additives.
These could be constructed of less flammable fibers or plastics, or better
flammability characteristics could be designed into the product. The new
products should be as similar as possible to the original in performance,
esthetic characteristics, and cost.
i. Textiles
A fabric's texture and weave influence its flam-
mability. Tightly woven, smooth-surfaced fabrics manufactured from heavy
fibers are less flammable than loosely woven, napped surfaces, and sheer or
fluffy piled textiles (USCPSC, 1975). Although the manufacture of the less-
flammable fabrics could reduce the amount of fire retardant required, con-
sumer demands for the more flammable textiles make it unlikely that any sig-
nificant reduction of DBPP could be achieved.
Few additives are effective fire retardants for
polyester or cellulosic acetate fibers (Drake, 1971). DBPP has been the
additive of choice, since it is relatively inexpensive, is effective as a
fire retardant, and has excellent performance. Some success has been reported
for fire-retarding polyester fibers with 2,5-dibromoterephthalic acid and
tetrabromobisphenol (McGeehan and Haddock, 1975). These additives are spun
into the fiber. Other potential replacements might be found among combina-
tions of phosphorus and halides such as halogenated phosphines, phosphites,
or phosphonates (Howarth et al., 1973).
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Cellulosic acetate and polyester can be replaced by
less flammable, although more expensive, fibers. Children's sleepwear which
meets flammability standards has been produced from modacrylic fibers.
Modacrylics contain 35 to 85% acetonitrile copolymerized with vinyl chloride,
vinylidene chloride, or vinyl bromide (McGeehan and Maddock, 1975; Wallace,
1974). Fire-retarded polyester fibers can be produced from copolymers
(Wallace, 1974). Fire-retarded copolymers are formed by blending polyethylene
terephthalate with a non-combustible polymer. Less flammable polyesters are
produced by copolymerization with modified diols or substituted terephthalic
acid.
McGeehan and Maddock (1975) have suggested that
research conducted by the chemical industry is more concerned with developing
fire retardants which can be topically applied by textile dyer-finishers.
The greater commitment to research on new additives apparently results, in
part, from demands for non-additive fire retarded copolymer fibers beyond
their available production capability.
ii. Plastics
Several alternatives to the use of haloalkyl phosphates
as fire retardants for polyurethane foams have been suggested. These sug-
gestions include improved design, substitute additives, or inherently less
flammable polyurethanes. McGeehan and Maddock (1975) suggest that matresses
and automobile upholstery can be designed to meet existing flammability
standards without any need for fire retardant chemicals, but no details are
given.
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For flexible and rigid polyurethane foams, haloalkyl
phosphates can be replaced by other phosphorus- and halogen-containing additives.
Industry sources (Monsanto, 1975; Stauffer Chemical Co., 1975) state that
Hromopropanol can successfully replace DBPP for some uses and is cheaper.
Where more durability is required, an alternative phosphorus compound might
be used. Howarth and coworkers (1973) suggest phosphites, phosphonates, and
amino phosphates as possible additives for polyurethanes.
Fire-retarding monomers can be built into poly-
uiethane foam. Brominated isocyanates or halogenated prepolymers/polyols,
which can be polymerized into the polymer backbone, will yield foams surpassing
flammability requirements (Howarth et^ al., 1973). While the required
polyols are available to produce fire retarded foams, they apparently are
not widely used (Frey, 1974b).
b. Insecticides
Alternatives to naled and dichlorvos include substitute
insecticides or physical control methods. The old methods of household insect
control, such as screening and fly-swatting, reduce insects to acceptable
levels. In commercial establishments, physical methods, such as air doors,
light traps, and electric grids are excellent controls and could replace
dichlorvos strips for flying insects. Naled use for community mosquito spray
programs can be reduced by better drainage and general maintenance of breeding
areas.
Alternative insecticides, such as pyrethroids and other
organophosphates such as malathion, also have low toxicity and short life
times. Pyrethrum vapor dispensing devices, such as "Time Mist," can usually
replace dichlorvos where a continual low level insecticide atmosphere is wanted.
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G. Environmental Contamination Potential
1. General
a. Fire Retardants
Little information on haloalkyl phosphates is available
from which an accurate assessment of environmental contamination potential
can be made. No significant monitoring data is available on their presence
in industrial waste streams, in municipal sewage, or at solid waste disposal
sites. This is further complicated by the ambiguous information on biodegrada-
tion or chemical degradation in the environment (See p. 89).
The following evaluation of environmental contamination
potential is quite speculative. Transport and storage are probably insignifi-
cant sources. Contamination from industrial waste streams, use (including
laundering of textiles containing the compounds), and disposal is uncertain.
With the possible exception of CEP, there are no apparent inadvertent sources
of haloalkyl phosphates.
b. Insecticides
Naled and dichlorvos are not long-term environmental con-
taminants. They are relatively quickly degraded by hydrolysis. Their use
as pesticides is almost their exclusive source of release to the environment.
2. From Production
No specific monitoring data or other information is available
on losses of haloalkyl phosphates from production. However, relatively low
losses are expected. All the esters are produced in batch reaction kettles.
Since their vapor pressures are low, atmospheric emissions are expected to be
insignificant. Chances of atmospheric emission are probably highest for
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• processes which use solvent and subsequently recover the solvent by vacuum
or inert gas streams. Industrial sources suggest that no solid or liquid
0 organic wastes are produced (See "Disposal Methods," p.. 73). Aqueous
«. wastes could be produced from washing reaction kettles or equipment or from
work-up. While the haloalkyl phosphate insecticides are easily degraded by
•
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chemical or biological treatment of water, it is not clear how effective
these treatments are with the fire retardants.
3. From Transport and Storage
Transport and storage losses are probably negligible. Fire
retardants are transported in bulk carriers or sealed metal containers.
Insecticides are transported in sealed metal drums. All the haloalkyl
phosphates are usually stored in sealed containers. Since their vapor
pressures are quite low, venting losses should be virtually non-existent.
Accidental spills and mishandling may result in some losses.
While no specific information is available on such losses, they probably
• are not significant.
4. From Use
I a. Fire Retardants
The haloalkyl phosphate fire retardants could potentially
reach the environment from waste streams generated in plants where they are
added to fabrics and plastics or from the final product during its use,
disposal, or recycling. Their transport to the environment could occur by
^ atmospheric emissions, by leaching, or with the movement of small pieces of
_ treated fabrics or plastic products. This last potential source is discussed
™ in "Disposal" Methods" (See p. 73).
I
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Experimental laundering of treated fabric demonstrated
that DBPP can be leached into wash and rinse waters. Morrow and coworkers
(1975) measured DBPP surface concentrations on dacron polyester and cellulose
acetate during the course of fifty launderings; their observations are sum-
marized in Table 30. DBPP was spun into the cellulose acetate and topically
applied to the polyester by the pad-dry method (See "Major Uses," p,. 46).
The authors observed that approximately 12% of the DBPP is lost from the
polyester and that most of this loss apparently happens in the first three
washings. They also concluded that negligible DBPP was lost from the cellu-
lose acetate. Gutenmann and Lisk (1975) estimated DBPP loss during simulated
laundering of a treated polyester fabric. No information is given on the
initial fabric treatment. In the simulated laundering, the fabric was
heated in distilled water at 140°F for 20 minutes. The authors reported
that up to 10 yg DBPP per square inch of fabric are dissolved. They esti-
mated that in a typical home laundering of six sheets (dimensions 72" x 81")
in 30 gallons of water, a concentration of 6 ppm of DBPP would be released
in the combined wash and rinse. No information is available on losses during
laundering of polyurethane foam products, such as pillows, which would contain
chloroalkyl phosphates.
65
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1
1
1
1
1
•
1
1
1
1
1
1
Table 30. Effect of Scouring on Surface
(Morrow et_ al_. , 1975)
DBPP Concentration
Total - Initial, %
Surface, Initial, ppm
Surface, 1 Wash, ppm
Surface, 3 Washes, ppm
Total - Final (After 50 Washes)
®
* Commercial fabric - Dacroir^ Type 54
** Yarn with spun-in DBPP
Tris(2,3-dibromopropyl) Phosphate
DacroiT^ Experimental
Polyester* . Acetate**
5.8 8.9
4300 600
780 90
65 90
5.1 ***
- Thermosor^ treated
*** Not tested - similar tests showed essentially complete retention of DBPP
Some evidence suggests
sewage microorganisms (See Section III-A,
are discharged with sewage (sewer systems,
that DBPP is biodegraded by
p. 87). Thus, if laundry wastes
septic tanks, etc.), DBPP (and
possibly chloroalkyl phosphates) might degrade before release to the environ-
1
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ment.
Haloalkyl phosphates could be lost to the environment
if a treated product is inadvertently dry
cleaned with a chlorinated solvent.
Since this is not typical of the recommended care of the product, it is
probably not a significant contamination source.
1
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B There is no information available on atmospheric emissions
of haloalkyl phosphate fire retardants. Atmospheric emissions during their
• addition to fabrics and plastics are considered insignificant (Stauffer Chemical
— Co., 1975). In the lifetime of the treated material, it is possible that
™ some haloalkyl phosphates might be exuded (Darby and Sears, 1968). Their low
B vapor pressures and studies on their compatibility with the resins in which they
are used suggest that such release should be slow. However, there is no
• confirmatory experimental evidence.
_ b. Pesticides
™ The major environmental contamination source of naled
JH and dichlorvos is quite obviously their use as pesticides. Most of the dich-
lorvos is apparently applied indoors and might be degraded before reaching
B the outdoors. Some naled is also used indoors.
5. From Disposal
B a. Fire Retardants
JH Industrial wastes seem a minor potential source of
environmental contamination. Waste streams from production are generated
B mostly by equipment and product washing. Blowing and molding of polyurethane
foams and spinning of cellulose acetate create no-waste streams (Burr, 1971;
B Stauffer Chemical Co., 1975). The only major addition process of haloalkyl
• phosphates which might create a waste stream is the topical addition of DBPP
to fabrics. This will include aqueous wastes and small quantities of
B organic solvent wastes. There is no information on absolute or relative
quantities of these wastes. Aqueous wastes generated by textile plants
B will probably be treated with active sludge (Burr, 1971; Schlesinger et al.,
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• 197L). Organic wastes are probably not released directly into the environ-
ment but are probably disposed of in chemical disposal plants or incinerators
• (Spencer, 1971). Overall, industrial wastes may not be an important contain!-
^ nation source, but monitoring data is needed to confirm this suggestion.
* Potential environmental contamination from disposal of
B treated products is inconclusive. Some of these products are recycled, but
che amount is uncertain. Some of the material is apparently reused after
• only physical treatment, e.g., the reuse of flexible polyurethane foams for
stuffing pillows and flexible and rigid polyurethane foams for carpet backing
™ (Stauffer Chemical Co., 1975). It is also reported that some polyurethane
A foams are hydrolyzed for recovery of polyols (Campbell and Meluch, 1976).
However, the fate of any haloalkyl phosphate additives under these conditions
• is unknown. One industrial source (Stauffer Chemical Co., 1975) has suggested
that the majority of polyurethane foams used in automobile interiors are
™ recycled material.
tt There is no information available on recycling of poly-
ester or cellulosic fabrics. Discarded household articles probably go into
• municipal landfills. There is no information on how much might be incinerated,
illegally dumped, or disposed of by other methods. McGeehan and Maddock
• (1975) have suggested that DBPP will accumulate in trash dumps and other
A disposal sites. However, they cite no documenting evidence.
There is no pertinent information on the potential
• degradation, loss, or accumulation of haloalkyl phosphates at disposal sites.
They could possibly biodegrade, but this has not been tested under field
I
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conditions (Ham, 1975; Fungaroli, 1971; Kerst, 1974).
68
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It is possible that some environmental contamination might
' result from transport of particulate matter containing haloalkyl phosphates.
fl Colt on and coworkers (1974) examined the possible origin of plastic materials
foM( •] in the Atlantic Ocean, While the plastic particles gathered in rhe
I Atlantic are not of the type expected to be treated with haloalkyl phosphates,
it is quite possible that some treated plastics could enter surface waters by
™ a similar pathway. Colton ej^ al_. (1974) suggest that plastics found in the
A ocean could have resulted from municipal solid waste disposal at sea, coastal
landfill operations, or ocean disposal of wastes from vessels.
• b. Pesticides
It is expected that dichlorvos and naled may be released
V to the environment with spent dichlorvos strips and empty pesticide containers.
M Some unwanted or contaminated pesticide will probably be discarded also.
Because of their rapid hydrolysis, dichlorvos and naled are not expected to
I
become a contaminant.
6. Potential Inadvertent Production in Other Industrial Processes
fl CEP might be formed during the production of tris(2-chloroethyl)
M phosphite, which is commercially prepared from phosphorus trichloride and
ethylene oxide (Kosolapoff, 1950; Mobil Chemical Co., 1976). Its major producer
• (Mobil Chemical Co., 1976) states that, under the reaction conditions used,
ethylene oxide would not form CEP with any phosphorus oxychloride present as
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an impurity in the phosphorus trichloride. The production of CEP as a by-
product is concluded to be minor (less than 0.1%).
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7, Potential Inadvertent Production in the Environment
Tris(2-chloroethyl) phosphite might also be a potential
• precursor for inadvertent environmental production of CEP(l).
|[0]
223 > 223
™ Although most phosphites are readily oxidized to phosphates (Kosalopoff, 1950;
ft Cherbuliez, 1973), tris(2-chloroethyl) phosphite is reportedly stable to
chemical oxidation (Mobil Chemical Co., 1976). However, since there is no
• confirming evidence to support the claim, some CEP may be formed from this
^ source. Tris(2-chloroethyl) phosphite is produced on a commercial scale by
• Mobil Chemical Co. (Richmond, Va.) and Telron Chemicals (Chicago, 111.).
ft Phosphite analogs of CPP, DCPP, or DBPP are not produced on a
commercial scale. If one can safely judge from phosphorus chemistry, none of
• the commercially produced alkyl phosphates, phosphonates, phosphines, or
other phosphorus compounds should yield any of the selected fire retardants
• in the environment.
• The insecticide trichlorfon is a precursor of dichlorvos.
In weakly alkaline media it hydrolyzes, as illustrated in (2). Its insectici-
• dal activity parallels that of naled (Fest and Schmidt, 1973; Eto, 1974).
0 0
II II
PCHCC13 - »• (CH30)2 POCH=CC12 (2)
OH
I
While trichlorfon is less toxic than dichlorvos, its insecticidal activity
is considered to rely upon its conversion to dichlorvos. Its annual production
is estimated at less than three million pounds (Sittig, 1971).
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D. Current Handling Practices and Control Technology
1. Special Handling in Use
a. Fire Retardants
Product bulletins for fire retardant haloalkyl phosphates
(Stauffer Chemical Co., 1972 a, b, 1973 a, b; Great Lakes Chemical Corp.,
1973 a, b, c; Tenneco Chemicals, Inc., undated) claim that they have low
hazard by ingestion, inhalation, or skin absorption. The bulletins suggest
that good industrial hygiene practices, such as avoidance of prolonged skin
contact, are sufficient precautions. In case of contact, soiled clothes
should be removed and affected areas washed.
Since haloalkyl phosphates are excellent plasticizers,
storage or transport with certain plastic equipment, in particular vinyl-based
resins, should be avoided (Stauffer Chemical Co., 1972 a, b, 1973 a, b).
b. Insecticides
The insecticides dichlorvos and naled require somewhat
more care in handling than the fire retardants. They are moderately toxic
and can corrode metal equipment. Special instructions for handling specific
insecticide formulations are specified on the product label (Chevron Chemical
Co., undated a, b; Shell Chemical Co., 1973a).
