Hydrogenated Polysobutene

CIR Supplement Manuscript
International Journal of Toxicology

2020, Vol. 39(Supplement 2) 59S-90S
Safety Assessment of Polyene Group as ª The Author(s) 2020
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Used in Cosmetics DOI: 10.1177/1091581820952385
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Christina L. Burnett*, Wilma F. Bergfeld**, Donald V. Belsito**,

Ronald A. Hill**, Curtis D. Klaassen**, Daniel C. Liebler**,
James G. Marks, Jr.**, Ronald C. Shank**, Thomas J. Slaga**,
Paul W. Snyder**, Lillian J. Gill***, and Bart Heldrethy
Abstract
The Expert Panel for Cosmetic Ingredient Safety (Panel) reviewed the safety of polyenes, which are reported to function in
cosmetics primarily as film formers and viscosity increasing agents. The Panel reviewed relevant data related to these ingredients,
not inggaps in the available safety data for some of the polyenes in this safety assessment. The data available for many of the
ingredients are sufficient and can be extrapolated to support the safety of the entire group because of the similarities in the
chemical structures, chemical properties, use concentrations, and reported functions across the group. The Panel concluded that
polyenes were safe in cosmetics in the present practices of use and concentration described in this safety assessment.
Keywords
polyene group, safety, cosmetics
Introduction Polybutene (published in 1982), Polyethylene (published in

2007), Polyisobutene (published in 2008), and Hydrogenated
The 26 ingredients listed below are simple polyolefins that are
Polyisobutene (published in 2008) have previously been
the polymerization products of vinyl-type monomers and are reviewed by the Expert Panel for Cosmetic Ingredient Safety
reported to primarily function as film formers and/or viscosity (Panel), which concluded that these ingredients are safe as
increasing agents—nonaqueous in cosmetic products. cosmetic ingredients in the practices of use and concentration
Although the molecular weights of the polyenes reviewed in as described in each safety assessment.1-4 Information from
this report vary over a wide range, structurally, these ingredi- these safety assessments are summarized in appropriate sec-
ents have many similarities, including (1) each is the product of tions of this report; the complete reports are available on the
the same vinyl-type polymerization methodologies; (2) each is Cosmetic Ingredient Review (CIR) website (http://www.cir-saf
manufactured from very similar starting materials (ie, olefin/ ety.org/ingredients).
alkene monomers); (3) each has similar, simple hydrocarbon Some chemical and toxicological data on Hydrogenated
structures without functional groups other than alkanes or Polydecene and Polybutene included in this safety assessment
alkenes; and (4) many are of sufficient molecular size to sig- were obtained from robust summaries of data submitted to the
nificantly decrease the chance for dermal penetration. European Chemical Agency (ECHA) by companies as part of
the REACH chemical registration process. These data summa-
ries are available on the ECHA website.5,6 The ECHA data
Butene/Propylene Copolymer Isobutylene/Isoprene Copolymer
Butylene/Ethylene Copolymer Isoprene/Pentadiene Copolymer summaries include information on analogs (eg, diisobutylene,
Butylene/Ethylene/Propylene Polybutene di-n-butene, tributene, triisobutylene, and tetrabutene for Poly-
Copolymer butene; hydrogenated decene dimer and trimer for
Decene/Butene Copolymer Poly(C4-12 Olefin)
Ethylene/Octene Copolymer Poly(C6-14 Olefin)
Ethylene/Propylene Copolymer Poly(C20-28 Olefin) * Cosmetic Ingredient Review Senior Scientific Analyst/Writer
Hydrogenated Poly(C6-12 Olefin) Poly(C30-45 Olefin) ** Expert Panel for Cosmetic Ingredient Safety Member
Hydrogenated Poly(C6-14 Olefin) Polydecene *** Cosmetic Ingredient Review Former Director
y
Hydrogenated Poly(C6-20 Olefin) Polyethylene Cosmetic Ingredient Review Executive Director
Hydrogenated Polybutene Polyisobutene
Hydrogenated Polydecene Polyisoprene Corresponding Author:
Hydrogenated Polydodecene Polypentene Bart Heldreth, Cosmetic Ingredient Review Executive Director, 1620 L Street,
Hydrogenated Polyisobutene Polypropylene NW, Suite 1200, Washington, DC 20036, USA.
Email: [email protected]
60S International Journal of Toxicology 39(Supplement 2)
Figure 1. An example of polyene synthesis (Isobutylene/Isoprene Copolymer).
Hydrogenated Polydecene; and hydrogenated dodecene trimer other than alkanes or alkenes. These ingredients are completely
for Hydrogenated Polydodecene) for read-across purposes. insoluble in aqueous solutions or organic solvents but may be
Where deemed appropriate, information from the summaries swellable in certain organic solvents.
has been included in this report.
Method of Manufacturing
Chemistry Hydrogenated Polyisobutene. According to a supplier, Hydroge-
The definitions and CAS registry numbers, where available, of nated Polyisobutene is produced from the polymerization of
the polyene ingredients are presented in Table 1. isobutene, which is then hydrogenated, purified, and super
Polyenes are the polymerization products of vinyl-type refined before yielding the final product.9
monomers (ie, alkenes or olefins; eg, Figure 1). These poly-
olefins are either homopolymers (eg, Polybutene) or vinyl-type Composition and Impurities
copolymers of 2 or more monomers (eg, butene/propene copo-
lymers). The term “vinyl-type copolymers” means that all the Ethylene/Octene Copolymer. A supplier reported that a trade
monomers utilized to make these polymer ingredients have in name mixture comprised in part of Ethylene/Octene Copoly-
common an ethylene unit whose pi electrons are directly mer contains 14% to 16% Ethylene/Octene Copolymer and
involved in the polymerization process. Typically, a catalyst 84% to 86% C14-22 alkane.10 Residual monomer levels are
is utilized to initiate the polymerization.7 There are a large 2 ppm octene and 0 ppm ethylene. Ethylene oxide,
number of relevant initiating catalysts, ranging from ultraviolet 1,4-dioxane, and heavy metals were reported to be below the
(UV) light to Ziegler-Natta-type catalysts, which can result in a detection limit of 0.1 ppm.11
range of varied characteristics, such as crystallinity (and resul- A second trade name mixture was reported to contain
tant hardness). The synthesis of these ingredients is typically 30% to 50% Ethylene/Octene Copolymer and ethylene/sodium
conducted in one or more organic solvents in the presence of acrylate copolymer, and 50% to 70% water.10 The residual
one or more of these catalysts. monomer levels were reported to be less than 165 ppm acrylic
For example, formation of Polyisoprene occurs by reacting acid, less than 5 ppm ethylene, and less than 52 ppm octene.
the isoprene monomer in the presence of catalyst in a hydro- A heavy metals analysis reported arsenic was not detected
carbon solution, usually hexane.8 The process is stopped with (limited of detection, 27 ppb); however, lead and mercury lev-
the addition of a terminating reagent. The in situ stabilization of els were 22 ppb and 52 ppb, respectively (limits of detection for
the polymer is often enhanced with the addition of an antiox- each were 5 ppb).12
idant. Subsequent steps in the process include stripping of the
Ethylene/Propylene Copolymer. A redox titration of Ethylene/
solvent, water washing of the polymer to remove catalyst and
Propylene Copolymer measured 0.8 ppm of the starting mate-
reagent residues, and finally pressing and formation of a gran-
rial residue in the final product.13
ular product (for nonliquid polyenes).
Polybutene. Impurities of Polybutene include isoparaffins, viny-
Chemical Properties lidene and terminal vinyl structures, chloride, and
sulfur-containing compounds.3
Table 2 summarizes available data on chemical properties,
including information from the original Panel safety assess- Polyisobutene. A supplier reported that Polyisobutene does not
ments of Polybutene, Polyethylene, Polyisobutene, and contain detectable levels of residual solvents or monomers and
Hydrogenated Polyisobutene. Further chemical data on these has heavy metal specifications of lead < 10 ppm, arsenic
previously reviewed ingredients can be found in those < 2 ppm, and mercury < 1 ppm.14,15
reports.1-3
Many of these polyene ingredients are high-molecular-weight, Hydrogenated Polyisobutene. A supplier reported that Hydroge-
large, inert polymers. The smaller, liquid ingredients in this group nated Polyisobutene does not contain detectable levels of resi-
have a simple hydrocarbon structure, without functional groups dual solvents or monomers and has heavy metal specifications
Burnett et al 61S
Table 1. Definitions, Idealized Structures, and Functions of the Ingredients in this Safety Assessment.a,48
Ingredient CAS No. Definition and structure Function(s)
Butene/Propylene Copolymer Butene/Propylene Copolymer is a copolymer of butene and propylene Film formers; slip modifiers;
29160-13-2 monomers. viscosity increasing agents—
nonaqueous
Butylene/Ethylene Copolymer Butylene/Ethylene Copolymer is a copolymer of butylene and ethylene Viscosity increasing agents—
monomers. nonaqueous
Butylene/Ethylene/Propylene Butylene/Ethylene/Propylene Copolymer is a copolymer of butylene, Film formers

