~~~' ~
',l'~' ,
-:1' : ~?
\fJ.'''''. :
~\ .{
-::~~,~;(.,,:.
"", '.~,J
-------
EPA-560j2-7S-004
6JUJ
CRAI
~o
'"
2.-1 S
/ooi
TR-74-572.2
ENVIRONMENTAL HAZARD ASSESSMENT
OF
LIQUID SILOXANES (SILICONES)
By
P.H. Howard
P.R. Durkin
A. Hanchett
Life Sciences Division
Syracuse University Research Corporation
Merrill Lane, University Heights
Syracuse, New York 13210
r.-
September 1974
Final Report
Contract No. 68-01-2202
Project L1205-05
<..!)
~
Proj ect Officer
Farley Fisher
0PPTS Us EPA
40 Chemical Lib
1 M Sf. SW rary
Wash'Q "'r, 0' MC7407
(2! - .C 20450
J 26()..3944
Prepared for
Office of Toxic Substances
U.S. Environmental Protection Agency
Washington, D.C. 20460
Document is available to the public through the National Telhnical
Information Service, Springfield, Virginia 22151
-------
NOTICE
The 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.
i
-------
.
II.
III.
IV.
I.
V.
TABLE OF CONTENTS
STRUCTURE AND PROPERTIES
. . . .
. . . .
A.
B.
C.
D.
Chemical Structure. . . . . . . . . . . . . . . . . .
Physical Properties of the Pure Materials. . . . '.' .
Physical Properties of Commercial Materials. . . . . .
Principal Contaminants in Commercial Products. . . . .
PRODUCTION
. . . . .
. . . .
. . . . .
. . . . .
. . . . .
A.
B.
C.
D.
E.
Quantity Produced. . . . . . . . . . . . . . . . . . .
Producers, Major Distributors, and Importers. . . . .
Production Sites. . . . . . . . . . . . . . . .
Production Methods. . . . . . . . . . . . . . . . . .
Market Price. . . . . . . . . . . .
USES
. . . . . .
. . . . .
. . . . .
. . . . .
A.
Major Uses
. . . .
. . . .
. . . . .
. . . . . .
1.
2.
3.
4.
5.
Waxes and Polishes. . . . . .
Antifoam Applications. . . . . . . . . . . . . . .
Foaming of Polyurethane. . . . . . .
Release Applications. . . . . . . . . . . . . . .
Protective Coatings for Textiles,
Glass and Leather. . . . . . . . . . . . .
Lubricant Applications . . . . . . . . . . .
Cosmetic Uses. . . . . . . . . . . . . . .
. . . . . . .
. . . .
6.
7.
B.
C.
D.
E.
Minor Uses . . . . . . . . . . . . . . . . . . .
Discontinued Uses. . . . . . . . . . . . . . . . . .
Projected or Proposed Uses. . . . . ',' .
Possible Alternatives to Use. . . . . . . . . . . . .
CURRENT PRACTICE
. . . . . .
. . . . .
. . . . . . .
A.
B.
C.
D.
Special Handling in Use. . . . . . . . . . . . .
Methods of Transport and Storage. . . . . . . . . . .
Disposal Methods. . . . . . . . . . . . . . . . . . .
Accident Procedures . . . . . . . . . . .
ENVIRONMENTAL CONTAMINATION
. . . . .
. . . . . . . .
A.
B.
C.
D.
E.
From Production. . . . . . . . . . . . . . . .
From Transport and Storage. . . . . . . . . . .
From Use. . . . . . . . . . . . . .
From Disposal. . . . . . . . . . . . . . . . . . . . .
General Environmental Contamination.
ii
Page
2
2
8
10
14
15
15
17
17
18
22
23
23
23
24
24
24
25
26
26
27
27
27
28
29
29
29
29
29
30
30
31
31
32
32
-------
VII.
VIII.
VI.
IX.
X.
XI.
Table of Contents
(continued)
CONTROL TECHNOLOGY
. . . . . .
. . . . .
A.
B.
Currently Used
Under Development
. . . . .
. . . . . . . . . . .
. . . . . .
. . . . .
MONITORING AND ANALYSIS.
. . . . . .
. . . . . . . .
A.
B.
Analytical Methods
Current Honitoring
. . . .
. . . .
. . . . . . . . . .
. . . . . . .
. . . .
. . . .
CHEMISTRY
. . . . . .
. . . . . .
. . . . . . . . .
A.
B.
C.
D.
E.
Reactions Involved in Use. . . . . . . .
Hydrolysis. . . . . . . . . .
Oxida tion . . . . . . . . . . . . .
Photochemistry. . . . . . .
Other. . . . . . . . . .
. . . .
. . . . . .
. . . . . .
. . . .
. . . . .
. . . . .
. . . .
BIOLOGY. .
. . . .
. . . . .
. . . . . .
A.
B.
C.
D.
E.
Absorption. . . . . . . . . . . . . . . . . . .
Excretion. . . . .
Transportation and Distribution. . . . . . . . . . . .
Metabolic Effects. . . . . . . . . . . . . . . . . .
Metabolism. . . . . . . . . . . . . . . . . . .
ENVIRONMENTAL TRANSPORT AND FATE
. . . . .
. . . . .
A.
B.
C.
D.
E.
Persistence. . . . . . . . . . . . . . . . . . . . . .
Biological Degradation. . . . . . . . . . . . . . . .
Chemical Stability in the Environment
Environmental Transport. . . . . . . . . . . . . . . .
Bioaccumulation . . . . . . . . . . . . . . . . . . . .
. . . . .
TOXICITY - HUMAN EXPOSURE.
. . . . . .
. . . . . . . . . .
A.
B.
C.
D.
Controlled Studies. . . . . . . . . . . . . . . . . .
Occupational Studies. . . . . . . . . . . . . . . . .
Epidemiology. . . . . . . . . . . . . . . . . . . . .
Medical Applications . . . . . . . . . . .
1.
2.
3.
Retinal Detachment Therapy
Antifoams and Lubricants
8ofl,: 'ri~/iiue Augmentation
. . . . . .
. . . . . .
. . . . .
. . . . .
. . . . . " . .
. . . . .
Hi
Page
35
35
35
35
35
36
37
37
37
38
40
40
41
41
44
45
49
49
50
50
50
51
51
52
53
54
54
55
56
57
58
59
-------
XII.
XIII.
XIV.
XVI.
XVII.
XVIII.
XV.
Table of Contents
(continued)
TOXICITY TO BIRDS AND MAMMALS
. . .
. . . . .
. . . .
A.
Ingestion
. . . . .
. . . .
. . . . . . .
. . . .
l.
2,
3,
4.
Acute Oral Toxicity. , . . . . . . . . . . . ,'. .
Subacute Oral Toxicity. . . . . . , . . . . . . ,
Chronic Oral Toxicity. . . , . . . . . . . .
Siloxanes and Cholesterol Metabolism. . . .
B.
C.
D.
E.
Inhalation. . . , . . . . . . . . . . . . . . .
Dermal Administration . . . . . . . . . . . . . .
Ocular Tolerance. . . , , . . . . . . . . . . . . , .
Tissue Response to Siloxane Injections. . . . .
l.
2.
3.
4.
5.
6.
Subcutaneous Injections. . . . . . , . . . . . ,
Intraperitoneal Injections. . . . . . . . . . . .
Intravenous Inj£ctions . . . . . . . . . . .
Intravitreous Injections. . . . . . . . . .
Intra-articular Injection . . . . . .
Other Injections . . . . . . , , . . . . , .
F.
G.
H,
I.
J.
K.
Sensitization
Teratogenicity. . . , . . , . . . . . , . , , . , , .
Mutagenicity
Carcinogenicity. . . . . . . . . . .
Behavioral Effects. . . . . . . . . . . . . . .
Possible Synergism. , . .
. . . . .
. . . . . .
. . . . . .
. . . . .
. . . .
. . . .
. . . . .
. . . . . . . .
TOXICITY TO LOWER ANIMALS.
. . . . . . .
TOXICITY TO PLANTS
. . . .
. . . . .
. . . . . . . . . . .
TOXICITY TO MICROORGANISMS
. . . . . .
. . . . . . .
CURRENT REGULATIONS.
. . . . . . .
. . . . . .
CONSENSUS AND SIMILAR STANDARDS.
. . . .
. . . . . . . . .
SILOXANE FLUIDS: SUMMARY AND CONCLUSIONS
. . . . .
. . . .
REFERENCES
. . . . . . . . . . . . . . .
. . . . . .
iv
Page
62
63
63
67
68
68
72
74
75
77
77
78
79
79
81
81
82
83
86
86
88
93
94
97
97
98
98
99
102
-------
Number
II.
III.
IV.
V.
VI.
VII.
VIII.
IX.
X.
XI.
XII.
XIII.
XIV.
XV.
XVI.
XVII.
XVIII.
XIX.
XXI.
XXII.
XXIII.
XXIV.
XXV.
XXVI.
XXVII.
XXVIII.
XXIX.
xxx.
XXXI.
TABLES
Title
I.
Structure and Nomenclature of Several Silicone
Compounds. . . . . . . . . . . . . . . . . . . . . . .
Shorthand Letter Designations for Silicone Compounds. . .
Viscosity and Calculated Weight-Average Molecular Weights
Synthesis of Silicone-polyether Copolymers. . . . . . .
Physical Properties of Low Molecular Weight. . . .
Typical Physical Properties of Dow Corning Silicone
Fluids. . . . . . . . . . . . . . . . . . . . . . . .
Vapor Pressures of Silicone Fluids. . . . . . . . . . . .
Estimated Silicone Usage in U.S. Market - 1973 . . . . . .
Sites of Production of Silicone Manufacturers. . . . . .
Approximate Highest Concentrations of Silicone Fluids
in the Great Lakes. . . . . . . . . . . . ; . . . . . .
Gelling Time of Silicone Fluids. . . . . . . . . . . . .
Balance Data on Polydimethylsiloxane Ingestion and Fecal
Excretion in Rats, Rabbits, and Man. . . .
Balance Data on Polymethylphenylsiloxane in Rats. .
Distribution of 14C-labelled Silicone in Rat Tissues etc..
Distribution of 14C-labelled Silicone in Rat Tissues etc..
Biologically Active Organosilicon Compounds. . . .
Acute Oral Toxicity of Single Doses of Various Siloxanes
to Guinea Pigs. ....................
Histopathology in Rabbits after 8 Months of Specified
Diet. . . . . . . . . . . . . . . . . . . . . .
Cholesterol Levels in the Serum, Liver and Aorta of
Rabbits Fed Specified Diets . . . . . . . . . . .
Mortality of Various Mammals Exposed to Mists of DC200
and DC701 etc. . . . . . . . . . . . . . . . . . . . . .
Eye Irritation in Rabbits after Direct Application
of Various Liquid Siloxanes ... . . . . . . . . . . .
Ocular Tolerance of Guinea Pigs to Direct and Vapor
Application of Various Liquid Siloxanes . . . . .
Results of Teratogenic Testing in Rats Injected with
Polydimethylsiloxane . . . . . . . . . . . . . . . . . .
Results of Teratogenic Testing in Rabbits with
Polydimethylsiloxane . . . . . . . . . . . . . . . . . .
Rabbit Teratogenic Study with Cyclic... . . . . . .
Positive Pathological Findings in Mice and Rats
Injected with Polydimethylsiloxane ..........
Oral Potency Comparison of Selected Phenyl-Subsituted
Siloxanes on Rat Seminal Fluid etc. .......
Comparative Relative Activities of 32 Organosiloxane
Compounds Based on Effects on the Ovariectomized
Immature Female Rat.. Uterus etc. .......
Effect of Selected Cyclotrisiloxanes and Cyclotetra-
siloxanes on the Uterine Weight... ..........
Daphnia Mortality in Static Exposure to Siloxane
Emulsions. . . . . . . . . . . . . . . . . . . . . . .
Daphnia Magna Mortality in Static and Dynamic Exposures
to a 30% Polydimethylsiloxane Emulsion. . . . . . . .
XX.
v
Page
2
4
6
7
9
11
12
16
18
34
39
42
43
47
48
62
64
70
71
73
75
76
83
84
85
87
89
91
92
94
95
-------
Number
1.
2.
3.
4.
5.
FIGURES
Title
Viscosity-Temperature Curves for Various
Silicones. . . . . . . . . . . . . . . . . . . .
Synthesis of Organoch1orosi1anes . . . . . . . . . . .'. .
Flow Diagram for Dimethy1dich1orosi1ane Production.
Mo1ecul~r Distribution of Linear Dimethy1si1oxane
after Equilibration with Chain Stopper. . . . . .
Price History of Dimethyl Silicone Oil. . . . . .
vi
Page
12
18
20
21
22
-------
LIQUID SILOXANES (SILICONES)
This review assesses the potential environmental hazard from the commercial
.
use of silicone fluids. These have been broadly defined aR any commercial
" ,
composition which contains the si10xane polymer chain ([-Si-O-]) and has a
. I x
R
measurable viscosity. A broader review of environmental hazard from the
commercial use of silicone fluids, elastomers, and resins has previously been
reported (Howard and Durkin, 1973).
Organosi1icon chemistry gained a foundation through the classical studies of
Kipping during 1900-1940 (see Lichtenwalner & Sprung, 1970).
Kipping used the
term "silicone" in expectation that the organosi1icon compounds would form
compounds analogous to the ketones of organic chemistry, in which the carbon
of the carbonyl group would be replaced by a silicon atom (Hyde, 1965).
However, the organosi1icon compounds did not form silicon-oxygen double bonds,
but instead they condensed to higher molecular-weight si10xane (Si-O-Si)
compounds.
Nevertheless the term silicones has remained and is generally
applied "to "polymeric si10xane products, usually complex, often undefinable
in exact scientific terms, frequently mixtures of many components, and in many
cases useful in one or more practical ways" (Litchtenwa1ner & Sprung, 1970,p.466).
Silicones became commercially important after a large development effort
by Hyde, Sullivan, and associates of the Corning Glass Company, McGregor and
associates of the Mellon Institute, and Rochow, Patnode, Marshall and
associates of the General Electric Company.
The first silicones operation
was established in 1943 as a joint program between the Corning Glass Works,
1
-------
the Corning Fellowship at Mellon Institute, and the Dow Chemical Company.
Today, hundreds of silicone products are manufactured throughout the world
and find uses in virtually every industry.
1.
Structure and Properties
A.
Chemical Structure
Silicon, like carbon, forms four sigma bonds to other atoms and maintains
a tetrahedral configuration.
Silicones must have at least one siloxane chain
(-Si-O-Si-), and, therefore, the silicones can be composed of four types of
units:
R
i
-Si-O-
I
o
I
R
I
-Si-O-
I
R
R
I
R-1i-0-
R
and
I
o
j
-O-Si-O- .
I
o
I
Various combinations of these four units can result in such compounds as the
following:
Table I.
Structure and Nomenclature of Several
Silicone Compounds
CH3 CH3
",/
/Si,
CH3 0 0 CH3
" I ,/
Si, /Si
/0""-
CH3 CH3
hexamethylcyclotrisiloxane
2
L
-------
1H 3 iH 3
S ......-0......... S.
C6HS/ /1 ,1- C6HS
o 0
\ / /" CH 3
'. /' Si-"""""O........-Si
C6HS I I
CH3 C6HS
l,3,5,7-tetramethyl-l,3,5,7-tetra-
phenylcyclotetras~loxane
CH3
I
+Si-O:7.=
I n
CH3
poly (dimethylsiloxane)
CH3
I
-f-Si-07
I
C6HS
poly (methylphenylsiloxane)
C1I3 C6Hs
I I
-f-Si-O~Si-O-+=
I I m
CH3 C6Hs
Poly (dimethylsiloxane-co-diphenyl-
siloxane)
As can be seen from Table I, the siloxane nomenclature becomes very cumbersome
and, therefore, the industry has adopted a convenient shorthand which identifies
the four types of units by letters, as depicted in Table II.
3
-------
Table II.
Shorthand Letter Desigpations for Silicone Compounds
R
I
R-Si-O-
I
R
R
I
-O-Si-O-
I
R
R
I
-O-Si-O-
I
o
I
I
o
I
-O-Si-O
I
o
I
Examples:
(CH3)3SiOSi(CH3)3
(CH3) Si-O[Si(CH3)20]2Si(CH3)3
.'
R = CH r
R + CH3-
M
M'
D
D'
T
T'
Q
Q
M2
MD2M
4
-------
The commercial silicones are extremely complex polymer mixtures.
The
fluids normally consists of long, straight-chain polydimethylsiloxanes (MD M)
. x
which can vary in molecular weight from 162 for the dimer(hexamethyldisiloxane-
CH3 CH3
I I
CH3-SiOSiCI13)
I I .
CH3 CH3
to molecular weights of several hundred thousand.
Organic
substituents, such as 0-'
Ct-0-' CH3CH2-, CH2=CH2-, CH3CH2CH2-,
CF3CH2CH2- and H-, can also form covalent bonds with the silicon, and provide
such mixtures as methylphenyl-, diphenyl-, and methylvinyl- polysiloxanes.
The fluids may have an open end
CH3
I
(-OSi-OH)
I
CH3
but more frequently they are
terminated with M units
CH3
I
(-OSi CH3)
I
CH3
In many cases, a mixture bf organic
substituents is used to form a copolymer which possesses the appropriate
physical properties.
For example, a common fluid is polydimethylsiloxane
with a small percentage of methylphenyl substituted groups evenly distributed
throughout the polymer chain
CH3 (/J
I I
[-SiO-] [-Si-O-] .
I x I Y
CH3 CH3
In contrast to the straight
ohain fluids, the elastomers and resins contain T and Q groups or reactive
organic side chains (e.g. vinyl) which allow crosslinking of the polymers
resulting in a more rigid matrix.
5
-------
The low molecular-weight oligomeric polysiloxanes have definite
molecular weights and can be isolated by distillation or crystallization.
However, once the number of difunctional units (D) reaches 10, identification
of individual compounds is no longer possible.
The number of difunctional
groups may continue to at least 10,000D units (Noll, 1968, p 249).
Since
the commercial polysiloxane fluids consist mostly of high molecular weight
formulations, they are made up of a broad molecular size distribution.
B"ecause of this lack of sharply defined molecular size, the practice of
referring to the fluids in terms of viscosity has arisen.
Since the
viscosity correlates to some degree with the mean molecular weight (Noll,
1968, p.250) as can be seen in Table III, the viscosity roughly corresponds
to the degree of polymerization.
Table III.
Viscosity and Calculated Weight-Average Molecular
Weights (M) and Average Number of Siloxane Units
(N) per Molecule in a Series of Linear Polydimethyl-
siloxanes (Noll, 1968, p 253)
\l20[CSt] M N
60 3600 50
140 8000 no
440 17000 230
680 21000 280
1440 30000 400
10000 60000 800
50000 88000 1200
100000 103000 1400
300000 143000 1900
The siloxane polymer chain can also be connected to non-siloxane
polymers to form copolymers.
Commercially one of the most important of
6
-------
these combined polymers is the silicone-polyoxyalkylene (also referred to as
silicone polyether copolymers or silicone glycols) block
block copolymers.
The block block refers to the fact that these copolymers consist of a block of
siloxane polymers attached to a block of polyether (PE) polymer: These copolymers
can be divided into two large groups, (1) those with Si-O-C bonds, and (2) those
with Si-C bonds.
Table IV illustrates some of the synthesis routes used.
Table IV.
Synthesis of Silicone-polyether (PE) Copolymers
Si-O-C Bridges
I
-Si-OR + HO-PE ---+
I
I
-Si-H + HO-PE
I
I
-Si-NH2 + HO-PE
I
Si-C Bridges
I
-Si-H + CH2 ~ CH-PE
I
I
-Si-CH2Br
I
+ HO-PE
I
-Si-O-PE + ROH
I
I
-Si-OPE
I
I
) -Si-OPE + NH3
I
I
) -Si-CH2-CH2-PE
I
I
) -Si-CH20PE
I
The polyether most frequently consists of ethylene oxide and propylene oxide
units, and the copolymer may be linear (I) or branched (II) (Noll, 1968).
7
-------
(I)
CH3 CH3
I I
-(0-Si-)-(CH2-CH20) -CH2CH2Si-OSi(CH3)
I x y I 3
CH3 CH3
(II)
CH3
I
0-[-~iO-](C2H40)
I n
CH3
(C3H60) C4Hg
P
CH3
I
CH3Si-OfSi-0- ]
I
CH3
(C2H40) (C3H60) C4Hg
n p
CH3
I
0- [-Si-O-] (C2H40) (C3H60) C4Hg
I n p
CH3
B.
Physical Properties of the Pure Materials
Only the low molecular weight cyclic and linear siloxanes have been
isolated and characterized in pure form.
The physical properties of the
volatile dimethylsilicone oligomers are presented in Table V.
8
-------
Table V.