The concentrated insecticides can cause eye or skin
damage and can be absorbed through the skin. It is recommended that the
concentrates be handled with waterproof gloves and face shield or goggles.
In spraying operations, protection against inhalation and skin or eye contact
should also be taken.
In application, care should be taken to avoid contamination
of feed, foodstuffs, and drinking water. Dichlorvos strips should not be used
in rooms where people remain immobilized (e.g., with infirmed people or infants)
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The concentrated insecticides can corrode metal spraying
V or mixing equipment. All equipment should be thoroughly flushed with aromatic
m solvents after use.
2. Methods for Transport and Storage
• a. Fire Retardants
Tris(haloalkyl) phosphates are stable to normal conditions
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of transport and storage. Storage in carbon steel, glass, or glass-lined
steel containers is recommended (Stauffer Chemical Co., 1972a, b, 1973 a, b;
Michigan Chemical Corp., 1974 a,b). Heating to approximately 120 F may be
• necessary to facilitate pumping and handling of DBPP. Heating at this tempera-
ture should be limited to three days (Michigan Chemical Corp., 1974 a, b;
I Stauffer Chemical Co., 1972 b) . Prolonged heating can cause some evaporation
M loss, increase in acid number, and/or discoloration.
Tris(haloalkyl) phosphates can be shipped in quantities
up to tank or railroad car lots. Manufacturers will sell quantities as small
as one pound (Stauffer Chemical Co., 1972 a, b, 1973 a, b; Michigan Chemical
| Corp. , 1974 a, b) .
M b. Insecticides
In storage of dichlorvos and naled one must consider health
• and safety factors as well as stability of the chemicals.
To prevent degradation of the insecticide, the chemicals
| should be kept free of water and away from light. Light protection can be
A achieved by using brown glass bottles or other light-proof packaging, or by
storage in light-free areas. Since the chemicals are corrosive to iron and
• other metals, they are generally stored in glass or polyethylene liners
(Shell Chemical Co., 1973 a, 1975; Chevron Chemical Co. 1970, 1975).
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For health and safety reasons, naled and dichlorvos
• should never be transferred to containers in which they could become confused
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with foods, beverages, drugs, etc. Containers should always be clearly labeled.
They should be stored in a secure, locked area away from food.
Neither naled nor dichlorvos requires a Class B Poison
label, and both are exempt from Department of Transportation packaging re-
strictions. Both can be shipped in DOT 6 D steel drums with polyethylene
inserts (Shell Chemical Co., 1973 a, 1976; Chevron Chemical Co., 1976).
3. Disposal Methods
a. Fire Retardants
If disposal is necessary, high temperature incineration
with adequate scrubbing of the acidic gases formed is recommended (Stauffer
Chemical Co., 1975). However, Stauffer Chemical Co. (1975) does attempt to
recycle any unwanted phosphates by reprocessing. Those which are not recycled
are sometimes combined with other phosphorus-containing wastes in a central
disposal pit. The accumulated wastes in some cases may be sold for use as
fire retardants in railroad ties.
b. Insecticides
Several alternative methods are available for disposal of
unwanted pesticides. The U.S.E.P.A. (1974) recommends that whenever possible
the pesticide be used up according to label directions. When necessary,
incineration is considered the primary disposal method. Incinerators must
be capable of operating at a temperature and dwell time which will completely
destroy all the pesticide. Scrubbing equipment must remove hydrogen halides
and other gases, to meet emission requirements of the Clean Air Act.
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Alternative disposal practices include burial of the
pesticide in a specially designated land fill or disposal by soil injection.
Chemical degradation (hydrolysis) is recommended prior to landfilling.
Containers should be destroyed after use. The recommended
procedure is to rinse the container with an appropriate solvent, punch holes
in the container, and bury it in a manner that the pesticides will not pollute ground
or surface water, or to burn the container in accordance with state and local
regulations (U.S.E.P.A., 1974; Chevron Chemical Co., undated, a, b) .
4. Emergency Procedures
a. Fire Retardants
Procedures for emergency action are specifically concerned
with fire and human health hazards (Stauffer Chemical Co., 1972 a, b; 1973 a, b) .
Tris(haloalkyl) phosphates are not immediate fire hazards, since the products
are self-extinguishing once the source of ignition is removed. If fire does
occur, the vapors will contain the highly toxic fumes of phosphorus oxides
and hydrogen halides. In case of fire, it is recommended that the source of
ignition be removed or the fire cooled with water. Dry powder or carbon monoxide
are alternative measures (Stauffer Chemical Co., 1972 a, b; 1973 a, b) .
—
™ The following first aid measures are recommended (Stauffer
• Chemical Co., 1972 a, b; 1973 a, b) :
Ingestion - Induce vomiting
• Eye contact - Flush the eyes with large quantities of
water for a minimum of 15 minutes
Skin contact - Immediately flush affected areas with
water. Do not attempt to neutralize with chemical
agents.
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b. Insecticides
• In case of an insecticide spill, the United Parcel
Service (1974) recommends that all cleanup personnel wear protective
• clothing and that the vehicle or facility affected should be hosed down
• with water. The waste liquids should not be allowed to enter sewer systems.
The area should then be dried with a commercial non-organic drying agent.
• First aid for contact with skin or eyes was discussed
previously (See p. 74). In case of human poisoning, the recommended
B antidotes are atropine or 2 PAM (Chevron Chemical Co., undated a and b).
• 5. Current Controls
a. Fire Retardants
I There was no specific information in the literature on
controls for tris(haloalkyl) phosphates.
• b. Insecticides
• Air pollution problems can result from vapors or from
airborne dust formulations of insecticides. Sittig (1971) considers the
• dusts to be the greater health threat. According to Sittig (1971), the
largest sources of emissions result from crushing and grinding processes in
•I formulating dusts. Other sources of dusts include conveyers, blenders, storage
• hoppers, and packaging apparatus.
Control of the insecticide dusts and vapors consists of
• collection through hood and ventilation equipment followed by treatment.
To prevent occupational health hazards, Sittig (1971) notes that sources of
I
dust and vapors should be enclosed or tightly hooded. He recommends that
ventilation rates for crushers and mills should be 400 fpm or higher. For
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other operations, hoods should be ventilated at 200 to 300 fpm.
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Air pollution control for the collected dusts is achieved
• by filtering through cloth bags. With high through-puts, a conventional bag
_ house can be used (Sittig, 1971).
™ With vapor phase insecticides, air pollution control
• requires scrubbing. Sittig ( 1971) describes the use of a scrubbing tower
(14 cubic foot volume) packed with 1 inch intalox saddles to 4% feet high.
I Water rate through the tower is described as 20 gpm.
No specific recommendations for the treatment of liquid
* wastes containing dichlorvos or naled were found. Liquid effluents containing
flj organophosphate insecticide wastes have been successfully treated by chemical
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hydrolysis or with activated sludge (Atkins, 1972; Lawless et a.1. , 1972;
Lue-Hing and Brady, 1968).
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E. Monitoring and Analysis
• 1. Analysis
Although the literature contains extensive information on
| analytical methods for organophosphate insecticides, including naled and
• dichlorvos, rather limited data is available on haloalkyl phosphate fire
retardants. Since the two groups of haloalkyl phosphates possess similar
• physical and chemical characteristics, some of the analytical techniques
developed for the insecticides could be applied to the fire retardants.
| This section emphasizes the analytical methods which have been or could be
im applied to the fire retardants. However, the pesticide analytical methods
will be briefly reviewed first.
I a. Pesticides
Residue analysis generally consists of three stages:
| (1) collection; (2) sample preparation; and (3) analytical measurement (Van
H Middelem, 1963; Osadchuk et^ al. , 1971). Sources sampled for haloalkyl phos-
phate pesticide residues include ambient air, water, soil, food, polyvinyl
• chloride resin, crops, and animal tissues (Van Dyk and Visweswariah, 1975:
Wiersma et_ al., 1972 a, b; Shell Chemical Co. 1971a, 1973b; McCully, 1972;
| Burchfield et al., 1965). The collected sample should be kept at cold tempera-
g| tures during storage periods to prevent pesticide degradation (Van Middelem,
" 1963).
• Collection methods developed for haloalkyl phosphate
insecticides have varied considerably; many of the techniques could be applied
| to fire retardants. Water samples may be collected in all glass containers
• for subsequent work-up in the laboratory. (Zweig and Devine, 1969; Schulze
et al., 1973). Large volumes of water have been sampled by passing the water
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at a known rate through a suitable adsorption column (Hindin 1967; Hindin
• £t 5i-> 1964). Van Dyk and Visweswariah (1975) have reported that air has
been sampled for organophosphates by the use of impingers, scrubbers and
• adsorption columns. The efficiency of collecting air samples can be increased
• by lowering column temperature. They noted that particulate filtering yields
poor results, since the particles collected on the filter can either desorb
• or adsorb pesticides. Prager and Deblinger (1967) describe a gas chromato-
graphic unit for continuously monitoring airborne phosphate insecticides.
B However, the technique measures total phosphorus-containing compounds rather
• than a specific substrate. Solid samples, including foods, plant and animal
tissues, and resins, are usually chopped-up and then extracted with a suitable
• solvent, e.g.}chloroform, ethyl acetate, or hexane (Shell Chemical Co., 1964,
1973b; Chevron Chemical Co., 1973).
• Sample preparation usually consists of extracting the
• substrate of interest into an appropriate solvent, removing interfering sub-
stances and sometimes concentrating the solution containing the compound of
• interest. Gas chromatography, which is the most sensitive method available
for haloalkyl phosphates, is very sensitive to interferences. Interferences
• can foul equipment, overload the column or detector, or cause peak tailing,
• or might inadvertently be measured along with the substance of interest.
Zweig (1970) and McCully (1972) suggest extraction of the pesticide into a
• suitable solvent followed by a chromatographic clean-up procedure. They favor
acetonitrile as the solvent and suggest acetonitrile-petroleum ether portion-
m ing if the removal of lipids is necessary. Column chromatography is then
• suggested using Florisil, Celite, alumina, and aluminosilicate, or charcoal
as the adsorbant (Watts et al., 1969; Zweig, 1970; McCully, 1972).
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I Table 31 lists the lower detection limits for some common
methods of dichlorvos and naled analysis. With the exception of enzymatic
I techniques, these methods could be used to analyze the fire retardants.
_ In choosing a method, one must consider the residue
™ concentration, the purpose of the work, and the cost for equipment and man-
I power. For example, gas chromatography combined with mass spectrometry is
unexcelled for unequivocal identification and measurement of low concentrations
• of residues in environmental samples. The equipment and operating costs are,
however, relatively high. When multiple samples of a known haloalkyl phosphate
™ in the absence of interferences must be quantitatively analyzed, a total halide
H or total phosphorus determination would be a more efficient technique (Ott,
1975). The haloalkyl phosphate fire retardants are not sufficiently active
• esterase inhibitors for successful use of an enzyme inhibition technique.
_ Table 32 lists some of the many techniques used to analyze
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naled and dichlorvos.
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Table 31. Lower Limit of Detection for Analysis
Analytical
Technique Detected
Gas Chromatography
Electron capture detector Cl, Br, P
Sodium thermionic detector P
Flame photometric detector P
Microcoulometric detector Cl, P
Thin-layer chromatography
Silver nitrate spray detection Cl, Br
Acid-molybdate spray detection P
Esterase spray detection Esterase
inhibition
Infrared spectrometry
Mass spectrometry
Elemental analysis
Molybdenum complex P
Specific ion electrode Cl, Br
Enzymatic analysis Esterase
inhibition
80
of Haloalkyl Phosphates
Lower Limit
of Detection Reference
0.1 - 1 ng Zweig; 1970;
1.0 - 10 ng Westlake and
1 ng Gunther, 1967;
10 - 100 ng McCully, 1972
Wise, 1967;
Watts, 1967;
5 ng Mendoza and
Shields, 1971
10 yg Widmark, 1971
10 ng Widmark, 1971
40 ng Kirkbright, et al. ,19
100 ng Buchler, 1971;
Thomas Co. , 1974
5 ng Mendoza and
Shields, 1971;
Burchfield et al. ,
1965
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Table 32. Summary of Analyses of Dichlorvos and Naled
Reference
Gluffrida, 1964
El-Refai and Gluffrlda, 1965
Ruzicka e_t ai., J967a, b
Minett and Belcher, 1969
Bechman and Garber, 1969
McCully, 1971
Machln et al_. , 1973
Chevron Chemical Co., 197!
Shell Chemical Co., 1973b, 1971a
Askew et, al. , 1969
Srhultz et aK , 1971
Crisp and Tarrant, 1971
Ivey and Claborn, 1969
Scolnick, 1970
Boone, 1965
Bache and Lisk, 1966
Pardue, 1971
McKinley and Read, 1962
Getz and Friedman, 1963
Mendoza and Shields, 1971
Analyt ical
Technique
GC-AFD
GC-AFD
GC-AFD
GC-AFD
GC-AFD
GC-AFD
GC-AFD
GC-AFD
GC-AFD
GC-AFD
TLC-Molybdate spray
GC-AFD and GC-ECD
GC-AFD
GC-FPD
GC-chemlcal lonization
detector sensitive to
phosphorus
Food GC-microcoulometric
detector
Food GC-microwave powered
detector set selective
for phosphorus
Experimental mixture GC-ECU
PC-Esterase spotting
PC-Esterase spotting
TLC-Esterase spotting
Sample
Source
Food
Food
Food and river water
Food
Food
Crops
Blood
Plant tissue and
milk
Air, food, animal
tissues, formulated
products
River water, sewage
effluent
Tissues and urine
Crops
Food
Experimental mixture
Sherman, 1968
al. , 1973
lunther, 1966
id Scudamore, 1966
- and Van Gend, 1968
is chromatography
Animals
Air
Food
Air
Food
TLC-AgN03
Enzymatic
Enzymatic
Enzymatic
Enzymatic
spotting
inhibition
inhibition
inhibition
inhibition
AFD — Alkaline flame detector
ECD — Electron capture detector
PC — Paper chromatography
TLC — Thin-layer chromatography
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Gas chromatography is the most frequently chosen technique
I for measuring low residue levels in samples from the ambient environment where
related materials might be present. Glass columns are recommended over stain-
• less steel or other metal tubing, because metals can decompose halogenated
• hydrocarbons (Zweig, 1970). A polar liquid phase such as one of the silicone
oils (e.g., SE 30 or DC-200) is recommended for phosphate insecticides
I (Zweig, 1970). The alkaline flame detectors (AFD), which are also known as
thermionic detectors, are an excellent choice for the haloalkyl phosphates.
' Advantages include their high specificity and sensitivity for phosphorus over
• other elements, their low detection limits, and the excellent linearity of
their response curves at lower limits of detection (Westlake and Gunther, 1967;
I Zweig, 1970; Widmark, 1971; McCully, 1971, 1972). Other phosphorus-specific
detectors have also been used successfully. These detectors, such as flame
• photometric detectors and microwave powered detectors, filter out all wavelengths
• other than those specific for phosphorus. For example, the flame photometric
detector filters out irradiation other than the phosphorus-specific wavelength,
• 526 nm (Zweig, 1970). Electron capture detection is not recommended for naled
and dichlorvos, although it does permit detection of low concentrations. Its
H disadvantages include its high potential for inadvertent measurement of other
• substrates and its lack of a linear response curve at low concentrations.
Unequivocal gas chromatographic analysis requires
• some confirmation that the observed peak corresponds to only the compound of
interest. Some chromatographic techniques have been used as confirmation
• (e.g., by retention time on two different packing materials). However, con-
• firmation by a totally independent analytical technique is preferred. Mass
spectroscopy in conjunction with gas chromatography has often been the method
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of choice (Widmark, 1971; Biros, 1971). Gas chromatography combined with
I infrared spectroscopy can also be used, but this technique requires some
• three orders of magnitude higher concentration of the substrate (Widmark, 1971),
TLC has also been used for quantitative analysis. Getz
• (1971) suggests that optical techniques are the most sensitive quantitative
method.
