Polybutene Human Health Risk Assessment DP No. D392729

Page 3 of 16 1.0 Executive Summary

The Pesticide Re

- evaluation Division has requested that the Health Effects Division (HED)

per form an assessment of human health risk to support the registration review of polybutene. Polybutene is a viscous, non

- drying polymeric liquid that is registered as a repellent to prevent
birds from roosting on the inside or outside of buildings. Product formulations are available as a gel for outdoor application to buildings or other structures using a caulking gun or putty knife and a liquid for application to indoor structures using a low

- pressure spray gun or paint brush

. The liquid product is also u sed to repel beavers from gnawing on and damaging the trunks of
trees and shrubs . It is not toxic to the target species , but discourages contact by creating an unpleasant, sticky surface. There are no registered food/feed uses and existing use patterns a re

not ex p ec ted to contaminate surface or ground water; a dietary exposure assessment was
therefore not required

. Polybutene is exempt from the requirement of a tolerance when used as a sticker agent in packaging of insect control products used on food cr ops.

Polybutene is approved by the Food and Drug Administration (FDA) as an indirect food additive and is used as an ingredient in cosmetic products that are applied directly to the skin such as sun block or moisturizer, and that may be incidentally inges ted, such as lipstick. Concentrations of polybutene in cosmetic products may range from 1% to 50%. The use of polybutene in cosmetic products is considered safe, according to a review of available toxicity information by the Cosmetics Industry Review (CI R) Scientific Panel report. The report was taken into
consideration in this assessment.

The toxicological database is considered adequate for characterizing hazard and assessing risk from polybutene. No additional studies were requested during registra tion review scoping.

Most oral studies show no toxicity at the limit dose , although in a rat two

- year dietary study

, possible treatment

- related mortality in males (but not females) was observed in the absence of
other effects

. Dermal toxicity is not ant icipated based on the lack of oral toxicity. Acute lethality studies indicate low oral and dermal toxicity. Polybutene is not a dermal irritant, although moderate primary eye irritation was observed with the technical product. An acute inhalation study w as waived due to the viscosity of the test substance. A published two

- week inhalation study in the male rat was conducted using polybutene vapor. Mortality

, and pulmonary edema and hyperemia in the rats that died

, w ere observed at the higher of two dose levels; ho wever , this endpoint was not considered appropriate for select ing an inhalation exposure endpoint for human health risk assessment . A dose

- response could not be determined
and the effects likely result ed from direct lung effects due to the viscous nature of the test
substance at a high concentration that is not relevant to the low level of human inhalation

exposure expected from application of polybutene products

. Based on these findings and the conclusions of the CIR panel report, no toxicological endpoints of concern were identified for dermal or inhalation exposure to polybutene.

A number of studies required under the revised 40 CFR Part 158 guidelines , including immunotoxicity and neurotoxicity, were not submitted. However, b as ed on a consideration of
the available information on polybutene toxicity , including the safety of polybutene as a food additive and cosmetic ingredient, additional studies are not expected to identify effects of

concern. An inhalation study is not requir ed

, based on the minimal potential for inhalationPolybutene Human Health Risk Assessment DP No. D392729

Page 4 of 16 exposure due to the type of application

, and the limited use of the products, particularly the liquid formulation

, as determined from recent annual usage information.

The registered end

- use products of polybutene are intended for professional and commercial application

, but there are no restrictions for homeowner use. Therefore, both residential and occupational applicator and post

- application exposure s w ere considered in this assessment. Dermal exposu re may occur from application of polybutene gel and liquid products; inhalation exposure may result from spray application of the liquid formulation.

Although exposure may occur during application of these products, quantitative exposure

assessments wer e not performed for polybutene. Dermal or inhalation endpoints of concern were not identified. Dermal toxicity is not anticipated based on lack of oral effects and the expectation of low absorption due to the relatively large size of polybutene molecules

. Inhalation toxicity is of low concern due to the expectation of limited exposure via this route. Furthermore, exposure from use of the liquid formulation product , which is applied via a low

pressure spray, is limited . The product is applied to a limit ed physical area on an intermittent
basis and represents a low level of usage , based on recent information on lbs. sold per year ( personal comm unication, Joel Wolf, PRD ; 2012 ).

Post

- application residential exposure is n ot of concern because no contact is expected with
treated surfaces and due to the non

- volatile properties of the formulations. Post

- application occupational exposure is not anticipated based on the current use patterns.