Physical Properties of Low Molecular Weight
Dimethyl Silicones (Meals, 1969, p. 226)
Melting Boiling Density, Refractive Viscosity, n, Flash
Symbol point, 0c point, 0c d20 Index, n20 at 250C, cSt. point, of
D
MM -67 99.5 0.7636 1.3774 0.65 15
MDM -80 153 0.8200 1.3840 1. 04 98
MD2M -76 194 0.8536 1.3895 1. 53 158
MD3M -80 229 0.8755 1.3925 2.06 202
MD4M -59 245 0.8910 1.3948 2.63 245
MDsM -78 270 0.9012 1. 3965 3.24 272
\0 MD6M -63 290 0.9099 1. 3970 3.88 292
MD7M 307.5 O. 9180 1.3980 4.58 318
D3 (cyclic) 64.5 134
D4 17.5 175.8 0.9561 1. 3968 2.30 156
Ds -44 210 0.9593 1. 3982 3.87
D6 -3 245 0.9672 1.4015 6.62
D7 -32 154a 0.9730 1. 4040 9.47
D8 31. 5 290 1.1770b 1. 4060 13.23
a b
At 20 rom Hg. Crystals.
-------
C.
Physical Properties of Commercial Materials
The higher viscosity polydimethylsiloxanes and polymethylphenylsiloxanes,
which make up the bulk of the technical products, have the following character-
istic properties: "heat resistance; low-temperature resistance; Jesistance to
weather, ozone, and corona discharge; low variability of the physical constants
with temperature; good dielectric properties; film-forming ability; hydrophobic
behavior; release action; surface activity; and physiological inertness" (Noll,
1968, p 437).
These properties are intimately related to the commercial
application of the compounds.
This section will discuss the physical properties;
chemical properties will be discussed in Section VIII; and physiological pro-
perties will be discussed in Sections XI-XV.
Table VI presents some general physical properties of a number of
silicone fluids sold by Dow Corning.
A more detailed discussion of the
physical properties is presented in the following paragraphs.
Many of the commercial applications of silicone fluids are due to their
ability to function at extreme temperatures (both high and low).
The low
variation of the viscosity of methylsilicone oils with temperature provides a
striking illustration of that property, as is shown in Figure 1.
However,
replacement of the methyl groups by other groups
tends to increase the
temperature dependence of the viscosity.
Pressure has only a slight effect on the viscosity.
For example,
a pressure of 2000 atmospheres increases the viscosity of mineral oil by a
factor of about 50-500, but silicone oil (140 cSt.) viscosity is increased
by only a factor of 16 (Noll, 1968).
Furthermore, for liquid siloxanes of
up to 1000 cSt., shear forces have little effect.
10
-------
Table VI.
Typical Physical Properties of Dow Corning Silicone Fluids
(Dow Corning, 1972a)
Flash Surface Thermal Dielectric
Point Pour Specific Coefficient Tension Conductivity Constant
Fluid Type Viscosity Open Point Gravity of Expansion at 23°C at 25°C Volatility Refractive 100 H2
II Type cSt. Cup °c °c (25°C) cc/ccoC dyne/em col/sec-cmoC % at Temp. Index 25°C 1S0°C
200 Dimethyl 5.0 135 -65 0.920 0.00105 19.7 0.00028 1.397 2.59 2.24
10 165 -65 0.940 0.00108 20.1 0.00032 1. 399 2.64 2.28
20 230 -60 0.955 0.00107 20.6 0.00034 1.400 2.68 2.32
50 280 -55 0.960 0.00104 20.8 0.00036 150, 2.0% 1. 402 2.71 2.35
100 300 -55 0.968 0.00096 20.9 0.00037 150, <0.5% 1.403 2.73 2.37
200 315 -52 0.971 0.00096 21. 0 0.00037 150, <0.5% 1.4031 2.74 2.38
350 315 -50 0.972 0.00096 21.1 0.00038 150, <0.5% 1. 4032 2.75 2.39
500 315 -50 0.972 0.00096 21.1 0.00038 150, <0.5% 1. 4033 2.75 2.39
1,000 315 -50 0.972 0.00096 21. 2 0.00038 150, <0.5% 1. 4035 2.77 2.41
12,500 315 -46 0.973 0.00096 21. 5 0.00038 150, <2% 1.4035 2.77 2.41
30,000 315 -44 0.973 0.00096 21. 5 0.00038 150, < 2% 1.4035 2.77 2.41
60,000 315 -41 0.973 0.00096 21. 5 0.00038 150, <2% 1.4035 2.77 2.41
f-'
f-' 203 1,200 232 0.91 1. 464
230 1,400 204 1.009 1. 462 2.74 --
330 Branched
Dimethyl 50 279 -73 0.97 0.00107 20.5 0.00034 200, 2.0% 1.4025 2.72 --
510 Phenylmethyl 50 275 -73 1. 00 0.00096 25.0 0.00035 200, 2.0% 1. 425 2.77 2.42
100 275 -73 1. 00 0.00096 24.1 0.00036 200, 1. 5% 1. 425 2.78 2.44
500 275 -73 1. 00 0.00096 24.4 0.00037 200, 1. 5% 1. 425 2.80 2.46
550 Phenyl-
methyl 125 300 -51 1.07 0.00075 24.5 0.00035 250, 9% 1.50 2.90 2.57
560 Chloropheny1-
methyl 75 288 -65 1. 040 0.00095 22.7 1.434
710 Phenyl-
methyl 500 300 -20 1.11 0.00077 28.5 0.00035 250, 9% 1.533 2.95 2.65
FS Fluoro- 300 260 -47 1. 25 0.00095 25.7 200,10% 1.381 ' 6.95 --
1265 silicone 1,000 290 -40 1. 28 0.00095 26.1 200, 3.0% 1. 382 7.35 --
10,000 315 -30 1. 30 0.00095 28.7 200, 1. 5% 1. 383 7.35 --
-------
10,000,000 ,-
l,()')II,(j.)O ':,
ll'O,OO:) :.
10,000 ::..
rrr'Trn-rrrrrTIlTlfTrIIIIIIII I I I I I I I rrrrrrrrrrr
..
"
.~
l:
..
"
~
100.000 cSt Me7SiO
-
1.000 -
10,000 cSt M~2SiO-
c/j
u
i-
'.Ii
()
~~
':;
10 "
'-.
'-.
.......
'-.
.......
'-.
.......
.......
.......
.......
'-.
'-.
.......
'-. MIL;-L-780El Diester
5 cSt Me2SiO
1000 cSt M~2SIO
-
100 :-
-,
"
'-.
"
.......
'-.
'-.
"-
.......
'-. ,SAE-IOW f'clfoleum oil
-,
100 cSt r,le2SIO
-
I I I I I I I 1 1...l..1 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I LL.LL.,L
-100 0 100 200 300 400 ~oo
TemperJture, 'F
GOO
700
Figure I
Viscosity-Temperature Curves for
Various Si] i cones Utea.ls, 1969);
reprinted by permission.
Copyright ]969, J. \Hley and Sons
The vapor pressure of the commercial silicone fluids, with the
exception of the lower members, is generally very low.
This can be attributed
to the recycling of the volatile siloxanes by distillation during manufacture
of the higher polymeric siloxanes.
However, even the high polymer fluids have
measurable
vapor pressures at elevated temperatures, as illustrated in
Table VII.
Table VII. Vapor Pressures of Silicone Fluids (Noll, 1968)
cSt (20°C)
Vapor Pressure (mm Hg)
140
200-1000
30,000
(dimethyl)
(methylphenyl)
(methyl)
-------
The surface tension of all liquid silicones is surprisingly low (see
Table VI) and can be attributed to the low strength of the intermolecular
binding forces between polymer chains.
This low strength of the intermolecular
binding forces also results in a high film-forming ability.
Films of molecular
dimensions can be rapidly formed on both solids and liquids.
Such films 'can
reduce adhesion to sticky materials and impart water repellancy to the
surfaces that are coated.
These properties are "an expression of a fundamental
chemical characteristic of the polymeric organosiloxane skeleton:
its paraffin
nature, the saturated character of the molecules, and the corresponding
smallness of Van der Waals forces which permit the appearance of only slight,
if any, affinity for substances of different nature"(Noll, 1968, p 452).
The compressibility of the liquid polysiloxanes is comparatively high.
This results in their application as liquid springs, shock absorbers, and
damping devices.
The high compressibility is a result of the unusual flexi-
bility of the ,molecule, leading to loose coiled configurations (helical) with
a large amount of internal free space.
This free space allows compression
to occur relatively easily.
The dielectric properties are characterized as good in terms of
dielectric constant, loss factor, specific resistance, and dielectric strength
and vary only slightly with temperature (Noll, 1968).
The lubricating properties of silicone oils are generally poor.
The
load-bearing properties of the methyl siloxane films are especially low because
of the weak intermolecular forces.
Improved lubricating properties are
obtained by incorporation of phenyl groups (especially halogenated phenyl groups)
13
-------
and long chain alkyl groups.
Recently, the CF3CH2CH2- group has also been
incorporated in siloxanes in order to increase the load bearing capacity.
The silicones also display surface active properties which result in
their use as foaming and antifoaming agents.
The foaming action can be
attributed to the lowering of the surface tension by the siloxane.
The anti-
foaming activity results from effects on bubble elasticity at low siloxane
concentration (see Noll, 1968, p 454).
Dimethylsilicone and phenylmethylsilicone are soluble in many solvents,
but their solubility is dependent to some extent on viscosity, molecular weight,
and organic substitution.
Good solvents include hydrocarbons (gasoline, benzene,
toluene), chlorinated hydrocarbons (chloroform, carbon tetrachloride, trichloro-
ethylene), ethers, esters, and higher alcohols from butanol onward.
The lower
viscosity (60-140 cSt) dimethylsilicones dissolve in isopropanol, n-propanol,
n-butanol, acetone, and dioxane.
The low molecular weight (5, 10, and 25 cSt)
methylphenylsilicone oils dissolve in methanol and, unlike the other types of
oils, are compatible with paraffins, most vegetable oils and petroleum jellies
(Noll, 1968).
The fluorosilicone fluids are only soluble in ketones and low
molecular weight esters (Dow Corning, 1972a).
D.
Principal Contaminants in Commercial Products
The silicone fluids are formed by the hydrolysis of organochlorosilanes
(see Section lId).
These compounds are highly purified (93-98%) by distillation
and the most frequently used, dichlorodimethylsilane (used to synthesize the
polydimethylsiloxane fluids), is available in purities above 99.5% (Meals, 1969).
14
-------
The hexamethyldisiloxane can be purified by distillation to remove impurities
resulting from hydrocarbons, SiC14' and other chlorosilanes in commercial
Me3SiCl.
Thus, when the dimethylsilicone fluids are made by reacting
(equilibration process) the dimethyl silicone stock (hydrolysis' product of
(CH3)2SiC12) with hexamethyldisiloxane, the result is a mixture of many
siloxane isomers relatively free of non-siloxane contaminants.
For the more
viscous fluids, this equilibration reaction is followed by a devolatilization
process which removes the light ends (cyclic and low molecular weight siloxanes)
for recycling.
In some instances, these light siloxanes could be considered
to be impurities, but they are probably mostly removed by the devolatilization
process which consists of heating in vacuum.
II.
PRODUCTION
A.
Quantity Produced
Details on plant capacities are not available and total production
figures lack precision due to the fact that many manufacturers fail to
differentiate between finished products, which contain water and solvent.
and 100% silicone material.
The diversity of the applications also contributes
to the lack of precise information.
An estimate for 1965 placed the total production of silicones (fluids
and silicone content of resins and elastomers) at apout 25 million lbs.
(Anon., 1965).
In 1971, elastomers and resins only totaled approximately
40 million lbs. (U.S. Tariff Commission, 1972).
However, it is unclear how
15
-------
much of the 40 million lbs. is 100% silicone material (e.g. silicone-alkyd
resins contain as little as 15% silicones).
Union Carbide (Bailey, 1973) has
suggested that the total market (including water in silicone emulsions and
solvents in resin solutions) is approximately 200-300 million lbs.
Table VIII
presents some estimates of the silicone market provided by the Dow Corning
Corporation (1973).
The total silicone market is estimated to be 91 million lbs.
with approximately 30 million lbs. of 100% silicone fluids and 18 million lbs.
of silicone glycol fluids (~30% siloxane content).
This is comparable to the
estimate of Lewis (1967) that 45% of the total silicone production goes into
silicone fluids.
Table VIII.
*
Estimated Silicone Usage in U.S. Market - 1973
(Dow Corning Corporation, 1973)
106lbs.*
% of total
Methyl Siloxanes (fluids (~50% of
total), compounds, rubber,
sealants) .
Dimethyl siloxanes
Methyl and small quantities of
phenyl, vinyl, chlorophenyl, etc.
30
33
30
33
Silicone Glycols (used with
polyurethanes)
18
20
Chemicals
3
3
Miscellaneous (resins, resin inter-
mediates, fluorosilicones)
10
11
Total
91
100
*
Represents silicone content except for silicone
Approximately 30% of the silicone glycol figure
siloxane compound.
glycols.
represents
16
-------
B.
Producers, Major Distributors, and Importers
In the United States there are four major manufacturers of silicones:
Dow Corning Corporation, General Electric Company, Union Carbide Corporation,
and Stauffer Chemical Company.
Dow Corning is the largest producer (approxi-
mately ~ the total); General Electric produces somewhat less; Union Carbide
production amounts to about 15-25% of the total (Bailey, 1973); and Stauffer
is the smallest producer, with about 5% of the market.
Outside the United States, silicone producers include: Imperial
Chemical Industries and Midland Silicones (United Kingdom), Societe des Usines
Chemiques Rhone-Poulenc and Societe Industrielle des Silicones et des Produits
Chemiques du Silicium (France), Union Chimique BeIge (B~lgium), Farbenfabriken
Bayer, Wacker-Chemie, and Theo. Goldschmidt (West Germany), V.E.B. Siliconchemie
and VF-V Chemie-Werk (East Germany), Societa Italiana Derivati Silicio (Italy),
and Shin-etsu Company, Tokyo Shibaura Company, and Japan Silicone Company
(Japan).
There are also manufacturing plants in several
locations in the
USSR and in Czechoslovakia, as well as in Australia, and probably some in
Mainland China (Lichtenwalner and Sprung, 1970).
Since silicones are in most cases a speciality commodity, there are
no major distributors.
However, in some cases, like with electronic fluids,
authorized distributors are utilized.
C.
Production Sites
Table IX lists the producer, Lhe type. of product made, and the site
of the manufacturing plant.
Capacities of individual plants are not available,
but the total capacity in 1967 was estimated at 50 million 1bs. (Lewis, 1967).
17
-------
Table IX.
Sites of Production of Silicone Manufacturers
(Lewis, 1967)
eompany
Product Type
Location
Dow Corning Corporation
Fluids, resins, elastomers
Dimethyl silicones
($15 x 106 plant)
Silicone Sealants
Medical-grade Silicones
Silicone Rubber
Mad1and, Michigan
Carro11ton, Kentucky
E1izabethtown, Ky.
Hemlock, Michigan
Trumbull, Conn.
General Electric
Fluids, resins, elastomers
Silicone resins
Waterford, N.Y.
Coshocton, Ohio
Union Carbide
Fluids, resins, elastomers
Sistersvil1e, W. Va.
Stauffer Chemical Co.
Fluids, elastomers
Elastomers
Adrian, Michigan
Matawan, N.J.
D.
Production Methods (Gutoff, 1957; Forbath, 1957; Weaver and O'Connors,
1958; and Lichtenwalner and Sprung, 1970).
The silicone fluids are synthesized from the hydrolysis products of
organoch1orosi1anes.
The organoch1orosi1anes can be produced by a number of
different routes, as demonstrated in Figure 2.
C
D
2CH3C1 + Si ) (CH3)2SiC12
C6HsMgC1 + SiC14 ~ C6HsSiC13 + MgC12
C6HsMgC1 + CH3SiC13 ~ C6Hs(CH3)SiC12 + MgC12
RCH = CH2 + HSiC13 ) R CH2CH2SiC13
HC=CH + HSiC13 ~ CH2 = CHSiC13
CH3C1 + HC1 + Si ---- CH3HSiC12
A
B
E
F
Figure 2.
Synthesis of Organoch1orosi1anes
Reaction A in Figure 2 is the most important commercially and is commonly
referred to as the "direct process".
The process is used mostly for the
production of methy1ch1orosi1anes and sometimes for the pheny1ch1orosi1anes.
18
-------
Reactions Band Care Grignard processes which commercially are important in
the production of methylphenylchlorosilanes.
Reaction D is termed the olefin
process.
It is used to synthesize alkylchlorosilanes (e.g., CF3CH2CH2-)'
The direct process, which is used to produce methylchlorosilanes, consists
of reacting metallic S1 with methylchloride using a copper catalyst.
The
silicone metal is prepared by reacting coke and silica in an electric furnace.
CH3C1 + Si 30~~C )
(CH3)2SiC12' (CH3)3SiC1, CH3SiC13
The mixture of chloromethylsilanes resulting from the direct process
typically
falls in the general range given below (Lichtenwalner and Sprung,
1970)
(CH3)2SiC12
CH3SiC£3
CH3SiHC1z
(CH3)3SiC1
>50%
10-30%
<10%
<5%
other monosilanes
~5%
up to 10%
higher-boiling residue
The chloromethylsilanes are isolated from each other by distillation.
The
most important commercial compound, dimethyldichlorosilane, can routinely be
prepared in high purity (99.9%) by using more than 100 actual plates in the
distillation (CH3SiC13 boils only 40 lower).
A representative flow diagram
is presented in Figure 3.
19
-------
,tf
"
-~
I
co
J
m ~/!@
~
UnreaLted methyl
chloride 10
compression and
dislillation
Me thyllr ichlorosila ne
Bulk silicon
Crusliing and
grindi,,~
- ~ Dimetliyldichlorosilane
Mi'ed
clilorosilanes
Iliglier-boiling lower-boiling
residue chlorosllanes
(bp < WC)
Figure 3. Flow Diagram for Dimethyldichlorosilane Production
(Lichtenwalner and Sprung, 1970)
reprinted by permission, Copyright 1970, J. Wiley & Sons
A crude mixture of straight chain and cyclic siloxanes is formed by
the hydrolysis of the difunctional chlorosilanes.
This is illustrated for
(CH3)2SiC£2in the equation below:
(CH3)2SiC£2 + H20
) [(CH3)2Si)]
n
cyclic
+ HO[(CH3)2SiO] H + HC£
m
straight chain
The proportion of cyclic material can vary from 20-80% depending upon the
conditions.
The siloxanes are decanted~ washed with water or neutralizing
bicarbonate solution, and dried.
The hydrolysis step is typically run in
glass, glass-lined steel, or plastic of suitable chemical and thermal
resistance.
Both batch and continuous operations (commonly used with the
dimethylsili~ones) are possible.
The next step to the silicone fluid product involves the equilibration
of the crude siloxane mixture with either acid or base catalyst in the presence
of a chain stopper (an M group such as
CH3
I
CH3Si-).
I
CH3
Normally the chain stopper
20
-------
1----"----
is added in the form of a disiloxane which has previously been hydrolyzed
CH3
I
2 CH3SiC.Q,
I
CH3
H20
CH3 CH3
I I
) CH3Si-OSiCH3
I I
CH3 CH3
+ 2HC.Q,
[(CH3)2SiO] + HOt(CH3)2SiOtH +
n
H+
(CH3)3SiOSi(CH3)3-
OR
(CH3)3SiOt(CH3)2SiOt Si(CH3)3 + H20
P
) [(CH3) 2SiO] +
n
The proportion of chain stopper to difunctional
siloxane will determine the
molecular distribution of the linear chains in the fluid as illustrated in
Figure 4.
012
I
Mul fract1onl(C"J)~SIOI = 0.60
0.10
- - -- ..
-'... . -. -. --
.. - .--.------.
. .-.--..- -----
.0
. :=
o OS -
---_..-- .. -.---- .-
c-
9
u
~
006
- --.----.. -----..-.--..--.-...-..------.-----.--
CD
f;
---
0.02
-,--
o
o
5
10
15
20
2~
30
3~
Number of silicon ~lol1ls 11,-r molecule
Figure 4. Molecular Distribution of Linear Dimethylsiloxane
after Equilibration with Chain Stopper
(Lichtenwalner and Sprung, 1970, p 524)
reprinted by permission, Copyright 1970, J. Wiley & Sons
21
-------
The fluid is then washed with water, neutralized, and dried by passing through
an absorbent medium.
The final step to the finished product involves devolatizing
the fluid which removes most remaining cyclic siloxanes and low-molecular
straight chains.
This step yields a somewhat higher viscosity fluid.
E.
Market Price
The market price of the fluids varies considerably depending upon the
grade and organic substitutents used.
For example, prices can be as low as
under $2/lb for some dimethylsilicone fluids in drum lots to over $50/lb for
specialty items (Lewis, 1967).