• b. Fire Retardants
• Table 33 lists methods by which DBPP has been analyzed.
It is the only haloalkyl phosphate fire retardant for which analytical
I techniques capable of measuring low concentrations have been developed and
reported in the literature.
I Gutenmann and Lisk (1975) used a colorimetric phospho-
• molybdate complex technique for quantitative analysis of aqueous DBPP. The
water sample was either evaporated to dryness (This work-up procedure is
I susceptible to many phosphorus interferences) or DBPP was partitioned into
benzene and the benzene stripped off. The detection method consists of
I hydrolysis of the ester to yield ortho phosphoric acid, subsequent preparation
• of the phosphomolybdate complex and finally colorimetric measurement of its
concentration. Hydrolysis of the ester required a four hour reflux with
• hydrobromic acid.
Morrow and coworkers (1975) determined DBPP in treated
• fiber by bromide analysis following a benzene-hexane extraction. The benzene-
• hexane solution of DBPP was burned in oxygen, and the bromide was collected
and determined by specific ion electrode. Concentration of parts per million
m based on original fiber were reported (See Table 30, p. 66).
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Table 33. Summary of Analyses Techniques for Tris(2,
Phosphate
Sample Sampling
Reference Source Technique
Cope, 1973 Treated fiber Pyro lysis
Morrow et al. , 1975 Treated fiber Extracted
by organic
solvent
Gutenmann and Treated fiber Extracted
Lisk, 1975 with water
3-3ibromopropyl)
Analytical
Technique
Gas chromatography-
flame photometric
detector
Bromide electrode
Colorimetric measure-
ment of phosphomolybdate
complex
Cope (1973) examined the gas chromatograph of DBPP
pyrolysate (Figure 6). Samples of DBPP reagent and DBPP
pyrolyzed at 400 C and passed onto the g.c. column. The
on polyester were
resulting chromato-
grams are rather complicated, and the method does not appear to be suitable
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for identification or measurement of ambient levels.
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(a)
(b)
Figure 6. Gas Chromatographs of Tris(2,3-dibromopropyl) Phosphate Reagent (a)
and on Polyester (b) (Cope, 1973)
Conditions:
Injection - Pyrolysis at 400 C
Column - 6' stainless steel packed with 5% OV-1 silicone
on 60/80 Chromosorb
Temperature - 50 to 180° C at 10°/minutes
Detection - flame photometric
Reprinted with permission from the American Chemical Society.
Although gas chromatography is theoretically the most
sensitive technique for analyzing haloalkyl phosphate flame retardants, their
relatively low thermal stabilities and vapor pressures might limit the appli-
cation of the technique. In gas chromatography the sample must be vaporized
in the injection port and then separated into the individual components on
the chromatographic column. Naled does exhibit minor degradation to yield
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dichlorvos during chromatographic analysis (Chevron Chemical Co., 1973).
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Haloalkyl phosphate fire retardants are thermally less stable and have lower
« vapor pressures than naled or dichlorvos. Thus, it might not be possible to
pass tris(haloalkyl) phosphates through a gas chromatograph at temperatures
" at which they are stable.
M Thin layer chromatography should be effective for
analysis of haloalkyl phosphate fire retardants. TLC conditions discussed
• for dichlorvos and naled probably would be applicable to fire retardants.
Silver nitrate techniques are suggested for their spotting. Esterase and
• phosphomolybdate sprays are not expected to be useful. Acid hydrolysis,
which is necessary for the phosphomolybdate technique, would probably be
too slow.
• 2. Monitoring
CEP has been listed as an organic compound found in U. S.
• drinking water (WSRL, 1975). Except for this listing, no monitoring study
• has listed any of the six haloalkyl phosphates discussed in this report.
Several groups have monitored for ambient pesticides, including
• organophosphates. The following studies, which used gas chromatography with
alkaline flame detection, did not list naled or dichlorvos: Surface Waters -
m Schulze and coworkers (1973),Zweig and Devine, 1969; Ground Water - Schulze
<• and coworkers (1973); and Soils - Wiersma and coworkers (1972 a, b),
Crockett and coworkers (1974). The investigation by Zweig and Devine (1969)
• was the only study to specifically confirm their absence.
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III. Health and Environmental Effects
• A. Environmental Effects
m 1. Persistence
a. Biological Degradation, Organisms, and Products
M Microbial degradation of haloalkyl phosphates has been
the subject of only a few reported studies. Among the compounds on which
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some biological fate-related information is available are: dichlorvos,
an organophosphorus insecticide, and tris(2,3-dibromopropyl) phosphate,
a fire retardant.
• In view of the fact that dichlorvos reaches soil most
often as a result of direct application, its fate in soil has received the
• most attention. Matsumura and co-workers (Matsumura and Boush, 1968; Boush
M and Matsumura, 1967) reported that Trichoderma viridis, a soil fungus, and
Pseudomonas melophthora, an insect symbiote, had the ability to degrade
• dichlorvos. The fungus was isolated from soil which had been heavily
contaminated with a number of insecticides. The bacterium was obtained from
| the larvae of the insect, apple maggot. In the degradation studies C-labelled
j| dichlorvos (0.22ppm) was incubated with the organism in a liquid medium
containing yeast extract and mannitol as nutrient source. The criteria used
• for degradation was conversion of the organophosphate to water-soluble
metabolite(s). The authors reported nearly 85% conversion to water-soluble
| metabolites by the bacterium and nearly 95% conversion by the fungal culture.
M Although the breakdown of dichlorvos by the insect symbiote may be important
from the point of view of the protective mechanism of the host, the environ-
• mental significance of such breakdown appears to be very limited. The results
of the study may suggest, however, that other more environmentally significant
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Pseudomonas sp. may also have the potential to attack this compound.
I The bacterial attack on dichlorvos gave rise to two
^ water-soluble metabolites, which separted when thin layer chromatography
™ was used. The number of metabolites formed in the fungal cultures was not
fl determined. No attempts were made to identify the metabolites of dichlorvos.
It is generally assumed that conversion of a compound to water-soluble
• metabolites implies the compound is biodegradable. This is, however, not
always true, and, unless the identity of the metabolites is known, it remains
™ uncertain if the metabolites may be more toxic and/or persistent than the
fl parent compound.
A bacterium isolated from mosquite breeding waters
V (where the organophosphorus pesticide had presumably been applied) and later
identified to be Serratia plymuthica, was also reported to catalyze the
" breakdown of dichlorvos (Hirakoso et_ cil. , 1968). It was noted that the
• products of breakdown by ^. plymuthica were devoid of pesticidal activity.
Other details of the study are not available.
• In an effort to ascertain the contribution of biological
and non-biological agents to the degradation of dichlorvos in soil, Getzin
^ and Rosefield (1968) studied pesticide degradation in non-sterile, gamma
• radiation-sterilized, and autoclaved soil. The organophosphate was degraded
nearly 100% in non-sterile soil and nearly 88% in the gamma-irradiated soil,
• which suggested that microorganisms were partly responsible for the
degradation process. In the irradiated soil, the breakdown was attributed
• to a non-viable, heat-labile substance (suspected to be cell-free enzymes).
This conclusion was based on the observation that in heat-sterilized soil
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(autoclaved soil), degradation of dichlorvos was only 17%. The method
• of assay of insecticide residue in soil in this study involved extraction
with hexane, followed by measurement with a gas liquid chromatograph
equipped with a phosphorus detector. The chemical nature of the breakdown
• products was not determined.
The ability of a mixed culture of microorganisms present
• in raw sewage to degrade the flame retardant DBPP was evaluated by Kerst
(1974) in a shake flask test (Soap and Detergent Association, 1965). Sewage
• microorganisms, following acclimation by two 72-hour adaptive transfers, were
£ incubated in SDA basal medium (containing 0.3 g/1 yeast extract) with DBPP.
A flask to which linear alkylbenzenesulfonate (LAS) had been added was
V also incubated simultaneously and served as a positive control. Since DBPP
is soluble to only 1.5 ppm, an increase in the bromine content of the aqueous
• phase in excess of the solubility of DBPP was presumed to be due to bromide
• release from DBPP degradation. The total bromine content was estimated using
neutron activation analysis. Employing this criteria, the authors reported
• that slow degradation of DBPP was occurring and that nearly 0.3-0.5% of the
total added DBPP (calculated fjrom the bromine equivalents of DBPP) had been
I degraded after an incubation period of 5-15 days. (See Table 34.)
• However, very little can truly be concluded from the
data because the observed change of bromine concentration can be attributed
• to a variety of causes. For example, an increase in the solubility of DBPP
will also result in increased bromine levels in the liquor. In the inoculated
V samples, the bacterial metabolism of the basal medium may cause
medium compositional changes which may subsequently affect the solubility
of DBPP.
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• Slow or no biodegradability of DBPP has also been
• suggested by McGeehan and Maddock (1975) who state that DBPP will tend to
bioaccumulate in trash dumps and other disposal sites.
• In summary, the persistence of haloalkyl phosphates in
the environment is not well understood. The available information on DBPP
W and dichlorvos suggests that these compounds may be susceptible to tnicrobial
• attack to some extent. The identity of the products or the mechanisms of
their breakdown are not known. It is also unclear if the haloalkyl phosphates
• will undergo only hydrolysis or are susceptible also to further breakdown.
b. Chemical Degradation in Environment
• Experimental data on the degradation of haloalkyl
M phosphates in the environment by chemical agents is not available. The
chemical reactions and other characteristics of these compounds in relation
• to materials such as water, air, etc., have been reviewed in Section I-B,
p. 13). Hydrolysis of dichlorvos and naled in aqueous solution is fairly
•i rapid under conditions similar to those found in nature. Dichlorvos also
•j decomposes rapidly when sorbed onto solid carriers, even when the carriers
have been dried (Attfield and Webster, 1966). Getzin and Rosefield (1968)
V have reported nearly 17% breakdown of dichlorvos in soil in 24 hours by
chemical mechanism(s). The fire retardant haloalkyl phosphates have been
described to undergo only slow hydrolysis under neutral conditions (Tenneco
• Chemicals, Inc., undated).
The transformation of haloalkyl phosphates as a result
W of chemical oxidation in the environment is unlikely except in the case of
dichlorvos, which has a double bond. Available information suggests that the
commercial haloalkyl phosphates are not photodecomposed by sunlight to any
measurable extent (Stauffer Chemical Co., undated, a,b,c,d).
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2. Environmental Transport
B No experimental work relating to the environmental transport
fl| of haloalkyl phosphates has been reported. The fairly low vapor pressure
of these compounds (Table 2, p. 4 ) suggests that they will not rapidly
I vaporize and distribute through the atmosphere. Mackay and Leinonen (1975)
have presented equations which allow estimations of approximate evaporation
V rates of low water-soluble contaminants from a water body to the atmosphere.
Using this approach, the evaporation half-life for haloalkyl phosphates
DBPP and dichlorvos for a cubic meter of water would be 59.5 and 2111 hours
K respectively (See Table 35). Thus evaporation will probably have only a
small role in the distribution of haloalkyl phosphates in the environment.
• Calculation of the evaporation half-lives for certain low
m* molecular weight chlorinated hydrocarbons for which experimental values
are known (Dilling e_t^ al. , 1975) has revealed that the calculated values
• are in general much longer than the experimental values. (e.g., for methylene
chloride, calculated and experimental values are 5.35 hours and 21 minutes>
W respectively.) In view of this discrepancy, it needs to be emphasized
im that the calculated half-lives for haloalkyl phosphates should only be
relied upon to obtain a rough order of magnitude of their evaporation from
• water.
No laboratory and/or monitoring studies have been reported
I which deal with the mobility of haloalkyl phosphates in the aquatic environ-
M ment. Haloalkyl phosphates in general are sufficiently water-soluble
(except perhaps for DBPP) to suggest that at environmentally significant
• concentrations they will more likely remain dissolved in water rather than
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93
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be absorbed on particulate matter or sediment. Consequently, these com-
* pounds and perhaps also their hydrolysis products may be expected to be trans-
fl ported with water. On the other hand, DBPP is so insoluble in water (1.5ppm)
that adsorption to particulate matter and sediment may play an important role
• in its environmental transport.
3. Bioaccumulation and Biomagnification
• Laboratory studies on the bioaccumulation and biomagnification
• potential of haloalkyl phosphates are not available. Physical and chemical
characteristics of their molecules may allow prediction of their behavior
• to some extent. Accumulation of a chemical occurs when the chemical is
taken into biological material faster than it is eliminated. The appreciable
™ water solubility of many haloalkyl phosphates (CEP, CPP, DCPP and dichlorvos),
4| coupled with their susceptibility to biological and/or chemical hydrolysis
whereby they may be converted to even more water soluble compounds (See Sec-
• tion III-A-1), suggests that they will have relatively low
bioconcentration potential. Tris(2,3-dibromopropyl) phosphate, on the other
• hand, has very low water solubility and it may be bioconcentrated.
M Biomagnification refers to concentration of a compound
through the consumption of lower organisms by higher food chain organisms
• with a net increase in tissue concentration (Isensee et^ ai_., 1973). Metcalf
and Lu (1973) have noted that the biomagnification potential of the chemicals
• evaluated in their model aquatic ecosystem showed a relationship with water
M solubility; they described a regression equation for the line fitted by the
method of least squares. Using this relationship, the biomagnification
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t
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potential for haloalkyl phosphates has been calculated and the values are
given in Table 36. From the data, it appears that haloalkyl phosphates in
general will not biomagnify to a significant extent in the food chain
organisms. Some biomagnification in the food chain, however, may be
possible in the case of DBPP.
Table 36. Biomagnification Potential of Haloalkyl Phosphates (Calculated
from the Regression Equation of Metcalf and Lu (1973))
Compound
Log Water Sol., ppb,
Biomagnification
potential, Fish
.Concn. in Fish.
DBPP
CEP
CPP
DCPP
Dichlorvos
DDT (for comparison)
3.17
6.84
6.0
5.0
7.0
0.079
Concn.
338
1.
5.
24.
1.
16950
in Water
7
63
0
3
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^ B. Biological Effects
1. Biology
• a. Absorption, Transport, and Distribution
i. Tris(haloalkyl) Phosphates
I Little information is available on the absorption,
_ distribution, and transport of the tris(haloalkyl) phosphates. Specific in-
* formation is limited to data on tris(2,3-dibromopropyl) phosphate (DBPP).
9 These data suggest, however, that the tris(haloalkyl) phosphates may not be
absorbed and metabolized in the same fashion as dichlorvos and naled.
• A study was conducted on the absorption of DBPP in
_ rats and humans by St. John and coworkers (1976). In one portion of the
•
— study, 100 mg of pure liquid DBPP was spread on the gauze pad of a I'1 bandaid
A and pressed tightly to an area of shaved skin on a rat's back where it re-
mained for seven days. The bandage was tightly secured with adhesive tape.
• In the second part of the study, the entire body of a rat was shaved and
covered by a close-fitting sleeve of flannel treated with the fire retardant.
~ This exposure was continuous for nine days. Two humans (one adult and one
ft child) were also exposed nightly for seven nights to fire retardant-treated
flannel pajamas. Urine samples were monitored for the appearance of a
I suggested metabolite, 2,3-dibromopropanol, which would have indicated absorp-
tion.