2.0 HED Recommendations

Sufficient data are available to support the human health risk assessment of polybutene. No changes to current product labels are needed.

3.0 In troduction

Polybutene is a viscous, sticky, non

- drying polymeric substance with an average molecular weight of 320 to 420 or higher. Current ly registered uses are limited to surface applications on indoor and outdoor sites (structures, trees or shrubs) as a repellent to prevent (1) birds such as starlings or pigeons from roosting in unwanted structures or trees/shrubs and to prevent (2)
beavers f rom gnawing on and damaging trunks of trees and shrubs. Polybutene is not toxic to these species; rather, it acts as a repellent because they find the sticky surface unpleasant. There

are no registered food/feed uses. There is an exemption from the requ irement of a tolerance for polybutene when it is incorporated into the packaging of insect control products used on food

crops.

There are also numerous other uses of polybutene. It is a common ingredient in cosmetic products, including lipstick, eye ma keup, sunscreen and moisturizers , at concentrations ranging from 1% to 50% (w/w). The Food and Drug Administration (FDA) approved polybutene as an indirect food additive for use in packaging that may come into contact with food ( § 177.1430 of
the 21 CFR, t he Food Additive Regulation of FDA). Other uses include as a lubricating

- oilPolybutene Human Health Risk Assessment DP No. D392729

Page 5 of 16 additive, polymer modifier and to increase viscosity or tackiness in products such as cable insulators, adhesive s, special sealants, films and coatings

.

3.1 Chemical Identity

T he chemical identit y and chemical structure for polybutene is shown below in Table 3.1.

Table 3.1 Test Compound Nomenclature

Chemical Structure See empirical formula

– polymeric structure of varying size

Empirical Formula R 3 C

- [C 4 H 8 ]

n - CH=CR 2 , where R=CH 3
Common Name Polybutene

Company experimental name NA

CAS Name 1

- butene polymer
CAS Registry Number 9003

- 29

- 6

End

- use product/EP Tanglefoot Bird Repellent; 4 the Birds Repellent; Hot Foot Bird Repellent

Chemical Class Trisubstituted olefin
Known Impurities of Concern None

3.2 Physical/Chemical Characteristics

Polybutene is a polymer of isobutene and n

- butene with an average molecular weight of 320

- 420 . It is a light

- colored, viscous liquid that is non

- drying and sticky: the viscosity is proportional to its polymeric molecular weight. It is stable to light and is not reactive. Although it may soften in heat, once the product is set it does not liquefy and run at temperatures likely to
be encou ntered in the outdoor or indoor environment

. Polybutene is insoluble in water

, and has a specific gravity of 0.8 9 g/mL at 37°C

. The boiling point is 160°C and the vapor pressure is 0.1 3 mm Hg at 25 ° C

.

3.3 Pesticide Use Pattern

The registered product fo rmulations containing polybutene are listed in Table 3.3. 1. There is no registration on a technical product and the four active registrations are end

- use product (EP)
formulations. Three of the four EPs are formulated as gels and packaged in ready

- to

- use tubes and the fourth is a liquid.

Table 3.3 .1

. Registered Product s of Polybutene.

EPA Reg. No. AI % Formulation Type Product's Name

1621

- 17 97.0 Gel Tangle foot Bird Repellent

8254

- 3 49.0 Liquid 4 The Birds, Transparent Bird Repellent LiquidPolybutene Human Health Risk Assessment DP No. D392729

Page 6 of 16 Table 3.3 .1

. Registered Product s of Polybutene.

EPA Reg. No. AI % Formulation Type Product's Name

8254

- 5 93.0 Gel 4 The Birds, Bird Repellent

55943

- 1 93.5 Gel Hot Foot Bird Repellent

Polybutene formulations are registered to repel birds such as pigeons, starlings and sparrows
from roosting inside and outside of homes and structures

, and beavers from damaging trees and
shrubs. The use patte r n for registered products is su mmarized in Table 3.3.2

.

Table 3.3

. 2. Use Pattern of End

- use Product Formulations of Polybutene.

EPA Reg. No.
And Name. Appl. Sites Appl. Equipment

and rate Comments

1624

- 17, (97% ai) Bird Repellent

8254

- 5, (93% ai), 4 The Birds Bird Repellent

55946

- 1, (93.5% ai) Hot foot Bird Repellent Outdoor: on buildings and other

exterior structures Caulking gun or a putty

knife @ 1 oz product per

linear ft. To reduce exposure to bird related diseases, wearing water proof gloves and a respirator (approved for dust) is recommended for cleaning the areas before

treatment.