Copolymer ethylene and propylene monomers.
Decene/Butene Copolymer Decene/Butene Copolymer is a polymer of butene and decene Viscosity increasing agents—
monomers. nonaqueous
Ethylene/Octene Copolymer Ethylene/Octene Copolymer is a copolymer of ethylene and 1-octene Film formers; viscosity increasing
monomers. agents—nonaqueous
(continued)
Table 1. (continued)
Ethylene/Propylene Copolymer Ethylene/Propylene Copolymer is the copolymer of ethylene and Film formers; viscosity increasing
9010-79-1 propylene monomers. agents—nonaqueous
Hydrogenated Poly Hydrogenated Poly (C6-12 Olefin) is a series of low molecular weight Skin-conditioning agents—
(C6-12 Olefin) polymers of olefin monomers, each containing 6 to 12 carbon atoms. occlusive; viscosity increasing
agents—nonaqueous
Hydrogenated Poly Hydrogenated Poly (C6-14 Olefin) are a series of low-molecular-weight Skin-conditioning agents—
(C6-14 Olefin) polymers of olefin monomers, each containing 6 to 14 carbon atoms. occlusive; viscosity increasing
agents—nonaqueous
Hydrogenated Poly Hydrogenated Poly (C6-20 Olefin) is a polymer synthesized from Epilating agents
(C6-20 Olefin) hydrogenated C6-20 olefins.
69430-35-9
Hydrogenated Polybutene Hydrogenated Polybutene is the end product of the controlled Viscosity increasing agents—
hydrogenation of Polybutene. nonaqueous
Hydrogenated Polydecene Hydrogenated Polydecene is the end product of the controlled Fragrance ingredients; hair
68037-01-4 hydrogenation of Polydecene. conditioning agents; skin-
conditioning agents—
emollient; skin-conditioning
agents—misc.; solvents
(continued)
Burnett et al 63S
Hydrogenated Polydodecene Hydrogenated Polydodecene is the hydrogenated homopolymer of Binders; hair conditioning agents;
Dodecene. skin-conditioning agents—
emollient; solvents; viscosity
increasing agents—
nonaqueous
Hydrogenated Polyisobutene Hydrogenated Polyisobutene is the polymer that conforms generally to Skin-conditioning agents—
68937-10-0 the formula: emollient; viscosity increasing
agents—nonaqueous
Isobutylene/Isoprene Copolymer Isobutylene/Isoprene Copolymer is a copolymer of isobutylene and Viscosity increasing agents—
9010-85-9 isoprene monomers. nonaqueous
Isoprene/Pentadiene Copolymer Isoprene/Pentadiene Copolymer is a copolymer of isoprene and 1,3- Viscosity increasing agents—
pentadiene monomers. nonaqueous
Polybutene Polybutene is the polymer formed by the polymerization of a mixture of Binders; epilating agents;
9003-28-5 iso- and normal butenes. viscosity increasing agents—
9003-29-6 nonaqueous
Poly(C4-12 Olefin) Poly (C4-12 Olefin) is a polymer synthesized from C4-12 olefins. Skin-conditioning agents—
occlusive
(continued)
Poly (C6-14 Olefin) Poly (C6-14 Olefin) is a polymer synthesized from C6-14 olefins. Viscosity increasing agents—
nonaqueous
Poly (C20-28 Olefin) Poly (C20-28 Olefin) is a polymer synthesized from C20-28 olefins. Binders; film formers; skin-
64743-02-8 conditioning agents—
occlusive; surface modifiers;
viscosity increasing agents—
nonaqueous
Poly (C30-45 Olefin) Poly (C30-45 Olefin) is a polymer synthesized from C30-45 olefins. Film formers
Polydecene Polydecene is the polymer formed by the polymerization of decene. It Skin-conditioning agents—
25189-70-2 conforms to the formula: occlusive
37309-58-3
Polyethylene Polyethylene is a polymer of ethylene monomers that conforms generally Abrasives; adhesives; binders;
9002-88-4 to the formula: bulking agents; emulsion
stabilizers; film formers; oral
care agents; viscosity
increasing agents—
nonaqueous
Polyisobutene Polyisobutene is the homopolymer of isobutylene that conforms Binders; film formers; viscosity
9003-27-4 generally to the formula: increasing agents—
nonaqueous
(continued)
Burnett et al 65S
Polyisoprene Polyisoprene is the polymer of isoprene that conforms generally to the Viscosity increasing agents—
9003-31-0 formula: nonaqueous
Polypentene Polypentene is the polymer formed by the polymerization of pentene. It Film formers; viscosity increasing
9078-70-0 conforms to the formula: agents—nonaqueous
Polypropylene Polypropylene is a polymer of propylene monomers that conforms Bulking agents; viscosity
9003-07-0 generally to the formula: increasing agents—
nonaqueous
a
The idealized copolymer structures herein present a depiction of block copolymers only for the sake of simplicity and are not intended to suggest that block is the
dominant form.
of lead < 10 ppm, arsenic < 2 ppm, and mercury < 1 ppm.16-19 survey of the maximum reported use concentrations by category
An anonymous source reported that Hydrogenated Polyisobu- conducted by the Personal Care Products Council (Council).
tene may contain a maximum of 10 ppm n hexane as residual According to the 2015 VCRP data, Polyethylene is reported
solvent.9 to be used in 2,773 formulations; the single category with the
most reported uses was lipstick with 885 (Tables 3 and 4).24
Hydrogenated Polydecene. A supplier reported that Hydroge- Hydrogenated Polyisobutene is reported to be used in 1,963
nated Polydecene does not contain residual solvents, has a formulations; the single category with the most reported uses
residual monomer specification (decene) of < 10 ppm, and has was lipstick with 865. Most of the other in-use ingredients are
heavy metal specifications of lead < 10 ppm, arsenic < 2 ppm, primarily used in leave-on products and lipsticks. The results of
and mercury < 1 ppm.20-23 the concentration of use survey conducted in 2013 and 2014 by
the Council indicate Hydrogenated Polyisobutene has the high-
est reported maximum concentration of use; it is used at up to
Use 95% in lipsticks.25,26
Both historical and current use data for Polybutene, Poly-
Cosmetic ethylene, Polyisobutene, and Hydrogenated Polyisobutene
The safety of the cosmetic ingredients included in this safety are provided in Table 4. Concentrations of use for Polybu-
assessment is evaluated based on the expected use in cosmetics. tene and Hydrogenated Polyisobutene have remained about
The Panel utilizes data received from the US Food and Drug the same, with the highest maximum use concentration of
Administration (FDA) and the cosmetics industry in Hydrogenated Polyisobutene at 95% in lip products. The
determining the expected cosmetic use. The data received from highest maximum use concentration for Polyethylene has
the FDA are those it collects from manufacturers on the use of increased from 24% (eye shadow) to 67.6% (skin cleansing
individual ingredients in cosmetics by cosmetic product category agents), while the highest maximum use concentration for
in its Voluntary Cosmetic Registration Program (VCRP), and Polyisobutene has decreased from 76% to 40% (both con-
those from the cosmetic industry are submitted in response to a centrations in lip products). Uses for all 4 ingredients have
Table 2. Physical and Chemical Properties of Polyenes.
Property Value Reference
Ethylene/Octene Copolymer
10
Molecular weight (Da) 24,038 (number average), 52,743 (weight average) with 0.06% below 500 and
0.29% below 1,000
Polybutene
49-51
Form Light colored, nondrying, sticky viscous liquid
49-51
Solubility Insoluble in water, soluble in hydrocarbon and chlorinated hydrocarbon solvents
49-51
Melting point ( C) 124-130
49-51
Density (g/mL) 0.92
Polyethylene
1,52
Molecular weight (Da) 198-500,000
53
Odor Odorless
1
Melting point ( C) 85-110
1
Flash point ( C) 221
1
Density (g/mL) 0.910-0.925
54
lmax (nm) 161.5
Polyisobutene
2,14,15,37,38
Molecular weight (Da) 900 minimum, 654-2,168
2
Form White to yellowish or pale rubbery solid
2
Odor Slight rubber/petroleum odor
2
Flash point ( C) 165
2
Solubility Insoluble in water
2
Density(at 20 C; g/mL) 0.92
Hydrogenated Polyisobutene
2,9,16-19,39-42
Molecular weight (Da) Average 430, range 187-468
55
Form Clear liquid
55
Odor Odorless
2
Log Kow 13.27
2
Solubility Negligible in water
56
Boiling point ( C) 35
55
Freezing point ( C) Below 30
55
Density (at 20 C; g/mL) 0.819-0.830
Hydrogenated Polydecene
20-23,43
Molecular weight (Da) 367-596
5
Form (at 20 C and 1,013 hPa) Clear liquid
5
Odor Odorless
5
Log Kow > 6.5
5
Solubility in water (at 20 C; mg/L) < 0.1
5
Vapor pressure (at 20 C) < 0.545
5
Freezing point (at 1,013 hPa; C) 57
5
Density (at 15.6 C; g/mL) 0.82-0.83
increased by several fold since their original reviews. The Hydrogenated Poly (C6-20 Olefin) had no reported uses in the
ingredients not in use according to the VCRP data and VCRP, but a use concentration in a lipstick was provided in the
industry survey are listed in Table 5. industry survey. Therefore, it should be presumed there is at
In some cases, reports of uses were received from the least one use in every category for which a concentration is
VCRP, but concentration of use data was not provided. For reported.
example, Hydrogenated Polybutene is reported to be used in Some of these ingredients were reported to be used in pump
51 formulations, but no use concentration data were reported. and aerosol hair sprays, underarm deodorant sprays, face and
In other cases, no uses were reported in the VCRP, but con- neck sprays, body and handsprays, and aerosol suntan products
centration of use data were received from industry. and could be incidentally inhaled. For example, Hydrogenated
Table 3. Frequency (2015) and Concentration of Use (2013) According to Duration and Type of Exposure for Polyene Ingredients.24-26
# of uses Max conc. of use (%) # of uses Max conc. of use (%) # of uses Max conc. of use (%) # of uses Max conc. of use (%)
Butylene/Ethylene/Propylene
Butylene/Ethylene Copolymer Copolymer Decene/Butene Copolymer Ethylene/Propylene Copolymer
Totalsy 1 1.5 14 4.5 3 NR 107 0.0063-12.5

Duration of use
Leave on 1 NR 14 4.5 3 NR 107 0.0063-12.5
Rinse off NR 1.5 NR NR NR NR NR 2
Diluted for (bath) use NR NR NR NR NR NR NR NR
Exposure type
Eye area NR NR 2 NR 1 NR 11 0.0063-4
Incidental ingestion 1 NR 8 NR 2 NR 72 0.0097-12.5
Incidental inhalation—spray NR NR Spray: NR NR NR NR Spray: 4 Spray: 0.11
Possible: 1a Possible: 6a; 1b Possible: 0.21a
Incidental inhalation—powder NR NR NR NR NR NR Powder: 1 NR
Possible: 1b
Dermal contact NR 1.5 5 4.5 NR NR 32 0.0063-4
Deodorant (underarm) NR NR NR NR NR NR NR NR
Hair—non-coloring NR NR NR NR NR NR 3 2
Hair—coloring NR NR NR NR NR NR NR NR
Nail NR NR NR NR NR NR NR NR
Mucous membrane 1 1.5 8 NR 2 NR 72 0.0097-12.5
Baby products NR NR NR NR NR NR NR NR
c
Hydrogenated Poly (C6-14 Olefin) Hydrogenated Poly (C6-20 Olefin) Hydrogenated Polybutene Hydrogenated Polydecene
Totalsy 82 0.25-58 NR 10 51 NR 713 0.005-59

Duration of use
Leave on 79 58 NR 10 47 NR 681 0.035-59
Rinse off 3 0.25-1 NR NR 4 NR 32 0.005-49
Diluted for (bath) use NR NR NR NR NR NR NR 35
Exposure type
Eye area 9 NR NR NR 14 NR 77 2-38
Incidental ingestion 16 58 NR 10 26 NR 188 5.2-59
Incidental inhalation—spray Spray: NR NR NR NR NR NR Spray: 17 Spray: 1.8-42
Possible: 10a; 14b Possible: 224a; 115b Possible: 0.88-5a
Incidental inhalation—powder Powder: 2 NR NR NR NR NR Powder: 4 Powder: 0.9-10.5
Possible: 14b Possible: 115b
Dermal contact 66 NR NR NR 24 NR 482 0.035-49
Deodorant (underarm) NR NR NR NR NR NR NR Not spray: 2-13.8
Hair—non-coloring NR NR NR NR NR NR 38 0.005-36
Hair—coloring NR 0.25-1 NR NR NR NR 2 1-11
Nail NR NR NR NR NR NR 1 NR
Mucous membrane 16 58 NR 10 28 NR 191 5.2-59
(continued)
67S
68S
# of uses Max conc. of use (%) # of uses Max conc. of use (%) # of uses Max conc. of use (%) # of uses Max conc. of use (%)
Poly (C30-45 Olefin) Polydecene Polyisoprene Polypropylene
Totalsy 2 0.6-26.1 156 0.098-47.9 28 0.098-47 24 0.05-68.6

Duration of use
Leave on 2 0.6-26.1 129 0.098-47.9 26 0.098-47 20 0.05-68.6
Rinse off NR NR 27 25 2 1.8 4 0.2-66
Diluted for (bath) use NR NR NR NR NR NR NR NR
Exposure type
Eye area 1 NR 8 0.098-6 2 0.49-47 6 0.4-68.6
Incidental ingestion NR NR 75 10.2-47.9 3 2-12.2 NR 4
Incidental inhalation—spray NR Spray: 26.1 Spray: 1 NR Spray: NR NR Spray: NR NR
Possible: 12a; 8b Possible: 9a; 6b Possible: 2a; 6b
Incidental inhalation—powder NR NR Powder: 7 NR Powder: 3 NR Powder: NR Powder: 2.8
Possible: 8b Possible: 6b Possible: 6b
Dermal contact 2 0.6-26.1 63 0.098-25 25 0.098-47 18 0.05-66
Deodorant (underarm) NR NR NR NR NR NR NR NR
Hair—non-coloring NR NR 2 NR NR NR NR NR
Hair-coloring NR NR 16 NR NR NR NR NR
Nail NR NR NR NR NR NR 1 NR
Mucous membrane NR NR 75 10.2-47.9 3 1.8-12.2 1 4-66
NR ¼ not reported; VCRP ¼ Voluntary Cosmetic Registration Program.
y Because each ingredient may be used in cosmetics with multiple exposure types, the sum of all exposure types may not equal the sum of total uses.
a
It is possible these products may be sprays, but it is not specified whether the reported uses are sprays.
b
Not specified whether a powder or a spray, so this information is captured for both categories of incidental inhalation.
c
Hydrogenated C6-14 Olefin Polymers is a synonym for Hydrogenated Poly(C6-14 Olefin). The VCRP database has entries for both names and the data have been added together.
Table 4. Current and Historical Frequency and Concentration of Use According to Duration and Exposure.1-3,24,26
# of uses Max conc. of use (%) # of uses Max conc. of use (%)
Polybutene Polyethylene
2015 1976 2013 1976 2015 2002 2013 2004
Totalsy 1,823 85 0.1-82.4 >1->50* 2,773 717 0.0097-67.6 0.09-24

Duration of use
Leave on 1,808 83 0.1-82.4 >1->50 2,271 615 0.0097-52.6 0.09-24
Rinse off 15 2 8-20 >5-10 501 92 0.05-67.6 0.3-11
Diluted for (bath) use NR NR NR NR 1 10 10 4-18
Exposure type
Eye area 239 10 0.5-13.1 >1-5 734 382 0.06-21 3-24
Incidental ingestion 1,322 70 6-82.4 >1->50 885 67 0.0097-18.9 3-16
Incidental inhalation—spray Spray: 2 Spray: NR Spray: 0.1 Spray: NR Spray: 17 Spray: 1 Spray: 0.5-52.6 Spray: 3-5
Possible: 12a; 8b Possible: 2a Possible: 20a Possible: >1-25a Possible: 120a; 70b Possible: 23a; 17b Possible: 0.47-12a Possible: 0.5-10a; 1-16b
Incidental inhalation—powder Powder: 11 NR Powder: 0.92-4 NR Powder: 82 Powder: 32 Powder: 4-30 Powder: 3-10
Possible: 8b Possible: 70b Possible: 17b; 1c Possible: 1-16b
Dermal contact 425 13 0.1-73 >1-25 1,765 603 0.03-67.6 0.2-24
Deodorant (underarm) NR NR NR NR Possible spray: 8 NR Spray: 1.6 Possible spray: 7
Not spray: 1-12.1
Hair—non-coloring 4 2 NR >5-10 19 5 0.26-6 2
Hair—coloring NR NR NR NR 2 3 5-6 NR
Nail NR NR 8 NR 32 NR 0.42-15 0.09-3
Mucous membrane 1,327 70 6-82.4 >1->50 1,185 93 0.0097-18.9 0.3-18
Baby products NR NR NR NR NR 1 NR 3
Polyisobutene Hydrogenated Polyisobutene
2015 2005 2013 2005 2015 2005 2013 2005