The general price trend for the dimethyl-
silicone fluids has been downward as illustrated in Figure 5.,
6
5
n
,
~ 4
-
~
~
~
~
3
2
1 -
1945 1950 1955 1960 1965
Figure 5.
Price History of Dimethyl Silicone Oil
(Lichtenwalner and Sprung, 1970, p 471)
by permission, Copyright 1970, J. Wiley & Sons
reprinted
22
-------
III.
Uses
A.
Major Uses
The silicone fluids are used commercially for literally hundreds of
applications due to the flexibility allowed by the various synthesis routes
and formulation techniques.
Applications resulting from both their bulk
properties (thermal and oxidative stability, electric properties, and viscosity/
temperature characteristics) and from their surface properties (water repellency,
low surface tension, and release properties) are important.
Early applications
of the fluids included coolants in pumps, transformers, and other mechanical
and electric equipment, and as dielectric fluids.
However, because the silicone
fluids are relatively expensive, their major commercial applications today
employ their surface characteristics since only small amounts of material are
required.
These applications include polishes for automobiles, furniture, and
major appliances, use as release agents, as antifoam agents, as foaming agents
for polymers, and for paper and textile treatment(Lichtenwalner and Sprung, 1970;
Lewis, 1967).
Because of their widespread use in large numbers of industrial
and consumer applications, it appears likely that the geographical consumption
and disposal pattern generally follows the same pattern as the U.S. population.
1.
Waxes and Polishes
Most furniture, car and glass waxes and polishes contain silicone
fluids.
They reduce the work required to spread the polish, improve the gloss,
and increase the weatherability of the finishes.
The silicone ~ontent in most
polishes varies from 2-10%.
Production figures from 20 polish manufacturers
estimate' that approximately 1,350,000 units of polish and 4,700,000 units of
paste were annually produced in the late 1960's(Todd, 1971).
23
-------
2.
Antifoam Applications
Silicone fluids, usually in an emulsified form, have been widely
used as antifoaming agents.
The extremely small amount of material necessary
for activity (0.0001 to 0.02%), makes the use of the defoamer relatively
inexpensive.
Industries which utilize the silicone antifoams include the
chemical, metalworking, paper and printing, plastic and rubber, petrochemical,
textile, water and waste water treatment, and food processing industries
(Dow Corning, 1972b).
It is estimated that quantities of silicone fluids used
for antifoamingapplications amount to approximately 1 million lbs. annually.
3.
Foaming of Polyurethane
Sizable quantities of silicones, in the form of a silicone-polyether
(silicone glycols) block - block copolymer fluid, are used to assist in the
foaming of polyurethane.
The silicone-polyether fluid allows the polyurethane
to be foamed in a one step process, the fluid giving control to the pore sizes
of the foam (Meals, 1965).
The dimethyl silicone portion of the fluid normally
consists of 15-30% of the total composition.
The copolymer fluids are also
used in cosmetic preparations, such as hairsprays, and as paintable mold
release agents for plastics (Thimineur, 1972; Meals, 1965).
Dow Corning (1973)
has estimated the 1973 u.S. market of silicone glycols at 18 million lbs.
4.
Release Applications
Silicones represent one of the most important classes of abherents
(release agents} (Kovach, 1963).
This is a direct application of the low
surface tension properties of the silicones.
The dimethylsilicone fluid is
the most important fluid abherent and it can be applied full strength to the
mold being treated, but more frequently the material is in a solution or
24
-------
,-
emulsion.
Silicone abherents are indispensib1e for high temperature app1i-
cations such as those found in metal processing and glass molding.
Other
industries using silicone fluids as release agents include the food, rubber
processing, and plastics industries.
In some cases, the silicone release agents
impart abherent properties to the material being released, which does not. allow
painting of the released molded part.
To overcome this problem, silicone
glycols have been used as paintab1e release agents.
5.
Protective Coatings for Textiles, Glass, and Leather
Silicone fluids are frequently used to provide water repellent and
smooth textured coatings to textile, glass and leather materials.
With glass
the methy1ch1orosilanes were first used to produce silicone films by reacting
the methylch1orosi1ane vapor with water adhering to the glass.
Today, the po1y-
dimethyl fluids are used as the silicone components.
An important part of
the treatment process consists of heat treatment (300-400°C) to permanently
anchor the fluid to the glass.
The silicone fluid allows liquids to drain
without leaving any residue behind (important in pharmaceutical preparations)
and reduces the breakage rate by affecting the mechanical strength of the
glassware.
Silicones used in the textile industry have found ever-increasing
acceptance.
The fluids have two major advantages over conventional treatments:
(1) the finish can be made semipermanent by cross-linking the siloxanes polymer
chain, and (2) the finish can be applied in such a dilution that only the fibers
are coated thus allowing the passage of water vapor but not liquid water (Ames,
1958).
Commonly, the f1uid contains a mixture of methy1hydrogen- and
25
-------
dimethylsiloxanes (60:40, Bajaj, 1973) with an organometallic catalysis to
assist the cross-linking after the fabric is coated.
The silicone treatments
resist washing and drycleaning as well as impart a softening and smoothing
effect to the textile (Blumenstein, 1968; Noll, 1968).
The silicones are also used in the leather industry to impart water
repellency.
The silicones are usually applied by immersion of the leather in
a dilute silicone solution.
6.
Lubricant Applications
The dimethylsilicone fluid's lubricant performance with plastics
and rubber is excellent, but because of their poor load bearing capacity (weak
intermolecular forces) they are rarely used in high friction applications.
However, when combined with fillers to form greases, they are excellent
lubricants at extreme heat or cold.
Also, if the fluid is chemically modified
(e.g. methylphenyl, methylchlorophenyl, or fluoropropyl groups are attached
to the silicone),
the fluids can be very valuable for extreme temperature
friction lubricating problems (Schiefer et al., 1961).
7.
Cosmetic Uses
The dimethylsilicone fluids are used in sizable quantities in the
cosmetics and toiletries industries.
The following properties make them ideal
for this application: colorless, odorless, tasteless, resistant to oxidation
and do not become rancid, low surface tension (spread easily), incompatible with
most organic oils and waxes (spreading aid), water-repellent but allow free
passage of water vapor and carbon dioxide, chemically inert (do not react
with cosmetic materials), and a very low order of toxicity (Saunders, 1969).
26
-------
Cosmetic applications include hand, lip, shaving, hair and sun-oil preparations.
They are also used in powders, anti-perspirants, and sometimes toothpastes
(Thimineur, 1969; Lewis, 1967; Saunders, 1969).
The concentration of the fluid
in the preparation may vary from 1-5%, although protective cream~ can contain
as much as 20% fluid.
B.
Minor Uses
Relatively small amounts of silicone fluids have been used in aerosol
starch, domestic oven cleaner and ironing aids (Lewis, 1967).
Dow Corning
(1972a) recommends their fluids for use in such functions as damping (dash pots,
meter indicators, etc.), dielectric cooling and impregnating (power tubes,
transformers, capacitors, magnets, electromechanical devices), working media
(gyro flotation, shock absorbers, magnetic amplifiers, fluid clutch in rotating
equipment, fluid drive in aircraft, diffusion and high vacuum pumps), and heat
transfer, as well as the functions discussed in the previous section.
The
dimethylsilicone fluids have also been cleared by FDA for use as coatings in
food-packaging material and as defoaming agents in food.
Most of these appli-
cations are very specialized and the quantities utilized are relatively small.
C.
Discontinued Uses
Lewis (1967) has reported that silicone fluids are no longer used to
coat bread baking pans (displaced by fluorocarbon polymer coated pans) or as
hydraulic fluids in airc~aft ~pplications.
D.
Projected or Proposed Uses
Thimineur (1972) has suggested that considerable work is being done
by General Electric with dimethylsilicone and silicone glycol fluids as
27
-------
.,
possible brake fluids for automobiles.
Dow Corning (1973) was reported that
it is contemplating using fluids as antitranspirants for plants in order to
reduce the loss of water in dry terrain.
In general, it is anticipated that
silicone fluids will be replacing other chemicals in uses that provide human
exposure or release to the environment, where the physical properties of the
silicones are appropriate and the extra cost is justified.
E.
Possible Alternatives to Use
Because silicone fluids are relatively expensive, they are frequently
applied only as a last resort.
For example, the one shot polyurethane process
is designed around the silicone glycols (Bass, 1961).
High temperature release
applications in the glass and metals processing industries can only be done
with silicone abherents (Kovach, 1963).
Other antifoaming agents are known,
but few work at such low concentrations or are as inert.
With some of their
bulk applications, such as use as dielectric fluids, hydraulic fluids, and
shock absorbers, other chemicals such as epoxy fluids, diphenyl-diphenyloxide
mixtures, and other high boiling liquids can be used.
However, when it is
expected that the application will be exposed to extreme temperatures, the
silicone fluids cannot be replaced.
28
r
-------
IV.
Current Practice
A.
Special Handling in Use
A1thoMgh the organoch10rosilane precursors are corrosive, toxic and
.
form hydrogen chloride on contact with water, the si10xane fluids are quite
stable at ambient temperatures and relatively physiologically inert.
Therefore,
no special handling is necessary other than procedures normally followed for
inert, low-volatile liquids.
No occupational difficulties have been identified
(see Section XI, B).
B.
Methods of Transport and Storage
The silicone fluids are transported principally in 55 gallon epoxy
lined steel drums, although" some of the standard dimethylsilicone fluids are
sold in carload lots (Lichtenwalner and Sprung, 1970), when they are shipped
to big users such as automobile and furniture polish manufacturers.
The fluid
products are obtainable either as straight oils, or as emulsions or solutions
in several types of organic solvents.
C.
Disposal Methods
Disposal of silicone fluids are as varied as the many formulations and
applications.
Unwanted products from production are either incinerated (to C02
and Si02) or 1andfi11ed (Bailey, 1973).
Where the fluid is used as a coating,
disposal is with the material treated, in refuse dumps or by incineration.
D.
Accident Procedures
Because the fluids exhibit a low degree of toxicity and irritability
and are not highly flammable, accident procedures are simply ori8nted at
cleanup.
Dow Corning (1973) has demonstrated that roadway spills of fluid can be
29
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removed by using finely divided solid absorbents.
Roadway spills can also be
removed by high pressure streams of water, although this would result in water
contamination.
When the fluids are spilled on water, they gathe~ed into pools
and may be removed by procedures found effective for oil spills.
v.
Environmental Contamination
Environmental contamination by silicone fluids deserves special consider-
ation because of the exceptionally inert properties and stability of these
chemicals.
The long residence time in the environment that may consequently
occur as well as the rapid growth in consumption, suggest that although
generally inert and non-toxic, the compounds may at some time reach
undesirable concentrations.
This section will discuss environmental contam-
ination from production, transport and storage, use, and disposal, and then
make some projections of possible contamination levels both now and in the
future.
A.
From Production
Environmental contamination from silicone fluids during the manu-
facturing operations should not be significant due to the physical properti~s
of the materials.
The low volatility and noncorrosive characteristics remove
tendencies for the materials to escape or leak from the process steps.
Accidental spillages are the exception.
Minor losses, however, may accompany
other materials that flow from the operation, such as the by-product hydrogen
chloride, the wasted impurities from the distillation operations and the salts
and wash water from the hydrolysis, neutralizing and washing steps.
30
-------
The foregoing waste materials and streams are disposed of by clarifi-
cations, biological treatment, incineration and neutralization (Bailey, 1973).
Any solids and sludges from these operations are disposed in land fills.
Loss
of silicone fluids to the environment from production operations' is, therefore,
judged to be relatively low, especially as compared with that which reaches
the environment from use and final disposal.
However, actual monitoring data
is not available.
B.
From Transport and Storage
Loss of silicone products during transport and storage is conceivable
only as a result of accidental spillage.
Because the products are noncorrosive
and practically nonvolatile, leakage from containers and storage tanks is
unlikely.
A possible exception is that residual material left in nonreturnable
containers may eventually drain away.
The overall loss from transport and
storage is considered to be very small.
c.
From Use
Of the major silicone fluid uses, the applications for waxes and
polishes, antifoams, and cosmetics probably result in the most direct source
of environmental contamination.
Polishes used on automobiles would eventually
wash off and be conveyed to a lake or stream.
Similarly, cosmetic preparations
would wash off and pass into the sewage system.
Antifoams, especially those
used in aqueous systems, such as at sewage treatment plants, would directly
enter the water systems from the water effluents.
31
-------
Silicone fluids used in bulk quantities in such applications as lubri-
cants, heat exchange fluids, shock absorbers, and dielectric fluids may also
be released directly to the environment either by intentional disposal or
through leaks.
However, since those applications are a.relatively minor
part of the fluids market, they are probably not a major source of contamination.
Silicone glycols used in polyurethane foams probably are' retained in
the foam and eventually deposited in a land fill or incinerated.
Release agents
eventually wear-off onto the molded product which is again ultimately deposited
in a land fill or incinerated.
The siloxane coatings of textiles and glass
are permanently attached either around the fabric or on the glass wall.
However,
the treatment baths may be a major source of environmental contamination.
D.
From Disposal
Disposal by incineration should result in C02 and SiOZ',
disposal of the fluids in land fills would allow the possibility of leaching
However,
into aquatic systems.
Such processes are little understood.
Permanently bonded
protective coatings would probably not migrate from the landfill.
E.
General Environmental Contamination
The degree of environmental contamination resulting from commercial
use of silicone fluids is unknown.
No ambient monitoring data is available.
Estimates of environmental release are very crude and amounts used in most
applications are unknown.
Silicone fluids that might enter the environment
are suspected to be persistent (either as the parent fluid or as cyclic species
or low molecular weight fragments terminated with silanol groups) and mobile
(see Sections VIII and X).
Even though the available information is not very
exact, we have attempted to make some very approximate estimates of possible
concentrations of silicone fluids in the environment.
32
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The Great Lakes drainage basin was taken as a definable area for which
1.
Half of the
The following assumptions were made:
production of silicone fluids (15 x 106 lbs in
calculations could be made.
1973) is immediately released to the environment.
2.
Rate of production growth of silicone fluids = 10%/year. .
3.
Residence time of silicone fluids in the environment = infinite.
4.
All silicone fluids consumed and released to the environment
in the Great Lakes drainage basin are proportional to the
u.s. population (~l5% of U.S.) and reach the Great Lakes.
5.
The Great Lakes have a surface area of 100,000 sq. miles and
a volume of about 50 x 1015 ft.3.
6.
Effluent flow from the Great Lakes was assumed to be equal
to the St. Lawrence flow (~l%/year)
Table X presents the calculations for determining the highest possible
concentrations of silicone fluids in the Great Lakes.
The concentrations
reported in the last two columns assumed that either all the silicones reside
evenly dispersed throughout the lake waters or that all the silicones reside in
the top one foot of lake sediment.
Another possibility not tabulated is that the
silicone fluids will reside in a thin layer on the water surface (dimethyl
fluids are slightly lighter than water).
The assumptions were purposefully chosen to provide the highest level
possible.
These estimates can only be considered as an order of magnitude of
contamination.
The concentrations in Lake Erie could be much higher since
it is shallower and is fed by large populated areas.
On the other hand, the
33
-------
following assumptions are probably somewhat high: (a) 10% growth rate in the
market, (b) 50% release factor, (c) infinite environmental stability.
Table X.
Approximate Highest Concentrations of Silicone
Fluids in the Great Lakes
Annual Average Concentration
Consumption Total ( p pm)
at 10% Released
Growth Rate Total to Area Balance Lost in Net in Deposited
Total Great Used in the in Lake Great Suspended in 1 Foot
for Lakes to Previous Great Effluent Lakes in Bottom
Year U.S. Area Decade Decade Lakes l%/vear System ake Water Silt
1953 0.5 0.1 0.1 <0.1 <0.1 -- <0.1 -- --
1963 12 2 10 5 5+ -- 5- -- --
1973 30 4.5 40 20 25+ 2.5 22.5 .0004 0.1
1983 80 12 110 55 80 8 72 .001 0.4
1993 210 32 270 135 215 21.5 193 .003 1
2003 560 85 660 330 545 54.5 490 .01 3
2013 1500 225 1700 850 1395 139.5 1255 .02 7
2023 4000 600 4500 2250 3645 364.5 3280 .06 18
34
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VI.
Control Technology
A.
Currently Used
Waste water from Union Carbide's silicone
plant is neutralized,
clarified, and then undergoes secondary biological treatment to remove soluble
organics.
The sludges are landfilled (Bailey, 1973).
Similar water treatment
is used by Dow Corning (1973).
In general, the liquid and soluble residues
from silicone processing are incinerated and the solid wastes are landfilled.
B.
Under Development
General Electric Co. has taken out a patent for waste water treatment
from silicone manufacturing plants (Lapidot, 1973).
The process consists of
running the waste water into a flotation and sedimentation basin where the
insoluble material is removed.
The semipurified water is then adjusted to
pH ~ 12 and the alkali water is passed into an ozonizing tank at a rate
dependent on the COD level in the water.
The purified water is degassed
before release.
VII.
Monitoring and Analysis
A.
Analytical Methods
Although analytical methods for monitoring environmental samples of
silicones have not been reported in the surveyed literature, a number of
methods have been developed for detecting silicones in the ppm range in
food and beverage samples.
Horner, ~ al. (1960) reported both a specific and non-specific method
for detecting trace amounts of silicones in foods and biological material.
The nonspecific method consisted of a colorimetric silica analysis of
35
-------
silicones in foods digested with fuming sulfuric and nitric acids.
Jankowiak
and LeVier (1971) later modified this procedure in order to eliminate phos-
phorus interferences.
This method is best appliaab1e to samples which contain
negligible amounts of residual silica.
The high level of silicon occurrences
in nature precludes the use of such nonspecific methods for detecting silicones.
The specific methods used by Horner, et ale (1960) was a selective extraction
of silicone with infrared quantification (7.95 ~ band, (CH3)2Si).
The method
was utilized in the 2 to 20 ppm range in pineapple juice.
Sinclair and
Hallam (1971) have used a similar technique to determine polydimethylsiloxane
in the 0.2 to 2.00 ppm range in beer and yeast.
A low temperature specific
extraction of siloxanes from fatty foods with quantification by atomic absorp-
tion (nonspecific but more sensitive than IR) or UV spectrometry has been
reported by Neal, ~ ale (1969).
The Dow Corning Corporation (1973) has reported that it uses an
extraction procedure to determine low levels of silicones in soil and water.
The preferred solvent is methyl isobutyl ketone (MIBK) which can be used
directly for the atomic absorption quantification of silicone.
Preliminary
investigations show this method to be sensitive at the ppb range for water
samples.
B.
Current Monitoring
No monitoring information on effluent or ambient levels of silicones
is available.
36
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VIII.
Chemistry
A.
Reactions Involved in Use
One of the reasons that silicone fluids are used commercially is a
result of their chemical inertness.
.
Thus there are only a few reactions which
are invo1~ed in their applications.
For example, when po1ymethy1hydrogensi1oxanes
are used in water repellent coatings of textile fibers, they are usually heat
cured in order to cause crosslinking between siloxane chains by replacing
the Si-H with a Si-O-Si bond.
When glass is treated with silicone fluid, the
films are fixed by heating, but in this case it is felt that the heat treat-
ment orients the oxygens of the siloxane chain along the surface of the
glass (Noll, 1968).
B.
Hydrolysis
The SiO bond is about 50% ionic, with silicon the positive member
(Meals, 1969).
The high heat of formation (108 Kca1/mole) of the Si-O bond
makes it very resistant to homolytic cleavage.
However, because of its polar
nature it is susceptible to heterolytic cleavage - attack by acids or bases
(Meals, 1969; Voronkov and Zhagata, 1968; Carmichael et a1.., 1966; Noll, 1968).
--
(1950)
However, at neutral pH hardly any hydrolysis takes place.
Fox et a1.
have suggested that "appreciable" hydrolysis may take place when a large
interface exists between water and silicone.
Such an interface might occur
in an emulsion, aerosol, or a porous polymeric form (Fox ~ a1., 1950).
The relative rate of such a process at ambient conditions is unknown,
although at elevated temperatures using steam, hydrolysis takes place fairly
rapidly (Noll, 1968).
The products resulting from hydrolysis would be
37
-------
silanol-ended (-Si-OH) species, which should be much more water soluble than
the parent siloxane.
During the review of the preliminary draft of this report, Dow Corning
studied the soil indu~ed hydrolysis and depolymerization of polydimethylsiloxane.
Preliminary results of these tests are important enough to have required their
being mentioned in the final report.
Ingebrightson (1975) observed that a
sample of polydimethylsiloxane (100 cSt.) labelled on its methyl groups with C14
decayed with a half life of about 10 days when coated on a sample of neutral soil.
By this conversion high molecular weight siloxanes were degraded to cyclic species
and to low molecular weight fragments terminated with the silanol group.