8254

- 3 (49% ai) 4 The Birds Transparent Bird Repellent Interior: buildings

Exterior: trees and
shrubs Spray to the point of run

- off

using a low

- pressure spray gun or use a paint brush to
treat surfaces that are difficult to spray. Do not dilute before spraying. Do not apply to exterior of buildings and

structures. D o not apply using aerial equipment.

The treated sites include window sills, cornices, roof lines, gutter edges, signs, ledges, bridges, overpasses, beams, girders, struts, and supports where birds can sit and roost. Exterior sites are trees, bushes and vines adjacent to buildings and structures.

The gel formulati ons are applied in bands, two inches apart for the length of the area in broken strips, leaving a one inch gap between beads to allow drainage of water. A putty knife can also be used to apply the gel. The recommended application rate is approximately 1 oz. of product per linear foot. Repeat a pplication s may be made if the applied gel is flattened with time or covered with dirt and debris due to heavy bird traffic

.

The liquid product is either sprayed with a low pressure handgun or applied using a pai nt brush to the surface of beams and rafters (indoors) or around the trunks of trees and bushes (outdoors). In outdoor areas, repeat applications may be made at 2

- 3 week intervals when the applied area has a weathered appearance. For indoor areas , no rep eat applications have been recommended.

Table 3.2.3 summarizes the total product s (pounds ai) sold in 2011 for each registration number (Joel Wolf, BEAD, personal communication ; 2012 )

. Polybutene products represent a fairly
limited use. Of the liquid f ormulations, the “4 the Birds ” formulation has the lowest annual use rate (<6000 lbs.).Polybutene Human Health Risk Assessment DP No. D392729

Page 7 of 16 Table 3.2.3. Pounds of Polybutene Sold in 2011 by Product Registration EPA Registration No. Product Name % AI Lbs. AI Sold in 2011

8254

- 3 4 the Birds Transparent Bird Repellent Liquid 49 5,954

8254

- 5 4 the Birds Bird Repellent 93 29,993

55943

- 1 Hot Foot Bird Repellent 93.5 4,353

1621

- 17 Tanglefoot Bird Repellent 97 48,736

3.4 Anticipated Exposure Pathways

Based on the currently registered uses, humans could be exposed to polybutene through professional and homeowner application of products. Exposure via the dermal and inhalation routes is possible. Occupational and residential p ost

- application exposure (d ermal, inhalation, incidental oral) are considered unlikely due to the nature of the applications. Di etary exposure
from the current ly registered uses of polybutene is not anticipated. T here are no food/feed uses
and contamination of ground or surface wa ter is not anticipated from existing use patterns due to the nature of the applications and the minimal overall use of the product.

Polybutene is also a commonly used ingredient in many cosmetics. Humans may be exposed through use of cosmetic products, such as lipstick, eye makeup, moisturizers and sun block

, containing polybutene at concentrations ranging up to 50% (w/w).

3.5 Consideration of Environmental Justice

Potential areas of environmental justice concerns, to the extent possible, were conside red in this human health risk assessment, in accordance with U.S. Executive Order 12898, "Federal Actions to Address Environmental Justice in Minority Populations and Low

- Income Populations," ( http://www.eh.doe.gov/oepa/guidance/justice/eo12898.pdf

. As a part of every pesticide risk

assessment, the Office of Pesticide Programs ( OPP ) considers a large variety of consumer subgroups according to well

- established procedures. In line with OPP policy, HED estimates risks to population subgroups from pesticide exposures that are based on patterns of that subgroup’s food and water consumpti on, and activities in and around the home that involve pesticide use in a residential setting. Extensive data on food consumption patterns are compiled by the USDA under the Continuing Survey of Food Intake by Individuals (CSFII) and are used in pesticide risk assessments for all registered food uses of a pesticide. These data are analyzed and categorized by subgroups based on age, season of the year, ethnic group, and region of the country. Additionally, OPP is able to assess dietary exposure to smaller , specialized subgroups and exposure assessments are performed when conditions or circumstances warrant. Whenever appropriate, non

- dietary exposures based on home use of pesticide products and associated risks for adult applicators and for toddlers, youth s, and adults entering or playing on treated areas
post