Totalsy 310 30 0.24-40 0.3-76 1,963 654 0.00055-95 0.001-96
Duration of use
Leave on 295 29 0.24-40 0.3-76 1,916 639 0.001-95 0.001-96
Rinse off 15 1 1.1-3.5 4 47 15 0.00055-51 2-85
Diluted for (bath) use NR NR NR NR NR NR NR 3-85
Exposure type
Eye area 108 11 0.45-36.3 1-30 227 78 0.09-67.7 0.1-40
Incidental ingestion 54 12 6-40 4-76 865 318 0.29-95 0.001-96
Incidental inhalation—spray Spray: 6 Spray: 2 Spray: 5.5-7 Spray: NR Spray: 10 Spray: 5 Spray: 0.048-31 Spray: 10
Possible: 42a; 30b Possible: 1a Possible: 0.5a Possible: 0.5a Possible: 196a; 219b Possible: 39a; 18b Possible: 0.53-58.9a Possible: 3-15a; 0.5-42b
Incidental inhalation—powder Powder: 4 NR NR NR Powder: 42 Powder: 24 Powder: 1-4 Powder: 0.1-5
Possible: 30b Possible: 219b Possible: 18b Possible: 0.5-42b; 4c
Dermal contact 186 7 0.24-36.3 0.3-46 1,058 325 0.001-93 0.1-85
Deodorant (underarm) NR NR NR NR Possible spray: 4 NR NR Possible spray: 2
Hair—non-coloring 5 3 NR NR 15 NR 0.00055-58.9 15-17
Hair—coloring NR NR NR NR 3 1 0.048-20 NR
Nail NR NR NR NR 7 5 23-68.5 0.2-3
Mucous membrane 54 12 6-40 4-76 871 323 0.29-95 0.001-96
Baby products NR NR NR NR NR NR NR 4
CIR ¼ Cosmetic Ingredient Review; NR ¼ not reported.

y Because each ingredient may be used in cosmetics with multiple exposure types, the sum of all exposure types may not equal the sum of total uses.
* Earlier CIR safety assessments reported concentrations as ranges, not exact values.
a
It is possible these products may be sprays, but it is not specified whether the reported uses are sprays.
b
Not specified whether a powder or a spray, so this information is captured for both categories of incidental inhalation.
69S
c
It is possible these products may be powders, but it is not specified whether the reported uses are powders.
Table 5. Polyene Ingredients With No Reported Uses.24-26 hydrocarbon structure without functional groups other than
alkanes or alkenes. Thus, dermal penetration is limited for the
Butene/Propylene Copolymer
Ethylene/Octene Copolymer
large and small polymers in this group. These ingredients are
Hydrogenated Polybutene completely insoluble in aqueous solutions or organic solvents
Hydrogenated Polydodecene but may be swellable in certain organic solvents.
Isobutylene/Isoprene Copolymer
Isoprene/Pentadiene Copolymer
Poly (C4-12 Olefin)
Absorption
Poly(C6-14 Olefin) Hydrogenated Polydecene. In one study, the absorption potential
Poly(C20-28 Olefin) of undiluted Hydrogenated Polydecene was assessed in male
Polypentene Fischer rats.5 Groups of 3 rats/time point received a single or
daily (for 15 days) oral gavage dose of 30, 210, or 1,500 mg
Polyisobutene was reported to be used in face and neck sprays [3 H]-Hydrogenated Polydecene. Tissues and body fluids were
at a maximum concentration of 8.5%, and Polyethylene was sampled at 0.08, 0.25, 0.5, 1, 2, 4, 8, 24, 48, 72, 120, and/or
reported to be used in aerosol deodorants at a maximum con- 168 h post-dosing. With all 3 dose levels, very little of the
centration of 1.6%. In practice, 95% to 99% of the droplets/ administered dose was absorbed. What was absorbed was
particles released from cosmetic sprays have aerodynamic found in the liver, fat, lymph nodes, kidney, and spleen. The
equivalent diameters >10 mm, with propellant sprays yielding majority of the test compound was excreted in the feces
a greater fraction of droplets/particles below 10 mm compared (> 92%). Urinary excretion was low (< 1%), and very little
with pump sprays.27-30 Therefore, most droplets/particles inci- of the dose was recovered in the bile (0.01%).
dentally inhaled from cosmetic sprays would be deposited in
the nasopharyngeal and bronchial regions and would not be Biocompatibility
respirable (ie, they would not enter the lungs) to any
Polyethylene. Cellular and tissue responses to Polyethylene,
appreciable amount.28,29 There is some evidence indicating
determined as part of implant biocompatibility testing, include
that deodorant spray products can release substantially larger
fibrous connective tissue build-up around the implant material
fractions of particulates having aerodynamic equivalent dia-
that varies as a function of the physical form of the implant
meters in the range considered to be respirable.29 However, the
material.1 Specific assays for osteoblast proliferation and col-
information is not sufficient to determine whether significantly
lagen synthesis demonstrated a reduction as a function of expo-
greater lung exposures result from the use of deodorant sprays,
sure to Polyethylene particles that is inversely related to
compared to other cosmetic sprays. The polyene ingredients in
particle size. However, Polyethylene particles had a stimula-
this safety assessment currently are not restricted from use in
tory effect on monocyte-derived macrophages, prolonging the
any way under the rules governing cosmetic products in the
survival of these cells in culture.
European Union (EU).31
Non-Cosmetic Toxicological Studies

Many of the polyene ingredients have been approved by the US Single Dose (Acute) Toxicity
FDA for use as indirect food additives and in medical devices.
Animal acute dose toxicity studies are presented in
Additionally, Isobutylene/Isoprene Copolymer, Polyethylene,
Table 7.5,6,37-43 In acute oral toxicity studies in rats, the
and Polyisobutene are approved direct food additives for chew-
LD50sof diisobutylene and triisobutylene were > 2,000 mg/
ing gum bases.
kg/body weight (bw) each. The oral LD50 s of di-n-butene,
Polyethylene and Polypropylene are used as negative
tributene, and tetrabutene (containing 30% pentabutene) in rats
control materials for International Organization for Standardi-
were > 10,000 mg/kg each. The oral LD50 values for Ethylene/
zation (ISO 10993-6) international standard biological evalua-
Octene Copolymer, undiluted Hydrogenated Polydecene and
tion of medical devices. 32 Ultra-high-molecular-weight
undiluted Hydrogenated Polydodecene, were > 5,000 mg/kg
Polyethylene is the most used biomaterial for the articulating
in rat studies. The LD50 of undiluted Polyisobutene was
surface of total joint replacements.33 Polyisobutene is used in
> 15,400 mg/kg in an oral rat study.
transdermal drug delivery patches and patch adhesives.34,35
Acute dermal studies of diisobutylene and Hydrogenated
Polyisoprene (trans-1,4) is widely used as a component of root
Polydodecene found the LD50 values > 2,000 mg/kg in rats. In
canal filling material.36 Table 6 lists regulated uses in foods and
rabbit studies, the dermal LD50 values for Ethylene/Octene Copo-
medical devices.
lymer, hydrogenated decene dimer, Hydrogenated Polyisobu-
tene, and Polyisobutene were > 5,000 mg/kg, > 3,000 mg/kg,
Toxicokinetics >2,000 mg/kg, and > 25,000 mg/kg, respectively.
Although many of these polyene ingredients are In acute inhalation studies, the LC50 of diisobutylene vapor in
high-molecular-weight, large, inert polymers, the smaller, albino rats was > 4,185 ppm (19,171 mg/m3) after a 4-hour,
liquid ingredients in this group each comprise simple single, whole-body exposure. The LC50 for an aerosol of
Burnett et al 71S
Table 6. FDA-Approved Uses of Polyenes.
Ingredients Regulation CFR reference
Food use
Isobutylene/Isoprene Copolymer; Polyethylene; Food additives permitted for direct addition to food 21 CFR172.615
Polyisobutene for human consumption—chewing gum base
Hydrogenated Polyisobutene; Isobutylene/ Adhesives approved for use as indirect food 21 CFR175.105
Isoprene Copolymer; Polybutene; Polyethylene; additives
Polyisobutene; Polyisoprene; Polypropylene;
Hydrogenated Polybutene;
Polybutene; Polyisobutene; Polyisoprene; Pressure-sensitive adhesives approved for use as 21 CFR175.125
indirect food additives
Hydrogenated Polyisobutene; Polybutene; Resinous and polymeric coatings—adhesives and 21 CFR175.300
Polyethylene; Polyisobutene; Polypropylene; components of coatings approved for use as
Hydrogenated Polybutene indirect food additives
Hydrogenated Polybutene Components of paper and paperboard in contact 21 CFR176.170
with aqueous and fatty foods approved for use as
Isobutylene/Isoprene Copolymer; Polybutene; Components of paper and paperboard in contact 21 CFR176.180
Polyethylene; Polyisobutene; Polyisoprene; with dry food approved for use as indirect food
Hydrogenated Polybutene additives
Polyethylene Defoaming agents used in coatings approved for use 21 CFR176.200
as indirect food additives
Polyethylene Defoaming agents used in the manufacture of paper 21 CFR176.210
and paperboard approved for use as indirect food
additives
Polyethylene; Polyisobutene; Polypropylene Cellophane approved for use as indirect food 21 CFR177.1200
additives
Ethylene/Propylene Copolymer; Isobutylene/ Approved for use in closures with sealing gaskets for 21 CFR177.1210
Isoprene Copolymer; Polyisobutene food containers—indirect food additives
Isobutylene/Isoprene Copolymer; Polyisobutene Isobutylene polymers approved for use as indirect 21 CFR177.1420
food additives
Butylene/Ethylene/Propylene Copolymer; Olefin polymers approved for use as indirect food 21 CFR177.1520
Ethylene/Octene Copolymer; Ethylene/ additives
Propylene Copolymer; Polyethylene;
Polypropylene
Butylene/Ethylene Copolymer; Poly-1-butene resins and butene/ethylene 21 CFR177.1570
copolymers approved for use as indirect food
additives
Ethylene/Propylene Copolymer; Isobutylene/ Rubber articles intended for repeated use approved 21 CFR177.2600
Isoprene Copolymer; Polybutene; Polyethylene; for use as indirect food additives
Polyisoprene
Polybutene; Polyethylene; Polyisobutene; Lubricants with incidental food contact approved as 21 CFR178.3570
Hydrogenated Polybutene indirect food additives (addition to food not to
exceed 10 ppm for Polybutene, Hydrogenated
Polybutene, and Polyethylene; for use only as a
thickening agent in mineral oil lubricants in
Polyisobutene)
Polyisobutene; Hydrogenated Polybutene Plasticizers in polymeric substances approved as 21 CFR178.3740
Polyethylene Reinforced wax approved for use as indirect food 21 CFR178.3850
additives
Hydrogenated Polybutene Release agents approved for use as indirect food 21 CFR 178.3860
additives
Polyisobutene; Hydrogenated Polybutene Surface lubricants used in the manufacture of 21 CFR178.3910
metallic articles approved for uses as indirect food
additives
Polypropylene Packaging materials for use during the irradiation of 21 CFR179.45
prepackaged foods
Polyethylene Polyethylene—approved as a food additive 21 CFR573.780
permitted in feed and drinking water of animals
(continued)
Ingredients Regulation CFR reference
Drug/medical use
Polypropylene Intercardiac patch or pledget—cardiovascular 21 CFR 870.3470

device
Polyethylene Ear nose and throat devices—prostheses of the ear 21 CFR874.3430; .3450; .3495;
and mandible .3620; .3695; .3880; .3930
Polypropylene Nonabsorbable Polypropylene surgical suture— 21 CFR878.5010
general and plastic surgery device
Polypropylene Approved use as a finger joint polymer constrained 21 CFR888.3230
prosthesis—orthopedic device
Polyethylene Approved use as bone cap; ankle joint prosthesis, 21 CFR888.3000; .3100; .3110;
elbow joint prosthesis; finger joint prosthesis; hip .3120; .3150; .3160; .3200; .3220;
joint prosthesis; knee joint prosthesis; shoulder .3310; .3340; .3350; .3353; .3358;
joint prosthesis; wrist join prosthesis— .3390; .3490; .3500; .3510; .3520;
orthopedic devices .3530; .3535; .3540; .3550; .3560;
.3565; .3640; .3650; .3660; .3670;
.3680; .3800; .3810
FDA ¼ Food and Drug Administration.
Hydrogenated Polydecene was > 5.2 mg/L with a 4-hour expo- Dermal
sure in rats. The LC50 for the dimer of hydrogenated decene was Polybutene. In acute dermal toxicity tests, Polybutene in for-
1.17 mg/L in rats. In another acute inhalation study of the dimer of mulations produced no abnormalities or irritation in rabbits.
hydrogenated decene, the LC50 could not be determined in rats The LD50 of Polybutene in formulation was greater than
tested at 5 mg/L because 9/10 animals died within 3 days of 10.25 g/kg (average molecular weight not specified).3
administration of the test material. The LC50 for Hydrogenated
Polydodecene was > 5.06 mg/L. The LC50 for 100% Hydroge- Repeated Dose Toxicity Studies
nated Polyisobutene was > 5 mg/L. The oral, inhalation and
Repeated dose toxicity studies in animals are presented in
dermal acute dose toxicity data that were presented in the original
Table 8.5,37-43 No treatment-related gross microscopic changes
reviews of Polybutene, Polyethylene, and Hydrogenated Polyiso-
were observed following exposure to 100% Polyisobutene in a
butene are summarized below and not in the tables.
90-day dietary study of rats and 2-year dietary studies in rats
or dogs. No adverse effects were observed in oral repeated
Oral dose studies of Hydrogenated Polydecene, with the no
Polybutene. When tested for acute oral toxicity in albino rats, observed adverse effect levels (NOAELs) determined to be
concentrations of Polybutene ranging from 15% to 75% were 1,000 mg/kg/d in one 90-day rat study and over 4,000 mg/kg/
relatively harmless (average molecular weight not specified).3 d in another. In a 4-week oral repeated dose rat study, the
Polyethylene. The LD50 for Polyethylene (average molecular NOAEL for Hydrogenated Polydecene was 6,245 mg/kg/d in
weight of 450) in rats (201-223 g) was found to be > 2,000 mg/kg, males and 6,771 mg/kg/d in females. Gross necropsy, histo-
and in Polyethylene with an average molecular weight of 655 Da, pathology, and microscopic findings did not reveal any signif-
the LD50 was determined as >5.0 g/kg.1 icant treatment-related findings. The NOAEL for the oral
administration of the trimer of hydrogenated dodecene in
Hydrogenated Polyisobutene. No deaths in mice were observed 2 respective oral repeated dose toxicity studies in rats was
in an acute oral toxicity test at a maximum dose of 89.608 g/kg 1,000 mg/kg/d. Treatment-related effects on mortality, clinical
of a Hydrogenated Polyisobutene mixture.2 No deaths were signs, bw, food consumption, hematology, clinical chemistry,
observed in several oral toxicity rat studies of 5 g/kg Hydro- organ weights, or gross and histologic pathology were not
genated Polyisobutene; however, lethargy and wetness in the observed in either study. In a 4-week dermal study in rats,
anogenital area after dosing was observed. The authors of these 100% Hydrogenated Polyisobutene produced minimal to mild
studies also concluded that the LD50 is greater than 5.0 g/kg dermal irritation in the majority of treated animals. Histopatho-
bw. The average molecular weight was reported to be 900 Da in logic examinations of the high-dose group found effects limited
one of the studies. to the application site and included minimal to mild epidermal
hyperplasia and hyperkeratosis with reactive hyperplasia of the
Inhalation underlying inguinal lymph nodes.
Polybutene. Polybutene produced no abnormalities in rats The oral and dermal repeated dose toxicity data that were
during a 4-hour inhalation exposure up to concentrations of presented in the original reviews of Polybutene and Polyethy-
18.5 mg/L.3 lene are summarized below and not in the tables.
Burnett et al 73S
Table 7. Acute Toxicity Studies in Animals.
Ingredient and concentration/