Experi-
mental work is continuing on quantitatively characterizing the nature of the
low molecular weight siloxanes.
C.
Oxidation
The high heat of formation of the SiO bond results in considerable
oxidative stability for siloxane fluids.
The polydimethylsiloxane fluids
are stable up to l50°C for practically an unlimited time when exposed to
air.
Above l50°C, the viscosity gradually increases until a gel is formed
{in a few hundred hours at 250°C) (Lichtenwalner and Sprung, 1970).
The
increase in viscosity is caused by the oxidation of the methyl groups to
formaldehyde resulting in crosslinking of the siloxane chains by a siloxane
bridge.
The oxidative stability is increased by replacing the dimethyl
38
-------
functional groups with methylphenyl or diphenyl groups (Scala and Hickam,
1958).
The alkyl substituted fluids are generally less stable than the
dimethyl fluids (Meals, 1969).
Table XI depicts the gelling time for a
variety of silicone fluids.
The gelling time is defined as the time in
hours for a fluid to gell when it is heated in air at 250°C in a layer
3 rom thick in a glass dish 35 rom in diameter.
Ozone does not affect the
silicone fluids.
Table XI.
Gelling Time of Silicone Fluids
(Noll, 1968, p 460)
Fluid
Gelling Time (hrs)
Methylsilicone
10
Methylphenylsilicone, high MW
Low phenyl content
400
High phenyl content
1750
Chlorophenylmethyl
(with addition of iron octoate)
1000
39
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D.
Photochemistry
Exposure of silicone
fluids to light has a tendency to cause cross-
linking of the polymer.
For example, Delman
~ ale (1969) found that
exposure of a methylsiloxane resin to a xenon arc lamp (>281 nm) resulted in
the formation of Si-CH2-Si as determined by infrared absorption.
When the
resin was irradiated with lower wavelengths from a mercury vapor lamp,
SiOH and Si-CH2CH2-Si linkages were formed.
E.
Other
By removing the silicone fluids from exposure to air, the oil remains
usable up to temperatures of 200°C.
Above that temperature, depolymerization
occurs resulting in mixtures of low molecular weight polysiloxanes.
The
methylphenylsilicone fluids can be used up to 250-300°C in closed systems and
in an inert gas up to 400°C (Noll, 1968).
In a thermal gravimetric investi-
gat ion in vacuum, Thomas and Kendrick (1970) postulated that the activation
energy of depolymerization is mainly a function of the inductive effect of
the substituent group (withdrawing groups increase the activation energy).
At normal temperatures, the siloxanes are stable to metals, wood,
paper, plastics, and also to solutions of metal salts, liquid ammonia, and
3% hydrogen peroxide; with concentrated hydrogen peroxide, they give explosive
mixtures.
The fluids will react, especially at elevated temperatures, with
strong mineral acids, particularly hydrofluoric acid, alkalis, and strong
oxidizing agents such as concentrated nitric acid or elemental chlorine
(Noll, 1968).
40
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IX.
BIOLOGY
A.
Ab sorp tion
Althoughsiloxanes might conceivably be absorbed on inhalation, their
physical and chemical properties, as well as their uses and probabJe environmental
fate, suggest that ingestion and skin contact most probably would be the only
routes of potential significance.
As a rule, long chain polymers are less readily
absorbed than their component monomers
(Bi.,schoff, 1972).
The absorption of
most macromolecular compounds often involves either cleavage prior to crossing
membrane barriers, or direct phagocytosis.
On the basis of available information,
the commercially important siloxanes seem to follow this pattern being relatively
refra~tory to either dermal or gastrointestinal absorption (Hine- et-al, 1969).
In a series of feeding experiments, Frazer (1967a and b, 1968, 1970)
did not find significant evidence for the gastrointestinal absorption of a
polydimethylsiloxane or an antifoam
preparation (96% siloxane, 4% silica) in mice,
rats, rabbits, dogs or man.
Mice, rats, and dogs were fed 2.5% siloxane x 80 weeks,
1% x 90 days, and 300 mg/kg body weight/day x 120 days, respectively.
In these
animals, silicate excretion in urine did not rise above control levels, and i.r.
spectral
analysis failed to reveal siloxanes in various body tissues.
In a
study on rats, rabbits, and man, failure to absorb the siloxanes was indicated
by balance data on the amount ingested and the amount excreted in the feces
(see Table XII) .
Similar results have been found for a polymethylphenylsiloxane (DC 703
Fluid, viscosity unspecified cSt.). This fluid was fed at 4% of diet along with 16%
olive oil to facilitate any potential absorption (Paul and Pover, 1960).
Siloxane content was measured as silicon.
As indicated in Table XIII, almost all
41
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TABLE XII: Balance data on polydimethylsiloxane
ingestion and fecal excretion in rats, rabbits, and man (Frazer, 1967b).
Subj ect Siloxane intake Siloxane content of faecal
in mg. samples in mg.
Before ingestion After inges tion
of siloxane of siloxane
Rat 1 270 0 260
2 270 0 280
3 270 0 270
4 270 0 260
average 267 (99%)
Rabbit 3. 1350 0 1160
4 1350 0 1060
average l110 (82.5%)
Human
subjects
MS day 8 753 0 725
" 9 753 0 1356
" 10 753 0 588
average 893 (118.5%)
AC day 8 753 0 1010
" 9 753 0 Nil
" 10 753 0 1450
average 820 (108.5%)
The relatively low level of siloxane recovery in the rabbits was thought
to reflect an error in sampling and fecal consumption (Frazer, 1967b).
42
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Table XUI:
Balance data on Polymethylphenylsiloxane (DC 703 Fluid) in rats
(Paul and Pover, 1960)
~
w
Total Silicon Content Silicon Content Found in % Siloxane
In Food Consumed Recovered
(mg.) Gastrointestinal Feces Urine Liver Kidney Fat
Tract (mg.) (mg.) (mg.) Depot
(mg.)
982.8 - 979.2 - - - - 99.6
1058.4 1.48 1011.0 - - - - 95.7
961. 2 2.50 929.9 - - - - 97.0
1071.0 - 1001. 0 - - - - 93.4
1063.0 - 975.0 - - - - 91. 7
1026.0 1.63 1019.0 - - - - 99.5
944.0 - 898.0 - - - - 95.1
Mean % siloxane fluid recovered = 96.0 +1.0
DC Silicone fluid 703 fed with olive oil and rat cake powder to seven rats for a period of
eight days. Tissues and feces were examined for organosilicon compound and urine.for soluble
silica.
No silicon was found in the lipids of the gastrointestinal tract, faeces, liver, kidney, or
fat depot of control animals maintained on a diet of rat cake powder and olive oil.
-------
ingested siloxane was recovered as silicon in the feces or gastrointestinal
tract, indicating no siloxane absorption.
Although these high molecular weight siloxanes do not appear to be
detectably absorbed across the gastrointestinal membranes, smaller siloxanes of
six polymer units or less are absorbed (Bennett, 1973).
Specifically, both
octarnethylcyclotetrasiloxane
and 2,6-cis-diphenylhexarnethylcyclotetrasiloxane
are readily absorbed by monkeys at doses of 1 mg/kg (LeBeau and Gorzinski, 1973)
and hexamethyldisiloxane is completely absorbed in monkeys after oral administra-
tion of 20-80 mg/kg (Bennett and Statt, 1973).
The siloxanes are less readily absorbed dermally than in oral
administration.
In humans, polydimethylsiloxane (100 cSt.) and trifluoropro-
pylmethylpolysiloxane (300 cSt.) applied to the back at levels of 50 mg/kg/day,
20 hr/day x 10 days did not result in elevated levels of blood or urinary
silicon, indicating no dermal absorption (Hobbs et aI, 1972).
Under the same
conditions of exposure, a cyclic [(PhMeSiO) (Me2SiO) ] - where x > 1 and x + y =
x Y
3 to 8 - was also not absorbed by man (Palazzolo ~ aI, 1972). Even the sm~llest
si1oxane, hexamethy1disiloxane, does not irritate rabbit skin on dermal
application even though irritation is induced on subcutaneous injection (Rowe
et aI, 1948).
B.
Excretion
As indicated in the previous section, the higher molecular weight
si10xanes do not appear to be absorbed and thus, on ingestion, they are
eliminated in the feces.
This is particularly evident in the data presented
frow Frag~r (1967b) and Paul and pove.r (1960).
Further, a variety of h~gh
molecular weight po1ydirnethylsiloxanes and polyrnethylpheny1siloxanes have
44
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been shown to exert marked laxative effects on guinea pigs (Rowe et aI, 1948, see
Table XVII), which is consistent with the premise that these compounds are not
absorbed.
In the same study, no laxative effect was noted for hexamethyldi-
siloxane and only a very mild effect for dodecamethylpentasiloxane.
This also
agrees with absorption data indicating that hexamethy1disi1oxane is completely
absorbed but that the pentasi10xane approaches the upper limit of gastro-
intestinal absorption.
The excretory patterns of these lower molecular weight siloxanes have
only recently received careful study.
Bennett and Statt (1973) indicate that
monkeys excrete about 90% of ingested hexamethyldisiloxane after 24 hours.
14
Using C-labelled material, 10%-30% was expired, 70%-85% excreted in the urine,
and less than 1% in the feces.
Octamethylcyc10tetrasiloxane and 2,6-cis-diphenyl-
hexamethylcyc10tetrasi10xane seem to be excreted somewhat less readily than the
disiloxane, with only 89% recovered with 80% of the dose excreted 48 hours after
administration.
The methy1cyclosiloxane had a similar pattern of excretion to
the hexamethy1disiloxane:
23.5% in expired air, 55.5% in urine, and 8.4% in
feces.
The phenyl containing siloxane evidenced a notably different excretion
pattern:
3.3% in expired air, 60% in urine, and 28% in the feces (LeBeau and
Gorzinski, 1973).
C.
Transportation and Distribution
Because the higher molecular weight siloxanes are so little - if at all -
absorbed on oral administration, no data on transport or distribution is avail-
able for this route with one exception.
In a 400 day feeding of polydimethyl-
siloxane fluid (unspecified viscosity, total dose of 10-29 ml) to rats, no toxic
effects were noted but siloxane deposits were reportedly found around the spleen
and liver (Po1emann and Froitzheim, 1953).
45
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In that a greater percentage of the di- and tetrasi10xanes tested by
Bennett and Statt (1973) and LeBeau and Gorzinski (1973) pass through the bile
than are excreted by the feces, enterohepatic circulation seems evident.
The distribution of silicones in the body and the transport mechanisms
involved in distribution are highly dependent upon the route of administration.
Intraperitoneal injection results in high silicone concentrations in the liver,
gastrointestinal tract, and fatty tissue (Hine et a1, 1969). In contrast to the intra-
peritoneal route, intracisternal injection results in high concentrations in the
brain and vertebral column [see Tables XIV and XV
from Hine ~ a1, 1969).
This type of route dependent distribution does not necessarily reflect
passive transport mechanisms.
\Vhen po1ydimethy1si10xanes (350 and 100 ~St.)
are injected intra-articu1ar1y - i.e., into the knee joint of the male rabbit -
the silicone fluid is gradually removed.
However, the rate of 105s does not
vary with the degree of joint immobilization, thus suggesting an active
distribution mechanism (Donahue
eta1, 1971).
Artifica11y induced blood transport
has been examined by I.V. injections but to what extent the circulatory system
is used naturally is not clear (Reed and Kittle, 1959).
The commonly noticed
distribution of silicones in the kidney and liver might be explained in terms
of filtration of silicones from the blood but further experimentation is
necessary (Nosanchuck, 1968; Cutting, 1952).
Because of the general imperme-
ability of membrane systems to si10xanes, phagocytosis by wandering cells may
also be a prime method of transport (Hine et a1, 1969; Bennett, 1973).
46
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TABLE XIV:
in rat tissues
of 15
Distribution of 14C-1abe11ed silicone
25 days after intraperitoneal injection
~Ci per rat (Hine et aI, 1969)
rat number
Average percent
Tissue 1 2 3 activity/organa
Fat 59.00 43.00 51. 00
Heart 0.00 0.00 0.00 0.00
Kidney 0.74 0.51 0.63
Liver 16.1 13.5 14.80
Lung 0.08 0.05 0.08 0.07
Muscle 1.50 0.82 0.79 0.10
Skin 0.08 0.10 0.097 0.09
Brain 0.03 0.05 . 0.04
Spleen 2.80 0.17 0.30 1.56
Testes 1. 70 0.12 0.98
Whole blood 0.00 0.00 0.00 0.00
Gastrointestinal 16.80 37.70 27.25
apercent activity based on total counts received.
47
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TABLE XV: Distribution of l4C-labelled silicone'
in rat tissues 45 days after intracisternal injection
of 6 ~Ci per rat CHine et aI, 1969)
rat number
Average percent
Tissue 1 2 3 4 activity/organa
Fat 5.0 6.1 10.0 10.3 7.9
Brain 38.9 43.4 40.0 42.0 41.1
Vertebral colunm 33.9 32.0 27.9 32.0 31.4
Sp inal cord 8.5 12.6 6.5 12.0 9.9
Spleen 0.09 0.58 0.0 0.16 0.21
Lungs 0.36 0.04 0.06 0.20 0.16
Liver 1. 78 2.96 0.0 0.0 1.19
Gastrointestinal 0.0 0.0 0.0 0.0 0.0
tract
Whole blood 0.0 0.0 0.0 0.0 0.0
aAverage of 4 animals.
48
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D.
Metabolic Effects
The si10xanes have not been extensively studied for metabolic effects
£.I:.E. ~.
Metabolic effects may be inferred based on toxicity data but they have not
--
Franklin (1972) has shown that a pure.po1ydimethy1-
been demonstrated in vivo.
si10xane (unspecified viscosity) as well as various antifoams
produce a type I
substrate binding spectrum in rat hepatic microsomal
suspensions.
The pure
si1oxane, however, produced this effect only after sonication was used to disperse
the compound in the suspension.
It should be emphasized that this study was
undertaken primarily because si10xane antifoams
are used in microsomal studies
and the relevance of this effect to in vivo conditions has not been demonstrated.
--
E.
Hetabo1ism
Dow Corning Corporation recently completed a study for the World
Health Organtzation on the metabolism of po1ydimethylsiloxanes in mice, rats,
and primates including man.
The results have been submitted (Bennett and Statt,
1974) but are not included in this review.
49
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x.
Environmental Transport and Fate
A.
Persistence
The stability of silicones under environmental conditions has not
received a great deal of study.
The available information is discussed
in the following two sections.
B.
Biological Degradation
A number of studies have shown that microorganisms may grow on the
surface of silicone rubbers and resins but will not degrade them (Greathouse
~ al., 1951; Glazar, 1954; Hueck, 1960; Ross, 1963; Caldron and Staffeldt,
1965; Muraoka, 1966; Zharikova et al., 1971; Inoue, 1973).
However, the
silicone fluids have not been as intensely studied.
Olson and coworkers (1962)
reported that coating cotton with silicone fluids made the textile more
resistant to biodeterioration.
In a study of the possible biodegradation of
cosmetic
ingredients, Yanagi and Ouishi (1971), using pure cultures of
23 strains of bacteria, 25 strains of yeasts, and 17 strains of fungi, found
that the dimethyl and methylphenyl silicones tested could not be utilized
by the organisms.
In a comprehensive biodeterioration appraisal of silicones,
Sharp and Eggins (1970) concluded that dimethyl silicones were resistant to
deterioration by common fungi.
They find no difference between the pure
cultures of fungi isolated from a soil perfusion apparatus used with or
without silicone fluids (0.65, 2.0, and 3.0 cSt.).
Dow Corning has eV21uated the effect of polydirecthylsiloxar.e fluids
of varying viscosities on the growth of bacterial species.
The fluids were
non-toxic, but the organisms could not grow without exogenous nutrients.
50
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Examination of the fluids (20 cSt. and 100 cSt.) showed no alteration in the
molecular distribution of the fluid components following the growth of E. coli
--
and S. aureus (Bennett, 1973).
Both Union Carbide and Dow Corning have run biodegradability tests
on silicone fluids.
Union Carbide (Waggy, 1971) determined the stability
a silicone fluid (50 cSt.) (330 ppm) and two silicone glycol fluids (660 ppm
and 1000 ppm) with a Warburg respirometer system and dilution bottle BOD
procedure (silicone glycol only).
These compounds were found to be completely
nonbiodegradable.
Dow Corning (Hobbs, 1973) ran a 70 day aerobic biodegradability
14
C-labelled dimethylpolysiloxane exposed to sewage microorganisms.
test on
No biodegradability was noted under the experimental conditions.
C.
Chemical Stability in the Environment
Ingebrightson (1975) has recently observed a half life of 10 days for
a C14 methyl labelled polydimethylsiloxane (100 cSt.) coated Qn neutral soil.
The high molecular weight siloxanes were converted to cyclic species and to
low molecular weight fragments terminated with silanol group (-Si(CH3)2-0H.
See section VIII, B for further information on acid/base catalyzed hydrolysis.
D.
Environmental Transport
Little information is known about the transport of silicones through
the environment mainly because of the lack of monitoring data.
Dow Corning
(1973) has conducted some preliminary studies on leaching properties of the
polydimethylsiloxanes in soil.
With damp soil they have concluded that
silicones are fairly mobile.
-5 -6
The vapor pressure of silicone fluids (10 -10 rnrnHg)
51
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-4 -6 -5 -7
is similar to PCB's (10 -10 rnrnHg) and DDT's (10 -10 rnrnHg) , and, therefore,
atmospheric transport may be an important environmental route.
If the soil induced depo1ymerization noted by Ingebrightson (1975)
occurs at appreciable rates in nature, the resulting products (cyclic products
and lower molecular weight silano1s) should be significantly more mobile in
the environment.
The cyclic materials will be much more volatile (boiling
point of trimer and tetramer are 134°C and 175°C, respectively).
The si1ano1s
should be considerably more water soluble, suggesting water transport and
leaching from landfills as important transport processes.
E.
Bioaccumulation
Although bioaccumu1ation studies of silicones in low trophic levels
of the food chain have not been reported, some study with fish has been under-
taken by Dow Corning (Hobbs, 1973).
Bluegill sunfish were exposed to
14
C-1abe11ed po1ydimethy1si10xane for 30 days at 1 and 10 ppm.
No evidence
of accumulation was observed and the tissue storage in these fish was minimal.
Studies on bioaccumu1ation of products of the soil induced depolyrnerization
have not been reported.
52
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XI.
TOXICITY - HUMAN EXPOSURE
Pure preparations of commercially important liquid siloxanes are generally
considered to have very low levels of biological activity (see Section XII..
Toxicity to Birds and Mammals).
.
Because of this and their unique physical and
chemical properties, these siloxanes are widely used as additives in a variety
of commercial products to which humans may be exposed by ingestion (food
addivites), dermal absorption (e.g. shampoos and hand lotions), or inhalation
(e.g. aerosol products including antiperspirants, hair sprays, and insect
repellents).
In addition, liquid siloxanes have found broad areas of appli-
cation in the biomedical sciences including use in soft tissue augmentation
or reconstruction, anti foaming agents during extracorporeal circulation,
and as lubricants in a variety of procedures.
It is important to emphasize
that almost all of these uses involve or have involved liquid siloxanes with
additives rather than the pure polymer.
In normal consumer use - food,
cosmetic, aerosols - there is no concrete evidence and barely a suggestion
that the commonly used liquid siloxanes are in any way detrimental to humans.
Although the various medical uses have stimulated some controversy, evidence
for adverse tissue reactions caused by the pure polymer is at best equivocal.
However, low levels of biological activity and toxicity are not to be equated
with biological inertness or lack of toxicity.
Thus, discussing human exposure
to the liquid siloxanes in an attempt to assess their environmental safety,
emphasis will be placed not only on their apparent harmlessness but also on
studies defining some degree of biological activity or indicating a need
for such definition in Q specific area.
51
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A.
Controlled Studies
For the most part, toxicity studies on non-human mammals and information
in other areas of human exposure have not indicated the need for extensive con-
trolled testing in humans.
A pilot study has been recently completed on the absorp-
tion, metabolism and elimination of polydimethylsiloxane in humans (Bennett and
Statt, 1974).
In that silicones are used widely in the cosmetics industry
(Thimineur, 1969), polydimethylsiloxanes (20, 50, and 100 cSt.) have been tested
and found not to be fatiguing, irritating, or sensitizing to human skin on repeated
insult patch tests (Barry, 1973).
Four human volunteers were fed a 7530 mg.
mix-
ture of 6% silicon dioxide and 94% polydimethylsiloxane (1000 cSt.) for ten days.
Neither adverse affects nor intestinal absorption were noted (Frazer, 1967b).
B.
Occupational Studies
Certain compounds used in the manufacture of various siloxanes are
highly toxic: these compounds include silicon tetrachloride, the ch1orosi1anes,
and tetraethyl orthosi1icate (Rowe et al., 1948; Taylor, 1950).