• Results of the first rat study (with direct applica-
A tion of the chemical) indicated dermal absorption of DBPP had occurred. This
absorption process resulted in a slow appearance of the metabolite in urine
• (See Section III-B-1-b, p. 99). However, in both rats and humans exposed
to the fire retardant-treated fabric, the presence of 2,3-dibromopropanol,
96
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in either the free or conjugated form, could not be identified in the urine.
St. John and coworkers (1976) concluded that if any of the chemical did mi-
grate from the fabric to the skin and was actually absorbed, the resulting
amount of urinary 2,3-dibromopropanol was too small to be detected (sensi-
tivity = < 0.4 ppm in the rat and < 0.2 ppm in the humans). Small amounts
of the metabolite were isolated in rat urine when the rat was allowed to
I
chew on the fabric. Apparently, sufficient amounts of DBPP were absorbed
from the fabric by the oral route. It is not known from the above study,
however, whether 2,3-dibromopropanol was the most appropriate metabolite to
be monitored. Furthermore, lacking evidence from a study using radiolabeled
material, it is difficult to determine, (1) the percent of the applied dose
I
which is actually absorbed, (2) the amount and location of the parent com-
1
B pired CO , biliary, etc.).
pound and its metabolites in various body tissues, including their time of
retention, and (3) the. major routes of excretion (i.e. , urinary, fecal, ex-
2'
After oral absorption of DBPP, bromine residues are
I
stored in various body tissues for an extended period. Kerst (1974) deter-
V mined the distribution of bromine residues after an experiment in which rats
were fed 100 and 1000 ppm of the fire retardant in their diet for 28 days.
9 The results (see Table 37) showed that dose-related levels of bromine, ex-
A pressed as ppm equivalents of the parent compound, remained in the muscle,
fat, and liver after the treatment was discontinued. The residue concentra-
• tions returned to the control levels by six weeks after discontinuation of
the DBPP feeding. The tissue levels of bromine remaining after two weeks
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•
indicate storage does occur and suggest the possibility of some cumulative
effects. This retention is consistent with the somewhat slow appearance of
the brominated metabolite after administration of DBPP, as found by St. John
and coworkers (1976) . The actual identity of the bromine-containing residues
was not determined.
W Table 37. Tissue Residue Levels - ppm of Bromine in Tissue (Kerst, 1974)
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Withdrawal Time
(wks)
0
0
0
2
2
2
6
6
6
Number of
Test Animals
5
5
5
5
3
3
2
2
2
Feed Level
ppm
0
100
1000
0
100
1000
0
100
1000
ppm
Muscle
1.0
6.1
48.2
1.1
1.9
8.2
1.0
0.8
0.8
of Bromine
Liver
2.4
17.1
122.0
3.2
6.2
23.2
2.1
2.4
2 3
Fat
1.3
7.9
55.3
1.4
1.3
7.7
0.7
0.6
0.6
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ii. Dichlorvos
w Dichlorvos is very well-absorbed into mammalian
fl systems by virtue of its high lipid solubility (which enhances oral and dermal
absorption) and high vapor pressure (which enhances inhalation absorption).
• Radiotracer studies have indicated (Gaines et^ al_. , 1966; Casida et^ al^. , 1962;
Laws, 1966; Potter et_ a^. , 1973a,b) that dichlorvos, when administered by
w oral and parenteral routes, can be monitored in the hepatic and systemic cir-
A culation within minutes of its administration to various animals. Inhalation
exposure to dichlorvos in rats produced a similar pattern of rapid uptake
• and tissue distribution with elimination being almost complete in less than
one hour (Blair et al., 1975).
W iii. Naled
A Being somewhat less volatile and lipid soluble than
dichlorvos, naled may not be as readily absorbed. However, when administered
• orally to the cow, naled followed a pattern of uptake essentially identical
to that of dichlorvos (Casida et al., 1962). This may be due to its rapid
I~~
biotransformation to dichlorvos (Menzie, 1969). Peak blood levels were ob-
f| tained within two hours of treatment, with elimination from the blood being
complete after five days.
• b. Metabolism and Elimination
i. Tris(haloalkyl) Phosphates
|| Little information is available on the metabolism
m of tris(haloalkyl) phosphates. Considering their chemical nature (See Sec-
tion 1-B), these compounds would probably undergo hydrolysis to some extent,
• although much more slowly than dichlorvos or naled.
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Johnson (1965) determined that the glutathione level
in female rat livers was not affected by the oral administration (200 g/rat)
• of either DBPP or CEP. The metabolism of dichlorvos, however, is strongly
influenced by glutathione levels in the liver (See Section III-B-1-b-ii, p. 101)
0 Limited studies on the metabolism of DBPP in rats
M were conducted by St. John and coworkers (1976). An initial assumption was
made that DBPP would be hydrolyzed to an alcohol or acid in the same fashion
• as organophosphate insecticides. Therefore, DBPP should yield 2,3-dibromo-
propanol (DBP) as an alcohol hydrolysis product, and subsequently be elimlna-
ff ted in either free form or as a conjugate in the urine.
» In order to determine whether the hydrolysis of DBPP
to DBP occurred in rat liver tissue, St. John and associates (1976) conducted
• in vitro studies with the 10,000 x g supernatant fraction of fresh rat liver.
This fraction contained both microsomes and soluble enzymes. Their results
I indicated about a 5% conversion of DBPP to DBP after a 30-minute incubation
— period, suggesting that DBP may not be a major metabolite of DBPP.
* When tested in vivo by exposing rats to concentrated
• DBPP applied dermally, urinary excretion of DBP and its conjugates was detec-
ted. The data in Table 38 reveal that only small quantities of DBP were
• excreted in the urine. The apparently elevated levels of DBP in later
_ samples are probably due to a concentrating effect produced by a decreased
™ urine output. The investigators verified their analytical methods by treat-
fll ing control urine samples with 5 ppm of DBP. Recovery ranged from 84 to 90%
with the limits of detection being 0.4 and 0.2 ppm in rat and human urine,
• respectively.
100
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Table 38. Concentrations of Free and Conjugated 2,3-Dibromopropanol (DBF)
in Rat Urine as a Function of Time After Dermal Application of
Liquid DBPP on Day Zero (Modified after St. John et al^. , 1976)
Day
0 (control)
1
2
4
5
7
Urine
Production
(Daily
total in
g)
12.2
8.8
11.0
9.2
6.2
4.1
Urinary concentration as DBPP
DBP (free) DBP
nd1
nd
0.80
2.67
12.81
1.33
(ppm)
(conjugated)
nd
1.28
1.17
2.83
10.67
7.63
detectable
The lack of radiolabeled DBPP prohibited a more
quantitative investigation of excretion patterns and the isolation of all
biotransformation products. It is apparent from the data which are available,
however, that DBPP is probably not metabolized in the same fashion as the
insecticidal organophosphate compounds.
ii. Dichlorvos
The pattern of tissue distribution of radioactivity
32
from P-dichlorvos is typical of a compound that is rapidly hydrolyzed and
101
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excreted (Casida et al., 1962). Two major pathways of dichlorvos degradation
0 have been determined, one in which the P-0-vinyl bond is hydrolyzed and the
• other in which demethylation occurs (Figure 7). Radiotracer studies have
indicated that the former is the predominant route (Casida e_t_ a^. , 1962;
• Hut son et_ al. , 1971a,b; Hutson and Hoadley, 1972a,b).
I
• O.-HV °
t \»>
> T>ln nu — p
1^ P40-CH =
CH^O/ ^ \
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3 £ A Cl
B
• A: phosphate-vinyl bond
B: phosphate-methyl bonds
Figure 7. Sites of Metabolic Cleavage of Dichlorvos
— Studies on the in vitro degradation of dichlorvos
* in the rat kidney and in whole blood of the rat, rabbit, and human indicated
• that dichlorvos is very rapidly metabolized (Blair et al., 1975). Hodgson
and Casida (1962) determined the metabolic pathways of dichlorvos degradation
• based on in vitro studies in the rat (Figure 8).
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OCH=CC12
CH3OH
HO"rv-OCH=CCl2
S2N
CH30X ^0
COOH
HO
CH3OH
OH
OCHCHC!
2
OH
[CC12=CHOH]
INE
CHC12CHO
U / \A
CHC12COOH CHC1ZCH2OH
Figure 8. Metabolic Pathways of Dichlorvos in the Rat Based on In Vitro
Studies (Hodgson and Casida, 1962)
P Plasma enzyme hydrolyzing dichlorvos to dimethyl phosphate, activators
not studied.
pl Plasma enzyme hydrolyzing monomethyl phosphate to inorganic phosphate,
activators not studied.
S Soluble liver enzyme hydrolyzing dichlorvos to dimethyl phosphate,
i i
activated by Mn
S1 Soluble liver enzyme hydrolyzing dichlorvos to des-methyl dichlorvos,
activators not studied.
S^ Soluble liver enzyme hydrolyzing des-methyl dichlorvos to monomethyl
-4 ++
phosphate, activated by 1 x 10 M Co
Q
S3 Soluble liver enzyme hydrolyzing monomethyl phosphate to inorganic
phosphate, no known activators, inhibited by — SH inhibitors, pH
optimum phosphate, 6.8-7.2.
M Liver mitochondrial enzyme hydrolyzing dichlorvos to dimethyl phosphate,
i t
activated by Ca
A Reduction of dichloroacetaldehyde to dichloroethanol by alcohol dehydro-
genase, requires DPNH.
NE Nonenzymatic.
U and U1 Pathway probably present, nature of enzymes not studied.
103
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Numerous studies
dichlorvos in animals and man verify that
on the in vivo degradation of
rapid detoxification occurs via
hydrolysis cf the vinyl-phosphate bond and 0-demethylation (Hutson et al..
1971b; Casida et . al. , 1962; Blair and Rees, 1972; Loeffler e_t al . , 1971;
Potter et aj_. , 1973a,b; Page et a^. , 1971
, 1972; Hutson and Hoadley, 1972a, b)
Certain investigators have pointed out that the
0-demethylation of dichlorvos in vivo and
in vitro is influenced by liver
glutathione levels (Hollingworth, 1970; Dicowsky and Moreilo, 1971; Hutscn
et_ al. , 1971b) . Apparently, glutathione
methyl groups in a reaction catalyzed by
dealkylates dichlorvos by accepting
the enzyme glutathione S-alkyl
transf erase. Desmethyl dichlorvos emerges as the product of this metabolic
reaction. However, Miyata and Matsumura
(1972) have presented conflicting
evidence which discounts the importance of glutathione-mediated demethyla-
1
tion of dichlorvos.
iii. Naled
Few studies on the metabolism of naled have been
conducted. According to Matsumura (1975)
, naled must be converted in vivo
into dichlorvos to cause anti-cholinesterase effects and any resultant tox-
1
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•
1
1
1
icity. Kohn (1969) cited unpublished data (Chevron Chemical, no date, c)
indicating the degradation of naled to dichlorvos is almost instantaneous
and proceeds in the following manner:
CH^O r ir
3 \t 1
Pf-% f-t p -i i o-pn
— L — C L.X T/Kb
CH 0 1
H Cl
naled cystine
ion
104
0 H Cl
CH.,0 ; | /
3y 1 /
v ^p r\ r\ — r\ i
*• r U L. U "T
CHO \
J Cl
dichlorvos
RSSR + 2Br
cystine bromine ion
-------
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Menzie (1969) has presented a scheme of degradation of naled which involves
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two pathways — one via debromination and the other in which the phosphate-
ethyl bond is cleaved (See Figure 9).
c. Metabolic Effects
i. Cholinesterase Inhibition
Organophosphate chemicals have been widely used as
insecticides, nerve gases, and therapeutic drugs primarily because of their
pharmacologic properties as inhibitors of cholinesterase. Cholinesterasa&
M
are enzymes whose function is to catalyze the hydrolysis of acetylcholine,
• an important neurohumoral transmitter substance, into acetate and choline.
In catalyzing the hydrolysis of acetylcholine, cholinesterases are responsi-
fj ble for the termination of action at the neuroef fector junction.
. Two types of enzymes catalyze the hydrolysis of
acetylcholine: 1) "pseudo" or "plasma" cholinesterase, which is found widely
• in plasma, liver, gut, and glial cells, and 2) acetylcholinesterase, or so-
called "true" cholinesterase, which is present in erythrocytes and also is
• located within cholinergic nerves and external to the nerve membrane in
— cholinergic synaptic regions. Plasma or pseudo cholinesterase may catalyze
™ the hydrolysis of many esters, including acetylcholine, succinylcholine, or
fl procaine. It is an important enzyme in limiting the effects of drugs, but
not so much in terminating acetylcholine action at nerve terminals. Acetyl-
• cholinesterase, on the other hand, is associated with all cholinergic nerves
_ and is relatively specific for acetylcholine. There is according to Casida
• (1973) "as yet no clear indication that inhibition of cholinesterase other
• than acetycholinesterase is responsible for significant physiological dis-
ruptions in poisoned animals."
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0
Br Br
I I
CH3-0-P - 0-C - C - Cl
0 0 Cl
CH30-P-OH + C-C-Br
6 I /I
OCH3 H Cl
V
0
II
CH3OH + CH30-P-OH
OH
0
II
CH3OH + HO-P-OH
OH
I
OCH3 H
Naled
Cl
0 Cl
CH3-0-P-0-CH=C
OCH3
C1
0,0-Dimethyl-2,2-dlchlorovi ->->
phosphate (Dichlorvos
0
II
CH30-P-OH
OCH3
Dichloroacetaldehyde
\/
0
II
CHaO-P-OCH=C
^ I
OH
Cl
Cl
+ CH3OH
O-methyl-2,2-dichlorovinyl
phoshate
Figure 9. The Major Pathways of l,2-Dibromo-2,2-dichloroethyl Dimethyl Phosphate
(Naled) Metabolism (Menzie, 1969)
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Cholinesterase inhibitors may be either reversible
or irreversible in their action. Reversible cholinesterase inhibitors form
a dissociable complex with the enzyme, and inhibition disappears with removal
of the drug from the environment. Irreversible inhibitors, which include th«
organophosphates, form a covalent bond between the inhibitor and esteratic
site of both cholinesterase and acetylcholinesterase. Phosphorylation of the
esteratic site produces a stable bond between inhibitor and enzyme and re-
suits in a very slow regeneration of enzyme activity. In fact, phosphate
appears to be more firmly attached to the enzyme with time and results in
an "aging" phenomenon such that effects are more easily reversed shortly after
poisoning than when a long period has elasped. Furthermore, regeneration of
enzyme activity is so slow that recovery usually occurs by de novo enzyme
synthesis. However, regeneration rates vary with the inhibitor used.
The pharmacologic effects of acetylcholinesterase
inhibition result in the prolonged action of acetylcholine when released by
impulse of cholinergic nerves. Effects would be seen on heart rate, body
secretions, gastrointestinal tract tone and motility, bladder muscle tone,
and skeletal muscle twitch response. In acute overdosage, respiratory em-
barrassment, shock, diarrhea, and convulsions would result.
Dichlorvos is recognized as an effective inhibitor
of cholinesterase in various tissues of animals and man (Van Asperen and
Dekhuijzen, 1958; Witter and Gaines, 1963; Ecobichon and Comeau, 1973;
Reiff ert al. , 1971; Braid and Nix, 1969). In summarizing the action of organo-
phosphate chemicals, Reiff and coworkers (1971) indicated that the in vivo
inhibition of cholinesterase by compounds such as dichlorvos is directly
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related to their water-lipid partitioning characteristics and inversely related
to the biomolecular rate constant measured in vitro. They also found that
• cholinesterase of the central nervous system is readily accessible by all the
organophosphates they studied, regardless of lipophilicity of the compound.
p The anticholinesterase activity of the tris(haloalkyl)
— phosphates has not been extensively studied. It has been demonstrated, however,
™ that DBPP exhibits anticholinesterase effects in goldfish (Gutenmann and Lls^j
• 1975). The activity of DBPP was measured to be about 16% of that of an eqai-
molar concentration of the insecticide, Tetram [0,0-diethyl-S-(beta diethyl-
• amino) ethyl phosphorothiolate]. The anticholinesterase activity of Tetram
_ at a 3 x 10 M solution was 0.68 optical density units per minute at 412 mp
™ (measured by the method of Ellman et al., 1961).