dose Method Results/conclusions References
Oral
11
Ethylene/Octene Copolymer Acute oral toxicity study in rats LD50 > 5,000 mg/kg
(14%-16%) in a trade name (no further details provided)
mixture
12
Ethylene/Octene Copolymer Acute oral toxicity study in rats LD50 >2,000 mg/kg
and sodium acrylate (no further details provided)
copolymer (30%-50%) in a
trade name mixture
6
Polybutene analog Acute oral toxicity study in rats LD50 > 2,000 mg/kg, no mortalities observed
diisobutylene (no further details provided
6
Polybutene analog Acute oral toxicity study in rats LD50 >2,000 mg/kg, no mortalities observed
triisobutylene (no further details provided)
6
Polybutene analog di-n-butene Acute oral toxicity study in rats LD50 >10,000 mg/kg, 1 animal had partial thickening of the
(no further details provided) forestomach and another had partial hyperemia of the
small intestine membrane, no mortalities observed
6
Polybutene analog tributene Acute oral toxicity study in rats LD50 > 10,000 mg/kg, no mortalities observed
(no further details provided)
6
Polybutene analog tetrabutene Acute oral toxicity study in rats LD50 > 10,000 mg/kg, no mortalities observed
(containing 30% (no further details provided)
pentabutene)
37,38
Polyisobutene (100%), MW Acute oral toxicity study in rats LD50 > 15,400 mg/kg
range 654-2168 (no further details provided)
39-42
Hydrogenated Polyisobutene Acute oral toxicity study in rats LD50 > 5,000mg/kg
(100%), MW range 187-468 (no further details provided)
5
Hydrogenated Polydecene Acute oral toxicity study in LD50 > 5,000 mg/kg
(undiluted), average MW not Sprague-Dawley rats (5 rats/sex)
specified
43
Hydrogenated Acute oral toxicity study in rats LD50 > 5,000 mg/kg
Polydecene(100%), MW (no further details provided)
range 367-596
5
Hydrogenated Polydodecene Acute oral toxicity study in LD50 > 5,000 mg/kg
(undiluted), average MW not Sprague-Dawley rats (5 rats/sex)
specified
Dermal
11
Ethylene/Octene Copolymer Acute dermal toxicity study in Estimated LD50 > 5,000 mg/kg
(14%-16%) in a trade name rabbits (no further details
mixture provided)
12
Ethylene/Octene Copolymer Acute dermal toxicity study in Estimated LD50 > 2,000 mg/kg
and sodium acrylate rabbits (no further details
copolymer (30%-50%) in a provided)
trade name mixture
6
Polybutene analog Acute dermal toxicity study in rats; LD50 > 2,000 mg/kg; no mortalities or overt signs of
diisobutylene exposure under occlusive patches toxicity were observed
for 24 hours (no further details
provided)
37,38
Polyisobutene (100%); MW Acute dermal toxicity study in LD50 > 25,000 mg/kg
range 654-2168 rabbits (no further details
provided)
39-42
Hydrogenated Polyisobutene Acute dermal toxicity study in LD50 > 2,000 mg/kg
(100%); MW range 187-468 rabbits (no further details
provided)
5
Hydrogenated Polydecene Acute dermal toxicity study in New Estimated LD50 > 3,000 mg/kg; skin reactions observed at
analog hydrogenated decene Zealand White rabbits (2 rabbits/ 24 hours post-patch removal included pale red
dimer (undiluted); dose sex); material applied to clipped erythema and slight to mild edema; by day 14, only slight
tested ¼ 3,000 mg/kg edema and desquamation were observed; 1 female
(continued)
Ingredient and concentration/

dose Method Results/conclusions References
skin on the back for 24 hours; rabbit that died on day 9 of the observation period was
occluded and rinsed observed to be emaciated prior to death; no other
clinical, behavioral, or systemic signs of toxicity were
observed; no treatment-related signs of toxicity were
observed at necropsy
5
Hydrogenated Polydodecene Acute dermal toxicity study in LD50 > 2,000 mg/kg; no clinical signs of toxicity or skin
(undiluted); concentration Sprague-Dawley rats (5 rats/sex); irritation were observed; bw appeared unaffected by
tested ¼ 2,000 mg/kg; material applied to an area of treatment and there were no treatment-related signs of
average MW not specified 37 cm2 clipped skin for 24 hours; toxicity observed at necropsy
occluded and rinsed
Inhalation
6
Polybutene analog 4-hour, single, whole-body inhalation LC50 4,185 ppm (19,171 mg/m3), no mortalities or overt
diisobutylene toxicity study in albino rats signs of toxicity were observed
(no further details provided)
39-42
Hydrogenated Polyisobutene 4-hour inhalation study in rats LC50 > 5 mg/L
(100%), MW range 187-468 (no further details provided)
5
Hydrogenated Polydecene, 4-hour, nose-only inhalation toxicity LC50 > 5.2 mg/L, no mortalities were observed, no
average MW not specified study in Sprague-Dawley-derived significant clinical signs were observed during and after
rats (6 rats/sex) the exposure period, and no treatment-related signs of
toxicity were observed at necropsy
5
Hydrogenated Polydecene 4-hour inhalation (aerosol/vapor) Combined LC50 ¼ 1.17 mg/L; all animals treated with 5.1
analog hydrogenated decene toxicity study in groups mg/L died within 2 days, 2-5 females each from all the
dimer, concentrations tested Sprague-Dawley rats (5 rats/sex) remaining treatment groups died, no males in the 0.77
¼ 0.77, 0.94, 1.1, 1.4, or 5.1 or 0.94 dose groups died but 2 males each in the
mg/L remaining dose groups died; clinical signs included
dyspnea and nasal discharge; bw gain was reduced in the
first week, but within normal parameters the second
week; treatment-related effects of the lung were
observed during gross necropsy of only the animals that
died during the study; microscopic lesions in the lung
were observed in all of the high-dose animals
5
Hydrogenated Polydecene Acute whole-body 1-hour inhalation LC50 not determined; 9/10 treated animals died within 3
analog hydrogenated decene toxicity study in Sprague-Dawley days; clinical signs included reduced activity, increased
dimer, concentration tested rats (5 rats/sex) respiration rate, respiratory sounds, labored breathing,
¼ 5 mg/L irregular breathing, muzzle and abdominal staining,
partially closed eyes, hunched back, and lying on the side;
in the one female that survived treatment, all respiratory
signs were normal by day 5, but muzzle staining
persisted until day 9 and marked loss in bw was
observed through day 4; at necropsy, the surviving
female had absolute and relative lung and trachea
weights greater than the controls and the heart
appeared to be affected (no further details); in the
animals that died following treatment, treatment-related
increases in respiratory findings were observed (no
further details)
5
Hydrogenated Polydodecene, 4-hour, nose-only inhalation toxicity LC50 > 5.06 mg/L; clinical signs observed after removal
average MW not specified study in Sprague-Dawley rats (5 from the exposure chamber included wet fur, hunched
rats/sex) posture, piloerection, increased respiration rate, ptosis,
and isolated incidents of decreased respiration rate and
red/brown stain on the head; 1 hour after exposure, the
only observable clinical signs included hunched posture,
piloerection, and increased respiration rate; by day 2
postexposure, all animals had recovered and appeared
to be normal; no treatment-related changes observed in
bw; no treatment-related signs of toxicity observed at
necropsy.
Burnett et al 75S
Table 8. Repeated Dose Toxicity Studies in Animals.
Ingredient and
concentration/dose Method Results/conclusions References
Oral
37,38
Polyisobutene (100%); 2-year dietary toxicity study in After 12 months, no treatment-related gross or microscopic
concentrations tested ¼ 0; Charles River rats changes were observed; following 24 months, no treatment-
800; 4,000; or 20,000 ppm; (no further details provided) related effects on bws, feed consumption, mortality, clinical
MW range 654-2,168 observations, hematology, or urinalysis were observed; in the
high dose group, 3 of 6 males that died between weeks 17 and
24 exhibited hematuria while another male in this dose group
exhibited similar reactions but recovered within 2 weeks;
necropsy of the 3 rats found that 2 of the rats had clotted
blood in the urinary tract, bladder, stomach, and intestines
while the third rat had no significant gross pathologic changes;
no increases in frequency of neoplastic lesions were observed
in any dose group
37,38
Polyisobutene (100%); doses 2-year oral toxicity study in No treatment-related effects on bw, feed consumption,
tested ¼ 0, 40, 200, or 1,000 Beagle dogs (no further mortality, clinical signs, hematology, blood chemistry,
mg/kg; MW range 654-2168 details provided) urinalysis, liver function, organ weights, or gross pathologic
and histopathologic changes ( no further details provided)
39-42
Hydrogenated Polyisobutene 90-day dietary toxicity study in No effects were observed on bw, bw gain, urinalysis, hematology,
(0% or 5%); MW range rats; half of the animal or clinical chemistry parameters; when compared to controls,
187-468 groups were killed at 90 liver weights were increased in both males and females and
days, and the other half kidney weights were increased in males; no organ weight
were killed 30 days later differences between treated and control animals were
following a recovery period observed following the recovery period; no treatment-related
( no further details histopathologic changes were observed (no further details
provided) provided)
5
Hydrogenated Polydecene; 4-week dietary toxicity study No observed adverse effect level (NOAEL) ¼ 6,245 mg/kg/d in
concentrations tested ¼ 0; in F-344 rats (5 sex/dose) males and 6,771 mg/kg/d in females; no clinical signs of toxicity
8,000; 20,000; or 50,000 or mortality were observed in any rats during the study;
ppm (equivalent overall overall bw gain and feed consumption of females in the 50,000
mean daily intakes were ppm dose group was higher than the controls; a dose-
1,039; 2,538; or 6,245 mg/ dependent decrease in mandibular lymph node weights
kg/d for males and 995; (absolute and relative to bw) was observed in males and
2,481; or 6,771 mg/kg/d for females but these results were statistically significant only for
females); average MW not 50,000 pm females and were not considered adverse effects
specified since there were no other findings; gross necropsy,
histopathology, and microscopic findings did not reveal any
significant treatment-related findings
43
Hydrogenated Polydecene 90-day oral toxicity study in No observed effect level (NOEL) ¼ 1,000 mg/kg/d
(100%); doses up to 1,000 rats (no further details
mg/kg/d; MW range 367-596 provided)
5
Hydrogenated Polydecene in 90-day oral toxicity study, NOAEL ¼ 1,000 mg/kg/d; toxicity of the test material was
Polyethylene glycol via groups of 20 male and 20 examined in F1 generation rats following reproduction study;
gavage at dose levels of 0, female Sprague-Dawley rats F1 generation rats of each dose group, including the vehicle
100, 500, or 1,000 mg/kg/ received test material via control, had minor gastrointestinal effects; transient changes in
bw/d for 91 days (average gavage. bw, bw gain, feed consumption, hematology, and organ weights
molecular weight not were observed but not considered to be treatment-related; a
specified significant increase in prothrombin time was observed in males
of the 1,000 mg/kg/d dose group but no corresponding
decreases in platelets or macroscopic or microscopic changes
were observed so this result was not considered biologically
significant; no treatment-related changes in clinical chemistry,
mortality, or ophthalmology were observed (no further details
provided)
5
Hydrogenated Polydecene; 90-day oral toxicity study of F- NOAEL ¼ 50,000 ppm (4,159.4 mg/kg/d in males and 4,619.9 mg/
concentrations tested ¼ 0, 344 rats (10 rats/sex/dose); kg/d in females); clinical signs of toxicity observed in the 50,000
1,000; 7,000; or 50,000 ppm an additional 5 rats/sex were ppm group included oily and ungroomed coats, soft feces, and
(continued)
Ingredient and
concentration/dose Method Results/conclusions References
(equivalent to 77.5, 553.7, administered control feed brown staining; hair loss occurred at a greater incidence in
and 4,159.4 mg/kg/d, or 50,000 ppm in their diet treated animals when compared to controls; oily coats
respectively, in males and for 13 weeks and left continued through the first week of the recovery period,
85.5, 611.5, and 4,619.9 mg/ untreated for the following particularly in females receiving 50,000 ppm; during recovery
kg/d, respectively, in 4 weeks to examine weeks 2-4, rats appeared ungroomed and exhibited hair loss;
females); average MW was recovery soft feces occasionally observed in the 7,000 ppm females;
not specified slight increase in feed consumption in the high-dose group
compared to controls (8% in males and 10% in females) that
continued through the recovery period but there was no effect
observed on either bw or feed efficiency; slight (<5%) but
significant increases in erythrocyte counts, hemoglobin, and
packed cell volume in males of the 7,000 and 50,000 ppm
groups with dose-related increase in hemoglobin was not
observed at the end of the recovery period; slight (6%) but
significant increase in platelet counts in high-dose males and
females was not observed at the end of the recovery period;
absolute and relative liver weights in treated males were
slightly lower but the liver weights were comparable to
controls at the end of the recovery period; no treatment-
related effects noted in the bone marrow, clinical chemistry,
urinalysis, gross pathology, or histopathology
5
Hydrogenated dodecene 28-day repeated dose oral NOAEL was determined to be 1,000 mg/kg/d; treatment-related
trimer (analog of toxicity study in Sprague- effects in mortality, clinical signs, bw, feed consumption,
Hydrogenated Dawley CD rats (5 rats/sex/ hematology, clinical chemistry, organ weights, or gross and
Polydodecene); doses dose: an additional 2 satellite histologic pathology were not observed
tested ¼ 0 or 1,000 mg/kg/ groups (0 and 1,000 mg/kg/
bw/d d) were also maintained
without treatment for 14
days following the end of the
dosing period
5
Hydrogenated dodecene 10-week oral gavage repeated NOAEL ¼ 1,000 mg/kg/d; during the dosing period, one rat in the
trimer (analog of dose toxicity study in 3 control group and one rat in the 250 mg/kg/d dose group died
Hydrogenated groups of 10 male and 10 but deaths were not treatment-related; no signs of clinical
Polydodecene) in arachis oil; female Sprague-Dawley toxicity or effects on behavioral and functional performance,
doses tested ¼ 0, 50, 250, or Crl:CD (SD) IGS BR strain sensory reactivity, bw, or feed and water consumption were
1,000 mg/kg/d rats (10 rats/sex/group). observed following treatment with the test material; no
significant treatment-related effects were observed in the
hematological and clinical chemistry assessments or during the
gross pathology examination
Dermal
39-42
Hydrogenated Polyisobutene 4-week dermal toxicity study No mortalities were observed during the study and no
(100%); doses tested ¼ 0, in Sprague-Dawley rats (no statistically significant differences in bws, bw gain, hematology,
0.5, 1.0, or 1.5 mL/kg for 5 further details provided) or clinical chemistry parameters were observed between
days/wk; MW range 187- treated and control animals; relative kidney weights were
468 increased in high-dose males and relative heart weights were
decreased in low-dose males but these changes were not
considered toxicologically significant because the kidney
weight changes were not accompanied with any
histopathologic effects and the heart weight changes were not
decreased in a dose-related manner; minimal to mild dermal
irritation consisting of redness, paleness, scaling, rippling and
pinpoint scabbing of the skin was observed in the majority of
treated animals; histopathologic examinations were performed
on the high-dose and control groups only; effects observed in
the treated animals were limited to the application site and
included minimal to mild epidermal hyperplasia and
hyperkeratosis of the application site with reactive hyperplasia
of the underlying inguinal lymph nodes
Burnett et al 77S
Oral At the end of mating, males were sacrificed. Females were