However, the
commonly used siloxanes themselves are not considered to be hazardous under
conditions of occupational exposure (Baily, 1973; Taylor, 1950).
Frequently,
very slight transient conjunctivitis is noted among users from either vapor
or direct exposure to these siloxanes.
This probably results from the
inability of the lacrimal gland to lubricate the eye due to the hydrophobic
properties of the siloxanes (Hobbs, 1973).
The type of irritation has been
described as similar to wind burn (Rowe et al., 1948).
However, claims of
conjunctivitis
resulting from vapor exposure seem questionable in that the
vapor pressure of most commercial fluid siloxanes would result in concentrations
not exceeding 1 ppb in confined atmospheres. In such cases, either volatile
54
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additives in the commercial preparation or incidental direct contact may be
factors.
Similarly, an individual spraying a water-proofing silicone-petroleum-
solvent material over a four hour period developed severe pulmonary complications.
Subsequent investigation revealed that the petroleum rather than the siloxane
was the damaging agent (Horn ~ al., 1957).
c.
Epidemiology
The liquid siloxanes have resulted in no documented wide-spread syndrome
of adverse affects and thus have not warranted epidemiologic investigations in
the strictest sense of the term.
Studies have not shown a correlation between
mammaplasty and breast cancer (Bowers and Radlauer, 1969; Hoopes et al., 1967).
The only other study relating to epidemiology was conducted by Talbot
and Meade (1971).
During the course of a routine anticoagulant clinic, these
investigators noted that several patients under treatment with warfarin or
phenindione had elevated thrombotest percentages indicating either insufficient
dosage or some interfering agent.
During questioning, all of these patients
indicated that they consumed potato
chips cooked in an oil containing additives
"allied" to the polydimethylsiloxanes.
When this product was eliminated from
the diet for seven days, thrombotest percentages returned to normal without
alteration of anticoagulant dosage (Talbot and Meade, 1971).
These investi-
gators have since warned their patients not to consume this product but have
conducted no experimental tests to validate the highly circumstantial association
between the polydimethylsiloxanes and decreased activity of anticoagulant drugs
(Meade, 1974).
No futher investigations into this potential effect have been
encountered.
55
-------
The apparent lack of interest in this effect is not difficult to
fathom.
As mentioned previously, the polydimethylsiloxanes are used in a
variety of foods.
They have been approved by the F.D.A. in dietary doses of
up to 10 ppm in most foods and up to 16 ppm in gelatin desserts (F.D.A., 1972).
Further, these compounds are used as antiflatulents at a suggested dose of
160 mg/day for man (Hobbs, 1973) and are present in a number of antiacid prep-
arations.
Freeman and coworkers (1973) have reported that foods fried in
siloxane containing oils have a siloxane residue of approximately 1 ppm.
These
results have been confirmed in further research using tritium labelled siloxane
(Freeman, 1974).
Thus, if the polydimethylsiloxanes did result in appreciable
altered metabolism of the anticoagulant or anticoagulant malabsorption, it seems
reasonable to expect that this condition would have been noted by many clinicians
involved in anticoagulant therapy. Nonetheless, it is regrettable that this ad-
mittedly tenuous connection has not been pursued with at least some preliminary
testing.
These compounds are widely consumed and prescribed largely on the basis
of their reputed lack of adverse effects:
the onus of maintaining this reputa-
tion would seem to fall on those who would recommend their use.
D.
Medical Applications
The study of the medical uses of compounds such as the polydimethyl-
siloxanes might seem remote to their potential environmental effects.
However,
such uses have stimulated by far the most detailed evaluation of these compounds
in a biolo~ical system.
Consequently, indications of biological activity in
these applications might serve to designate specific areas in which environ-
mentally oriented questions may arise.
Even accepting this line of reasoning,
however, only three broad applications need be considered: retinal detachment
therapy, antifoams and lubricants, and soft tissue augmentation.
56
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.-
r"
1.
Retinal Detachment Therapy
Various polydimethylsiloxane fluids (350-4500 cSt.) have been injected
into the vitreous as therapy for complicated forms of retinal detachments.
such as massive pre-retinal retraction and/or giant retinal breaks.
In some
instances, this treatment is beneficial and the siloxanes seem well-tolerated.
After this treatment, Labelle and Okun (1972) noted improvement in 13 patients
suffering from retinal detachments and massive pre-retinal retraction over
a four to ten year period.
In a gro~p of 200 patients, intravetreous
injection of polydimethylsiloxanes (400, 1000, and 2000 cSt.) resulted in
immediate retachment in 79 patients and improvements in visual acuity for
64 patients and a broadening in the visual field in 61 patients.
The retach-
ments were maintained by 56 patients and improvements were maintained by
44 patients in each category for periods of up to three years (Huratova, 1971).
However, other investigators and clinicians have noted either unsatisfactory
results, late complications, and/or adverse reactions apparently to the
siloxane.
In 100 cases of retinal detachments treated with siloxane injections,
Cockerham and coworkers (1970) noted success in only eleven cases.
Noting
the potential complications such as cor~eal damage due to siloxane mobility
in the anterior chamber, cataract formation, and corneal opacification, they
recommend the procedure only as a last alternative.
Formation of siloxane
bubbles in the anterior chamber of a patient two years after treatment,
followed by corneal degeneration has also been noted.
In this patient,
siloxanes were frequently associated with pigment dissemination and found in the
iris, stroma, retina, and corneal scar.
l~ile not indicating any definite adverse
57
-------
tissue response, this study does attest to a considerable degree of,mobility
(Blodi, 1971).
Retinal destruction has been attributed directly to the
injection of siloxane in a female patient after six years (Hoppenbrouwers
and Lanberg, 1971).
These rather disparate clinical results hav~ stimulated
detailed studies on non-human mammals in terms of both the efficacy of the
procedure and the possibility of adverse tissue responses to the siloxanes
(see Section XII, Toxicity to Mammals).
2.
Antifoams and Lubricants:
These two uses are somewhat interrelated in that both may involve
intravenous injection.
However, many lubricant uses', such. as lubrication of
urethra and endoscopic instruments during insertion, do not involve intravenous
exposures, and in that no adverse effects attributable to the siloxane h.ave been
reported, such applications need not be detailed (Lapides et al., 1968).
Medical grade polydimethylsiloxane (200 cSt.) has also been used as lubricants
in disposable syringes.
Miller and coworkers (1969) have noted that in such
syringes having visible accumulations of siloxanes on the tips of the plungers
this material may be released during injection by mechanical flushing
,action.
The quantities released ranged from 0.8 to 4.5 ug/injection in 10 mI.
plastic syringes.
No reports of adverse effects from this use have been
encountered.
Similarly, pure liquid siloxanes have also been used as lubricants
in artificial joints without marked adverse effects (Helal, 1968).
Unlike their use as lubricants, the siloxanes used as antifoaming
agents are not pure preparations but rather mixtures of polydimethylsiloxanes
artd various other agents.
The most commonly studied siloxane antifoaming
58
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agent is DC Antifoam A, a mixture of po1ydimethy1si10xane with 4-4.5% silica.
This type of mixture is sometimes combined in oil and water emulsions with
compounds such as glycery1 monostearate and propylene glycol mono1aurate
(Kimura et al., 1964).
Po1ydimethy1si1oxane/si1ica preparations'have been
used as anti foaming agents in pump-oxygenators during extracorporea1
circulation and have been associated with the formation of emboli.
A study
conducted by Thomassen and coworkers (1961) noted silica deposits in the
brains and livers of all eleven patients receiving this treatment and similar
deposits in hearts, lungs, spleen and kidney in several of these patients.
Po1ydimethy1si1oxane deposits were not noted.
Although He1a1 (1968) noted
that embolisms may result from intravascular injection of pure si10xanes,
such adverse effects have not been demonstrated in man from normal medical
uses.
3.
Soft Tissue Augmentation:
The fluid po1ydimethy1si1oxanes have been used widely for the
augmentation of soft tissue.
These applications have been reviewed and
summarized periodically (Ashley et al.', 1967; Ashley ~ al., 1971; Braley,
1973; Lejour and Mattin, 1971).
Of these procedures, mammaplasty - enlargement
of the breast by insertion of a foreign material - has received the most
attention because of the many adverse effects reported from this procedure.
Mammaplasty with si10xanes can be accomplished in two basic ways,
either
by direct injection of the po1ydimethy1si1oxane fluid into the breast or
by surgically implanting a mammary prosthesis containing various si10xane prod-
ucts.
In that this latter method does not involve direct fluid siloxane-tissue
contact, it need not be considered (see Braley, 1973; Johnson, 1969; Vrebos,
1972) .
59
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Polydimethylsiloxanes may be injected either in pure form or
with additives.
When injecting pure siloxanes the primary complication
is siloxane mobility from the injection site. Injection of pure siloxanes
into the breast has resulted in the gravitational migration of the siloxanes
to the inguinal regions and the abdominal wall (Delage ~ al., 1973).
Similar but less extreme mobility of injected siloxanes has been noted by
Boo-Chai (1969) as one of the major complications in dealing with pure
preparations of polydimethylsiloxanes.
Siloxane mobility may be attributed
at least in part to its low degree of tissue reactivity.
This is unlike the
behavior of many organic preparations such as vegetable fatty acids which
will cause relatively rapid tissue response with cyst formation and subsequent
immobility.
Consequently, in order to reduce mobility, reactive ingredients
such as vegetable oil are sometimes added to injectable siloxane preparations
(Braley, 1970).
A common preparation of this type is the "Sakurai formula"
consisting of about 99% polydimethylsiloxane and 1% animal or vegetable
fatty acids (Kagan, 1963).
It seems that from such adulterated preparations,
the major cases of "adverse tissue responses to siloxanes" have arisen.
Winer and cmvorkers (1964), Chaplin (1969), Nosanchuk (19~8), and SYmmers (1968)
have all reported severe adverse tissue responses to "silicone" injection in
the breast.
In only one of the cases reported (SYmmers, 1968, Case 2), however,
is there an even reasonable indication that the original injection contained
only pure siloxanes (reportedly 400 mI. DC 360 Medical Grade Fluid).
In this
individual periodic reinjections had been necessary to maintain desired contour
appar.ently indicating marked migration.
Histologic examination of mammary
nodules noted sclerosing granuloma and fat necrosis.
If based on such studies,
60
-------
the use of such phrases as "silicone granuloma" or "silicone mastitis" may
well be inappropriate, with a more plausable cause being organic additives
(Nosanchuk, 1968; Braley, 1970; Helal, 1968).
Hm.,ever, while many of the mos t
severe complications of "silicone" injections may not be caused by the poly-
dimethylsiloxanes, there are some indications that these pure compounds are
not entirely inert.
Boo-Chai (1969) cites inflammation with severe pain as the
most troublesome complication of pure siloxane injection.
Sometimes, this
condition is only temporarily relieved by broad spectrum antibiotics and
anti-inflammatory agents and the siloxane must be removed.
Delage and coworkers
(1973) have strongly implicated unadulterated polydimethylsiloxanes in a
foreign-body granulomatous reaction.
In a woman receiving siloxane injections
two and a half years previously, multicystic masses were noted surrounded by
foreign-body giant cells and containing pure polydimethylsiloxane identified
by infrared spectrophotometry.
Although the initial injection reportedly
consisted of pure polydimethylsiloxanes" the potential influence of unrecog-
nized impurities cannot be ruled out.
Thus, the role of siloxanes in causing adverse tissue responses in
man is still rather questionable.
Even though such operations are prohibited in
the United States, siloxane involvement in serious complications has not been
conclusively demonstrated (Bischoff, 1972), although it often seems to be
assumed by association (e.g. Malbec, 1967).
Siloxanes have been injected into
other sites using smaller quantities with highly therapeutic results
such
as in cases
of facial hemiatrophy (Ashley ~ al., 1971).
Conversely,
injection into areas not suited to this type of soft tissue augmentation
may be detrimental (Datta and Kern, 1973).
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XII.
TOXICITY TO BIRDS AND MAMMALS (Other than man)
Ever since the initial investigations of Rowe and coworkers (1948), the
commercially important silicon containing polymers have generally been
considered to have a low order of both toxicity and biological activity.
As
might be inferred from the discussion of siloxane absorption, the low order
of oral toxicity may in part be attributed to their lack of absorption.
However, siloxanes have also been tested by various routes of injection and,
while not inert, do not seem to act as specific toxicants but rather exert
their effects as a function of their physical-chemical properties or as non-
specific foreign body irritants.
Bischoff (1972) has recently reviewed the
general question of the biological activity of synthetic organic polymers.
In contrast to the high molecular weight polymers, silicon containing
non-polymeric molecules can have a very high degree of biological activity.
Some general classes are presented in Table XVI.
Tab Ie XVI:
Biologically active organosilicon compounds
(Voronkov, 1973)
Type of effect
Class of organosilicon
compounds'"
Type of effect
Class of organosilicon
compounds
Impairment of
co-ordination of
movement
R3SiZNR'R>
R~-nSi (OCII2CH2NRz ') n
(R3SiOCH2CHz)nNH3-n
Insecticidal
activity
R4-nSi(NCS)n
R3Si(CHz)nNR'R'
RSi(OCHR'ClI3) 3N
Chemosterilizing
activity
R3Si( ellz) n,1R 'R'
R3SiC=.C-Cllz
Reduction of blood
pressure
[R3SiCH N(CII3)ZCllzCllzX]+Y-
P.3S1 C=C-C(OIl) R'R'.
Fungis tatic
activity
R4-nSi(SCN) n
Stimulation of
breathing
+ I
RSi(OCHR'CIIZhN + -
[R3SiClIzN(CH3)zCHzC~z~] Y
[R3SiOCllzCHzN(CH3) ] X
R3SiCliz CII (COCH 3) CHzNRR'
. R 35iC= C(OIl) R'R.
R3Si(CIIZ)nCHm(SCN)3-m
Insect repellent
acti vity
Antibacterial
nc:tJ.vity
RR ':WI > (ClI3) S i (OR) z
R3Si7.NR'R'
Soporific activity
R3SiOH, R3SiNCO
Zoocidal activity
RSi(OCHR'Cl12) 3N
". R,R' ,R = Hydrocarbon or alkoxyl radical; Z = saturated or unsaturated, substituted or unsubstituted
three-carbon chain; X, Y = halogen, 011, OCOR'.
62
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As an example, the silatrane, 1-(p-chlorophenyl)2,8,9-trioxa-5-aza-l-siabicyclo[3.3.3]
undecane, has been developed as a rodenticide (Beiter ~ al., 1970). The biological
activity of these non-polymeric silicon compounds has been well reviewed by
Fessenden and Fessenden (1967) and Garson and Kirchner (1971), the latter
presenting acute lethality data on over a hundred such compounds.
While
indicating that silicon substitution does not in itself insure low toxicity
or biological inactivity, it must be emphasized that the siloxane polymers
would most probably not degrade to such compounds.
Of the commercially important siloxane classes, only the two most common -
polydimethylsiloxane and polymethylphenylsiloxane - have been extensively
tested fOT toxicity.
Of these, the dimethyl is the most widely used and has
generated the most detailed investigations.
In addition, various formulations
of these compounds, particularly the antifoaming agents, have been
screened for toxicity.
As in the human studies, care must be taken in such
studies to differentiate the toxic effects of the polymer from those .of the
additives.
Further paralleling the human investigations, ingestion, as the
most common route of entry, has received the greatest emphasis.
Alternate
routes such as inhalation, dermal absorption, and various routes of injection
have Also been tested reflecting the commercial and medical uses of these
compounds.
A.
Ingestion
1.
Acute Oral Toxicity (1-14 Days)
The siloxane polymers have an extremely low order of acute oral
toxicity.
This was first demonstrated by Rowe and coworkers (1948) in single
dose intubations of a series of dimethyl and me thy lpheny 1 siloxanes to
63
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guinea pigs.
The results of these experiments are given in Table XVII.
Table XVII:
Acute oral toxicity of single doses of
various siloxanes to guinea pigs.
(Rm~e et al., 1948)
Jis cos i ty Observations on the Laxative
'n cSt. Mortality Effects at Various Periods of
*
Siloxane :it 25°C. Dose Ratio Time After Administration,
Hours
:ul./kg. 2~ 8 24 48
Hexarnethyldisi10xane 0.65 3.0 0/7
(DC 200 Fluid) 10.0 0/7 - - - -
30.0 0/7 - - - -
50.0 1/10
Dodecarnethylpenta- 2.0 10.0 0/3 - + -
siloxane 30.0 0/6 - ++ - -
(DC 200 Fluid) 50.0 3/3
Po1ydimethylsi1oxane 50 10.0 0/2 +H- +H- +H- +
(DC 200 Fluid) 30.0 0/6 +H- +H- +H- +H-
50.0 0/3
Polyrnethy1pheny1- 75 3.0 0/3
siloxane 10.0 0/3 + + +
(DC 550 Fluid) 30.0 0/6 ++ +H- +H-
Polymethylpheny1- 35 3.0 0/3
si10xane 10.0 0/3 + ++ +H-
(DC 702 Fluid) 30.0 0/6 ++ +H- ++
Polydimethylsi1oxane 350 5.0 0/2 - - +
(DC 200 Fluid) 10.0 0/5 - + + -
30.0 0/6 - + + -
50.0 0/3 - - ++ ++
Po lydime thy Is i10xane
(DC 200 Fluid) 2,500 Could not be fed satisfactorily
Mineral Oil D.S.P. 10.0 0/2 ++ ++ +++ +
30.0 0/3 .+++ +++ +++ +
~ ~6se admtnisc6recl a~ ~ m~/30 mtnutes in ~6ses greater than 5 mI.
64
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Even at extremely high doses, only the lower molecular weight siloxanes
produced any marked toxic effects.
Between two and a half and forty-eight
hours, the higher molecular weight siloxanes produced only mild laxative
effects.
In that the less viscous compounds produced this effeet more quickly
and to a greater extent would seem to indicate that the laxative action reflects
the lubricant effect of these compounds in the intestinal tract.
Hexamethy1-
disi10xane did not produce any laxative effect but did result in one death
and mild intoxication and central nervous system depression hours (unspecified)
after intubation of 50 ml/kg.
Dodecamethylpentasi10xane causes more marked
lethality at 50 ml/kg but no
apparent central nervous system depression and
only a mild laxative effect (Rowe ~ a1., 1948).
This is consistent with
Bennett's (1973) explanation of siloxane absorption -only compounds of six polymer
units or less are absorbed to any marked extent-and with the low and possibly
zero level of DC 703 absorption in rats noted by Paul and Pover (1960).
The
mechanism of CNS depression shown by hexamethyldisiloxane cannot be inferred
from the data presented by Rowe and coworkers (1948).
Simi1&r intubation of
rats and rabbits of doses up to 54.0 m1/kg. polydimethylsi1oxane (DC. 200,
100 cSt) and 36.0 ml/kg polymethylpheny1siloxane (DC 701, 9.2 cSt. at 25°C)
resulted only in transitory weight loss without pathological changes being
noted in tissues (Treon ~ a1., 1954).
Somewhat longer term acute feeding studies have been conducted with poly-
dimethylsi10xane administered in the diet rather than by intubation.
Rats
and rabbits have been administered DC Antifoam A dispersed in olive oil
(Frazer, 1967b).
The doses of polydimethy1si10xane (1000 cSt.) contained in
this mixture were 270 mg. for rats and 1350 mg. for rabbits.
No signs of
65
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toxicity were noted.
Ti1 and Spanjers (1971a and b; 1972) and Ti1 and coworkers
(1971a and b) have also tested the acute oral toxicity to rats of both silicic
acid and non-ionic emulsions of si10xanes and found LD50s of single oral
administrations above 30 m1/kg with no signs of toxicity 14 day& after
. administration on autopsy.
Although mammals have been most widely tested to determine si10xane
toxicity, 5 day feeding studies of a po1ydimethy1si10xane (100 cSt.) in
mallard ducklings (Fletcher, 1973a) and bobwhite quail (Fletcher, 1973b)
have been carried out.
In both experiments, the birds were fed ad libitum
a commercial bird diet containing polydimethylsi10xane levels of 312.5,
625.0, 1250.0, 2500.0, and 5000 ppm.
Both negative (no si10xane) and
positive (dieldrin) control groups were used.
The animals were fed the
si10xane containing mixture for five days and allowed a three day recovery
period before sacrifice and autopsy.
None of the si10xane fed quail died
and no signs of toxicity, adverse gross pathology, abnormal weight gain
or food consumption were noted (Fletcher, 1973b).
Similarly, in the
experiment using ducklings, no signs of toxicity, adverse gross pathology,
abnormal weight gain or food consumption were seen although one of the ducklings
fed the 625.0 ppm si10xane diet died on the second day of feeding (Fletcher,
19 73a) .
In the absence of any clear indications of toxicity or lethality
at higher dose levels, this one death is probably insignificant.
66
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2.