- application are evaluated. Further considerations are currently in development as OPP has committed resources and expertise to the development of specialized software and models that consider exposur e to bystanders and farm workers as well as lifestyle and traditional dietary patterns among specific subgroups.Polybutene Human Health Risk Assessment DP No. D392729

Page 8 of 16 4.0 Hazard Characterization and Dose

- Response Assessment

4.1 Toxicology Studies Available for Analysis

The toxicity of polybutene was reviewed for the RED document (December, 1994). All toxicology studies, except for acute toxicity and genotoxicity, were waived in that assessment, based on lack of effects observed in the available studies and the expectation of minimal exposure from registered uses (Appendix A.1, Toxicology Data Requirements) . Additional toxicity data were reviewed (as brief summaries) subsequent to the RED, for a proposed amended tolerance exemption as an inert ingredient (see Appendix A .2

, Tables A. 2.1 and A.2.2

, for a profile of the studies reviewed by the Agency). Studies reviewed by the Agency include acute toxicity (with the exception of acute inhalation, which was waived based on the viscous nature of the test substance), genotoxicity studies and a subchronic dietary study in the rat. A published two

- week inhalation toxicity study (non

- guideline) was also reviewed. The Agency
also considered the Final Report on the Safety Assessment of Polybutene (1982) by the Cosmetic Ingredient Revi ew (CIR) Scientific Panel, which evaluated the toxicity of polybutene for use in cosmetic products from available toxicological studies. CIR is an industry trade organization that sponsors review of cosmetic ingredient safety by panels of expert scientist s. The Scientific Panel evaluated the available toxicological data on polybutene, including the subchronic oral and inhalation studies reviewed by the Agency, as well as numerou s other studies in test animals

. Animal studies included chronic (two

- year) d ietary studies in the rat and dog, reproductive and developmental studies in the rat and numerous acute studies.

Although a complete toxicological database based on current 40 CFR Part 158 guidelines has not
been submitted , t he available toxicological data for polybutene are considered adequate for

assessment of human health risk due to its low toxicity and the limited use of products containing polybutene

. No additional studies are required at this time. Additional toxicology data were not required during registration review scoping.

4.2 Toxicological Effects

In addition to the acute, genotoxicity, subchronic rat and two

- week rat inhalation toxicity studies reviewed by the Agency, the conclusions of the Final Report on the Safety Asse ssment of Polybutene by the CIR Expert Scientific Panel in 1982 (reaffirmed again in 2002) were considered in evaluating the toxicity of polybutene

. Based on their review, t he p anel determined that polybutenes are “relatively harmless” and “safe as presen tly used in cosmetics.”

No target organs were identified following oral exposure to polybutene. In a 90

- day dietary study in the rat, no toxicity in male or female rats (body weight changes, hematological and limited clinical chemistry parameters, orga n weights and histopathology) was noted at 2500 mg/kg/day , the only dose tested . Several oral studies, including subchronic rat, chronic dog, rat reproduction and developmental toxicity studies did not identify toxic doses at or above the limit
dose (the r at reproductive toxicity and chronic two

- year oral studies in the rat and dog were not considered acceptable by the Agency at the time of submission because the integrity of the data
was not validated )

. Rats fed polybutene for two years (30/sex/dose) at 0, 200, 4000 or 20,000

ppm showed no effects except for a possible treatment

- related mortality in males at the limitPolybutene Human Health Risk Assessment DP No. D392729

Page 9 of 16 dose of 20,000 ppm : six high

- dose males died between weeks 17

- 24 (three with reported hematuria), but no other findings were reported and no toxicity was observed in females. There was no evidence of carcinogenicity. A published study evaluating developmental toxicity reported that no effects were observed after six months’ administration of polybutene at 1% or 10% in the diet (1968) but details were not available for review.

No dermal absorption or toxicity data ar e available, but based on lack of toxicity in the oral studies, no toxicity from exposure via the dermal route is anticipated. In addition, as a polymeric compound of average molecular weight exceeding 300 , absorption is expected to be low. The lungs ar e a target organ with inhalation exposure at higher ambient concentrations. In a published two

- week inhalation study, mortality was observed in male Wistar rats exposed to polybutene aerosol ( 7 hrs/day, 5 days/week )

. Females were not tested

. At 700 mg/ m 3 , d eath
occurred in one of six animal s during the first day of exposure and two additional males on the sixth day of exposure (study Day 8). Pulmonary edema and hyperemia were also observed in
these animals , suggesting that the test material may have ha d local toxicity to the lung

. These effects are likely due to the viscous properties of polybutene at a relatively high ambient
concentration and would not occur at exposure levels resulting from current uses of polybutene products. No effects were seen a t 70 mg/m 3 , but intermediate doses were not evaluated and a
dose

- response could therefore not be evaluated

. Additional inhalation data was not required, since inhalation exposure is expected to be minimal and use of the liquid spray product is
limited. A s noted below, two acute inhalation studies identified by the CIR panel showed low toxicity.