Polybutene. A 2-year chronic oral toxicity study of Polybu- treated through gestation and until lactation day 21. No
tene (75% concentrate) in Charles River albino rats given up to treatment-related effects were observed on clinical signs, bw,
20,000 ppm Polybutene blended into their regular diets or gross pathology in the parental generation or in the pups
revealed no gross or microscopic pathological changes that through lactation day 21. There were no treatment related
could be correlated with Polybutene ingestion.3 No significant effects on reproduction or pup viability. The NOAELs for
differences were found after 24 months of feeding in the bws or parental systemic effects, parental reproductive effects, and
weight of food consumption, hematological results, urology, or offspring effects in this one generation rat study are each
tumor formation between the animals fed Polybutene and those 1,000 mg/kg/bw/d.
that were not. In the 20,000 ppm group, 3 of 6 males that died
between weeks 17 and 24 exhibited hematuria. In a 2-year Polyisobutene
chronic oral toxicity study of Polybutene (75% concentrate)
in Beagle dogs, daily oral administration of Polybutene at doses In a 3-generation reproductive toxicity study, an unreported
up to 1,000 mg/kg/d caused no abnormalities in bw, food con- number of Charles River rats received 0, 800, or 20,000 ppm
sumption, survival, behavioral patterns, hematology, blood 100% Polyisobutene in their feed (molecular weight range
chemistry, urinalysis, liver function, gross and histopathologic 654-2,168 Da).37,38 No further details about dosing were pro-
examinations, or organ weights and ratios. Average molecular vided. Weight gain was slightly reduced in the second gener-
weights of Polybutene were not specified in these studies. ation high-dose male rats, but the changes were within
normal control ranges. No other effects on bws, clinical
Polyethylene. Toxicity testing in rats showed no adverse signs, organ weights, or histopathology were observed. No
effects to Polyethylene at doses of 7.95 g/kg or at 1.25%, treatment-related reproductive effects were noted in any of the
2.50%, or 5.00% in feed for 90 days.1 The average molecular parameters measured (no furthered details provided). No dif-
weight of Polyethylene was not specified in this study. ferences were observed in offspring survival, litter size, num-
ber of stillborn pups, and number of viable pups in any
Dermal
generation of the treated groups when compared to controls.
Polybutene. Polybutene did not affect hepatic or skin enzy-
No remarkable postmortem findings were reported.
matic activities in rats following once daily treatments for
6 days (average molecular weight not specified).3
Hydrogenated Polydodecene
The reproductive effects of the trimer of Hydrogenated Poly-
Reproductive and Developmental Toxicology dodecene were studied in 1 generation of rats that received the
Polybutene test material via gavage.5 Groups of 24 male and 24 female
Sprague-Dawley rats received 0, 50, 250, or 1,000 mg/kg/d
No teratogenic effects were found when Polybutene was fed to of the test material in arachis oil daily for 20 weeks
rats at 1% or 10% in the diet for 6 months.3 A 3-generation (during maturation, mating, gestation, and lactation). No
reproductive study in Charles River albino rats that ingested up treatment-related effects on offspring growth or development
to 20,000 ppm Polybutene demonstrated that, except for the were observed. Litter sizes were comparable to controls in all
test (F2) male parental animals that were fed 20,000 ppm Poly- dose groups. No adverse effects were observed during gross
butene, none of the animals in successive generations differed necropsy or histopathological examination. The NOAEL for
from controls with regard to weight gains. The F2 male parental reproductive and development toxicity in this rat study is
animals showed slight weight gain depression, although their 1,000 mg/kg/d.
growth patterns were still within the normal range. In all 3 gen-
erations, there were no significant differences between test and
control animals regarding litter size, the number of stillborn, Genotoxicity
and the number of viable pups during lactation. The survival,
bws, and reactions of test animals were comparable to those of In Vitro
controls. Average molecular weights were not specified in Ethylene/Octene Copolymer. A trade name mixture containing
these studies. 30% to 50% Ethylene/Octene Copolymer and sodium acrylate
copolymer was not mutagenic in an Ames test or in an in vitro
Hydrogenated Polydecene chromosomal aberration test (no further details provided).12
The reproductive effects of Hydrogenated Polydecene were Polyethylene. Genotoxicity testing of Polyethylene was negative
studied in rats that received the test material via gavage (aver- in 2 bacterial studies.1 Average molecular weights were not
age molecular weight not specified).5 Groups of 30 male and 30 specified in these studies.
female Sprague-Dawley rats received 0, 100, 500, or 1,000 mg/
kg/bw/d Hydrogenated Polydecene in Polyethylene glycol Polyisobutene. In a study to determine the ability of various
daily for 4 weeks prior to mating and through mating. insulating fluids to induce transformation in the Syrian hamster
embryo cell transformation assay and to enhance frequencies were 122% to 80% for the same concentration
3-methylcholanthrene-induced transformation of C3H/10T1/2 range with metabolic activation. Relative cloning frequencies
cells, a low-viscosity Polyisobutene-based oil did not induce in the first mutation assay were 92% to 77% and 111% to 89%
transformation activity and was slightly cytotoxic.2 In the for concentrations ranging 313 to 5,000 mg/mL with and with-
2-stage transformation assay of C3H/10T1/2 cells, the Polyi- out metabolic activation, respectively. The activated portion of
sobutene oil had promoter activity. Average molecular weights the first mutation assay was repeated and RCE was 100% to
were not specified in these studies. 71% for the same dose range. In the confirmatory assay, the
RCEs among the test material-treated cultures ranged from
Hydrogenated Polydecene. Hydrogenated Polydecene was not 50% to 23% and 89% to 52% for the concentrations of 313
mutagenic in an Ames test at concentrations up to 500 mg/plate to 5,000 mg/mL with and without metabolic activation, respec-
(molecular weight range 367-596 Da; no further details tively. A significant response was observed at 625 mg/mL when
provided).43 compared to the solvent control data in the repeat definitive
Hydrogenated Polydecene (average molecular weight not mutation assay with activation; however, the increase was not
specified) was not mutagenic in a reverse gene mutation assay significant when it was compared to the historical, cumulative
in Salmonella typhimurium strains TA1535, TA1537, TA98, solvent control data. The same was true at 2,500 mg/mL, with
and TA100 and Escherichia coli strain WP2uvrA.5 The test activation, in the confirmatory mutation assay. The increase in
material was incorporated in emulsions with sorbitan stearate the number of mutants was not significant when compared to
and polysorbate 60 at concentrations of 156.25; 312.5; 625; historical, cumulative solvent control data. The response seen
1,250; 2,500; or 5,000 mg/plate, with and without metabolic in the definitive mutation assay at 625 mg/mL was not repro-
activation using the preincubation method. The positive con- duced in the confirmatory assay. Controls were within the his-
trols yielded expected results. torical negative control values. The trimer of Hydrogenated
In reverse mutation assays, S typhimurium strains TA98, Polydodecene was not mutagenic in this mammalian cell gene
TA100, TA1535, and TA1537 were treated with Hydrogenated mutation assay.
Polydecene (average molecular weight not specified) at con-
centrations up to 10 mg/plate.5 The positive controls yielded
Carcinogenicity
expected results. Hydrogenated Polydecene was not mutagenic
with or without S9 metabolic activation at all tested Polyethylene
concentrations.
Numerous investigations on the tumor production of Polyethy-
lene implantation have produced mixed results.1 Polyethylene
Hydrogenated Polydodecene. The genotoxic potential of the tri-
causes tumors in rats implanted with squares of the test sub-
mer of Hydrogenated Polydodecene was assayed in 2chromo-
stance; however, testing involving implanting coverslips and
some aberration experiments using human lymphocyte
powdered Polyethylene suggests that tumors are caused by the
cultures.5 In the first experiment, the concentrations tested
physical reaction to imbedded plastic films and not the Poly-
were 0; 39; 78.1; 156.25; 312.5; 625; 1,250; 2,500; and
ethylene itself. International Agency for Research on Cancer
5,000 mg/mL. In the second experiment, the concentrations
lists Polyethylene as “not classifiable as to carcinogenicity in
tested were 625, 1,250, 2,500, and 5,000mg/ml for 20 h or
humans” based on no adequate human data and inadequate
1,250, 2,500, and 5,000 mg/mL for a 44-hour harvest time. All
animal data. Average molecular weights were not specified.
experiments were conducted in duplicate, with and without S9
metabolic activation. Cytotoxicity was not observed in a range
finding test conducted prior to the main assay at concentrations Polyisobutene
5,000 mg/mL. The test material did not induce chromosomal In a carcinogenicity study conducted to determine the skin
aberrations or polyploidy cells, with or without metabolic acti- tumorigenicity effects of certain oils used for impregnation
vation. Positive controls, ethyl methane sulfonate in the of paper-insulated power cables and their synthetic alterna-
absence of S9, and cyclophosphamide in the presence of S9, tives, including Polyisobutene oil, no evidence of a direct
yielded expected results. The authors concluded that the trimer tumorigenic or carcinogenic effect was reported and Polyiso-
of Hydrogenated Polydodecene was not clastogenic to butene oil (average molecular weight 250 Da) appeared to
human lymphocytes in vitro when tested at concentrations reduce the number of 7,12-dimethylbenz[a]anthracene-induced
5,000 mg/mL. tumors in mice.2
In a mammalian cell gene mutation assay (HGPRT locus), Polyisobutene (100%) was not carcinogenic in rats (dosed up
Chinese hamster ovary (CHO) cells cultured in vitro were to 20,000 ppm) or dogs (dosed up to 1,000 mg/kg) in oral studies
exposed to the trimer of Hydrogenated Polydodecene in etha- described in Table 9 (molecular weight range 654-2,168 Da).37,38
nol at concentrations of 0; 313; 625; 1,250; 2,500; or 5,000 mg/
mL with and without metabolic activation for 4 hours.5 In the
range-finding test, relative cloning frequencies (RCEs) ranged
Polypropylene
from 97% to 73% for concentrations ranging from 0.5 to 5,000 International Agency for Research on Cancer determined that
mg/mL without metabolic activation. Relative cloning Polypropylene is not classifiable as to its carcinogenicity to
Burnett et al 79S
humans (group 3) based on no adequate human data and Hydrogenated Polyisobutene. A skin irritation study in 6 rab-
inadequate animal data.44 bits using four patches each containing 0.5 g/patch of a Hydro-
genated Polyisobutene mixture caused no reactions in any of
the animals on intact or abraded skin.2 The primary irritation
Irritation and Sensitization index was 0.0. There was a primary irritation index score of 1.8
Irritation for rabbits treated with undiluted Hydrogenated Polyisobutene
on the intact or abraded skin. Rabbits dosed dermally with
Nonhuman and human dermal irritation studies are presented in 0.5 mL Hydrogenated Polyisobutene) on intact and abraded
Table 9, and nonhuman ocular irritation studies are presented in skin exhibited a primary irritation index of 0.38; not a dermal
Table 10.5,12,37-43,45,46 Ethylene/octene copolymer and sodium irritant. In a similar study, Hydrogenated Polyisobutene
acrylate copolymer (30%-50% in a trade name mixture was produced a primary irritation index of 0.96; also not a dermal
minimally/slightly irritating to rabbit skin. Polyisobutene and irritant. Average molecular weights were not specified in these
Hydrogenated Polyisobutene at 100% were not irritating to studies.
rabbit skin in respective irritation studies. Hydrogenated Poly- In humans, no primary skin irritation was produced in a
decene and the trimer of hydrogenated decene were not pri- 72-hour primary skin irritation patch test study with 100%
mary irritants or corrosives in several rabbit studies. No Hydrogenated Polyisobutene in 25 male and female partici-
significant irritation was observed in human subjects in a pants.2 There was no irritancy observed in humans during a
cumulative irritation test of Ethylene/Octene Copolymer and 24-hour single-insult patch test with a lip gloss containing
sodium acrylate copolymer (30%-50%) in a trade name mix- 66.11% Hydrogenated Polyisobutene. Average molecular
ture. No adverse effects were reported in human subjects fol- weights were not specified in these studies.
lowing irritation studies of a formulation containing 8%
Hydrogenated Polyisobutene and Hydrogenated Polyisobutene
at 100%. No adverse effects were reported following dermal Ocular
exposure to formulations containing Hydrogenated Polydecene Polybutene. Rabbits suffered only minimal eye irritation
with equal amounts of cetyl ethylhexanoate and pentaerythrityl when Polybutene at concentrations up to 75% was instilled into
tetraethylhexanoate tested at total concentrations up to 35% in the eyes with and withoutwashouts. 3 Average molecular
a study in human subjects. weights were not specified.
Ethylene/octene copolymer and sodium acrylate copolymer Polyethylene. Polyethylene (molecular weight of 450 Da) was
(30%-50% in a trade name mixture) was minimally/slightly tested as a solid material (66 mg) in the eyes of rabbits.1 The
irritating to rabbit eyes. Polyisobutene and Hydrogenated Poly- test substance caused a maximum group mean score of 11.0 and
isobutene at 100% were not irritating to rabbit eyes in respec- was classified as a mild irritant. All treated eyes appeared
tive irritation studies. Two primary eye irritation studies in normal 48 hours after application. The same procedure, with
rabbits found undiluted Hydrogenated Polydecene not to be 55 mg of Polyethylene of average molecular weight of 655, was
an ocular irritant, while another study found the material to carried out on white rabbits. The mean maximum group score
be moderately irritating. produced by Polyethylene was 11.7, and it was classified as a
The dermal, ocular, and mucous membrane irritation data mild irritant. All treated eyes appeared normal 72 hours after
that were presented in the original reviews of Polybutene, Poly- treatment. When white rabbits were tested with 13% Polyethy-
ethylene, Polyisobutene, and Hydrogenated Polyisobutene are lene beads, the maximum ocular score was 8/110 with resolu-
summarized below and not in the tables. tion after 48 hours, and no corneal abrasions were observed.
Dermal Polyisobutene. Irritant and corrosive effects were examined
Polybutene. In primary skin irritation studies, Polybutene in following a single instillation of Polyisobutene into rabbit
formulations including lipsticks produced no abnormalities or eyes.2 No corneal or iridial damage was recorded in the study.
irritation in rabbits at concentrations up to 15%; however, mild One eye had irritation to the conjunctivae by 72 hours, which
irritation was observed at concentrations greater than 15%.3 was present as slight hyperemia. The average molecular weight
Average molecular weights were not specified. Human primary was not specified.
irritation tests of a lipstick formulation containing 20% Poly-
Hydrogenated Polyisobutene. When 0.1-mL Hydrogenated
butene produced no irritation. The average molecular weight
Polyisobutene was instilled into the conjunctival sac of rabbit
was not specified.
eyes, the test material caused slight conjunctival irritation in
Polyethylene. Dermal irritation studies on rabbits in which 33% of eyes which cleared up by day 2.2 The authors deter-
0.5 g of Polyethylene (average molecular weight of 450 Da) mined that Hydrogenated Polyisobutene is not an eye irritant.
was administered in 0.5 mL of water caused no irritation or Another study of Hydrogenated Polyisobutene under similar
corrosive effects.1 When the same procedure was used to test test conditions produced the same results. No signs of ocular
Polyethylene with an average molecular weight of 655 Da, a irritation were observed in a Draize study of 3 rabbits exposed
primary irritation index score of 0.2 was found and Polyethy- to a facial lotion containing 3% Hydrogenated Polyisobutene.
lene was classified as a mild irritant. In a 7-day eye irritation study on rabbits, no eye irritation was
80S
Table 9. Dermal Irritation Studies.
Test article Concentration/Dose Test population Procedure Results Reference
Nonhuman
12
Ethylene/Octene Copolymer and Concentration/dose Rabbit skin Details not provided Minimally/slightly irritating
sodium acrylate copolymer (30%- not reported
50%) in a trade name mixture
37,38
Polyisobutene; MW range 654-2,168 100% Rabbit skin Details not provided Nonirritating
39-42
Hydrogenated Polyisobutene; MW 100% Rabbit skin Details not provided Nonirritating
range 187-468
43
Hydrogenated Polydecene; MW range 0.5 mL of 100% Rabbits Modified Draize primary skin Nonirritating, primary irritation index 3.1
367-596 irritation test (no further
details provided)
5
Hydrogenated Polydecene; average 0.5 mL, 6 New Zealand - Primary skin irritation study - At 24 hours, slight erythema was observed in 4 of the
MW not specified concentration not White rabbits on clipped or abraded skin abraded sites and 5 of the intact sites, slight edema
reported - Test sites occluded was observed on 3 of the abraded sites, edema was
- Remaining test material was observed at an abraded site at the end of
washed off at 24 hours treatment, all effects had reversed 2 days
- Animals were observed for postexposure
skin reactions at 24 and 72 - After 72 hours, the mean erythema score was 0.42
hours for both the intact and abraded skin, the mean
edema score after 72 hours was 0.17 for intact skin
and 0.08 for abraded skin
- Based on these results, the study authors calculated a
primary dermal irritation index of 0.5
- Not a primary irritant or corrosive
5
Hydrogenated Polydecene, average 0.5 mL, 6 female New - Primary skin irritation study - Over 72 hours, the mean erythema score for intact
MW not specified concentration not Zealand White on clipped or abraded skin skin was 0.75, mean erythema score for abraded
reported rabbits - Test sites occluded skin was 0.67
- Remaining test material was - The mean edema score for intact and abraded skin
washed off at 24 hours over 72 hours was 0.25 and 0.08, respectively
- Animals were observed for - All rabbits had very slight to well-defined erythema
skin reactions at 24 and 72 on both intact and abraded sites and slight edema
hours on 3 intact and 1 abraded site at the end of
treatment
- No difference in severity between intact and abraded
sites
- 2 days after treatment, only 1 abraded site still had
evidence of slight erythema
- The primary dermal irritation index was calculated to
be 0.9
- Not a primary irritant or corrosive
(continued)