Subacute Oral Toxicity (15-90 Days)
In preliminary investigations on the subacute oral toxicity of
the siloxanes, Rowe and coworkers (1948) intubated rats with po1ydimethyl-
siloxane (35 cSt.)once a day for 28 days at doses of 1.0 to 20.0 g/kg/day.
No changes from controls were seen in growth rate, hematology, organ weights,
or histopathologic examination of the heart, spleen, liver, kidney, adrenals,
pancreas, bone marrow, stomach, and intestine.
Ninety-day feeding studies have been conducted by three groups
of investigators.
MacDonald and coworkers (1960) fed polydimethylsiloxanes
(50, 350, 1000, 10000, and 60000 cSt.) at levels of 10,000 ppm in chow to
rats for 90 days.
On an average, each rat consumed 175-192 mg of the siloxane
. per day.
No adverse effects were noted in food consumption, weight gain,
tissue weight, or on pathological examination.
DC Antifoam A (viscosity not
specified) has also been fed to rats at dietary levels of 1000, 2000, and
10000 ppm for 90 days (Rowe et al., 1948).
No adverse effects were noted
on blood urea nitrogen, organ weights, or on pathological examination.
Frazer (1967a) has also fed rats DC Antifoam A (1000 cSt.) at dietary levels
of 1000 and 10000 ppm for 90 days.
As in the previous studies, no adverse
effects were noted in blood chemistry, weight gain, tissue weights, or
tissue pathology.
67
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3.
Chronic Oral Toxicity (91 Days and Longer)
Of the commercial siloxanes, only the antifoams have been tested
for oral toxicity over prolonged periods.
An anti foaming agent (1000 cSt.)
containing 94% polydimethylsiloxane and 6% silicon dioxide were 'fed to beagle
dogs at 300 mg/kg/day for 120 days (Frazer, 1968).
The total siloxane
consumed was between 300 and 500 g.
No adverse effects attributable to the
siloxane were noted on weight gain, blood formation, serum urea, liver
function, serum electrolytes or tissue pathology.
Frazer (1970) also fed
the same compound to mice over an 80 week period at levels of 2500 and
25000 ppm.
No toxic effects due to the dietary siloxanes were noted based
on survival rates and pathology.
DC Antifoam A has been tested in long term
feeding studies on both rats (Rowe et al., 1950) and dogs (Child ~ al., 1951).
Rats fed 3g/kg feed for two years developed no signs of toxicity based on
weight gain, organ weights, blood count, urea nitrogen, liver lipids, or
pathology (Rowe et a1., 1950).
The dogs were fed 0.3, 1.0, and 3.0 g/kg feed
for 6 months.
Weight gain was normal in all groups but in all si10xane fed
animals bile deposits were found in the Kupffer and hepatic cells, the
quantities of such deposits being directly related to dietary si10xane levels.
In the group receiving the highest dose, such deposits were also found in
the interlobular bile ducts.
The investigators were not able to explain
the significance - if any - of these deposits (Child et a1., 1951).
4.
Si10xanes and Cholesterol Metabolism
The previous studies on the oral toxicity of the siloxanes might
be characterized as "standard" toxicity tests - i.e., studies monitoring
biological parameters such as weight gain, relative tissue weights, and
68
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lethality, which are frequently altered by common toxic agents.
Such tests
might fail to indicate certain very specific types of biological effects of
agents having a narrow range of biological activity.
There is some indication
that polydimethylsiloxanes and/or polymethylphenylsiloxanes may have this
type of biological specificity in exerting an influence on cholesterol
absorption and/or metabolism.
Cutting (1952) fed rats a diet containing 20,0~0 ppm DC Anti-
foam A over a four month period and noted no toxic effects.
In the same
experiment, a polydimethylsiloxane (DC 200) at 10,000 ppm in feed and
DC Antifoam A at 250 ppm in feed were given to rabbits along with 8000 ppm
cholesterol over a three to four month period.
In the rabbits fed DC 200
with cholesterol, microscopic examination of the kidneys revealed renal tubular
dam,lge.
A clear material was seen which did not stain with hemotoxylin and
iosin or Sudan IV (fat positive stain).
Brown pigment and a foamy cytoplasm
were found in some tubular cells.
None of these changes were seen in the
rabbits fed cholesterol without DC 200.
The rabbits fed DC Antifoam A with
cholesterol evidenced wide spread cellular infiltrations, especially in the
kidney and liver.
The histologic damage in rabbits attributed to the si10xanes by
Cutting (1952) is disputed by Carson and coworkers (1966).
These investigators
used two sets of controls, unaltered basal chow and 8000 ppm cholesterol in
an eight month feeding to rabbits of both 10 g/kg DC 360 (350 cSt.) and
10 g/kg DC Antifoam A with and without a 8000 ppm cholesterol supplement.
The histopathological findings in rabbits are given in Table XVIII.
69
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Table XVIII:
Histopathology in rabbits after
8 months of specified diet
(Carson et al., 1966).
Org;1n and Findings
--
Con-
trol
Choles-
terol
DC 360
350 cSt
+Cho1..
50 cSt
350 cSt
Liver
~o8i5, periportal
Ci r rhos is
Uiliary obstruction
Fat in vessels.
Vacuolated hepatic cells
Hepatic cells with foam
cy top la5m
Foamy depost ts
Fibrosis
Spleen
Hcmosiderosis
Foam ce 115
Foam cells Lo red pulp
Foamy dt!pos i ts
Gastrointestinal tract
Foam cells in mucosa and
muscle
Kidneys
Foam ce 115
FO.1m cells in pelvis
Foamy deposi ts
Focal chronj c inflammation
Oi laced tubules
Sclerosis of vc~sels
P rote lo cas ts
Foci of scarring
[nterstiti.al foamy deposits
10 medulla
Adrcnals
-Fo~11s
Foam cells 10 cortex
Foam cells in medulla
Fo.uny deposIts in par-
enchymatous cells
Lymph nodes
Foamy dcpos i ts
Hen rt
~ cells in coronary vessels
Fatty material in vessels
N~'ocarditis
Endocardial thromhus wi th under-
lying inflammation in myo-
cardium
Fibrosis, interstitial
Aorta
~ cells
Foam cells 1n intima
Foamy deposi tB
'l'hickt.:'nlng, Irregular
NedJal calclfl.catlon
Atherosclero~is with foam
cells i.n subcndothelium
Atherosclerosis, severe with
cald.ficatlon
LOOKS
Foam cells
Hema rrhage
Edema
in vesse 18
~
Faron cel19 in dermis
urdln
Perivascular cuffing
"in r raw
Congcstion/hypcrp las ia
2
1
4
2
3
1
1
3
3
1
1 '
6
2
1
3
3
3
1
3
3
2
Anti-
foam
A
An tifoam A
+
Cholesterol
?
. .
110 rabbits per seX in control group and 5 rabblts per sex in all other groups were examined.
The numbers indicate the total incidences of lLbnonoalities in each group.
70
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From these and other data on weight gain, blood chemistry, and other pathological
finding~, Carson and coworkers (1966) concluded that a11 changes in rabbits are
attributable to cholesterol and not si1oxanes.
Go11an (1961) has studied the effect of both po1ydimethy1si1oxane
and po1ymethy1pheny1si1oxane on rabbits fed both stock diets and diets containing
20,000 ppm cholesterol.
The cholesterol levels found in serum, iiver and aorta
are given in Table XIX.
Table XIX. Cholesterol levels (grams) in the serum, liver and
aorta of rabbits fed specified diets. (Gollan, 1961)
Serum Liver Aorta
Avg. S.D. No. Avg. S.D. No. Avg. S.D. No.
2% cho1es tero1 1. 373 .454 36 2.497 .701 27 .276 .171 27
Idem + .5% DC200* 1. 015 .334 6 1.867 1. 022 5 .543 .342 5
" + l~{ DC200 .689 .314 6
" + 2% DC200 2.084 .230 6 2.672 .515 6 .682 .366 6
" + 5% DC200 1.855 .763 6 2.123 1. 207 6 .669 .653 6
" + .5% XF-10050t .559 .240 6 2 . 786 1. 160 3 .557 .554 3
" + 1% XF-I0050 .412 .138 6
" + 2% XF-10050 .558 .124 12 5.497 1. 995 6 .135 .027 6
" + 5% XF-10050 .481 .156 6 3.589 .782 5 .218 .029 5
Stock diet .073 .019 30 .218 .044 17 .117 .030 ~3
I de.m + 2% DC200 .090 .034 24 .175 .032 16 .112 .041 11
" + 2% XF-10050 .072 .013 18 .170 .029 10 .083 .048 10
* Polydimethylsiloxane. t Polymethylphenylsi1oxane.
The polydimethylsiloxane did not effect the development of hypercholesteremia
except at the highest dose level, while the polymethylphenylsiloxane prevented
hypercholesteremia at all levels.
The dimethyl compound did not alter liver
cholesterol but the methylphenyl compound markedly increased liver cholesterol
at the 20000 and 50000 ppm siloxane level.
The reverse effect is seen in the
aorta where the dimethyl increases and the methylpheny1 at higher levels does
not effect cholesterol level.
In the aorta, cholesterol with po1ydimethy1si1oxanr:
71
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resulted in marked foam cells in the intima of the aorta.
The mechanism
of these biological effects was not determined (Gollan, 1961).
However,
previous studies indicate that the effect is not related to changes in
blood surface tension (Gollan, 1959; Merrill and Gollan, 1958).
The effect of polymethylphenylsiloxane on serum and liver cholesterol
parallels the activity of 2,6-cis-diphenylhexamethylcyclotetrasiloxane noted
by LeVier and Jankowiak (1972).
This cyclic tetrasiloxane when administered
to rats at 100 mg/day x 7 days decreased serum cholesterol (19.5 ~ 1.1 mg/lOO ml
in treated as compared to 38.8 ~ 4.4 in controls) and slightly increased liver
cholesterol (2.41 mg/lOO g in treated, 2.16 mg/lOO g in control).
The information currently available thus seems equivocal.
The
results of Cutting (1952) are in direct opposition to those of Carson and
coworkers (1966).
That the latter group uses a non-cholesterol control is
commendable but does not alter the fact that if cholesterol was the sole
cause of renal tubular damage, Cutting (1952) should have seen such damage in
the cholesterol control.
No such damage was noted.
The work of Gollan (1959
and 1961) definitely indicates effects on cholesterol metabolism and/or
absorption for both the dimethyl and the methylphenyl siloxanes.
These
effects, if better understood, might explain the bile deposits noted by Child
and coworkers (1951) and may relate to the stimulation of the conversion in
the liver of stored dietary cholesterol and mevalonate to bile acid by an
excess
of dietary cholesterol as noted by Bricker and coworkers (1974).
B.
Inhalation
The commercially important siloxanes have extremely low vapor pressures;
thus,under normal conditions, inhalation would not be a significant route of
exposure.
Treon and coworkers (1954) have exposed several mammalian species
to siloxane mists - not vapors.
The experimental conditions and mortality
results are summarized in Table XX.
72
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Table XX.
Mortality of various mammals exposed to mists of
polydimethylsiloxane (DC200), 100 cSt., and poly-
methylphenylsiloxane (DC70l), 9.2 cSt. at 25°C
for 7 hours/day x 10 days under the specified
conditions (Treon et al., 1954).
Rate of Supple- .
Passage of mentary Concen-
Air Through Flow tration Number of Fatalities/Number
Amount of Aspirator, of Air Found of Animals Exposed
Material (at Room Into in
Aspirated Condi tions) Chamber Chamber Guinea
Siloxane mg/min l/min l/min mg/l Cats Pigs Rab bits Rats
DC-200 (1) 43.5 24.1 0 0.36 - 0/2 0/1 1/4
DC-200 42.1 24.1 28.3 0.25 0/1 0/2 0/1 0/4
DC-70l 67.4 17.8 0 0.52 0/1 0/2 0/2 (2) 0/4
(1) One dog in this experiment survived exposure.
(2) One rabbit was exposed only during the final 7 periods.
None of the surviving animals showed any signs of intoxication
during or after
exposure.
Histopathological examination did reveal moderate degenerative
changes in the livers of cats and guinea pigs and a general increase in
pneumonitis in a exposed species (Treon ~ al., 1954).
In the absence of
specific information on control group histopathology, these effects can be
only circumstantially associated with siloxane exposure.
Unlike the higher molecular weight polymers, hexamethyldisiloxane
is
relatively volatile and a saturated atmosphere (40,000 ppm) caused respir-
atory failure in guinea pigs after 15-20 minutes.
At lower concentrations
or in shorter periods of exposure, the toxic effects are greatly reduced
or disappear (Rowe et al., 1948).
73
-------
Although there is little indication that these siloxanes are toxic
on inhalation, their antifoaming properties have been used with some success
in treating experimentally induced pulmonary edema (Nickerson and Curry,
1955; Princiotto et al., 1952).
C.
Dermal Administration
Similar to inhalation toxicity, the physical and chemical properties
of the long chain polymeric siloxanes would seem to preclude a high degree
of dermal toxicity because of their negligible degree of cutaneous absorption
(Hecht, 1968).
Rowe and coworkers (1948) applied various polydimethylsiloxanes
(0.65-25,000 CSL) and polymethylphenylsiloxanes (35 and 75 cSt.) to the ears
and shaven abdomens of rabbits twenty times in a one month period without
causing appreciable irritation.
Treon and coworkers (1954) have also applied
polydime.thylsiloxanes. (100 cSt.) and polymethylphenylsiloxanes (9.2 cSt. at
25°C) to both intact and abraded skin of rabbits at doses of 6.0 and 9.4 ml/kg.
The compounds were applied to an area of shaved skin 6-7 inches wide completely
encircling the trunk
and held in place by a sleeve for 24 hours.
Although no
skin reaction was noted, the higher dosage level caused death in two of three
rabbits with abraded skin exposed to the dimethyl fluid and one fatality in
each of two groups of three rabbits (intact and abraded skin) exposed to the
methylphenyl fluid.
pathological examination of fatally exposed rabbits
revealed pulmonary focal hemorrhage and edema and similar degenerative
lesioDS in the parenchyma of the kidneys, heart, and brain.
Surviving rabbits
showed no such changes (Treon et al., 1954).
Thus the relationship between
the noted pathology and siloxane exposure is by no means conclusively
established.
However, the results do indicate that, at relatively massive
7/f
-------
doses, both compounds may be passed through abraded skin and the methyl
phenyl fluid may be absorbed through intact skin with possibly harmful effects.
D.
Ocular Tolerance
Rowe and coworkers (1948) have applied various dimethyl and methyl-
phenyl fluids directly in the eyes of rabbits.
The results, summarized in.
Table XXI, are similar to the transient conjunctivitis noted in man (see
Section XI, B).
Tab 1e XXI:
Eye irritation in rabbits after direct application
of various liquid si10xanes (Rowe ~ a1., 1948)
Occurrence and Persistence
Viscosity of Irritation
Material in cSt. Im-
at 250C medi- 1 4 8 24 48
ate1y hr. hr. hr. hr. hr.
DC 200 Fluid * 0.65 + 0 0 0 0 0
DC 200 Fluid 2.0 0 0 0 0 0 0
DC 200 Fluid 50.0 0 + + + 0 0
DC 550 Fluid 75.0 0 0 + + 0 0
DC 702 Fluid+ 35.0 0 0 + + 0 0
DC 200 F1uid+ 350.0 0 + + + 0 0
DC 200 Fluid 12,500 0 + + + + 0
* po1ydimethy1si1oxanes
+ po1ymethy1pheny1siloxanes
Roughly, the viscosity seems directly related to the duration of irritation
but inversely related to the rapidity of onset.
Similar results were noted
for DC Antifoam A (Rowe ~ a1., 1948).
Badinand (1952) has also evaluated the ocular tolerance to both
direct and vapor administration of various siloxanes.
The applications and
results are summarized in Table XXII.
75
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Ocular tolerance of guinea pigs to direct and
vapor application of various liquid siloxanes
(adapted from Badinand, 1952)
Table XXII.
Siloxane
Application
Result
Hexarnethyldisiloxane
Vapor: 80-100 mg/l,
30-40 min/day x 20 days
Direct: 1-2 drops/day
x 15 days.
Octarnethylcyclotetra-
siloxane
Vapor: 80 mg/l,
30 min/day x 22 days
Direct: 1-2 drops/day
x 10 days
Polydirnethylsiloxane
(50 cSt.)
Vapor: 8-10 mg/l,
20 min/day x 10 days
Polydimethylsiloxane
(2,000 cSt.)
Direct: 20 days
Polydiethylsiloxane
(cSt. not specified)
Direct: 10 days
Very slight epithelial
disarrangement
Slight corneal opacity without
vascularization after 15 days.
Very slight clouding in the
central region of the cornea
Very slight epithelial
disarrangement with little
infiltration and without
perifocal reaction.
Profound corneal opacity with
an instance of vascularization
lasting for five months.
Slight erosions with neither
opacity nor vascularization.
Very slight erosion of the
corneal epithelium with
neither infiltration nor
vascularization, lasting
for ten days.
On topical administration to the eye, these compounds seem to induce a
minimal response.
More details on ocular tolerance are described in the
following section under "Intravitreous Injections."
76
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E. Tissue Response to Siloxane Injections
Most of the studies involving the injection of liquid siloxanes into
non-human mammals have been stimulated by the various medical uses of these
products (see Section XI-D).
Such studies might be seen to have'broader
applicability to siloxane toxicology if the various injection sites are
viewed as means of artificially crossing various membrane barriers to
siloxane absorption.
With this approach, emphasis will be placed on tissue
response rather than the overall suitability of these compounds in tissue
augmentation,
retinal retachment, and other medical uses.
Dow Corning
(1973a) has compiled an extensive bibliography on tissue reactions to poly-
dimethylsiloxane.
1.
Subcutaneous Injections:
Hexamethyldisiloxane (0.65 cSt.), dodecamethylpentasiloxane
(2.0 cSt.), various polydimethylsiloxanes (50, 350, and 12,500 eSt) and poly-
methylphenylsiloxanes (35 and 75 cSt.) have been injected subcutaneously
into rabbits at doses of 0.1 mI.
No effects were noted except for marked
irritation and necrosis at the injection site of hexamethyldisiloxane (Rowe
et a1., 1948).
In mice, subcutaneous injections of 2.0 and/or 3.0 ml.
polydimethylsiloxane (20, 100, and 1,000 cSt.) resulted in neither gross tissue
reaction nor inflammatory or foreign body reactions, although cyst formations
and fluid losses from injection sites were noted (Ben-Hur and Neuman, 1963
and 1965).
Although Ben-Hur and Neuman (1963) also noted areas of malignant
tumor formation in two of the thirty-six mice tested, these were probably
~p~tltaneous m3~~~Y adenoGarcinoma~ not related to siloxane injection (Grasso
et a1.' 1964).
An injection of 7-8 mI. polydimethylsiloxane (350 cSt.) in mice
77
-------
resulted in si10xane deposits in the spleen, liver, adrena1s, pancreas, ovaries,
abdominal lymph nodes, and kidneys but no apparent toxic effects attributable
to this distribution were noted (Rees et al., 1967).
Similarly, in injections
of 1 m1 polydimethylsiloxane (350 cS~) to mice, phagocytes were noted to ingest
si10xanes and accumulations were apparent near the adrenal glands but no
inflammatory response or tumor formation was evident (Ben-Hur et al., 1967).
Subcutaneous injection of 10 mI. dimethylpolysiloxane into the abdominal area
of an ape showed some indication of phagocytic histocytes and degenerative
connective tissue in the stoma and some cavities presumably filled with
si10xanes and lined by foreign body giant cells (Winer ~ al., 1964).
2.
Intraperitoneal Injections
Intraperitoneal injections follow much the same pattern as sub-
cutaneous injections.
Rowe and coworkers (1948) injected the same fluids
outlined under subcutaneous injection at doses of 0.1, 0.3, 1.0, 3.0, and
10.0 mIlk;!;.
Again, only hexamethy1disiloxane - at the three higher doses -
caused fatalities, considerable irritation, and extensive adhesions throughout
the viscera.
All other fluids caused only. non-inflammatory foreign body
reactions which did not result in any noticeable toxic effects.
Rees and
coworkers (1967) also injected intraperitoneally as well as subcutaneously,
the intraperitoneal doses in mice being 1 mI.
They noted that the siloxane
distribution paralleled the reticuloendothelial system indicative of possible
collecting and storing by that system.
o~ injecting rats with 10 mI.
dimethylpolysiloxane (350 eS~), Brody and Frey (1968) noted the typical
granulomas response seen in other studies and found that thE injections
did not assist in the healing of intestinal abrasions.
Using th.e same
78
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compoundt howevert Ballantyne and coworkers (1971) injected 2-3 or 16 mI. i.p.
into rats and found that peritoneal adhesions were reduced probably by
mechanical separation
of the abraded intestines from the peritoneal tissue.
Againt the siloxane fluid caused no inflammatory response.
3.