• ii. Alkylating Effects
It is well known that the ability of certain chemicals
• to cause spontaneous alkylation of biologically-important molecules has re-
suited in carcinogenesis and mutagenesis. The alkylating properties of the
• organophosphates are discussed in Section I-B (p. 13) of this report.
• From a biological standpoint, the importance of
dichlorvos as an alkylating agent is questionable. Having two electrophilic
• centers of reactivity, the phosphoryl ("hard") groups and the methyl ("soft")
groups, dichlorvos will react with nucleophilic groups of biological mole-
• cules which are "hard" and "soft," respectively (Bedford and Robinson, 1972).
• However, spontaneous alkylations (i.e., reactions not enzyme-mediated) proceed
at a rate which is extremely slow when compared to enzymic reactions. There-
• fore, the rapid enzymic hydrolysis of dichlorvos by esterases of the spleen,
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kidney, blood, and liver would result in a very short biological lifetime in
mammals, and consequently little opportunity to produce deleterious alkyla-
I tions (Bedford and Robinson, 1972).
The fire retardant haloalkyl phosphates, oeing
| hydrolyzed more slowly than the organophosphate insecticides (See Section I-B,
M p. 13), might reasonably be assumed to have greater biological alkylating
ability. These compounds have not been tested in biological systems,
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* 2, Toxicity and Clinical Studies in Man
flj a. Occupational and Accidental Exposures
i. Tris(haloalkyl) Phosphates
• Ingestion of the fire retardant haloalkyl phosphates
_ has been associated with the development of toxic symptoms in humans. Deaths
• from accidental exposure to any of these compounds have not been reported,
flj however. Stauffer Chemical Co. (undated, a, 1972a, 1973a,b) reported that
ingestion of DBPP, CEP, and DCPP may cause some abdominal discomfort and ivri -
• tation of the gastrointestinal tract. Ataxia and central nervous system de-
pression may occur from ingestion of DCPP, but no human poisonings have been
B reported (Stauffer Chemical Co., 1973a). Great Lakes Chemical Co. (1973b)
• has reported that DCPP has a low order of toxicity by ingestion. Severe
cases of poisoning by CEP may lead to convulsions, central nervous system
• effects, and cardiac and vascular system depression (Stauffer Chemical Co.,
undated a, 1972a). The above symptoms are characteristic of those produced
• by cholinesterase inhibition, and therefore it may be suggested that the
• toxic action of CEP and DCPP might be due to phosphorylation of cholines-
terase enzymes in humans. No information is available, however, to indicate
I the degree of exposure which may be required to produce toxic effects.
Dermal exposure to the tris(haloalkyl) phosphates
• apparently produces only minimal adverse effects. Stauffer Chemical Co.
• (1973b) reported that no sign of skin irritation appeared after contact
with DBPP. However, CEP is reported to produce mild skin irritation (Stauffer
• Chemical Co., 1972a). Great Lakes Chemical Co. (1973b) indicated that DCPP
has a low order of toxicity by dermal exposure.
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Exposure to the fire retardant haloalkyl phosphates
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through inhalation apparently does not present a significant acute toxic hazard,
Hopf (undated) indicated that DBPP presents a low hazard to health by the in-
halation route. Scauffer Chemical Co. (1972a, 1973a,b) reported that no
eflacts are known to occur from exposure to DBPP, CEP, and DCPP, although
some non-specific irritation may result.
ii. Dichlorvos
Incidents have been reported where numerous childrer
have been intoxicated by ingestion of dichlorvos from chewing on commercial
resin strips (Wolter, 1970; Verhulst, 1970; Gillett £t_ al., 1972). No
deaths from such exposures have been reported.
Several cases have appeared in the literature where
dermatitis has developed in persons exposed to animals wearing flea collars
which contained dichlorvos (Cronce and Alden, 1968).
Numerous incidents involving workers who were occu-
pationally exposed to dichlorvos vapors have been reported (Durham et al.,
1957; Stein et^ al. , 1966; Witter, 1960; Menz et^ ad. , 1974; Ember et ad. , 1972;
Bellin and Chow, 1974). In nearly all cases, the only consequence of exposure
by inhalation was a transient decrease in cholinesterase activity, which did
not produce clinical symptoms of any kind. It should be noted that a decrease
in cholinesterase activity in erythrocytes of 20 to 25% of pre-exposure
levels must be achieved before clinical symptoms appear (Zavon, 1965). Gage
(1967) has suggested that a reduction to 70% of normal pre-exposure levels
of acetylcholinesterase activity should be considered the bioloeical threshold
limit in humans.
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iii. Naled
I The available evidence indicates that naled may be
a serious hazard to humans by accidental overexposure. According to Chevron
• Chemical Co. (undated a, b) , naled in concentrated form (85% pure naled) may
• be fatal if swallowed. However, no deaths have been reported. Atropine and
2-PAM are listed as antidotes, and thereby indicate that cholinesterase in-
• hibition is the primary mechanism of toxic action.
Reports have been made (Edmundson and Davies , 1967)
which suggested that naled has produced occupational contact dermatitis in
M certain agricultural workers. Chevron Chemical Co. (undated a) has stated
that concentrated naled causes skin damage and may be fatal if absorbed
I through the skin. Pesticide workers who were routinely exposed to vapors of
various chemicals, including naled, were found to develop chromosomal aber-
| rations during peak exposure periods (Yoder trt al. , 1973) .
• b. Controlled Studies
i. Tris(haloalkyl) Phosphates
• Cases have been presented where skin has become
sensitized and irritated by flannel materials used in sleepwear which were
| fireproof ed by the Proban method (Martin-Scott, 1966). A controlled patch-
_ testing study using DBPP has been conducted by Kerst (1974) and no primary
skin irritation or delayed hypersensitivity was seen. The study involved
• 22 males and 39 females who were exposed to ten patch tests in a 24-day
period. Fifty- two of the 61 starting the study completed the ten patch
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test series as well as a challenge patch test 14 to 21 days later. In each
case, 1.1 gram of the compound was applied to the upper left arm and covered
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with a patch for 24 hours. At the end of that time period, the site was
I examined for any reaction. One to three days later another sample and patch
jm were applied until ten consecutive patch tests were completed. Fifty of the
52 completing the test series and the nine who left the experiment showed no
• adverse reaction to the chemical. One of the two individuals reacting to
the treatment developed itching and skin eruptions over his whole body after
I the seventh application; one month later, after the condition had cleared,
• a challenge test elicited no adverse effects. The other case, a man known
to have some allergies, developed itching and a pruritic plaque of the neck
• at the sixth application; the testing was stopped, the irritation cleared
and no adverse reaction was found after a challenge patch test one month later.
| Kerst (1974) concluded that these two reactions were unrelated to the test
• compound, and that no skin irritation or skin fatigue due to DBPP was demon-
strated in this study.
• Additional studies on the skin sensitizing properties
of DBPP were reported by Morrow et^ a\_. (1975). In early studies, four of
190 subjects became sensitized when exposed to an experimental fabric con-
_ taining high concentrations of DBPP. Subsequent studies were conducted in
humans by exposing them to a number of test fabrics which contained varying
I amounts of DBPP (Table 39). One-inch squares of the test fabrics were applied
to the arms of male volunteers and to the arms or legs of female volunteers
• for six days. After a 15-day rest period, 48-hour challenge patches were
_ applied. Skin reactions were recorded at two and six days after the initial
™ application and on removal of the challenge patches. Results from 200 sub-
jects indicated no instance of contact dermatitis.
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Table 39. Descriptions of Tris(2,3-dibromopropyl) Phosphate*-Treated Fabrics
•(Morrow et al., 1975)
~
1
1. Woven fabric (4 oz./sq. yd.) from Type 54 Dacron^ treated with 10%
|(S)
solution of DBPP* in Triclene^ heated to 200°C for 3 minutes, rinsed
1
with Triclene^ and laundered at 180°C for 15 minutes. The DBPP* content
calculated from x-ray analysis for bromine was 4.6%.
dD
2. Same base fabric and treatment as 1 except that the Triclene^rinse
and the laundering were omitted. X-ray analysis for bromine indicated
11.3% DBPP*.
3. Mill print clo^h woven from polyester yarns (finishing procedure unknown)
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4. Sample 3 scoured five times for 30 minutes at 210°F. (1.4% DBPP* by
B x-ray bromine analysis)
5. Mill print cloth woven from 100% polyester yarns (finishing procedure
unknown) .
6. Mill fabric knit from polyester yarns treated with LVT-23P* in dye bath.
• 7. Mill broadcloth woven from polyester yarns, padded with LVT-23P* and
thermally fixed.
8. Mill flannel woven from polyester yarns and treated as 7.
I/S)
9. Tricot knit from Acele^ acetate FLR yarn containing 4.5% spun-in DBPP*
_ and washed to remove processing finish.
10. Tricot fabric equivalent to above except that the DBPP* content of the
• experimental fiber was 8.0%.
I * Asterisk denotes tris(2,3-dibromopropyl) phosphate, DBPP, and LVT-23P
are the same compound.
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Human maximization tests for allergic sensitization
were conducted by Morrow et al. (1975) according to the method developed by
Kligman (1966). The experimental details and results are summarized in
Table 40. By varying the percentages of DBPP used for sensitization and chal-
lenge, different numbers of subjects were sensitized in each of three experi-
ments.
Table 40. Maximization Tests with Tris(2,3-dibromopropyl) Phosphate
(Morrow et al., 1975)
Test Protocol
SENSITIZATION
Concentration SLS %
Concentration DBPP^ ' %
Days Incubation
CHALLENGE
Concentration SLS %
(2)
Concentration DBPP %
RESULTS
No. Completing Test
No. Sensitized
Test No. 1
Oct. 1967
Du Pont DBPP
5
100
10
10
25
24
8
Test No. 2 Test No. 3
Nov. 1973 Mar. 1974
LVT-23P LVT-23P
5 5
20 20
10 14
10 1
20 20
25 20
2 2 (+1 Weak)
(1)
(2)
Sodium lauryl sulfate as aqueous solution.
Vehicle was petrolatum.
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The three sensitized subjects from Test No. 3
(Table 40) were rechallenged simultaneously with the eight polyester fabrics
treated topically with DBPP as described in Table 39. Their results, as
summarized in Table 41, demonstrate that seven of the eight fabrics pro-
duced an allergic skin response from one or more of the subjects. Reactions
were rated on a 0 to 4 basis, with 2 and above considered to be allergic re-
sponses .
Table 41. Challenge of Subjects with Fabrics (72-Hour Occlusive Contact)
(Morrow et al., 1975)
Subject
Response 96 Hours After Application
Multiple Patch
Test*
A. Polyester Fabrics
1
2
3
4
5
6
7
8
B. Acetate Fabrics
9
10
A
4
4
4
0
4
4
2
4
**
**
B
2
0
2
0
1
0
0
2
**
**
C
+
2
3
0
2
1
0
1
**
**
Patches Applied
Singly
A B
2 0
3 2
3 1
** **
** **
** **
** **
** if*
2 +
2 1
C
1
2
2
**
**
**
**
**
1
1
* Three nonsensitized controls gave no response when tested with the polyester
fabrics in a multiple patch test.
** Not tested.
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The degree of allergic reaction was positively correlated to some extent with
• the amount of surface DBPP available on the test fabric (Table 42) .
• Table 42. Correlation of Surface Tris(2 ,3-dibromopropyl) Phosphate Concentrator
with Sensitized Panel Response (Morrow et al . , 1975)
t
1 Surface
Tris (2 , 3-dibromopropyl)
fabric No.* phosphate
2 70,000
— 3 37,500
| 5** 20,000
6** 18,000
1 8** 5,000
7** 2,000
1 4** 100
9 80
110 65
1 35
*
* See Table 39.
** Fabric tested in multiple patch
1
Morrow and
Response of Sensitized Panel
(96 Hours After Application)
Subject A Subject B Subject C
322
312
412
401
421
200
000
211
2 + 1
201
protocol; others tested individually.
coworkers (1975) concluded from human
• maximization tests that DBPP can cause allergic contact sensitization which
_ is dose-related. These investigators have rated DBPP as a low level allergen
• of Class 1-2, capable of eliciting a
A of individuals .
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sensitization response in small numbers
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ii. Dichlorvos
In human tests designed to evaluate the anthelmintic
• efficacy of dichlorvos by oral ingestion, acute doses up to 117.6 mg/kg pro-
duced varying degrees of cholinesterase inhibition as the only significant
• side-effect (Hine and Slomka, 1968, 1970; Cervoni e^ a.L, , 1968).
Dermal exposure to dichlorvos by humans has resulted
• in no adverse effects other than slight cholinesterase activity variations
|(Zavon and Kindel, 1966; Cavagna et al., 1969). Slight skin irritation has
also been reported, but no cases of contact sensitization have appeared in
• the literature.
Numerous controlled studies have been conducted
• with humans to determine the effects of inhaling dichlorvos vapors (Hunter,
M 1971; Durham e± al_. , 1959; Tracy, 1960; Zavon and Kindel, 1966; Leary et al. ,
1971, 1974; Vigliani, 1971; Cavagna et^ al. , 1969, 1970; Schoof _ejt al_. , 1961;
• Jensen et^ a^. , 1965; Smith et_ al^. , 1972; Rasmussen e£ ad. , 1963). The only
apparent effect of exposure as noted in these studies was on plasma and
| erythrocyte cholinesterase activities.
« iii. Naled
Naled has been found to be a moderate to severe
• human skin irritant in a number of test situations. Phillips and coworkers
(1972) evaluated the primary effects of naled on human skin by several methods:
| 1) a modified Draize irritation test, 2) a 21-day continuous occlusive patch
JK test at 1% and 10% concentrations, and 3) in 21-day non-occlusive testing.
Marked blistering of the skin was produced by undiluted naled in the Draize
9 test and by concentrations above 10% in occlusive patch testing.
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3. Effects on Non-Human Mammals
a. Acute Toxicity
™ i. Tris(haloalkyl) phosphates
<• The tris(haloalkyl) phosphates are considerably less
toxic than the insecticidal organophosphates by acute exposure (See Tables 44,
J 45, and 46).
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g body weight.
A study on the acute oral toxicity of DBPP in rats
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The acute oral LD _ for DBPP in rats has been reporter
by Hopf (undated) to be 590 mg/kg. At this dose level, DBPP could be considered,
a moderately-toxic poison. The results of Shelanski and Moldovan (1972),
however, indicated that the oral LD n for DBPP was greater than 5 gm/kg of
has been published by Kerst (1974) which supplies dose-response data and provides
some indication of biological sensitivity in the animal population. The results
of this study agree with the oral LD _ for DBPP in rats reported by Shelanski
• and Moldovan (1972) and do not confirm the LD figure of Hopf (undated).
Male albino Spartan rats (five per group) were tested at five different
™ dosage levels. The animals were fasted overnight and given 10 ml/kg of a DBPP
solution suspended in propylene glycol. The dose-response data are shown in
Table 43. The LD over a 14-day observation period was determined to be 5.24
• g/kg. All of those dosed at 1.98 or 3.15 g/kg, except one at the lower dose,
showed normal weight gains throughout the 14-day period. The survivors in the
•
• 5.00 and 7.94 g/kg dosage groups had less than normal body weight gain.