5
Hydrogenated decene trimer 0.5 mL of undiluted Groups of 3 New - Draize study - No treatment-related changes in bw observed
test material Zealand White - Test area was 2.5 cm2 and - Very slight erythema and edema observed in 1 rabbit
rabbits semioccluded for up to 4 through 72 hours
hours - At 72 hours, the skin lost its elasticity and flexibility
- Animals observed for 7 days. - At 7 days, slight desquamation observed
- No effects observed in the other 2 rabbits
- Mild irritant according to Draize system but
nonirritating according to EU classification system
Human
12
Ethylene/Octene Copolymer and Details not provided Details not Cumulative irritation test (no No significant irritation
sodium acrylate copolymer (30%- provided further details provided)
37,38
Polyisobutene; MW range 654-2,168 100% Details not Human skin patch test (no Nonirritating
provided further details provided)
46
Hydrogenated Polyisobutene in 8% 10 female subjects Single application to the skin No adverse effects were reported
formulation, average MW not (no further details
specified provided)
39-42
Hydrogenated Polyisobutene; MW 100% Details not Human skin patch test (no Nonirritating
range 187-468 provided further details provided)
45
Hydrogenated Polydecene with equal Total concentrations 98 subjects A study of formulations with No adverse effects
amounts of cetyl ethylhexanoate and up to 35% in differing ratios of polyols
pentaerythrityl tetraethyl hexanoate; combined product and oils on the skin
average MW not specified.
EU ¼ European Union.
81S
82S
Table 10. Ocular Irritation Studies.
Ocular—Nonhuman
12
Ethylene/Octene Copolymer and Details not provided Rabbits Details not provided Minimally/slightly irritating
sodium acrylate copolymer (30%-
37,38
Polyisobutene; MW range 654-2,168 100% Rabbits Details not provided Nonirritating
39-42
Hydrogenated Polyisobutene; MW 100% Rabbits Details not provided Nonirritating
range 187-468
43
Hydrogenated Polydecene: MW range 0.1 mL of 100% test Rabbits Modified Draize primary eye irritation Nonirritating (irritation score 0 to 6 out
367-596 material test (no further details provided) of 110 in individual rabbits)
5
Hydrogenated Polydecene; average 0.1 mL of undiluted test New Zealand - Test material instilled into the - No corneal lesions or iris changes
MW not specified material White conjunctival sac of the right eye of - Conjunctival changes included mild
rabbits, 3/sex each animal erythema in 5 of the 6 rabbits that
- Eyes not rinsed. were still present in 3 of the rabbits at
- Animals then observed for 72 hours. 72 h and swelling occurred in 3 of the
rabbits
- None of the rabbits had any discharge
- Individual total scores over the 3 time
points for all changes observed ranged
from 0 to 4 of a possible score of 110
- Nonirritating
5
Hydrogenated Polydecene; average 0.1 mL, concentration not 9 male New - Test material instilled into the - None of the rabbits exhibited corneal
MW not specified reported Zealand conjunctival sac of one eye while the lesions or iris changes
White rabbits other eye served as control - In unrinsed eyes, moderate to severe
- Eyes were examined for ocular irritancy conjunctival redness with oily residue
at 1, 24, 48, and 72 hours was noted at 1 hours, but by 24 hours,
posttreatment there was only slight redness and the
- Both eyes of 3 of 9 treated rabbits were eye was clear by 48 hours
rinsed with distilled water and the - In rinsed eyes, there was no to slight
rinsed eyes were examined for ocular conjunctival redness 1 hours after
irritancy at 1, 24, 48, and 72 hours treatment with oily residue around
the eye; the eyes were clear by 24
hours
- Moderately irritating
Burnett et al 83S
observed in washed or unwashed eyes following treatment with after most inoculations, but no sensitization reactions were
0.1-mL Hydrogenated Polyisobutene. An unknown concentra- observed. Hydrogenated Polyisobutene injections (5%) in gui-
tion of Hydrogenated Polyisobutene instilled into the right eyes nea pigs using a maximization procedure resulted in no
of 6 rabbits produced a score of 1 on the Draize scale. No other observed reactions and an irritation index of 0.0 in both chal-
effects were observed. Average molecular weights were not lenge phases I and II. Average molecular weights were not
specified in these studies. specified in these studies.
In human, no adverse reactions or ocular irritation were Repeat-insult patch tests performed to evaluate the primary
reported in 59 subjects in a 29-day in-use study of 3different irritancy/sensitization potential of formulations containing
formulations of cosmetic foundations/concealer products that 1.44% or 4% Hydrogenated Polyisobutene in 54 male and
contained Hydrogenated Polyisobutene.2 The concentration of female subjects found no reactions greater than slight
Hydrogenated Polyisobutene was not specified in 2 of the 3 erythema. 2 In a modified repeat-insult patch test under
formulations, while the third contained 4% Hydrogenated double-blind conditions, no irritation or sensitization was
Polyisobutene. Average molecular weights were not specified. found in human skin patched with a makeup remover contain-
ing 51% Hydrogenated Polyisobutene. Hydrogenated Polyiso-
Mucous Membrane butene at up to 100% was not sensitizing in a Draize repeat
Polybutene. Undiluted Polybutene produced no irritation or insult patch in 200 subjects. Average molecular weights were
signs of systemic toxicity when applied to the vaginas of rab- not specified.
bits.3 Average molecular weight was not specified.
Phototoxicity
Sensitization Polybutene. Photo patch tests of formulations with concentra-
Nonhuman and human sensitization studies are presented in tions ranging from 15% to 50% Polybutene produced no reac-
Table 11.5,11,12,43,47 Tradename mixtures containing Ethy- tions.3 Average molecular weights were not specified.
lene/Octene Copolymer were not sensitizing in a guinea pig
maximization test (at 14%-16%) or in a local lymph node assay Hydrogenated Polyisobutene. The phototoxic potential of cos-
(LLNA; at 30%-50%). Hydrogenated Polydecene was not a metic foundations/concealer products containing 4% Hydroge-
dermal sensitizer in guinea pig maximization tests at concen- nated Polyisobutene or 1.44% Hydrogenated Polyisobutene,
trations up to 100%. The dimer of hydrogenated decene was not and a blank patch under long-wavelength UV light source
a dermal sensitizer in guinea pig maximization studies at 5%. (320-400 nm) was studied in 26 fair-skinned volunteers.2 No
The trimer of hydrogenated decene in propylene glycol was a significant reactions were reported. Formulations containing
slight sensitizer according to an LLNA. The stimulation indices 1.44% or 4% Hydrogenated Polyisobutene were evaluated to
were 1.56, 1.89, and 3.54 for the test concentrations of 25%, determine their potential to induce a photoallergic reaction in
50%, and 100%, respectively. Ethylene/octene copolymer was the skin of 30 subjects. No response was reported at induction,
not a sensitizer in a human repeat insult patch test (HRIPT). rest, or challenge. Average molecular weights were not
A lip gloss containing 12.33% Polyisoprene was not a sensiti- specified.
zer according to the results of an HRIPT.
The sensitization data that were presented in the original Comedogenicity
reviews of Polybutene, Polyethylene, and Hydrogenated Poly-
Polyisobutene. The comedogenic potential of Polyisobutene was
isobutene are summarized below and not in the tables.
studied using adult New Zealand White rabbits.2 The test mate-
Polybutene. Repeated insult patch tests of 3.1% to 50% Poly- rial was applied to the right ear of each animal daily on 5
butene in formulations produced no sensitization.3 Average consecutive days per week for 3 weeks. There were no signs
molecular weights were not specified. of hyperkeratosis or comedone formation during weeks 1 and 2.
By the third week, 2 treated ears exhibited signs of hyperker-
Polyethylene. Polyethylene (average molecular weight of atosis. The ear of the third rabbit, however, remained clear.
450 Da) did not cause dermal sensitization in guinea pigs tested Histological examination showed no signs of follicular hyper-
with 50% Polyethylene (wt/wt) in arachis oil BP.1 In a repeat keratosis on the treated, untreated, or control ears of any rab-
insult patch test of 201 volunteers, a product containing 13% bits. The average molecular weight of Polyisobutene was not
Polyethylene beads was tested in a series of 9 consecutive specified.
administrations. There was no irritation observed with any of
the induction patches. Challenge patches produced only a slight
response in 1 subject, and the investigators concluded that Clinical Studies
Polyethylene has a low irritation and sensitization potential. Polyethylene
Hydrogenated Polyisobutene. Hydrogenated Polyisobutene was There have only been a few cases of reactions to the implanta-
intradermally injected in an area of the skin on the back and tion of Polyethylene in humans.1 In the 3 published accounts,
flanks of guinea pigs.2 Erythema and edema were observed Polyethylene strips used for breast augmentation caused
Table 11. Sensitization Studies.
84S
Test article Concentration/dose Test population Procedure Results Reference
Nonhuman
11
Ethylene/Octene Copolymer Details not provided Guinea pigs Gguinea pig maximization and Buehler Not sensitizing
(14%-16%) in a trade name assays (no further details provided)
mixture
12
Ethylene/Octene Copolymer Details not provided Mice Local lymph node assay (LLNA; no further Not sensitizing
and sodium acrylate details provided)
copolymer (30%-50%) in a
trade name mixture
43
Hydrogenated Polydecene; Intradermal induction dose Guinea pigs Magnusson and Kligman skin sensitization Not sensitizing
MW range 367-596 was 5%; topical induction test (no further details provided)
and challenge doses were
10%
5
Hydrogenated Polydecene: Concentrations up to 10% v/v Hartley guinea pigs, - Guinea pig maximization test - One female in the test group exhibited
average MW not specified 10 male and 10 - Test material administered intradermally abnormal gait, flaccid body tone and
females at 5.0% vol/vol in mineral oil tremors on day 9 of the study and was
- One week after the intradermal found dead on day 10 of the study, but
induction, treatment groups were the death was not considered
induced by topical application of the treatment-related
10% vol/vol test material in mineral oil - No signs of skin irritation, edema, or
for 48 hours erythema were observed in any of the
- 14 days following topical induction, all remaining male or female treatment or
animals received a 10% vol/vol test vehicle control group animals
material in mineral oil challenge throughout the study period
application at naive sites - No other signs of clinical toxicity were
noticed following administration of the
test material.
- Animals that received the positive control
experienced expected results
- bws were comparable to vehicle controls
through the study period
- Not sensitizing
5
Hydrogenated Polydecene in Concentrations up to 100% 20 Dunkin-Hartley - Maximization study - During challenge, 2 test group animals
corn oil; average MW not guinea pigs - 6 intradermal injections of the test exhibited positive responses (details
specified. material (2 injections at 50% aqueous not provided) to the test material
Freund’s Complete Adjuvant, 2 - No positive responses were observed in
injections of 100% test material, and 2 the control animals
injections of 100% test material in 25% - A rechallenge was conducted using 50%
aqueous Freund’s Complete Adjuvant) and 100% Hydrogenated Polydecene
- Control group animals were treated with and a positive response was observed in
6 intradermal injections (2 injections of one animal exposed to 100%
50% aqueous Freund’s Complete Hydrogenated Polydecene
Adjuvant, 2 injections vehicle, and 2 - Not sensitizing
(continued)
injections of the vehicle in 25% aqueous