Intravenous Injection
Antifoaming agents rather than unadulterated siloxanes have been
tested for toxicity by intravenous injection.
DC Antifoam A administered to
dogs into the right jugular vein had an LDSO of 0.9-1.0 ml/kg.
Death was
characterized by massive obstruction of the pulmonary artery or branches.
In
fatal casest the right ventricles evidenced extreme distention not noted in
surviving animals.
Arterial administration via the carotid artery gave a
much smaller LDSO of 0.02 mg/kg.
In such exposurest fatal cases showed
necrosis due to impeded blood flow to the brain which was also seen to a
lesser extent in some surviving animals (Reed and Kittlet 19S9).
Smith (1960)
observed similar brain lesions in dogs subjected to extracorporeal circulation
in which a siloxane/silica antifoam was used. These lesions could have resulted
from emboli caused by either the silicat the siloxanest or both.
In a
recent studYt the polydimethylsiloxane component of an antifoamingagent was
shown to be able to occlude small pulmonary vessels but not produce
~y
tissue response (Gupta et al't 1972).
4.
Intravitreous Injections
As indicated previously (Section XI-D-l)t polydimethylsiloxane
fluids have been injected intravitreously in man as a therapy for complicated
forms of retinal detachments with mixed results.
In attempts to better define
the biological activity of these polymers in the eyet similar injections
79
-------
have been made in various laboratory mammals.
Polydimethylsiloxane fluids
(DC 360 Medical, viscosities of 500, 1,000, and 2,000 cSt.) have been intra-
vitreously injected into five rabbits (0.5 - 0.75 ml) and seventeen monkeys
(1.25 - 1.5 ml) after withdrawing an equal amount of fluid vitreous.
Initially,
a clear siloxane bubble was noted in the vitreous which occasionally showed
transient mild opacity.
In two monkeys, the surface of the retina evidenced
small bubbles.
Microscopic examination at periods of one day to one year
after injection reveal that the siloxane injections cause the ganglion cells
and inner nerve fiber layer of the retina to swell and vacuolize.
This
resulted in irreversible cellular damage to and loss of the ganglion cells
in the compressed inner layer as indicated by partial disappearance of the
cytoplasm.
Similar damage was seen in receptor cells (Lee et al., 1969).
In a subsequent study, one eye in each of eight monkeys was injected with a
polydimethylsiloxane fluid (DC 360 Medical Grade, 2,000 cSt.) and subjected
to histochemical and electron microscopic examination.
After 2-3 hours,
siloxane particles were noted in retinal tissue, particularly at the vitreo-
retinal interface.
These particles seemed to attract free lipids and lipid
accumulation surrounding siloxane particles was
noted in the inner layer
of the retina.
Intercellular gaps a few microns in size were also noted in the
superficial layers of the retina (Mukai ~ al., 1972).
In a similar experi-
ment, Labelle and Okun (1972) injected 0.4-0.6 mI. of polydimethylsiloxane
(DC 360 Medical Grade, 2,000 ~St.) into the vitreous of fifteen rabbits.
Histologic examinations were made after periods of one day to six months.
The siloxane bubble remained clear and intact and no adverse effects were noted
attributable to siloxane injection.
Transient edema was noted in both siloxane
80
-------
-~-,
and control eyes after one week.
Jodkaite (1971) also failed to note any
inflammatory response from the injections of polydimethylsiloxane (400 cSt.)
into the vitreous of rabbits although some tendency toward cataract formation
was found.
5.
Intra-articular Injection.
Siloxane fluids have been used to lubricate arthritic joints in
humans (Helal, 1968).
However, such si1oxanes, while not causing adverse
effects, are not well retained in such spaces.
Polydimethy1siloxane fluids
(350 and 1,000 ~St.) have been injected into mobile and immobilized knee joints
of rabbits.
The siloxanes were gradually removed from all spaces and completely
removed after three months.
Similar injections into the knee joints of dead
rabbits resulted in a much higher recovery of siloxanes.
Histological exam-
ination revealed a mild granuloma-like inflammatory response similar to that
noted in other injection sites.
The difference in si10xane removal seen
between living and dead rabbits seems to indicate that these compounds may be
actively transported (Donahue et al., 1971).
VonLuedinghausen and coworkers
(1972) also noted considerable absorption of po1ydimethy1si1oxane from the
knee joints of rabbits but no inflammatory response was seen after the
injection of one milliliter. Murray (1972) found that polydimethylsi1oxane
fluid (200 ~St.) will leave the synovial cavity of rabbits one week after a
one milliliter injection either by leakage or phagocytosis and result in mild
transitory inflammation.
6.
Other Injections
Siloxanes have been injected at various other sites with tissue
responses similar to those described above.
Rowe and coworkers (1948), using
81
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the same siloxanes described under subcutaneous injections, injected 0.1 ml
intraderrnally in the back of a rabbit.
As in the other sites, only hexa-
methyldisiloxane caused inflammation, edema, and necrosis.
The other
si10xanes formed b1ebs which disappeared after a few days.
Autopsy revealed
no organ dama~e on gross examination.
Polydimethylsi1oxane (DC 360
Medical Fluid, 12,500 cS~)has been injected into the cisterna magna of rats
and the spinal canals of rabbits and monkeys with no adverse effects attri-
butable to siloxane injection (Hine ~ al., 1969).
,
Imre and Pal (1968) have
been able to induce avascular edema of the cornea by the injection of po1y-
dimethylsiloxane (DC 200, 350 cSt.) into the anterior chamber of the eye of
rabbits similar to that seen by the introduction of vitreous.
Tusa and Avis
(1972) have injected po1ydimethylsiloxane intramuscularly into rabbits as a
vehicle for progesterone without noting adverse effects.
F.
SeRsitization
As indicated previously, po1ydimethylsiloxane fluids (DC 200; 20, 50,
and 100 cSt.) do not cause"sensitization on repeated insult patch tests to
humans.
Similar results were also found in rats (Barry, 1973).
In guinea
pigs injected with a 1:1 mixture of po1ydimethylsiloxane (DC 360 Medical Fluid,
350 cSt.) and complete Freund's adjuvant at doses of 0.5 ml in the heel pads
and 1.0 mI. subcutaneously in the flank, no antigen/antibody sensitization
could be stimulated.
Although repeated ~nject~ons are not cornmon, no inforrna-
tion currently available indicates that the commercially important siloxanes
are sensitizing by any route (Hobbs, 1973).
82
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G. Teratogenicity
Two extremely different types of siloxanes have been tested for terato-
genicity: a commercially available polydimethylsiloxane and an equilibrated
copolymer of mixed cyclosiloxanes containing phenyl groups no longer commercially
available.
A polydimethylsiloxane fluid (DC 360 Medical Fluid, 350 cSt.) has been
tested for teratogenicity in rats and rabbits.
The siloxane was administered
subcutaneously at levels of 20, 200, and 1000 mg/kg/day to pregnant rabbits
from day 6 to 18 and to pregnant rats from day 6 to 16.
Control anim als were
injected with sesame oil, 1000 mg/kg.
All litters were delivered by
Caesarean section in rats (day 20) and rabbits (day 29).
Summaries of results
indicating some deviation from the control groups in rats and rabbits are given
in Tables XXIII
and XXIV, respectively.
Ta':>le XXIII. Results of teratogenic testing in rats injected with
polydimethylsiloxane (Adapted from Food and Drug
Research LaborAtories, Inc., 1967).
Polydimethylsiloxane, mg/kg
Parameter Control 20 200 1000
Total Numb e r of Fetuses
(a11 alive) 104 120 130 97
Implant sites (mean/liter) 10.0 9.2 9.0 8. 7
Fetuses alive (mean/liter) 10.0 8.7 8.8 8.4
Pups with sternebrae not
fully developed (per cent) 27 17.5 31 40
Bipartite sternebrae
(per cent) 7.7 21.6 12.3 26.2
83
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'-
Table XXIV.
Results of teratogenic testing in Rabbits with
polydimethylsiloxane (adapted from Food and Drug
Research Laboratories, Inc., 1967).
Polydimethylsiloxane, mg/kg
Parameter
Control
20
200 .
1000
*Total Number of Fetuses:
ali ve
dead
96 (63)
o (1)
69 (48)
6 (6)
60 (33)
10 (0)
96 (46)
12 (6 )
Live Pups. litter
8.7
5.7
7.5
7.0
Implant sites (mean/liter)
8.8
6.7
9.9
8.2
Pups with sternebrae not
fully developed (per cent):
alive
dead
6
o
8
83
3
15
100
Bipartite sternebrae
(per cent)
o
o
3
2
* Number of animals examined for skeletal findings'given in parentheses.
Although these results indicate a greater incidence of adverse effects in the
siloxane groups, these findings are of questionable significance and do not
clearly indicate teratogenicity (Food and Drug Research Laboratories, Inc.,
1967) .
Palazzolo and coworkers (1972) have evaluated the teratogenic potential
in rabbits of an equilibrated copolymer of mixed cyclosiloxane with the
formula (PhMeSiO)x(Me2SiO)y where x ~ 1 and x + y = 3 to 8.
of administration, and results are summarized in Table XXV.
The dosages, routes
84
-------
Table XXV. Rabbit Teratogenic Study with Cyclic (PhMeSiO) (Me2SiO)
(Palazzolo et al., 1972). x y
Normal Abnormal
Route of Imp 1an- Resorp- Does young young 24-Hour
Test adminis- Dose Pregnant tation tion showing viabilitYb
a
Group material trati.on (mg/kg) does sites sites resorptions Alive Dead, Alive Dead index
_._--- ----
C None 15 120 6 4 105 8 1 0 91. 50
TC-I Sesame oil De 200 15 110 14 8 91 3 . 1 1 91. 30
TC-Il Sesame oil se 20 15 111 11 5 98 2 0 0 93.87
TC-lli Sesame oil se 200 15 112 14 5 92 6 0 0 68.04
TC-IV Sesame oil se 1000 15 109 27 9 74 8 0 0 90.54
T-I P~W!}!y 0 200 15 108 6 6 88 5 7 2 89.47
T-ll PNxHNy se 20 15 117 11 7 96 8 2 0 91. 83
T-Ill PNxI-!Ny se 200 15 93 23 9 62 0 6 2 91.17
T-IV PNxHNy se 1000 15 77 33 11 37 7 0 0 83.78
T-V PNxNMy D 50 10 70 6 3 64 0 0 0 65.60
T-VI PNxNNy 0 500 10 42 42 10
a C = control; TC = treated eOl;trol group; T = test group.
b ~_o..LY}i'ble young at 24 hr x 100.
No. of viable young at birth
e D = dermal.
Palazzolo and coworkers (1972) indicate that the abnormality rate noted in the
test group approaches "the upper limit of that expected for control rabbits of the
same s train" and do not consider these compounds to be "sJ?e.cifidtlJy" terato-
genic.
However, 6 of the 8 abnormalities in T-3 and 2 of the 9 in T-l were
clubbing of the extremities.
In addition, 2 of the 9 abnormalities in T-l
were partial acranius.
The remaining abnormalities noted were umbilical
hernias.
LeFevre and coworkers (1972) fed pregnant rats the same mixture at
levels of 200 mg/kg/day.
In rats fed from days 16-21, female - but not male -
offspring had urogenital malformations resulting in inability to control
urine flow.
A specific siloxane from this class, monophenylheptamethyl~
cyclotetrasiloxane, at doses up to 220 mg/kg/day did not produce this malformation
in rat offspring.
85
-------
._----_.
H. Mutagenicity
No detailed study on silicone mutagenicity was encountered.
Hobbs
(1973) reports of a study indicating that a polydimethylsiloxane fluid is
not mutagenic in albino mice.
Drosophila has recently been the subject of
a pilot study of the mutagenic activity of some organosilicones (Bennett,.
1973), but the results have not been screened for this report.
1.
Carcinogenicity
Frazer (1970) examined tumor induction in mice on diets of 0.25%
and 2.5%
polydimethylsiloxane (1000 cSt.) over an 80 week period as well as
in mice injected subcutaneously in the left flank with 0.2 ml of tILls compound.
Control groups consisted of those fed non-siloxane diets and mice injected
with 0.2 mI. liquid paraffin.
Tumor frequency was not greater in experimental
g~QUPS than in controls.
In the many other previously cited feeding studies,
no evidence for tumor induction was noted.
Thus, on oral administration,
the siloxanes do not seem to be carcinogenic.
The polydimethylsiloxanes, however, will absorb various steroids
such as testosterone, progesterone, cholesterol, and to a much lesser extent
estradiol and esterone.
Thus, siloxane injections could result in local
hormone imbalances which might be conducive to tumor induction (Bischoff,
1969) .
Bryson (1969) tested a polydimethylsiloxane fluid (DC 360 Medical,
350 cSt.) for tumor induction in female rats as well as male and female mice.
As summarized in Table XXVI,these animals demonstrated positive pathological
findin~not seen in controls unless otherwise indicated.
86
-------
Table XXVI".
Positive pathological findings in mice and rats
injected with polydimethylsiloxane (Bryson, 1969)
Animal (mnnber)
Initial Dye
Ra ts, female (34) Mice, male (22) Mice, female (22)
.
2 months 3 months 3 months
1. 0 m1., Lp. O. 4 m1. s.c. 0 .4 m1. Lp.
17 months 20 months 18 months
Dosage/Route
Exposure Period
Pathological
Findings
(number)
reticulum cell
sarcomas (8)*
local adeno-
carcinoma (1)
heterotopic bone
formation (1)
fibrosarcoma (1)
ne uro f ib roma (1)
diffuse lymphoma(l)
ulcerating benign
hyperplasia of
the skin (1)
malignant histiocytic
proliferation of the
liver (1)
fibrosarcoma (1)
extramedullary
hematopoiesis of the
liver (2)
fatty liver (1)
lipogranuloma (1)
fatty infiltration of
lymph nodes (1)
local necrosis with
focal calcification (1)
clear walled siloxane
cysts (1)
* One in control group.
In those mice and rats in which tumors or other pathological results
are not noted, the response was similar to the cyst formations and granulomatous
responses noted in other injections studied (Bischoff et al., 1972).
Rees and coworkers (1965) found no evidence of malignant tumor formation
in mice after subdermal or intradermal injections of polydimethylsiloxane in
45 rats over a 6 week to 12 month period.
Subsequent investigations by the
SM\a g~~yP nAv@ Eatl~d to indicQt~ eh~t injact@d M11Qxanes are carc~nogenic
(Rees ~ a1., 1970).
87
-------
J.
Behavioral Effects
An equilibrated copolymer of mixed cyclosiloxanes with the formula
>
(PhMeSiO) (Me2SiO) - where x=l and x +y = 3 to 8 - has recently been shown
x y
to produce pronounced effects on the sexual physiology of various non-human
mammals.
This mixture, which will be referred to as PMxMMy, had previously
been used in the cosmetic industry but has since been withdrawn from the'
market (Olson, 1972).
The teratogenic effects of this polymeric mixture
have been discussed in Section XII, G (p. 82).
This class of compounds has an androgen-depressant activity on male
mammals.
Palazzolo and coworkers (1972) have found that PMxMMy produced
marked testicular atrophy and spermatogenic depression both on oral (200 mg/kg
per day x 28 days) and dermal (5 mg/kg per day x 20 days) administrations to
rabbits.
These effects were reversible after exposure was terminated.
Similar effects were noted in two species of male monkeys after oral but not
dermal administration.
Stumptail monkeys (Macaca arctoides) receiving
2000 mg/kg/day x 90 days developed progressively decreasing sperm counts after
3 weeks of dosing.
After the 10th week of dosing, sperm samples could no
longer be collected.
Sperm production did not return to normal until 70 weeks
after dosing was discontinued.
Stumptail monkeys receiving 50 mg/kg/day x 90 days
were apparently not affected.
Rhesus monkeys (Mucaca mulata), however, were
much more susceptible.
Testicular atrophy with aspermatogenesis was produced
after 8 weeks in two of three monkeys receiving 50 mg/kg/day and after
10 weeks in all three monkeys receiving 2000 mg/kg/day.
Unlike the rabbits
and stumptail monkeys, the rhesus monkeys did not recover from this condition
during the investigation.
88
-------
The androgen-depressant activity of a series of substituted siloxanes
which might comprise the PMxMMy polymeric mixture has been examined by Bennett
and coworkers
(1972)
on the effect of these siloxanes on rat seminal
fluids,
seminal vesicle,
and
using male mice,
prostate are given in Table XXVII.
rats,
and rabbits.
Dose-response data
.
In this study, mice were less sensitive
and rabbits more sensitive than rats.
Table XXVII.
Oral Potency Comparison of Selected Phenyl-Substituted
Siloxanes on Rat Seminal Fluid, Seminal Vesicle and
Prostatea (Bennett et al., 1972)
--
----
Compound
._--'~'-'--
D_tsl1oxa~: RiSi-{}-SlRi
PhNc<,SiOSiMc)
1'1\"I~..S I OS I Me. Ph
I'h:,Me~iOSiNcJ
'!'.r)gi]ox~~
!illl'2r.: R,SlOSi(R,)OSiRJ
Me3S iDS i (Ph) }OS tHe)
Ph,NeSiOS I (He) ,OS INo J
1I0Phl1eS I OS IPhNoOSlNePhOH
Cye lie:
[(PhNeSIO) (He>SIO):>]
[( I'I"~,'SI 0), (No,SIO) )
.l-.!j~~-{ (PhN~SiO}:3)
;~ I"~-I (l'h1'leS iO),)
:r.1.!~r~"'!lo_~l~~..:!
.t.}.!~~!!..: R jSiOSiR20SiR20SIR:\
Me ISiOSil)Il1"eOSfPhM~OSiMej
~5l.!o. :
[ (l'hOHS 10) (l1e,SIO) J]
[(l'hHeSiO) (He/SiO) J)
I (l'hllS I 0) (1'k.,S I 0) ,)d
! (Ph,S 10) (Me ,S 10) J I
(9I'hNl~S (0);, (Me,'S IO};»
2,4-~~ l!-iomer
2,4-cfs iSIJmer
2. 6- t~,~;.!..:!.~ i Romer
~,o-(' I s isumer
I (l'hM,'S10) ,(No/SIO)]
I (l'hHc'SfO)" J
Dan dOBe i!!!&LkJ0.
100 JJ 10
-.- -- __4__-
o
82 51 9/
0
0
99 S7 ill 0
0
0
61 92 79
0
~d 91 78
o
13 :.] 59 62 S2 75 78 55 .\t, - C 39 57
./j .\ ~I 6./ 70 ill/ .\ ~
0
50 80 80
o
0
0
0
0
o
././ 71 C1 57 80
831
I
L
- - -----'-------.--'
--_.._-- --
iI Thl..! 1 numh\.'l"s in 6~quence fur any compound ~t nny ~tven dose denote rhe- percent of
'>tll\trol for st!mlnul fluid. sl.!mtn.ll vcs[clc. and prostatc. respt'ct ivcly, afl~r
cOl1vcrsJon to II nnlo of fluJd or orgnn ....eight to fln.:d body wl'ight. "0" J('nnt('ti
nil sIgnificant dtfferenct! from control for the) rcsponsf.! pllram~..t\'III. nod
thl.',>\>for", n>~)rl"HlI\tA 111\ Inl\l't.~,,<.1 (~ump\~und Ute thtH dUllu. lllllleli\j.t! nllmtH'r~
n~pl,..tHJnr. tH.ltlsli...::a1Jy slgnHtc.lI1t diffcre-nces from control when> p;;' 0.05.
Ten rats were lIsed at each dnsf'. Dosing 1ast.ed 7 days; alltop~y W .Ictu31ty 60 mg/kg.
89
-------
As can be seen from Table XXVII, a number of phenyl substituted
siloxanes cause statistically significant (p~ 0.05) effects at a dosing
schedule of 100 mg/kg/day x 7 days.
Two of the cyclic tetrasiloxanes are
active at a one hundred fold lower concentration.
Further, these two
siloxanes were found to be more potent when administered orally as opposed
to subcutaneous or intraperitoneal injections.
In oral administration to
rabbits, the effects of [(PhMeSiO)(MezSiO)3] on seminal vesicle and testes
weight were shown to correspond with a decrease in plasma testosterone.
LeVier and Jankowiak (1972a) have attempted to characterize in
greater detail the mechanism of action of the most active siloxane,
2,6-cis-diphenylhexamethylcyclotetrasiloxane - 2,6-cis[(PhMeSiO)2(MezSiO)2]
of Table XXVII.
As with [(PhMeSiO)(MeZSiO) 3], 2, 6-cis [ (PhMeSiQ) 2 (MeSiO) z]
caused a decrease in plasma testosterone.
Either testosterone propionate
or a combination of follicle-stimulating hormone, luteinizing hormone, and
prolactin blocked the effect of this cyclic siloxane, thus indicating that
the siloxane does not directly inactivate gonadotropins nor compete
with them
at receptor sites. However, the investigators were not able to determine if the
siloxane directly or indirectly inhibited gonadotropin synthesis or release.