M Additional data on the acute toxicity of the fire
retardant haloalkyl phosphates have been reported. The oral LD,.,, of DCPP in
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Table 43. Dose Response Data for Male Spartan Rats Given Acute Oral Doses
of Tris(2,3-dibromopropyl) Phosphate (Kerst, 1974)
No. Dosed
5
5
5
5
5
Dosage Level
(g/kg)
1.98
3.15
5.00
7.94
12.50
Mortality
(No. Dead/No. Dosed)
0/5
0/5
3/5
4/5
5/5
rats was given as 2830 mg/kg of body weight (Sanderson, 1975; Stauffer Chemical
Co., undated, b). The LD,_n in rats for CEP (route unknown) was reported to
be 521 mg/kg of body weight (Sanderson, 1975). Stauffer Chemical Co. (undated,
a) has indicated that the oral LD of CEP in the rat is 1230 mg/kg of body weight,
with a confidence interval of 930 to 1630 mg/kg. Smyth and co-workers (1951)
determined the oral LD of CEP in rats to be 1410 mg/kg of body weight, with
95% confidence limits of 960 to 2080 mg/kg.
When applied dermally to experimental animals, the
tris(haloalkyl) phosphates apparently do not produce a significant toxic
response. The acute dermal LD . in rabbits for DBPP is greater than 2 gm/kg
of body weight (Shelanski and Moldovan, 1972). Kerst (1974) exposed male and
female New Zealand white rabbits to DBPP, applied either to the intact or
abraded skin of the shaved back. The treatment area was occluded for 24 hours,
followed by removal of the bandages and washing of the skin with water.
Observations were made for a 14-day period after the initial treatment. At
dosage levels up to 8 gm/kg of body weight, DBPP failed to produce any
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• mortality or signs of dermal irritation. Fluctuations in body weight of the
experimental animals were considered to be within normal limits. DBPP did not
f irritate the skin when 1.1 gm was applied to the shaved back and flank areas of
— six albino rabbits (Kerst, 1974). The test material was applied to abraded
and intact skin, covered with gauze tape, and remained for 24 hours. Erythema
• and edema were absent at 24 hours, when the test material was washed from the
skin, as well as after 72 hours, when a second observation was made.
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The acute dermal LD for DCPP in rabbits is greater
— than 15.8 ml/kg of body weight (Stauffer Chemical Co., undated, b). DCPP
™ reportedly produced no skin irritation. Smyth and co-workers (1951) rated
1£ CEP as a grade 2 skin irritant in the rabbit (based upon a four point Draize
system), indicating a small degree of irritation equivalent to a trace of
• capillary injection.
_ Only limited data are available on the acute inhala-
* tion toxicity of the tris(haloalkyl) phosphates. Smyth and co-workers (1951)
fl reported that no deaths occurred in rats exposed to saturated CEP vapors in
air for a maximum of eight hours.
Eye irritation studies in rabbits have been conducted
_ with DBPP, DCPP, and CEP. Shelanski and Moldovon (1972) and Stauffer Chemical
™ Co. (1973, b) indicated that DBPP is not an eye irritant. Kerst (1974)
fl§ applied 0.22 gm of DBPP to the eyes of six rabbits and observed no adverse
effects at 24, 48, and 72 hours after the initial treatment. Additional reports
have stated that no damage to the eyes of rabbits was produced by CEP (Stauffer
Chemical Co., 1972a; Smyth jit_ al. , 1951). Stauffer Chemical Co. (undated b,
1973a) indicated that DCPP is a mild eye irritant in the rabbit.
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ii. Dichlorvos
Several investigators have determined that dichlorvos
100 mg/kg of body weight (Wagner and Johnson, 1970; Mattson et^ al,, 1955;
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is highly toxic by oral ingestion, with the acute LD in rats being less than
Durham e^ al., 1957; Gaines, I960, 1969; Tracy et al., 1960; Laws, 1966; Jones
• iejt al. , 1968; Pickering and Pickering, 1971; Shell Chemical Co., 1965; See
Table 44). Dogs and monkeys have also been shown to suffer severe effects at
acute oral doses less than 40 mg/kg of body weight (Snow and Watson, 1973;
m Snow, 1973; Northway, 1971; Pryor et ad., 1970; Wallach and Frueh, 1968).
Symptoms of poisoning were usually associated with marked depression of
• cholinesterase activity.
By dermal exposure, dichlorvos is only slightly
0 less toxic than by oral administration. Data indicate that female rats are
f| somewhat more susceptible than males (Durham _et_ auL. , 1957; Gaines, 1960,
1969; See Table 45).
V Inhalation of air saturated with dichlorvos vapors
(concentration > 30 yg/K.) proved fatal to rats in 4.8 to 83.0 hours (Durham
• ^ aJ_., 1957). More recent studies have shown that exposure of rats to concen-
mi trations of dichlorvos up to 90 yg/& for four hours were not lethal (Blair
e± al. , 1975; Shell Chemical Co., 1973a).
V Dichlorvos has been tested for toxicity by several
parenteral routes in various animals. These results are summarized in Table 45,
A single report by Tracy (1960) stated that the LD
M of undiluted dichlorvos when applied directly to the intact eye of rats is
10 mg/kg of body weight. This result indicates an extremely toxic response,
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and is somewhat inconsistent with the results of toxicity determinations by
other routes of exposure. No further details are available to clarify this
observation.
1| iii. Naled
Studies on the acute toxicity of naled have been
|| conducted with variable results. Naled is apparently less toxic than dichlorvos
~ under most circumstances. Oral administration produces greater toxic effects
than dermal exposures. Experimental data are summarized in Tables 44, 45,
V and 46.
iv. 0,0-Diethyl 2-chlorovinyl phosphate
• The limited acute oral toxicity data available on
— this compound indicate it is highly toxic to rats and mice (Corey et al. ,
™ 1953; Holmstedt, 1959). The chemical is structurally closely-related to
• dichlorvos, but is more acutely toxic to rodents. The oral LD n for rats for
dichlorvos is between 56 and 80 mg/kg, whereas the oral LD in rats for
| 0,0-diethyl 2-chlorovinyl phosphate is 7.0 mg/kg (See Table 44). By subcu-
taneous injection in rats, this compound was shown to be lethal at 0.2 mg/kg
of body weight, with a calculated LD _ of 15.5 mg/kg of body weight (Brimble-
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ff combe et^ al. , 1971).
t
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b. Subacute and Chronic Toxicity
i. Tris(haloalkyl) Phosphates
A subacute feeding study in male weanling rats was
conducted by Kerst (1974) to determine the effects of long-term exposure to
DBPP. The rats were fed for four weeks at 100 ppm and 1000 ppm in the diet
and sacrificed either at the end of the experimental period or after two or
six weeks of recovery. In addition to blood tests and urine analysis, the
rat tissues were analyzed for the presence of bromine. (More details on the
bromine residues are discussed in Section III-B-1-a-i, p. 96, of this report).
At both dose levels, rats displayed a decreased rate
of body weight gain when compared to control animals (Table 47). When ani-
mals were treated for 28 days and followed with a two-week recovery period
on a normal diet, body weight differences between treated and control animals
diminished somewhat (Table 48).
Table 47. Body Weights and Weight Gain of Rats Fed Tris(2,3-dibromopropyl)
Phosphate (Kerst, 1974)
Average Individual -
Weekly
0 Week
1 Week
2 Weeks
3 Weeks
4 Weeks
Total
Negative Control
DBPP,
DBPP,
Body Weight
Weight Gain
100 ppm
Body Weight
Weight Gain
1000 ppm
Body Weight
Weight Gain
(g)
(g)
(g)
(g)
(g)
(g)
49
—
49
—
50
—
80
31
74
25
72
22
123
43
115
41
104
32
170
47
159
44
144
40
210
40
199
40
172
28
161
150
128
133
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Table 48. Body Weight of Rats Treated with Tris(2,3-dibromopropyl) Phosphate
and Followed by a Recovery Period (Kerst, 1974)
ferage Individual Weekly
Sample Description
Negative Control
DBPP, 100 ppm
DBPP, 1000 ppm
Weeks
0 I 1 1 4. 15 6^
51 72 124 153 191 221 252
51 50 107 148 168 210 24'
51 60 100 132 156 188 23b
* Post treatment weeks - animals on unsupplemented basal ration.
The reduced body weight gains on DBPP-treated rats may have been due to de-
creased feed consumption as indicated in Table 49.
Table 49. Feed Consumption (Kerst, 1974)
Average Individual-Weekly
Sample Description Test Period Feed Consumption (2)
1 Week 2 Week 3 Week 4 Week
Negative Control 76 108 135 140
DBPP, 100 ppm 75 108 132 137
DBPP. 1000 ppm 61 100 122 120
Sample Description Withdrawal Feed Consumption (g)
1 Wk. 2 Wk. 3 Wk. 4 Wk. 5 Wk. 6 Wk
Total
459
453
403
. Total
Negative Control 167 164 164 154 165 182 996
DBPP, 100 ppm 158 138 138 154 152 176 916
DBPP, 1000 ppm 150 143 169 148 156 188 954
134
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In addition, a slightly poorer feed conversion efficiency (grams feed con-
sumed/grams body weight gain) in treated rats may reflect a toxic action
of DBPP and may have contributed to the reduced rate of weight gain (Table 50)
Table 50. Feed Efficiency* (Kerst, 1974)
Average Individual-Weekly
Sample Description Feed Efficiency (ratio)
1 Week 2 Week 3 Week 4 Week 4
Negative Control 2.5 2.5 2.9 3.5
TBPP,
TBPP,
100 ppm 3.0 2.6 3.0 3.4
1000 ppm 2.8 3.1 3.1 4.3
Week Cumulative
2.9
3.0
3.3
*Grams Feed Consumed
Grams
Gained
Detailed data from hematologic, blood chemistry and urine analyses in treated
and untreated control animals indicated that no changes could be attributed
to the DBPP treatment. The parameters which were measured included deter-
minations of red blood cells, white blood cells, hemoglobin, packed cell
volume, serum glutamic oxalacetic transaminase and blood urea nitrogen;
urinary measurements were made for excreted blood, bilirubin, ketones, glu-
cose, albumin, and pH.
A further examination of organ weight data conducted
by Kerst (1974) demonstrated that both mean organ weight and organ weight
expressed as percent of body weight were reduced in DBPP-treated rats (Table 51)
135
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In the absence of accompanying clinical evidence of intoxication, it was as-
sumed that differences in organ weights between treated animals and controls
were due to decreased food consumption resulting in a poor nutritional state.
Table 51. Organ Weights and Organ Weights Expressed as Percent of Body Weight*
(Kerst, 1974)
Average Values (g)
Body Weight Heart
205 1.191
(0.582)
200 0.945
(0.473)
173 0.856
(0.459)
Liver
11.60
(5.64)
10.33
(5.18)
8.54
(4.93)
Spleen
Negative Control
0.907
(0.442)
DBPP, 100 ppm
0.702
(0.351)
DBPP, 1000 ppm
0.608
(0.355)
Kidney
2.513
(1.22)
2.234
(1.12)
1.731
(0.99)
Gonads
2.808
(1.37)
2.385
(1.19)
1.911
(1.09)
* Organ weights expressed as percent of body weights are in parentheses.
Histopathologic examination of various organs revealed minor lesions of the
liver and kidneys (cloudy swelling and nephrosis) which could be demonstrated
in both treated and control animals, and therefore were assumed to be spon-
taneous .
ii. Dichlorvos
Several subacute and chronic toxicity studies have
been conducted in rats by oral exposures to dichlorvos for periods of up to
two years (Durham ert al. , 1957; Witherup et^ al. , 1971; Tracy et^ al. , 1960).
These studies have revealed that the primary effect of long-term treatment
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is a transient depression of cholinesterase activities. Histopathological
| examinations have demonstrated no adverse effects on body organs. Similar
M results were obtained in studies with dogs (Witherup et al. , 1971) and mon-
keys (Hass et al. , 1972) .
• Subacute and chronic studies on dichlorvos indicated
that skin irritation and variations in cholinesterase activity levels have
^ resulted from dermal exposures in some species, primarily cats and dogs
_ (Smith, 1968; Schnelle, 1969; Fox et_ al . , 1969a,b; Elsea £t al . , 1970; Cronce
and Alden, 1968; Ritter ej^ al_. , 1970). A monkey was reported to have died
• from ten daily dermal doses of dichlorvos at 75 mg/kg of body weight (Durham
jet a^. , 1957).
• Rats and monkeys chronically exposed to dichlorvos
_ vapors at levels as high as 5 mg/1 have developed only transitoary depression
™ of cholinesterase activities (Blair et_ al^. , 1975; Dix, 1975; Durham et al. ,
• 1957; Witter e^ al^. , 1961).
•
_
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iii. Naled
Both Standard Oil Co. (1964) and Chevron Chemical
Co. (1970) have reported no adverse effects in rats resulted from feeding a
dietary regimen containing naled. Sosnierz e_t^ al. (1971) indicated that
fl alkaline and acid phosphatase enzyme activities in the liver of rats were
disrupted by administering 90 oral doses of naled at 0.675 or 2.025 mg/kg
• of body weight.
Subacute exposures to 42 yg/1 of a naled aerosol
• resulted in decreased cholinesterase activity levels in rats along with symp-
toms of inactivity and obvious discomfort (Standard Oil Co., 1964).
137
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c. Sensitization
Studies on the sensitization of humans by exposure to
• the haloalkyl phosphates have been presented in Section III-B-2-b (p. 112) of
this report. Sensitization in animals has not been demonstrated for either
• dichlorvos or naled.
. Morrow and coworkers (1975) attempted to sensitize guinea
" pigs to DBPP. Attempts to enhance the sensitization reaction were made by
B injection (intraperitoneal) with Freund's Complete Adjuvant or intradermal
injection of DBPP mixed with methylene bis(4-cyclohexyl isocyanate). Five
• attempts to sensitize guinea pigs (five to ten animals per group) were all
_ unsuccessful.
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d. Teratogenicity
i. Tris(haloalkyl) phosphates
A search of the scientific literature has not
revealed any reports where the tris(haloalkyl) phosphates may have been
tested for teratogenic activity or other effects on reproduction.
ii. Dichlorvos
Several studies in rats and swine exposed to
dichlorvos in the diet or by inhalation have failed to reveal any signi-
ficant teratogenic effects (Kimbrough and Gaines, 1968; Witherup et al. ,
1971; Thorpe et al., 1972; Collins _et al., 1971). Minimal teratogenic
effects were noted in the offspring of rabbits exposed to dichlorvos
vapors at 4 ug/£ throughout the period of pregnancy (Thorpe et al., 1972).
Teratogenicity studies have also been conducted
with dichlorvos using fertile chicken and duck eggs. Injection of fertile
eggs with dichlorvos produced toxic reactions leading to death, but no
significant incidence of deformities in the hatching birds (Dunachie and
Fletcher, 1969; Khera and Lyon, 1968; Proctor and Casida, 1975).
iii. Naled
Proctor and Casida (1975) included naled among
the insecticides which they tested for teratogenicity and effects on
nicotinamide adenine dinucleotide activity in chick embryos. Although
specific data were not given, naled was reported to be among the substances
having the least teratogenic action of those tested.
e. Mutagenicity
Biological alkylations caused by foreign substances
can alter the chemical structure of cellular DNA and produce a mutagenic
139
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response. Many of the organophosphates, including dichlorvos and naled,
are effective alkylating agents (See Section III-B-1-c-ii, p. 108)_.and there-
fore highly suspect as potential mutagens.
i. Tris(haloalkyl) Phosphates
Preliminary results of studies conducted with
commercial preparations of DBPP have indicated that mutagenesis can be
induced in certain bacterial strains (Prival, 1975). Histidine-deficient
strains of Salmonella typhimurium were employed in disc plate assays with
DBPP, and in the plate incorporation assay, as developed by Ames. Using
the Ames assay system, DBPP was tested in the presence and absence of an
activating system prepared from extracts of rat liver. In certain cases,
extracts were prepared from the liver of rats whose microsomal enzymes
had been induced by the administration of polychlorinated biphenyls.