Polybutene was negative for genotoxicity in the Salmonella typhimurium reverse gene mutation, Chinese Hamster Ovary (CHO) cell mammalian forward gene mutation and in vivo mouse bone marrow micronucleus assays. Test material purity information on the bacterial reverse gene mutation assay was required at the time of review to upgrade it to "acceptable

. " However, based on the lack of concern for genotoxicity, no additional information is required at this time.

Although immunotoxicity and neurotoxicity studies are not available , the available information indicates that polybutene would not be expected to affect either the immune or nervous systems, particularly at the low exposure levels expected with the use of registered products. These studies are therefore not required; furthermore, as there are no endpoints identified for risk assessment, a 10x datab ase uncertainty factor is not applied.

Polybutene is of low acute toxicity by the oral and dermal exposure routes (Category IV and III, respectively). An acute inhalation toxicity study was waived based on the viscosity of the test
material . However, it is noted that the CIR report identifi ed two acute inhalation studies: in contrast to the published two

- week inhalation study, no toxicity was observed in rats exposed for 4 hour exposures to 17 or 18 mg/L ( Toxicity Category III ) . It is not a dermal ir ritant or sensitizer, but in one study was moderately irritating to the eye (Category II). Other primary eye
studies show ed low or no irritation.Polybutene Human Health Risk Assessment DP No. D392729

Page 10 of 16 4.3 Dose

- Response Assessment

A dose

- response assessment was not performed for polybutene . No toxicity endpoints or points of departure were identified

. In oral toxicity studies, no toxicological effects were reported, with the exception of possible treatment

- related mortality in males at the limit dose (20,000 ppm or approximately 1000 mg/kg/day ) in the t wo

- year rat study. No effects were seen in males at 4000 ppm or in females at any dose

, nor was toxicity observed at 2500 mg/kg/day in a 90

- day rat feeding study

. In a published two

- week inhalation study in the rat, mortality and pulmonary edema/hyperemia in 3/6 animals and increased lung weight w ere reported at the high dose of 700 mg/m 3 , but only one other dose level at a ten

- fold lower concentration (70 mg/m 3 ) was tes ted. The study was also limited by the small number of animals (6 males per group). Based on the viscous nature of polybutene, these effects appear to result from a direct effect to the respiratory tract (e.g., coating of alveoli , clogging of airways ) an d are likely to be more pronounced in the smaller airways of the rat than in humans. Such effects are not expected to occur at exposure levels that might be encountered from current uses of polybutene and are therefore not
considered relevant to human hea lth risk assessment.

4.4 Safety F actor for Infants and Children (FQPA Safety Factor)

An FQPA safety factor assessment was not performed because there are no food uses for polybutene.

5.0 Water Residue Profile

Based on the existing use patterns, conta mination of surface or ground water from outdoor use is not anticipated

. Use of this product is limited. Polybutene is a sticky , water

- insoluble substance
that r emains on the surface of the treated area

. An assessment of drinking water exposure was
ther efore not performed.

6.0 Residential (Non

- Occupational) Exposure/Risk Characterization

6.1 Residential Handler Exposure

Although all products are labeled for use by commercial and professional applicators, there are no restrictions on homeowner use and therefore residential applicator/handler dermal and inhalation exposure wa s considered in this assessment. Dermal exposure may occur from use of the gel or liquid products; inhalation exposure may also occur from spray application of the liquid product. Inhalation exposure from the gel formulation is not of concern due to the use pattern and application method (paintbrush an d caulking gun ) . The products are not highly
volatile.