Both of these active cyclic tetrasiloxanes were found to shorten hexobarbital
sleep time in mice, indicating liver microsomal enzyme induction.
The androgen-depressant activity of these low molecular weight siloxancs
in male mammals has been shown to correspond with a positive estrogenic activity
in female mammals.
LeFevre and coworkers (1972) noted that PMxMMy arrested the
estrus
cycle of mature female rats when administered orally at 100 mg/kg/day
x 30 days.
Rats on the first day of estrus
went into metestrus for a few days
90
-------
and then remained in diestrus.
A normal estrus cycle did not develop until
2-3 weeks after exposure was terminated.
Similar to the study by Bennett and coworkers (1972) on male mammals,
Hayden and Barlow (1972) determined the estrogenic potency of a series of
substituted siloxanes on female mammals.
The criterion for positive activity
was the effect of a three day dosing of the various siloxanes on the uterine
weights of ovarectomized immature female rats.
The relative activities thus
determined are summarized in Table XXVIII.
Table XXVIII.
Comparative Relative Activities of 32 Organosiloxane
Compounds Based on Effects on the Ovariectomized Immature
Female Rat Uterus Following Oral Administration [Hayden
and Barlow, 1972]; reprinted by permission. Copyright 1972,
Academic Press
Compound
Relativc
activit)'''
Compound
RelJI,,'e
activity.
A. SubJlil/llccl JtldXCIl1t'J
DiJilo.\(JlIcs
Phen)'1 subSliluled
PhMe,S,OSi~leJ
Phl\lc,S,OS,~le, II
PhI\1o,SiOSi~1l',l'h
Ph Vin)'I:, IcSiOSi ~ 10,
Ph,I\IeSiOSi~le,
(l'hCH(CII, ICII ,)~Ic,SiOSiMe,
TriJiln.nlllcJ
Phen)'1 sub'liluled
Lincar
Me,SiOSiPhOIIOSi~lc,
Mc,SiOSiPhiIOSii,le,
"le,SiOSiPh,OSiMe,
C)'clic
[(Phl\leSiO)(~Ie,SiO), J
1(l'h~ IeS,OI,(~Ie,SiO IJ
2,4-(1'(11/1"-11 Ph~ IeSiO 1,1 ~ Ie ,SiO 1 ]
2,4-fi,-{(l'h~IeS,O',1 ~ Ie ,S,O))
fiJ-( l'h~IeS,O' ,J
/,.,I/IX- [(Ph~ IcS,O), ]
o
o
+2
+1
o
+1
Trtrasiloxmlcj'
C)'clie .
[(l'hMcSiO)(~Ic,SiO)J ]
[(0-101)'1 ~ feSiO)( 1\1 c,SiO), J
[(II ~leSiO)(~le,SiO),J
{(Vinyl ~ IcSiO)( ~ Ie ,SiO I,]
[(I/.J>r~ feSiO I( ~ Ie ,SiO I,]
{(Ph~IcSiO),J
[(Me,SiO),J
{(J>h~lcSiOI,(~Ic,SiO),] (rocemic mixture)
2,4-cis-[(l'h~IeSiO),( ~ Ic,SiO),)
2,G-(I'(IIIJ-I(Ph ~leS,O),( ~ Ic,SiO), J
2,G-fis.[(Ph~loSiO',( ~1c,SiO),J
{(PhIISi(»(~Ic,SiOJ., )
[(Ph,5iO)( ~1c,SiO),J
{(PhOIISiO)(~le,SiO),J
B. AfiJcd/flJ/C'OIlJ
011 ~1c,SiPhSi~lc:OII
Ph~Ic[Sinl ,ClI ,Si\lcl'hOJ
[(~Ic,Si"'II)(~Ie,S,O),)
(~lc,SiO),Sil'h
o
+1
+1
+2
+3
+3
o
+1
+1
+4
+3
0-+1
0-+1
0- +1
+1
+1
+4
+1
+3
-14
+3
+1
.tl
o
+3
+1
o
. COOL': 0 i\'u dTI:l'I;; 1..- sl:\lj,lic:i!I) numigllill~'~nl illcrl'J~C ...:20~~;
+2 '3 ~1:Hi!>lic.llI\' sH~nili\::tnt incrca"c :It o.US Ii.'\cl of ~il:nili:::Jl1cc: ° 3 '". ~dali-
~tic~dl}' ~!I~llIli~:I~lI il~(IT:J"~ at 0 01 kn:1 uf;.it'ndll':Jn(,,'c;~' -I ,incrc3\C (,,°quallo
or r,rCJICr 1kln l'::.lrog'~'n Ir(,~llcd l"ontrobo
91
-------
As with the androgen-depressant activity in males, the two cy~lic tetrasiloxanes
[(PhMeSiO)(Me2SiO)3] and 2,6-cis-[(PhMeSiO)2(Me2SiO)2] are the most potent.
Dose-response data on various tri- and tetrasiloxanes summarized in Table XXIX
give a more concrete indication of relative potency.
Table XXIX:
Effect of Selected Cyclotrisiloxanes and Cyclotetrasiloxanes
on the Uterine Weight of Ovarectomized Female Rats Following
Three-Day Oral Administration (Hayden and Barlow, 1972)
Mean uterine wt. (mg/100 g body wt. t SE)
Castrate control
Positive control(O.1 pg estradiol benzoate)a
40.3 ' 5.9
182.9 i 10.4c
Dose of test compoundb
10.0 mg/kg
1. 0 mg/kg
0.1 mg/kg
0.01 mg/kg
[(PhMeSiO) (Me2SiO)2)
2,4-~.-[ (PhMeSi0>2(Me2SiO)]
2, 4-EJ s,- [ (PhMeSiO) 2 (Me2SiO) ]
[(Pt~eSiO)(Me2SI0)3]
2.6-cis-[(PhMeSI0)2(Me2SiO)2]
2.6-~-[(PhMeSiO)2(Me2SiO)2]
33.3 t 1. 0
99.9 t 2.2c
35.0 i 1.2
73.4 t 2.3c
173.6 i 13.9c
78.7 t 4.0c
35.5 :t 1.2
38.5 :t 0.5
38.1 i 1. 2
37.5 i 1.4
44.5 . 5.4
34.7 :t 0.7
40.3 i 1.9
30.2 i 1.3
35.7 :t 2.3
48.9 :t 4.9
45.0 i 6.4
:38.7 i 2.2
41.7 ~ 2.1
211. 3 i 21. 3c
37.8 :t 2.0
39.8 :t 2.5
82.5 ': 3.8c
39.2 :t 3-.8
a Total dose/animal/day.
b 6 animals/dose/compound.
c p " 0.01.
92
-------
From this data, it is evident that 2,6-cis-[(PhMeSiO)2(Me2SiO)2] is one hundred
times more potent than either the trans isomer or [(PhMeSiO) (Me2SiO)3]'
As in
the studies on male mammals, the siloxanes were more potent when administered
orally than when given by injection (Hayden and Barlow, 1972).
In a subsequent
study, it was found that the above cis-isomer administered to rats at 0.33 mg/kg/day
on days 1-5 of gestation acts like a 0.05 mg/kg dose of diethylstilbestrol in
effecting ova destruction
in the uterus and more rapid passage of the ova to
the uterus (LeVier and Jankowiak, 1972b).
The environmental significance of these findings is uncertain.
The
hormonally active compounds are no longer directly available commercially.
Other polysiloxane fluids that are more widely used do not demonstrate any
similar activity (Hobbs et al., 1972).
However, the recent work of
Ingebrightson (1975) on the breakdown of polydimethylsiloxane in soil suggests
the possibility that polymethylphenylsiloxane might also break down and perhaps
generate estrogenic low molecular weight siloxanes.
K.
Possible Synergism
There is presently no indicatton that any of the siloxanes have
synergistic effects.
93
-------
XIII.
TOXICITY TO LOWER ANIMALS
Toxicity studies encountered on non-mammals have concentrated primarily
on various antifoams in an aquatic environment.
.
Fish seem quite tolerant to relatively high concentrations of silicone.
SAG-lO, a polydimethylsiloxane oil and silica emulsion, and SAG-350, a poly-
dimethylsiloxane-oxyalkylene, both of Union Carbide, have no toxic effects
on the flathead minnow in concentrations up to 2,000 mg/l over a four day
exposure period (Spacie, 1972).
Similarly, 1% DC Antifoam C (0.3% DC200),
another polydimethylsiloxane, has no toxic effects on rainbow trout or
bluegill sunfish over a four day exposure period (Barry, 1973).
Daphnia, however, have shown much more pronounced toxic response
(See Table XXX).
Table XXX: Daphnia Mortality in Static Exposure to Siloxane
Emulsions (Spade, 1972)
A: Daphnia Mortality (%) in SAG 10 Solutions
Concentration - mg/l
Hours 0 1 10 100 500 1,000 2,000
24 0 0 20 10 40 30 60
48 a 20 20 10 40 50 100
96 a 30 40 40 50 100 100
B: Daphnia Mortality (%) in SAG 530 Solutions
Concentration - mg/l
Hours a 1 10 100 500 1,000 2,000
24 a a a a 10 10 40
48 a a a a 10 30 60
96 10 a 10 10 20 80 100
94
-------
The 96 hour LC50 of 500 mg/l SAG-IO and 500-1,000 mg/l SAG-530 might
seem
to indicate that these compounds are relatively non-toxic.
However, LC50's
are not absolute indicators of toxicity.
Note that after 96 hours a 30%
Daphnia
mortality is achieved at 1 mg/l SAG-10, approximately 1 ppm.
Needless to say, a 30% mortality of this important food source in aquatic.
systems would create considerable environmental stress.
Thus, while this
experiment was meant only as a preliminary evaluation and not as a definitive
study, Spacie's conclusion that further studies are not required because of
the high LC50s is questionable.
Rausina (1974) has recently completed 48 hour static and dynamic exposures
of Daphnia magna to a 30% polydimethylsiloxane emusion.
Twenty daphnia were
used in each group.
The results are given in Table XXXI.
Table XXXI: Daphnia Magna Hortality (%) in Static and Dynamic Exposures
to a 30% Polydimethylsiloxane Emulsion (Rausina, 1974)
Concentration (ppm): Emulsion (Siloxane)
Hours 0 LO 10 62.5 100 250 500 1,000
(0.3) * (3)* (18.8) ( 30) * (75) (1.'30) (300)
1-6 0; 0* 0 0 5 5 5 40 25; 15*
24 O. 10* 5 5 5 15 1.5 50 70; 60*
,
48 5; 10* 15 5 10 20 40 75 100; 85*
* static, all other figures indicate dynamic study.
Just as Spacie's study, because of limited number of specimens used
and the short period of exposure, is no cause for alarm, so Rausina's study
is no indication of aquatic innocuity.
Both studies show similar mortali~y
95
-------
in static exposures to 1 ppm emulsion for 48 hours - i.e., 20% in Spacie's
and 15% in Rausina's.
This is not particularly significant because a clear
dose-response relationship is not established in these small groups until
the concentrations reach about 100 ppm or until the exposure period is
. lengthened.
The only thing indicated by either of these screening experiments
is that the siloxane emulsions exert an adverse effect on Daphnia after a
couple of days at environmentally improbable concentrations.
'The siloxanes
themselves are, of cours~ not definitely implicated.
Subsequent experiments
using control, siloxane emulsion, and emulsifying agents without siloxane
exposures may well prove the siloxanes to be without significant effect.
Similarly, experiments outlined above reveal nothing about the effects of long
term low level exposure.
The death of a few Daphnia out of a group of 10 or 20
over a 2-3 day period may well be unrelated to exposure.
However, even if the
short-term lower limit of any aquatic biological activity is assumed to be
100 ppm siloxane, this is still the lowest level of biological activity thus
far demonstrated.
In that the aquatic environment may be a major site of
siloxane disposal and distribution, further studies including population
dynamics over periods of months may be indicated.
Taylor (1973), in discussing
the potential pollution of the marine environment by siloxanes and other
organo-silicon compounds, did not apparently have access to the above cited
studies and indicates that toxicity data on aquatic organisms are not avail-
able.
However, he reasons that because "of the considerable body of evidence
indicating the inertness of these compounds it seems safe to predict that the
majority of the silicones are not toxic to marine life" (Taylor, 1973).
The
Daphnia studies suggest that this line of reasoning requires further verification.
96
-------
No further toxicity studies were found.
Unspecified silicones at
0.1 - 2.0% diet are reportedly fed to silkworms to increase body and cocoon
weights, but no adverse effects are given (Hashimoto ~ al., 1972).
XIV.
TOXICITY TO PLANTS
Parkinson (1970) has applied polydimethylsiloxanes (1,000 and 12,500 cSt.)
to leaf surfaces of short grass, certain farm crops and trees as antitrans-
pirants.
While these applications have proven effective in conserving water,
no toxic effects have been noted.
A more detailed investigation of the
antitranspirant effect of these silicones is in progress.
Bennett (1973)
indicates that no toxic effects have been noted thus far on 32 plant species.
XV.
TOXICITY TO MICROORGANISMS
Various fluid polydimethylsi1oxanes have been found to elicit no toxic
response from the following bacteria: !. coli, ~. aeruginosa, !. aerogenes,
~. aureus, ~. megaterium, and~. subtilis (Bennett, 1973).
Similarly,
unspecified polydimethylsiloxanes and polymethylphenylsiloxanes have shown
no fungicidal properties (Sharp and Eggins, 1970).
97
-------
XVI.
CURRENT REGULATIONS
Polydimethylsiloxane (300-600cS~ at 25°C) has been approved by the FDA
as a food additive so long as the levels in prepared foods do not exceed
10 ppm except for gelatin desserts which may contain up to 16 ppm in prepared
serving and milk which may not contain any trace of the siloxane (F.D.A., 1969).
Polydimethylsiloxanes (>100 cSt.) and/or polymethylphenylsiloxanes (not
more than 2% cyclosiloxanes of up to 4 siloxy units) have been approved for
use on metal surfaces
which come in contact with food (F.D.A., 1972).
The Department of Transportation does not require a special label on
siloxane products except when the formulation contains other active ingredients
such as toluene (Union Carbide, 1973).
XVII.
CONSENSUS AND SIMILAR STANDARDS - None encountered.
98
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. --
XVII 1.
Siloxane Fluids:
Summary and Conclusions
The fluid siloxanes are a well-established group of commercial chemicals
with considerable potential for further growth and development.
Although a
variety of fluid siloxanes are available as specialty products, the poly-
dimethylsiloxanes are by far the most popular followed by the polyrnethyl-
phenylsiloxanes.
The remaining fluids are produced in relatively small
amounts.
Although exact production figures are difficult to estimate, the
total quantity of siloxane produced for fluid applications in 1973 probably
did not exceed 36 million pounds.
These siloxanes are used in a great variety
of applications including waxes, polishes, antifoams, lubricants, cosmetics,
food additives, and textile finishings.
Because the applications of these
products may well become increasingly diversified, the growth rate may vary
considerably but an estimate of ten percent per year seems reasonable for
the immediate future.
Although these siloxanes are relatively expensive and most of their uses
do not involve direct environmental release, many of the fluids are probably
eventually released into the environment through disposal or use.
However,
because no monitoring data is available, the environmental distribution and
fate of these compounds is a matter of speculation.
Fairly good experimental
data is available to demonstrate that the siloxanes are non-biodegradable,
at least in test systems.
However, a recent study has demonstrated that
neutral soil will catalyze the hydrolysis and depolyrnerization of poly-
dimethylsiloxanes (100 cSt.) at a relatively fast rate (t~ = 10 days) to
cyclic species and low molecular weight fragments terminated with the silanol
group.
This finding has considerable environmental significance since the
99
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degradation products are more mobile in the environment, may be very persistent,
could be bioaccumulated, and may be more toxic.
Similar degradation processes
are possible with other substituted siloxanes.
Consideration of the physical and chemical properties of the parent
polysLloxanes and the breakdown products suggests that most of the siloxanes
probably migrate to aquatic systems.
Based on the assumption of aquatic
accumulation, the highest probable concentration which would be found in the
Great Lakes by 2023 would be .06 ppm if suspended in the water or 18 ppm if
deposited in the bottom foot of silt.
These figures probably represent
maximum concentrations for most aquatic systems.
The potential for adverse environmental effects from such exposure is
not readily defined.
The high molecular polysiloxanes would seem to present
a low degree of mammalian hazard at environmentally probable concentrations,
even though the results of chronic feeding studies are equivocal.
However,
even assuming a negligible level of mammalian toxicity, the possibility of
no adverse effects of these compounds on aquatic species is questionable.
Although fish do not seem to be highly susceptible in four day exposures,
such brief periods are of limited use in assessing the effects of long-teLm
exposure.
The two studies presented on Daphnia clearly indicate the need
for further testing with larger groups over longer periods of time.
The possibility that high molecular weight polymethylphenylsiloxanes
might be converted to low molecular weight estrogenic siloxanes is disturbing.
The most potent of these siloxanes, 2,6-cis-diphenylhexamethylcyclotetra-
siloxane has been shown to exert estrogenic effects in female rats at
0.1 mg/kg/day x 3 days and androgenic-depressant activity in male rats at
100
-------
1.0 mg/kg/day x 7 days.
Related siloxanes, while not as potent, nonetheless
have similar effects.
Thus, if long term exposure even to relatively low
levels of such siloxanes were to occur, the potential effects on mammalian
fecundity could be quite substantial and, therefore, would deserve considerable
attention.
However, it should be emphasized that the soil catalyzed break-
down of polymethylphenylsiloxanes to estrogenic substances has not been
demonstrated experimentally.
Nevertheless, the recent results with polydimethyl-
siloxanes make such analogous reactions not unlikely and the possibility of
such reactions should be determined.
Further impediments to a sound evaluation of the potential environmental
hazard posed by the fluid siloxanes center around the lack of monitoring
data and the inadequate testing of aquatic invertebrate toxicity.
Although
present information in other areas does not indicate that high molecular
weight siloxanes do or are likely to present an appreciable hazard, the
above mentioned deficiencies should be corrected before new uses involving
gross environmental exposure are initiated.
101
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113
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TECHNICAL REPORT DATA
(1'1':Qse rrnd "'n.mlctioIlS un thc rCI'erst! bt!fure completjllg)
1. REPORT NO. 12. 3. RECIPIENT'S ACCESSION-NO.
EPA-560/2-75-004
<1 TITLE AND SUBTITLE 5. REPORT DATE
Environmental Hazard Assessment of Liquid Siloxanes September 1974
(Silicones) 6. PERFORMING ORGANIZATION CODE
7 AUTHORiS) 8. PERFORMING ORGANIZATION REPORT NO
P.H. Howard, P.R. Durkin, A. Hanchett SURC TR-7~-572.2
0 PERFORMING ORGANIZATION NAME AND ADDRESS 10. PROGRAM ELEMENT NO.
Life Sciences Division
Syracuse University Research Corporation 11. CONTRACT/GRANT NO.
Merrill Lane, University Heights
Syracuse, New York 13210 EPA 68-01-2202
1-- --
1:' SPONSORING AGENCY NAME AND ADDRESS 13. TYPE OF REPORT AND PERIOD COVE.RED
Office of Toxic Substances Final Technical Report
U.S. Environmental Protection Agency .--"
14. SPONSORING AGENCY CODE
Washington, D.C. 20460
15. SUPPLEMENTARY NOTES
16. ABSTRACT
This report reviews the potential environmental hazard from the commercial
use of large quantities of liquid siloxanes which are used for the most part
in waxes, polishes, cosmetics, and in the foaming of polyurethane; and as
lubricants, antifoaming agents, release agents, and protective coatings for
textiles, glass and leather. Polydimethylsiloxane and polymethylphenylsiloxane
were of major interest as commercial products, although low molecular weight
siloxanes were also reviewed. Information is presented on the chemical properties,
production methods, quantities produced and released, commercial uses and factors
affecting environmental contamination as well as data on health and biological
effects.
17. KEY WORDS AND DOCUMENT ANALYSIS
--- - ----- .- . .--- --_..
, DESCRIPTORS b.IDENTIFIERS/OPEN ENDED TERMS C. COSATI Ficld/C!oup
------.,- ----'---.----. --------------.-- -- - -- -- . "--
Siloxanes, silicones, organic silicon Pollution
compounds, polydimethylsiloxane, poly- Environmental exposure
methylphenylsiloxane, antifoams, Environmental effects
toxicology, chemical properties, pollution
production, utilization.
:8. DISTRIBVTION STATEMENT 19. SECVRITY CLASS (Tllis Rt~p()rIJ 21. NO. OF I'A(".~S
Document is available to pub 1 ic through Unclassified 113
the National Technical Information Service 20. SECURITY CLASS (This POIII') 22. PRlcr; .---- ------
Springfield, Virginia 22151 Unclassified
EPA Form 2220-1 (9.73)
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