Results from the disc plate assay indicated that
97% pure DBPP was mutagenic to strains of Salmonella typhimurium which
detected chemicals causing base pair substitution mutations, but not to
strains which detected frame shift mutagens.
In the plate incorporation assay, eight different
commercial preparations of DBPP were found to be mutagenic, but only to the
bacterial strains which detected agents causing base pair substitutions.
Mutagenesis was expressed both in the presence and absence of a metabolic
activation system, although activation enhanced the mutagenic response.
The activation system from induced rat liver produced greater mutagenic
activity than extracts from uninduced liver. Plate incorporation tests
were conducted three times, each by a different technician, and the test
results were confirmed in every instance.
140
-------
When CEP and DCPP were tested in the Ames plate
incorporation assay as described above, the results were negative in the
bacterial strain which detected base pair substitution mutagens.
Further tests are being conducted with DBPP using
two strains of Escherichia coli (a DNA polymerase-deficient strain and a
tryptophan-deficient strain), and in a tryptophan and adenine-requiring
strain of Saccharomyces cerevisiae. In addition, scientists at the National
Institute of Environmental Health Sciences will repeat the plate incorporation
assays of DBPP with Salmonella typhimurium and also test the compound in a
forward mutational system in E. coli and in Neurospora crassa.
Positive mutagenic data, such as that reported
with DBPP, is significant not only in its implication for identifying
potential reproductive hazards, but also in predicting carcinogenicity.
Kriek (1974) has stated that all carcinogens are mutagenic (but not neces-
sarily vice versa). Furthermore, the International Agency for Research on
Cancer now includes mutagenicity data in its monographs on the evaluation
of the carcinogenic risk of chemicals to humans.
ii. Dichlorvos
The majority of the mutagenicity studies using
dichlorvos have been conducted with deficient bacterial strains. Several
techniques, agar plates, paper disc, nutrient broth suspension, and host-
mediated assay, have been utilized. Dichlorvos caused increases in reverse
mutations in strains of Salmonella typhimurium (Dyer and Hanna, 1973;
Voogd e_t _al_. , 1972), Pseudomonas aeruginosa (Dyer and Hanna, 1973),
Klebsiella pneumoniae (Voogd et al., 1972), Citrobacter freundii (Voogd
et al. , 1972) , Enterobacter aerogenes (Voogd e_t al. , 1972), Serratia
141
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Imarescens (Dean et al., 1972), and Escherichia coli (Voogd et al. , 1972;
Bridges et al. , 1973; Wild, 1973; LHfroth eit al, 1969; Ashwood-Smith et al. ,
• 1972). In bacterial assay systems, dichlorvos was reported by several
^ investigators to be a much weaker mutagen than methyl methanesulfonate
™ (Bridges ie_t al. , 1973; Lawley et _al. , 1974). It was observed that dichlor-
fl vos methylates cellular proteins more readily than it methylates nucleic
acids (Lawley et^ al. , 1974).
• In a host-mediated assay in mice, dichlorvos
_ failed to induce reverse mutations in Saccharomyces cerevisiae (Dean et al.,
* 1972). The authors suggested that the extremely rapid in vivo metabolism
fl of dichlorvos prevented the induction of mutagenesis.
Cytogenetic studies in mice and Chinese hamsters
• exposed to acute doses of dichlorvos by ingestion or inhalation failed to
_ reveal significant chromosome damage (Dean and Thorpe, 1972a). Studies in
™ which mice were chronically exposed to dichlorvos produced similar negative
• results (Dean and Thorpe, 1972b).
iii. Naled
• No direct information on the possible mutagenicity
of naled has been encountered. The alkylating abilities of this chemical
™ and the fact that it is metabolized to dichlorvos might make it suspect
H as a possible mutagen.
f. Carcinogenicity
• To some extent, all organophosphates can act as
alkylating agents. The alkylating abilities of the haloalkyl phosphates
I
I
are discussed in Section I-B-2 (p. 18 ) and the biological significance of
alkylation is presented in Section III-B-1-c-ii (p. 108). With respect to
142
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• carcinogenicity, it is well-recognized that spontaneous alkylations of
biologically-important molecules, particularly DNA, can lead to tumor
• formation (Bedford and Robinson, 1972; Rosenkranz, 1973). Furthermore,
• che positive correlation between carcinogens and mutagens (Kriek, 1974)
is of considerable interest in light of recent evidence indicating that
• DBPP and dichlorvos can display mutagenic activity.
i. Tris(haloalkyl) Phosphates
• Information on the potential carcinogenicity of
• the tris(haloalkyl) phosphates is not presently available. However, the
National Cancer Institute initiated carcinogenicity tests in March, 1974
• on rats and mice exposed orally to DBPP (Prival, 1975). These studies
are not yet completed; animals are due to be sacrificed in the Spring of
• 1976.
• The key to whether or not DBPP is carcinogenic
may well be the rate at which it is metabolized in vivo to form non-alkylating
• products. It has already been recognized that the chemical hydrolysis of the
tris(haloalkyl) phosphates does not occur as rapidly as for dichlorvos (See
H Section I-B-2, p. 18). If the tris(haloalkyl) phosphates can remain intact
• within the body for a sufficient period to allow for biological alkylations
to occur at the subcellular level, a carcinogenic response may be predicted.
• ii. Dichlorvos
Specific data have not been encountered on the
I potential carcinogenicity of dichlorvos. One study (Preussmann, 1968) has shown,
• however, that trichlorphon (0,0-dimethyl-l-l-hydroxy-2,2,2-trichloroethyl
phosphonate), which is metabolized through dichlorvos, produced sarcomas in two
• of 24 rats when injected subcutaneously once weekly with the substance.
• 143
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I
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• ill. Naled
No data have been encountered on the carcinogenicity
• of naled.
m g. Possible Synergisms
No data are available on possible synergisms of chemical
I substances with the haloalkyl phosphates. As components of fabrics, however,
it might reasonably be expected that the fire retardant tris(haloalkyl) phosphate?
| would contact a number of compounds through normal use (e.g.,dyes, laundering
m agents) and in various hypothetical situations (e.g., spillage of chemicals on a
person's clothing).
• The insecticides, dichlorvos and naled, are frequently
mixed with other agricultural chemicals prior to application. Therefore, con-
• siderable opportunity for synergistic action does occur.
4. Effects on Other Vertebrates
a. Birds
I Avian toxicity studies involving the haloalkyl phosphates
have been limited almost exclusively to experimentation with dichlorvos.
| Chevron Chemical Co. (1970), however, reported that naled, when applied at
M recommended rates, did not cause any mortality in several species of birds:
quail, pheasant, duck, and others including shore birds and aquatic birds. Most
I
although LD,-_ data on two species of wild birds have also been reported (Table 52)
• of the available data on dichlorvos is derived from studies in chickens,
I
I
b. Fish
The toxicity of the haloalkyl phosphates has been studied
in numerous species of fresh and salt water fish. The methodologies for testing
I in fish range from continuous exposure over several days to a brief exposure in
I
144
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• minutes or hours. Data are often given as lethal tolerance (TL) or lethal
concentration (LC) figures.
I i. Tris(haloalkyl) Phosphates
• Gutenmann and Lisk (1975) evaluated the toxicity of
DBPP to goldfish after determining that the chemical could be leached from fire
• retardant-treated fabrics in a simulated laundering operation. A polyester
flannel fabric treated with DBPP was found to release up to 10 pg per square
• inch of fabric into the laundry water. The authors exposed goldfish to a
• concentration of 1 ppm of DBPP in water, based on the assumption that a typical
home laundering may involve the washing of six sheets, each 72 x 81 inches,
• which could result in a concentration of 6 ppm of DBPP in 30 gallons of combined
wash and rinse water.
• Six goldfish were placed in a tank with 20 liters of
• aerated water and exposed to four ml of a solution containing 5 mg/ml of DBPP
in acetone (final concentration = 1 ppm DBPP). Control fish were exposed to
M acetone only. Data on fish survival after exposure to DBPP and two other organo-
phosphorus fire retardants are presented in Figure 10. All of the goldfish
I exposed to DBPP died within five days. The fish were observed to swim in a
m completely-disoriented manner prior to death. Death may have been due to
cholinesterase inhibition, but DBPP had less anticholinesterase activity than
I THPOH [tetrakis (hydroxymethyl)phosphonium hydroxide] (DBPP and THPOH had 16%
and 25%, respectively, of the activity of Tetram). However, the authors suggested
| that the greater lipid solubility of DBPP may have enhanced absorption and thereby
M produced a greater toxic effect, in spite of its lower anticholinesterase
activity.
I
146
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Figure 10. Survival of Goldfish Exposed to 1 ppm of Flame Retardant Compounds
(Gutenmann and Lisk, 1975)
0
10 15 20
TIME OF EXPOSURE (DAYS)
I. tris(2,3-dibromopropyl) phosphate (DBPP)
II. Pyrovatex CP
(N-methylol dimethyl phosphonopropionamide)
III. THPOH
tetrakis(hydroxymethyl) phosphonium hydroxide
Reprinted with permission from Springer-Verlag
ii. Dichlorvos
Data on the toxicity of dichlorvos to fish are
summarized in Table 53. In some cases the TL^n or LC,-n (concentration to
cause death in 50% of the population) is less after 96 hours than after 24
hours of exposure, which indicates a cumulative toxicologic effect.
iii. Naled
A summary of the available data on the toxicity of
naled to fish is also presented in Table 53.
I
147
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• 5. Effects on Invertebrates
— a. Insects
* No information is available on the toxic effects of the
• fire-retardant haloalkyl phosphates to invertebrates. The toxicity of dichlorvoi
and naled to various insects has been studied in detail. On topical application
• to various insects, LD values of dichlorvos range from 0.694-18.0 Ug/g (Aziz,
1973; Drake et^ al. , 1971; Hutacharern and Knowles, 1974; Reiser e_t^ al. , 1:73,
• Metcalf jit al. , 1959; Van Asperen, 1958a; Yates and Sherman, 1970). CompaiaoK
• values for naled range from 0.483-124 yg/g (Chalfant, 1973; Drake £t al., 1971;
Reiser et al. , 1973; Lyon et_ ail. , 1972; Yates and Sherman, 1970).
• Esterase inhibition is commonly regarded as the primary
toxic effect of dichlorvos and naled to insects (Heath, 1961; Hutacharern and
• Knowles, 1974; Tripathi and O'Brian, 1973; Van Asperen, 1958a and b). The known
• secondary effects of these compounds seem to be related primarily to decreased
fecundity (Kreasky and Mazuranich, 1971; Zettler and LeCato, 1974). Both hydro-
• lysis and demethylation, common features in the mammalian metabolism of both
compounds, have been demonstrated in insects (Krueger and Casida, 1961; Miyata
I
and Matsumura, 197Z).
b. Other Invertebrates
The 48 hour EC for immobilization of two cladocerans
• species using both dichlorvos and naled are given in Table 54.
Tripp (1974) has studied the effects of naled on mortality
• and reproduction in oysters (Crassotrea virginica). Gross toxic response was
JB determined by immersing groups of oysters in 1 ppm and 10 ppm naled solutions
for 24 hours, twice weekly, for approximately four months. Only at the higher
• concentration was mortality markedly increased (25.2%) above control levels
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Table 54. Estimated 48-Hour ECsn Immobilization Values in yg/g for Two Species
of Daphnids Exposed to Dichlorvos and Naled at 60 F and 70°F. (Sanders
and Cope, 1966)
Toxicant Simocephalus serrulatus Daphnia pulex
Dichlorvos 60°F 70°F 60°F
0.26 0.28 0.066
(0.16-0.42)a (0.16-0.47) (0.049-0.088)
Naled 1.1 1.1 0.35
(1.0-1.3) (0.80-1.4) (0.22-0.75;
o
Figures in parentheses are confidence limits for P = 0.05.
(8.3%). No hictological damage attributable to naled was found in 153 treated
oysters. Based upon combination of field and laboratory exposures, Tripp (1974)
has concluded that chronic exposure to 10 ppm naled does not significantly
affect oyster reproduction.
6. Effects on Plants
Due to the insecticidal use of two of the haloalkyl phosphates,
dichlorvos and naled, considerable exposure to plants does occur. Evidence
presented in mutagenicity studies using dichlorvos on the broad bean root cells
and on onion root tip cells indicated some chromosomal effects (LHfroth et al.,
1969; Sax and Sax, 1968). Product information on dichlorvos (Shell Chemical Co.,
1973) reported no phytotoxicity in a wide variety of plants under normal appli-
cation conditions. Chevron Chemical Co. (undated b) product labels on naled
/RS
(Dibrom ) indicate that overtreatment of pests may lead to the injury of
plants. Naled vapors may injure certain roses, chrysanthemums, wandering jews,
poinsettias, and Dutchman's pipe. An additional warning is made to avoid
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_ spraying nectarines, ornamental cherries, liquidambar, or chrysanthemums
(Chevron Chemical Co., undated b).
fl| No information on the potential phytotoxicity of the tris(halo-
alkyl) phosphates is available.
• 7. Effects on Microorganisms
Some of the haloalkyl phosphates have been tested for mutagenic
•
™ effects in various microorganisms (See Section III-B-3-e, p. 139). The result^
•t of this work indicated toxic effects and some increase in chromosome aberrai.!.;>*.-
occurring in microorganisms treated with dichlorvos or tris(2,3-dibromopropyl)
• phosphate.
Dougherty and coworkers (1971) studied the effects of various
• concentrations of naled and dichlorvos on Bacillus thuringiensis. Agar plates
• were innoculated with bacterial spores. Each dilution of insecticide solution
was applied to a paper disc which was placed on the agar plate. After a 24-
• hour incubation at 31°C, the presence or absence of an inhibition zone (1 mm
minimum) was recorded. Dichlorvos failed to inhibit growth at any concentra-
• tion tested, but naled caused significant inhibition at a molar concentration
I
and coworkers (1971) indicated that the apparent difference in effect was
B probably due to the relative solubility of naled in each solvent.
Naled was found to be fairly toxic to bacterial populations in
• waste disposal lagoons by Steelman and coworkers (1967). The lagoons are uti-
fl| lized for disposal of livestock and poultry wastes. Due to the nature of the
materials in the lagoon, mosquitoes find the area an excellent breeding site.
H Naled, a mosquito larvicide, was tested for its effect on the microbial popula-
tion which is essential for waste degradation. Lagoon water (3000 ml) was mixec
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-5 -3
of 10 in benzene or Tween 80, and at 10 in dimethyl sulfoxide. Dougherty
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with each of five concentrations (0.0001, 0.1, 0.5, 1.0, and 5.0%) of naled.
Bacterial tests were made at 24 hours and, at the lowest concentration, colony
counts were determined after 24 and 48 hours of continuous exposure. Their
data showed an increase in mortality with increase in naled concentration in the
closed laboratory situation. Steelman and co-workers (1967) noted that in
operating lagoons, the addition of water to wash fecal material would tend to
dilute the naled concentration and, thereby, presumably reduce bacterial moitaii
These investigators felt that the level of bacterial mortality at 1 ppm nalt.a
would not disrupt the lagoon function.