The toxicity studies on end

- use products indicate that they have moderate acute toxicity and were assigned Signal Words such as CAUTION to WARNING. No personal protective equipment (PPE) is required on the labels for these products because polybutene formulations are used at sites exempted from the requirement for Worker Protection Standard (WPS) language on the
label.Polybutene Human Health Risk Assessment DP No. D392729

Page 11 of 16 A quantitative assessment of residential handler exposure was not performed , based on consideration of several factors

. N o endpoints of concern were identified for polybutene from
oral studies

. An endpoint for dermal toxicity was not selected based on lack of oral toxicity. In addition, low dermal absorption of polybutene would be pr edicte d due to its large size. An endpoint appropriate for inhalation exposure to humans was also not identified

. Inhalation exposure from use of the liquid spray is expected to be minimal based on the use pattern (application is to a limited physical ar ea and likely to be done on a sporadic basis )

. Additionally,
b ased on pounds sold per year (less than 6000 lbs. in 2011), there is limited usage of this product.

6.2 Residential Post

- Application Exposure

Residential p ost

- application dermal exposure to adults and children from gel and liquid formulations is expected to be negligible because of the lack of contact with the treated surfaces

, both inside and outside of structures; application inside homes does not occur, in accordance with the use patter n

. I nhalation exposure to occupants of indoor areas treated with the liquid product is not of concern because polybutene i s not highly volatil e

. There is no likelihood of children's post

- application incidental oral exposure from indoor uses as the treate d areas a re not
accessible . Due to the sticky nature of polybutene, flakes that could be ingested by children do
not form and fall to the ground.

7.0 Occupational Exposure/Risk Characterization

7

. 1 Occupational Handler Exposure

Occupational dermal and inhalation exposure may occur from current uses of polybutene. A quantitative assessment of occupational handler exposure was not performed

– see Section 6.1
for rationale.

7 .2 Occupational Post

- A pplication Risk

Based on current use pattern s of polybut ene products , no post

- application activities are expected to be performed in treated interior or exterior areas. Therefore, an occupational post

- application exposure assessment was not performed.

8 .0 References

Bradley, M. J. Inert Ingredients: Polyvinyl chloride, Butylbenzyl phthalate, and Polybutenes. Addition to Request of 6/24/81, August 12, 1982.

Bradley, M. J. Inert Ingredients: Polyvinyl chloride, Butylbenzyl phthalate, and Polybutenes on Artichokes. Additional Information to Request of 6/24/81, November 26, 1982. Cosmetic Ingredient Review (1982) Final Report on the Safety Assessment of Polybutene. J.
Am. Coll. Toxicol. 1(4):103

- 118.Polybutene Human Health Risk Assessment DP No. D392729

Page 12 of 16 Cosmetic Ingredient Review: Final Report on the Safety Assessment of Polybutene. J. Am. Coll.
Toxicol. 1(4):10 3

- 118, 1982.

Davis, D. S., D194367. PP# 3E4254: Polybutene: Request for Clearance as an Inert Ingredient under 40CFR§180.1001(c) an (e). November 24, 1993.

Jones, R. Structure Activity Team (SAT) Report for Polybutene. October 20, 1995

.

Liem, D.S., D1 94369, D214154. Review of Toxicological Data Package on Polybutene in Support for a Tolerance Exemption Under 40 CFR 180.1001© and (e) (Inert). April 21, 1995.

Liem, D.S.

, D216536, D217639. Review of a Toxicological Data Rebuttal and Additional Data on Polybutene in Support for an Amended Tolerance Exemption Under 40 CFR 180.1001(d) (Inert). November 1, 1995.

Liem, D. S.

, D223859. Review of a Proposal on a Selection of Polybutene Grade for a Subchronic Feeding and a Developmental Study (Inert). April, 26, 1996.

Oonnithan, S. and Hansen, L.

, D371748. Polybutene: Human Health Assessment Scoping Document in Support of Registration Review. April 23, 2010.

Ritter, D. Inert Ingredients for Use in an Insect Pheromone dispenser in Artichokes. EPA F ile Symbol: #8730

- EUP

- RR. October 13, 1981.

Ritter, D. Request to Broaden Exemption as an Inert Ingredient in all RACs, November 24,
1981.

Schmidt, R. P., Polyvis OSH

– Inert Ingredient Used in Proturf Systemic Fungicide, January 8,
1974.

US EPA. The HED Chapter of the Reregistration Eligibility Decision Document (RED) for Polybutene. Memo from M. Clock to J Ellenberger, December 7, 1994. HED Doc

. No. 011351.

US EPA: Reregistration Eligibility Decision (RED)

– Polybutene. http://ww w.epa.gov/oppsrrd1/REDs/4076, 1994.