Freund’s Complete Adjuvant)
- On test day 6, no irritation was observed
so the test sites were treated with 0.5
mL of 10% sodium lauryl sulfate
- On test day 7, each test group animal was
treated with a topical application of the
test material for 48 hours
- Control group received vehicle only
- On test day 20, animals were challenged
with 100% test material via topical
application
5
Hydrogenated Polydecene; Details not provided 10 male Hartley - Animals were patched with Webril pads - 8 of the 10 animals in the treated group
average MW not specified guinea pigs containing 0.5-mL test material on the had slight erythema and edema
midline of the back - All animals in the positive control group
- A positive control group was patched also exhibited slight erythema and
with DNCB edema
- A challenge dose of 0.5 mL of the test - Not sensitizing
material and the positive control was
administered 2 weeks after the final
sensitization dose.
5
Hydrogenated decene dimer Induction and challenge 10 male and 10 - Delayed contact hypersensitivity study - The primary challenge resulted in a grade
(an analog of concentration s ¼ 5% wt/ female Hartley - Animals induced 3 times weekly with 1 response, which was of less incidence
Hydrogenated vol in spectrum oil guinea pigs occlusive 6-hour exposures for 3 weeks and severity than the naı̈ve control
Polydecene) - Following a 2-week rest period, the test group.
animals and a naive control group were - Not sensitizing
challenged
- Animals were scored for skin reactions at
24 and 48 hours following the challenge
phase
5
Hydrogenated decene, dimer Intradermally induced with 5% 10 male and 10 - Magnusson-Kligman maximization test - No signs of skin irritation, edema, or
test material in mineral oil; female Hartley protocol erythema were observed in any of
topically challenged with guinea pigs - A negative control group was induced treated animals or vehicle control
10% test material with vehicle alone and a positive control group animals throughout the study
group received DNCB. period
- No other signs of clinical toxicity were
observed
- Individual and group mean bws were
comparable to vehicle controls through
the study period
- Not sensitizing.
(continued)
85S
86S
5
Hydrogenated decene trimer 25%, 50%, and 100% Mice LLNA (No further details provided) - Stimulation indices were 1.56, 1.89, and
in propylene glycol 3.54 for the test concentrations of 25%,
50%, and 100%, respectively
- EC3values were not provided
- Slight sensitizer
Human
12
Ethylene/Octene Copolymer Details not provided Details not HRIPT; no further details provided No irritation or sensitization observed
in a trade name mixture provided
47
Polyisoprene 12.33% in a lip gloss 103 subjects - HRIPT No irritation or sensitization observed
- 0.2 g test material applied to upper back
with a 1 in 2 pad and semioccluded for
24 hours
- Total of 9 induction patches
- After 2-week rest, challenge patch applied
to naive site for 24 hours and sites were
scored 24 and 72 hours postapplication
LLNA ¼ local lymph node assay.