8. Biochemical Studies
a. Effects on Cell Cultures
Dean (1972) determined the effects of dichlorvos on
cultured human lymphocytes by addition of the chemical at various stages of
development. He observed chromosome degeneration in certain cases, which was
different than the chromosome pulverization caused by high concentrations of
alkylating agents. Dean (1972) concluded that dichlorvos was cytotoxic to
cultured lymphocytes at concentrations up to 40 pg/tnl, but probably did not
affect chromosomes by direct alkylation of DNA.
b. Effects on Nucleic Acids and Protein
The known alkylating effects of the haloalkyl phosphates
has led to considerable discussion regarding their possible effects on nucleic
"acids, including RNA and DNA. Biological alkylations are often manifested as
mutations, and the mutagenic properties of several haloalkyl phosphates are
discussed in Section III-B-3-e (p.139).
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A few studies have examined the actions of dichlorvos on
isolated DNA. LBfroth et al. (1969) demonstrated that dichlorvos can cause a
1% conversion of guanine to N-7-methylguanine in calf thymus DNA. Rosenkranz
and Rosenkranz (1972) obtained decreases in the sedimentation coefficient of DNA
after exposure to dichlorvos. This change was presumably due to alkylation
followed by depurination. In addition, further changes were noted along the
single strands from denatured DNA.
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IV. Regulations and Standards
A. Current Regulations
The haloalkyl phosphate pesticides are heavily regulated by Federal
law. However, in contrast, the fire retardants have few restrictions placed
upon their commercial use. There are a number of Federal and state regula-
tions that apply to fire retarded products, but these are fire retardant
standards of the product and do not apply to any chemical additive in particu-
lar.
1. Food, Drug, Pesticide Authorities
Billings (1974) outlined the current system of Federal pesti-
cide regulation. The Federal laws primarily concerned with pesticides are
the Federal Environmental Pesticide Control Act (FEPCA) of 1972 (PL92-516),
which adds authority to the Federal Insecticide, Fungicide, Rodenticide Act
(FIFRA) of 1947 and the Federal Food, Drug and Cosmetic Act of 1938, which
was revised to include pesticides ("economic poisons") in 1954.
The established tolerances for food residues for dichlorvos and
naled vary from 10 ppm to 0.02 ppra depending upon the food crop being con-
sidered (EPA, 1971, 1972a,b,c, 1974, 1975a, b). Tolerances for dichlorvos
often include "expressed as naled" and naled tolerances also include "its
conversion product 2,2-dichlorovinyl dimethyl phosphate."
Dichlorvos is regulated by other sections of the Food, Drug
and Cosmetic Law, both as a food additive and as an animal drug. A level
of 0.5 ppm dichlorvos was permitted by the FDA (1968) as a food additive
residue from application as an insecticide on packaged or bagged nonperishable
processed food. The FDA (1975c) has established a tolerance of 0.1 ppm for
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• negligible residues of dichlorvos in the edible tissues of swine.
Dichlorvos is regulated as a new animal drug under the Federal
| Food, Drug and Cosmetic Act. The FDA (1975a) has general regulations con-
^ cerning adequate labeling of anthelmintic drugs and directions. In addition,
specific regulations for the anthelmintic use of dichlorvos on swine are givd..
• The FDA (1965) approved the prescription use of dichlorvos in
oral pellet form (Atgard V) as an anthelmintic in swine. The Federal Food,
M Drug and Cosmetic Act has established a 9.6% level of dichlorvos which may
^ be mixed in feed for swine (FDA, 1970) and the maximum dosage levels which
™ can be administered (FDA, 1971). These regulations were amended most recently
A in the fall of 1975 (FDA, 1975b).
2. Air and Water Acts
• The Federal Water Pollution Control Act (1970) and Amendments
_ (1972) regulate the presence of pollutants, including pesticides, in water
™ and waterways. Both dichlorvos and naled are included in this list of haz-
• ardous substances. Dichlorvos is listed under the EPA category "A" which
denotes an LC <1 ppm for aquatic animals over an exposure period of 96
• hours or less. The harmful quantity (HQ) in pounds (kg) is 1.0 (0.454).
Naled is also listed in category A with the same HQ.
3. OSHA
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The Occupational Safety and Health Administration provides
3
an exposure standard for dichlorvos of 1 mg/m (OSHA, 1974). In addition,
• OSHA provides general regulations on personal protective equipment for workers
in pesticide industry (Billings, 1974).
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4. Transport Regulations
The Department of Transportation (DOT) regulates interstate
and foreign transport of goods. The pesticides are regulated by the Hazardous
Regulation Board. Most pesticides are considered Class "B" poisons (Billings,
1974). According to Shell Chemical Co. (1973a), Vapona insecticide (dichlor-
vos) does not require a Class B Poison label and is thereby exempt from DOT
packaging restrictions.
5. Consumer Product Safety Commission (CPSC)
On March 24, 1976, the Environmental Defense Fund (EOF) petiticn;<
the CPSC concerning the use of DBPP as a fire retardant in sleepwear for child-
ren less than 12 years old. EOF asked that CPSC require that labels on sleep-
wear indicate that the material be washed three times before use. Also, EOF
requested that a scientific inquiry be initiated for considering a ban on
sleepwear use of DBPP. The petition was based upon (1) the mutagen effects of
DBPP in the Ames bacterial assay system, (2) migration studies by St. John et_
al. (1976), and (3) the studies of Morrow e_t_ al_. (1975), who demonstrated that
almost all of the DBPP lost (12%) occurred during the first three washings.
B. Concensus and Similar Standards
1. TLV
The American Conference of Governmental Industrial Hygienists
has established Threshold Limit Values (TLV's) in workroom air for the two
pesticides, dichlorvos and naled (ACGIH, 1974). The dichlorvos regulations
3 3
(skin) are 0.1 ppm and 1 mg/m . For naled a limit of 3 mg/m has been estab-
lished.
No TLV's have been established for the flame retardant halo-
alkyl phosphates.
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2. Public Exposure Limits
I
The Food and Agriculture Organization (FAO) of the United
• Nations and the World Health Organization (WHO) recommended a maximum accep-
table daily intake of dichlorvos at 0.004 mg/kg body weight (FAO/WHO, 1967).
• 3. Other
m Capizzi and Robinson (1973) have estimated the relative acute
toxic hazard of 85 pesticides to applicators. The chemicals are divided ii.'.o
• four groups, ranging from "most dangerous" to least dangerous." Dichlorvos
is placed in the "dangerous" group (the second most toxic) and naled in the
fl "less dangerous" category.
A Sasinovich (1968) recommended a maximum permissible concentra-
tion (mpc) for dichlorvos in workroom air at 0.2 mg/m for the USSR.
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V. Summary and Conclusions
There are six haloalkyl phosphate (HAP) compounds that are produced in
the U.S. in significant commercial quantities. Included are two pesticides,
dichlorvos and naled, and four tris(haloalkyl) phosphate (tris-HAP) fire
retardants: tris(2-chloroethyl) phosphate (CEP), tris(2-chloro-l-propyl)
phosphate (CPP), tris(l,3-dichloro-2-propyl) phosphate (DCPP), and tris
(2,3-dibromo-l-propyl) phosphate (DBPP). A new haloalkyl phosphate fire
retardant, tetrakis(2-chloroethyl) ethylene diphosphate, is just beginning
to reach commercial production. Emphasis in this report has been on the
tris-HAP fire retardants, with data on the pesticides used for comparison
purposes.
A total of approximately 30 million pounds of tris-HAP fire retardants
were produced and consumed in the United States in 1974. Their growth rate
is projected at over 20% annually into the 1980's. DBPP is apparently pro-
duced in the largest quantity (9-12 million pounds), while the chloroalkyl
phosphates are produced in slightly smaller quantities (DCPP, 6-10 million
pounds; CEP, 3-10 million pounds; and CPP, 3 million pounds).
The tris-HAP fire retardants are added to products which must meet
Federal or state fire retardancy standards. While products to which the
chloroalkyl phosphates are added are similar, they are substantially different
from those to which DBPP is added. The chloroalkyl phosphates are used in
flexible and rigid polyurethane foams (e.g., furniture, transportation, and
household goods). DBPP's major application is as a fire retardant additive
for cellulose acetate and polyester fibers, particularly for use in material
for children's sleepwear. The low water solubility of DBPP (1.5 ppm) compared
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• to the chloroalkyl phosphates allows for considerable fire retardancy dura-
bility for the textiles during washing.
• Unlike the HAP-pesticides, the tris-HAP fire retardants are not directly
^ released to the environment. Possible sources of release include effliients
' from production plants or textile and polyurethane plants, laundering oi tie?.*.'.
ti textiles, or leaching from materials treated with tris-HAP that have been
discarded in landfills or dumps. No effluent monitoring data are available
• to indicate the magnitude of release from these sources; however, CEP is IK--
cluded on EPA's list of organic chemicals detected in drinking water and twc
• studies have indicated that DBPP may be washed from textiles under home
A laundering conditions.
The stability of the tris-HAP fire retardants in the environment is un-
• known. The fire retardants appear to be much more resistant than the pesti-
cides to chemical hydrolysis. One biodegradability study on DBPP was reported,
• but the results are difficult to interpret. The pesticide HAP's are degraded
• rapidly in soil, probably by biological hydrolysis.
The chloroalkyl phosphates are sufficiently water soluble to expect that
V they are dissolved and transported in water systems. In contrast, DBPP is
very insoluble in water, and therefore, may be susceptible to some extent
I to absorption and bioaccumulation. This is very significant since 1 ppm
M| DBPP in water produced 100% mortality in goldfish in five days.
The limited biological data that are available concerning the tris-HAP
• fire retardants do not allow for definitive conclusions to be drawn regarding
their environmental hazard potential. However, two biological properties of
| concern become evident in view of the more extensively studied HAP insecticides-
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dichlorvos and naled. These are the potential to inhibit the activity of
cholinesterase enzymes and to act as alkylating agents within animal cells.
Both dichlorvos and naled are effective inhibitors, ill vivo and in vitrc >
of cholinesterase. The primary toxic effects associated with these chemicals
in acutely poisoned animals can be attributed to cholinesterase inhibition
which may culminate in death at very low doses (acute oral rat LD < 100 rag/kg)
Only data from studies with fish are available to indicate that DBPP exhibits
• definite anticholinesterase effects. The tris(haloalkyl) phosphates are muc_n
less acutely toxic than either dichlorvos or naled. The relatively reduced
w toxicity of the tris(haloalkyl) phosphates may be due to poor absorption, but
A confirming quantitative data are lacking. Humans have not been reported to
be adversely affected by exposure to the tris(haloalkyl) phosphates, whereas
• numerous human poisonings by dichlorvos have resulted in transitory depressions
of cholinesterase activity as the only consequence of exposure.
• The biological implications of the alkylation of important cellular con-
• stituents, particularly DNA, point toward the induction of a carcinogenic or
mutagenic response. Dichlorvos is an effective chemical alkylating agent,
• but no experimental information is available on the chemical alkylating ability
of the tris(haloalkyl) phosphates. It is generally regarded, however, that
j§ the rapid in vivo hydrolysis of dichlorvos would prevent its acting as a
M potent alkylating agent in biological systems. The tris(haloalkyl) phosphates,
on the other hand, are not subject to extremely rapid chemical hydrolysis,
• and thereby may be less susceptible to in vivo biotransformation resulting
in inactivation. Experimental data are not presently available to support
( the conclusion that the fire retardants are resistant to rapid metabolism and
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A excretion in mammals. Recent evidence has emerged, however, indicating that
DBPP caused mutations in the Ames bacterial assay system, which strengthens
I the argument that the tris(haloalkyl) phosphates are potentially significant
_ biological alkylating agents. These results warrant further investigations
™ in higher organisms.
A With respect to health effects, the pharmacokinetics and pathways of
metabolism for the tris-HAP's in mammalian systems must be delineated in ordti
• to provide an accurate picture of possible chemical-biological interactions
at the molecular level. Furthermore, additional data are necessary to determine
• whether the tris-HAP's are intrinsically potent inhibitors of cholinesterase
A to warrant concern with human exposure. In the final outcome, it must be
established whether possible exposure levels are high enough to present a real
I threat to health and the environment.
The positive results of DBPP as a mutagen in bacterial systems is of
• particular significance because of the implications they hold for the safety
A of this compound when used in materials where there is direct human exposure.
Notable is the fact that DBPP fire-retarded materials are used extensively
• for children's sleepwear, where in addition to dermal exposure, the possibility
of some oral exposure resulting from chewing on the garment must be considered.
• The forthcoming results of the mammalian studies on DBPP will be of considerable
M importance in determining the human hazard potential of this compound.
The currently available information presented in this report leads to
• several questions for which conclusive answers are not yet available. With
respect to environmental exposure, data are needed on the eventual release
| of the tris-HAP's from materials in which they are incorporated, and on the
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A stability and chemical/biological breakdown products of the tris-HAP's under
environmental conditions. Data are especially needed on transport into the
• aquatic media and the fate and effects of these compounds therein.
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9 Great Lakes Chemical Corp. (1973b), "Tris(2,3-Dichloropropyl) Phosphate", Great
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• Great Lakes Chemical Corp. (1973c), "Tris(2-Chloroethyl Phosphate)", Great Lakes
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I
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~
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176
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177
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TECHNICAL REPORT DATA
(1'leiUf rend Instructions on the reverse before completing)
3. RECIPIENT'S ACCESSION NO.
TITI fc AMD SUOTITLF
Investigation of Selected Potential Environmental
Contain i nants : Ha 1 oa3kyl Phosphates
PERFORMING ORGANIZATION NAME AND ADDRESS
Center for Chemical Hazard Assessment
Syracuse Research Corporation
Merrill Lane, University Heights
Syracuse, Mew York 33210
SPONSORING AGENCY NAMt AND ADDRESS
)
, 1 fc JUPPl.E Ml (V t AH Y NOTES
5. REPORT DATE
August 1976
6. PERFORMING ORGANIZATION CODE
• U. rHORlS)
Sheldon S. f,.-nde, Joseph Uantodonato, Philip H. Howard,
Doiothy Greninger, and Deborah H. Christopher
8. PERFORMING ORGANIZATION REPORT NO
TR 76-513
10. PROGRAM ELEMENT NO.
11. CONTRACT/GRANT NO.
EPA 68-01-3124
13. TYPE OF REPORT AND PERIOD C()VER(- '
__ JLinal Technical JReport
14 SPONSORING AGENCY CODE
In AilbVRAC'
Tin , n-nori- /?vJ.>.vr t.he potential environmental hazard from the commercial use
jf UaJoalNyi r-liu-ipb.-M.-es: (FA,?). Emphasis is placed mostly on the four tris(haloalkyl)
phosphates wh^'cb acp used as fire retardants. Data on the two pesticide HAP's, naled
and dicHlorvo-;, ?ru used for comparison purposes. The tris-HAP's (1) are produced
in bigni Li. am. qufMl" t U'S, (2.) have several potential sources of environmental con-
tamination, ( j) hf.'jij. im unknown fate in the environment, (4) may act as cholinesterase
cu-b «mt! (5) MTC potentially carcinogenic and inutagenic.
KEY WORDS AND DOCUMENT ANALYSIS
urc CHIPTORS
naled, dichlorvos
Iris (2-chloroethyl) phosphate
tris (2--chloro-l-propyl) phosphate
tris(l,3-dichloro-?,-propyl) phosphate
tris(2,3~dibromo-l-propyl) phosphate
organophosphates
toxicity , fire retardants
16 DISTRIBUTION STATEMENT
Document is available to the public through
the National Technical Information Service,
Springfield, Virginia 22151
b.IDENTIFIERS/OPEN ENDED TERMS
19. SECURITY CLASS (Tills Report)
20. SECURITY CLASS (This page)
c. COSATI I'leld/Group
21. NO. OF PAf.tS
192
22. PFflCE"
EPA Form 2220-1 (9-73)
193
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