Burnett et al 87S
increased histological activity around the implant. There have Acute dermal studies of diisobutylene and Hydrogenated
also been occupational case reports on ocular irritation and Polydodecene found the LD50 values > 2,000 mg/kg in rats. In
systemic sclerosis in workers exposed to Polyethylene. Such rabbit studies, the dermal LD50 values for Ethylene/Octene Copo-
workers are also exposed to other irritants. Clinical testing of lymer, hydrogenated decene dimer, Hydrogenated Polyisobu-
intrauterine devices made of Polyethylene failed to conclu- tene, and Polyisobutene were > 5,000 mg/kg, > 3,000 mg/kg,
sively identify statistically significant adverse effects, although >2,000 mg/kg, and >25,000 mg/kg, respectively.
squamous metaplasia was observed in treated women. In acute inhalation studies, the LC50 of diisobutylene vapor
in albino rats was > 4,185 ppm (19,171 mg/m3) after a 4-hour,
single, whole-body exposure. The LC50 for an aerosol of
Hydrogenated Polydecene was > 5.2 mg/L in rats. The LC50
Summary for the dimer of hydrogenated decene was 1.17 mg/L in rats. In
The polyene ingredients in this report are simple polyolefins another acute inhalation study of the dimer of hydrogenated
that are the polymerization products of vinyl-type monomers. decene, the LC50 could not be determined in rats tested at
The polyenes reviewed in this report cover a wide range of 5 mg/L because 9/10 animals died within 3 days of adminis-
molecular weights but have very similar structures and reaction tration of the test material. The LC50 for Hydrogenated Poly-
starting materials (monomers). Polyenes function primarily as dodecene was > 5.06 mg/L. The LC50 for 100% Hydrogenated
film formers and/or viscosity increasing agents—nonaqueous Polyisobutene was > 5 mg/L.
in cosmetic products. No treatment-related gross microscopic changes were
According to the 2015 US FDA VCRP data, Polyethylene is observed following exposure to 100% Polyisobutene in a
reported to be used in 2,773 formulations; the single category 90-day dietary study of rats and 2-year dietary studies in rats or
with the most reported uses was lipstick with 885.Hydroge- dogs. No adverse effects were observed in oral repeated dose
nated Polyisobutene is reported to be used in 1,963 formula- studies of Hydrogenated Polydecene, with the NOAELs deter-
tions; the single category with the most reported uses was mined to be 1,000 mg/kg/d in one 90-day rat study and over 4,000
lipstick with 865. Most of the other in-use ingredients are pri- mg/kg/d in another. In a 4-week oral repeated dose rat study, the
marily used in leave-on products and lipsticks. The results of NOAEL for Hydrogenated Polydecene was 6,245 mg/kg/d in
the concentration of use survey conducted in 2013 and 2014 by males and 6,771 mg/kg/d in females. Gross necropsy, histopathol-
the Council indicate Hydrogenated Polyisobutene has the high- ogy, and microscopic findings did not reveal any significant
est reported maximum concentration of use; it is used at up to treatment-related findings. The NOAEL for the oral administra-
95% in lipsticks. tion of the trimer of hydrogenated dodecene in 2 respective oral
For the ingredients that were previously reviewed by the repeated dose toxicity studies in rats was 1,000 mg/kg/d.
Panel, concentrations of use for Polybutene and Hydrogenated Treatment-related effects on mortality, clinical signs, bw, food
Polyisobutene have remained about the same, with the highest consumption, hematology, clinical chemistry, organ weights, or
maximum use concentration of 95%for Hydrogenated Polyiso- gross and histologic pathology were not observed in either study.
butene in lip products. The highest maximum use concentration In a 4-week dermal study in rats, 100% Hydrogenated Polyiso-
for Polyethylene has increased from 24% (eye shadow) to butene produced minimal to mild dermal irritation in most treated
67.6% (skin cleansing agents), while the highest maximum use animals. Histopathologic examinations of the high-dose group
concentration for Polyisobutene has decreased from 76% to found effects limited to the application site and included minimal
40% (both concentrations in lip products). Uses for all 4 ingre- to mild epidermal hyperplasia and hyperkeratosis with reactive
dients have increased by several folds since their original hyperplasia of the underlying inguinal lymph nodes.
reviews. In rat reproductive studies of Hydrogenated Polydecene
Many of the polyene ingredients have been approved by the and the trimer of Hydrogenated Polydodecene, the NOAELs
FDA for use as food additives and in medical devices. An oral for parental systemic and reproductive effects and for off-
study that assessed the absorption potential of undiluted Hydro- spring were 1,000 mg/kg bw/d for the respective studies. No
genated Polydecene in rats found that most of the test com- treatment-related effects were observed on clinical signs,
pound was excreted in the feces without being absorbed bw, or gross pathology in the parental generation or in the
(> 92%). Urinary excretion was low (< 1%), and very little pups. There were no treatment related effects on reproduc-
of the dose was recovered in the bile (0.01%). tion or pup viability. In a 3-generation reproductive dietary
In acute oral toxicity studies in rats, the LD50s of diisobu- toxicity study, an unreported number of Charles River rats
tylene, and triisobutylene were > 2,000 mg/kg/bw each. The received 0, 800, or 20,000 ppm 100% Polyisobutene pro-
oral LD50s of di-n-butene, tributene, and tetrabutene (contain- duced no treatment-related reproductive effects in any gen-
ing 30% pentabutene) in rats were > 10,000 mg/kg each. The eration of the treated groups when compared to controls.
oral LD50 values for Ethylene/Octene Copolymer, undiluted A trade name mixture containing 30% to 50% Ethylene/
Hydrogenated Polydecene and undiluted Hydrogenated Poly- Octene Copolymer and sodium acrylate copolymer was not
dodecene were > 5,000 mg/kg in rat studies. The LD50 of mutagenic in an Ames test or in an in vitro chromosomal aber-
undiluted Polyisobutene was > 15,400 mg/kg in an oral rat ration test Hydrogenated Polydecene at concentrations up to
study. 10 mg/plate was not mutagenic in Ames assays, with or without
metabolic activation. The trimer of Hydrogenated Polydode- lipsticks, but a human dermal sensitization study of 100%
cene was not clastogenic to human lymphocytes nor was it Hydrogenated Polyisobutene in the previous safety assessment
mutagenic in CHO cells (HGPRT locus assay) in vitro when of this ingredient was negative, and no irritation or sensitization
tested at concentrations up to 5,000 mg/mL. was observed in multiple tests of some of the other polyene ingre-
International Agency for Research on Cancer determined dients. The Panel recognized that polyenes are approved for use in
that Polypropylene is not classifiable as to its carcinogenicity foods (directly and indirectly) and drug and medical devices.
to humans (group 3). Polyisobutene (100%) was not carcino- The Panel also noted that although molecular weights are in
genic in rats (dosed up to 20,000 ppm) or dogs (dosed up to the range that could be dermally absorbed, the lack of heteroa-
1,000 mg/kg) in oral studies. tom functional groups dramatically limits solubility and would
Ethylene/octene copolymer and sodium acrylate copolymer prevent significant absorption. The lack of functional groups
(30%-50% in a trade name mixture) was minimally/slightly also limits interactions with other biomolecules and accounts
irritating to rabbit skin. Polyisobutene and Hydrogenated Poly- for the apparent biological inertness of these ingredients.
isobutene at 100% were not irritating to rabbit skin in respec- The Panel noted gaps in the available safety data for some of
tive irritation studies. Hydrogenated Polydecene and the trimer the polyenes in this safety assessment. The data available for
of hydrogenated decene were not primary irritants or corrosives many of the ingredients are sufficient and can be extrapolated
in several rabbit studies. No significant irritation was observed to support the safety of the entire group because of the simila-
in human subjects in a cumulative irritation test of Ethylene/ rities in the chemical structures, physicochemical properties,
Octene Copolymer and sodium acrylate copolymer (30%-50%) use concentrations, and reported functions across the group.
in a trade name mixture. No adverse effects were reported in The Panel discussed the issue of incidental inhalation exposure
human subjects following irritation studies of a formulation in pump and aerosol hair sprays, underarm deodorant sprays, face
containing 8% Hydrogenated Polyisobutene and Hydrogenated and neck sprays, body and hand sprays, and aerosol suntan prod-
Polyisobutene at 100%. No adverse effects were reported fol- ucts. The limited data available from inhalation studies, including
lowing dermal exposure to formulations containing Hydroge- acute exposure data, suggest little potential for respiratory effects
nated Polydecene with equal amounts of cetyl ethylhexanoate at relevant doses. The Panel considered pertinent data indicating
and pentaerythrityl tetraethyl hexanoate tested at total concen- that incidental inhalation exposures to polyenes in such cosmetic
trations up to 35% in a study in human subjects. products would not cause adverse health effects, including data
Ethylene/octene copolymer and sodium acrylate copolymer characterizing the potential for polyenes to cause systemic toxi-
(30%-50% in a trade name mixture was minimally/slightly city, ocular or dermal irritation or sensitization, and other effects.
irritating to rabbit eyes. Polyisobutene and Hydrogenated Poly- The Panel noted that 95% to 99% of droplets/particles produced in
isobutene at 100% were not irritating to rabbit eyes in respec- cosmetic aerosols would not be respirable to any appreciable
tive irritation studies. Two primary eye irritation studies in amount. The potential for inhalation toxicity is not limited to
rabbits found undiluted Hydrogenated Polydecene not to be respirable droplets/particles deposited in the lungs. In principle,
an ocular irritant, while another study found the material to inhaled droplets/particles deposited in the nasopharyngeal and
be moderately irritating. thoracic regions of the respiratory tract may cause toxic effects
Ethylene/octene copolymer was not sensitizing in a guinea depending on their chemical and other properties. However,
pig maximization test or in an LLNA. Hydrogenated Polyde- coupled with the small actual exposure in the breathing zone and
cene was not a dermal sensitizer in guinea pig maximization the concentrations at which the ingredients are used, the available
tests at concentrations up to 100%. The dimer of hydrogenated information indicates that incidental inhalation would not be a
decene was not a dermal sensitizer in one guinea pig maximi- significant route of exposure that might lead to local respiratory or
zation study and was given a grade 1 response in another. The systemic effects. A detailed discussion and summary of the
trimer of hydrogenated decene in propylene glycol was a slight Panel’s approach to evaluating incidental inhalation exposures
sensitizer according to an LLNA. The stimulation indices were to ingredients in cosmetic products is available at http://www.
1.56, 1.89, and 3.54 for the test concentrations of 25%, 50%, cir-safety.org/cir-findings.
and 100%, respectively. Ethylene/octene copolymer was not a
sensitizer in a HRIPT. Polyisoprene was not a sensitizer
according to the results of a HRIPT at 12.33% in a lip gloss. Conclusion
The Panel concluded that the following polyene ingredients are
Discussion safe in cosmetics in the present practices of use and concentra-
tion described in this safety assessment:
The Panel considered the available data on polyenes, including
those from the previous safety assessments on Polybutene, Poly-
ethylene, Polyisobutene, and Hydrogenated Polyisobutene, and Butene/Propylene Copolymer* Isobutylene/Isoprene Copolymer*
noted low systemic toxicity at high doses in single-dose and Butylene/Ethylene Copolymer Isoprene/Pentadiene Copolymer*
repeated-dose animal studies, no teratogenic effects in animal Butylene/Ethylene/Propylene Polybutene
studies, and no genotoxicity in in vitro and in vivo studies. The Copolymer
Panel noted that use concentrations were as high as 95% in (continued)
Burnett et al 89S
(Continued) 5. European Chemicals Agency. Dec-1-ene, homopolymer, hydro-

genated. Last Updated 2014. Accessed May 28, 2014. http://echa.
Decene/Butene Copolymer Poly(C4-12 Olefin)* europa.eu/
Ethylene/Octene Copolymer* Poly(C6-14 Olefin)* 6. European Chemicals Agency. Butene, homopolymer (products
Ethylene/Propylene Copolymer Poly(C20-28 Olefin)* derived from either/or But-1-ene/But-2-ene). Last Updated
Hydrogenated Poly(C6-12 Poly(C30-45 Olefin)
2014. Accessed May 29, 2014. http://echa.europa.eu/
Olefin)
Hydrogenated Poly(C6-14 Polydecene 7. Britovsek GJP, Gibson VC, Wass DF. The search for new-
Olefin) generation olefin polymerization catalysts: life beyond metallo-
Hydrogenated Poly(C6-20 Polyethylene cenes. Angew Chem Int Ed. 1999;38:428-447.
Olefin) 8. Leber AP. Overview of isoprene monomer and Polyisoprene
Hydrogenated Polybutene* Polyisobutene production processes. Chem Biol Interact. 2001;135-136:169-173.
Hydrogenated Polydecene Polyisoprene 9. Anonymous. Process flow: hydrogenated polyisobutene. Unpub-
Hydrogenated Polydodecene* Polypentene*
lished data submitted by Personal Care Products Council. 2015; 1.
Hydrogenated Polyisobutene Polypropylene
10. Personal Care Products Council. Ethylene/octene copolymer.
*Not reported to be in current use. Where ingredients in this group not in Unpublished data submitted by Personal Care Products Council.
current use to be used in the future, the expectation is that these ingredients Janury 30, 2015.
would be used in product categories and at concentrations comparable to
others in this group. 11. Dow Chemical Company. Ecosmooth™ delight sensorial enhan-
cer: toxicology & ecotoxicology summary. Unpublished data sub-
mitted by Personal Care Products Council. 2014.
Author Contributions 12. Dow Chemical Company. Ecosmooth™ silk global cosmetic dos-
Burnett, C. contributed to conception and design, contributed to acqui- sier. Unpublished data submitted by Personal Care Products
sition, analysis, and interpretation, drafted manuscript, and critically Council. 2015.
revised manuscript; Bergfeld, W., Belsito, D., Hill, R., Klaassen, C., 13. Japan Natural Products Inc. Potassium permanganate consump-
Liebler, D., Marks, J., Shank, R., Slaga, T., Snyder, P., and Gill, L. tion test on Ethylene/Propylene Copolymer. Unpublished data
contributed to conception and design, contributed to analysis and submitted by Personal Care Products Council. 2015; 1.
interpretation, and critically revised manuscript; Heldreth, B. contrib-
14. Création Coleurs. Creasil® IC CG (Polyisobutene). Unpublished
uted to design, contributed to analysis and interpretation, and critically
data submitted by Personal Care Products Council. 2014.
revised manuscript. All authors gave final approval and agree to be
accountable for all aspects of work ensuring integrity and accuracy. 15. Création Coleurs. Creasil® IP CG (Polyisobutene). Unpublished
data submitted by Personal Care Products Council. 2014.
Authors’ Note 16. Création Coleurs. Dedraflow® 20 (hydrogenated polyisobutene).
Unpublished sources cited in this report are available from the Exec- Unpublished data submitted by Personal Care Products Council.
utive Director, Cosmetic Ingredient Review, 1620 L Street, NW, Suite 2014.
1200, Washington, DC 20036, USA. 17. Création Coleurs. Dedraflow® 40 (hydrogenated polyisobutene).
Unpublished data submitted by Personal Care Products Council.
Declaration of Conflicting Interests 2014.
The author(s) declared no potential conflicts of interest with respect to 18. Création Coleurs. Dedraflow® 30 (hydrogenated polyisobutene).
the research, authorship, and/or publication of this article. Unpublished data submitted by Personal Care Products Council.
2014.
Funding 19. Création Coleurs. Dedraflow® 50 (hydrogenated polyisobutene).
The author(s) disclosed receipt of the following financial support for Unpublished data submitted by Personal Care Products Council.
the research, authorship, and/or publication of this article: The articles 2014.
in this supplement were sponsored by the Cosmetic Ingredient 20. Création Coleurs. Alphaflow® 30 (hydrogenated polydecene).
Review. The Cosmetic Ingredient Review is financially supported Unpublished data submitted by Personal Care Products Council.
by the Personal Care Products Council. 2014.
21. Création Coleurs. Alphaflow® 20 (hydrogenated polydecene).
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CIR Supplement Manuscript

International Journal of Toxicology

Christina L. Burnett*, Wilma F. Bergfeld**, Donald V. Belsito**,

Introduction Polybutene (published in 1982), Polyethylene (published in

Figure 1. An example of polyene synthesis (Isobutylene/Isoprene Copolymer).

Ingredient CAS No. Definition and structure Function(s)

Butylene/Ethylene/Propylene Butylene/Ethylene/Propylene Copolymer is a copolymer of butylene, Film formers

Ingredient CAS No. Definition and structure Function(s)

Ingredient CAS No. Definition and structure Function(s)

Ingredient CAS No. Definition and structure Function(s)

Ingredient CAS No. Definition and structure Function(s)

Table 2. Physical and Chemical Properties of Polyenes.

Property Value Reference

Totalsy 1 1.5 14 4.5 3 NR 107 0.0063-12.5

Totalsy 82 0.25-58 NR 10 51 NR 713 0.005-59

Poly (C30-45 Olefin) Polydecene Polyisoprene Polypropylene

Totalsy 2 0.6-26.1 156 0.098-47.9 28 0.098-47 24 0.05-68.6

2015 1976 2013 1976 2015 2002 2013 2004

Totalsy 1,823 85 0.1-82.4 >1->50* 2,773 717 0.0097-67.6 0.09-24

Polyisobutene Hydrogenated Polyisobutene

2015 2005 2013 2005 2015 2005 2013 2005

CIR ¼ Cosmetic Ingredient Review; NR ¼ not reported.

Non-Cosmetic Toxicological Studies

Table 6. FDA-Approved Uses of Polyenes.

Ingredients Regulation CFR reference

Ingredients Regulation CFR reference

Polypropylene Intercardiac patch or pledget—cardiovascular 21 CFR 870.3470

FDA ¼ Food and Drug Administration.

Table 7. Acute Toxicity Studies in Animals.

Ingredient and concentration/

Ingredient and concentration/

Table 8. Repeated Dose Toxicity Studies in Animals.

Oral At the end of mating, males were sacrificed. Females were

Test article Concentration/Dose Test population Procedure Results Reference

Test article Concentration/Dose Test population Procedure Results Reference

Test article Concentration/Dose Test population Procedure Results Reference

Test article Concentration/dose Test population Procedure Results Reference

injections of the vehicle in 25% aqueous

Test article Concentration/dose Test population Procedure Results Reference

LLNA ¼ local lymph node assay.

(Continued) 5. European Chemicals Agency. Dec-1-ene, homopolymer, hydro-

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Christina L. Burnett*, Wilma F. Bergfeld, Donald V. Belsito,