US EPA. EPA RED Facts: Polybutene, January, 1995.

Winfield, S.

, D 372034. Polybutene Resins: Review of Human Incidents, February 25, 2010.

Woodrow, W. S. Amendments to EPA # 36638

- EUP

- G, PP # 9G2226, Heliothis vire scens (tobacco budworm) Mating Disruptant Pheromone Used on Cotton, June 5, 1981.Polybutene Human Health Risk Assessment DP No. D392729

Page 13 of 16 A ppendix A

. Toxicology Profile and Executive Summaries

A.1 Toxicology Data Requirements

The requirements (40 CFR 158.340) for non food use for polybutene are in Table 1. Use of the new guideline numbers does not imply that the new (1998) guideline protocols were used.

Study Technical Polybutene

Required Satisfied

870.1100 Acute Oral Toxicity

................................ ....................... 870.1200 Acute Dermal Toxicity

................................ .................. 870.1300 Acute Inhalation Toxicity

................................ .............. 870.2400 Primary Eye Irritation

................................ .................... 870.2500 Primary Dermal Irritation

................................ .............. 870.2600 Dermal Sensitization

................................ ...................... yes

yes

no

yes

yes

yes yes

yes

- yes

yes

yes

870.3100 Oral Subchronic (rodent)

................................ ............... 870.3150 Oral Subchronic (nonrodent)

................................ ......... 870.3200 21

- Day Dermal

................................ .............................. 870.3250 90

- Day Dermal

................................ .............................. 870.3465 90

- Day Inhalation

................................ .......................... yes

no

no

no

no yes

-

-

-

-
870.3700a Developmental Toxicity (rodent)

................................ ... 870.3700b Developmental Toxicity (nonrodent)

............................. 870.3800 Reproduction

................................ ................................ . no

no

no -

-

-
870.4100a Chronic Toxicity (rodent)

................................ .............. 870.4100b Chronic Toxicity (nonrodent)

................................ ........ 870.4200a Oncogenicity (rat)

................................ .......................... 870.4200b Oncogenicity (mouse)

................................ .................... 870.4300 Chronic/Oncogenicity

................................ .................... no

no

no

no

no -

-

-

-

-
870.5100 Mutagenicity

— Gene Mutation

- bacterial

..................... 870.5300 Mutagenicity

— Gene Mutation

- mammalian

................ 870.5xxx Mutagenicity

— Structural Chromosomal Aberrations

... 870.5xxx Mutagenicity

— Other Genotoxic Effects

....................... y es 1

yes

yes

no yes

yes

yes

-
870.6100a Acute Delayed Neurotox icity (hen)

............................... 870.6100b 90

- Day Neurotoxicity (hen)

................................ ........... 870.6200a Acute Neurotox icity Screening Battery (rat)

................. 870.6200b 90

- Day Neuro toxicity Screening Battery (rat)

............... 870.6300 Develop. Neuro toxicity

................................ ................. no

no

no

no

no -

-

-

-

-

870.7485 General Metabolism

................................ ...................... 870.7600 Dermal Penetration

................................ ........................ 870.7800 Immunotoxicity

................................ ............................. no

no

no -

-

-

Special Studies for Ocular Effects

Acute Oral (rat)

................................ ........................... Subchronic Oral (rat)

................................ .................. Six

- month Oral (dog)

................................ .................. no

no

no -

-

- 1 Test material purity information not submitted but study accepted based on general lack of effects and negative results in other genotoxicity studies.Polybutene Human Health Risk Assessment DP No. D392729

Page 14 of 16 A.2 Toxicity Profiles for Polybutene

Table A .2.1. Acute Toxicity Profile

- Polybutene Technical.

Guideline No. Study Type MRID(s) Results Toxicity Category

870.1100 Acute oral

- rat 41772401 LD 50 >5.0 g/kg IV

870.1200 Acute dermal

- rabbit 41772402 LD 50 >2.0 g/kg III

870.1300 Acute inhalation

- rat 1

-- -- N/A 1

870.2400 Acute eye irritation

- rabbit 41772403 Eye irritant II

870.2500 Acute dermal irritation

- rabbit 41772404 Not a dermal

irritant IV

870.2600 Skin sensitization

- guinea pig 41772405 Not a sensitizer N/A

1

. The acute inhalation study was waived based on viscosity of test material.Polybutene Human Health Risk Assessment DP No. D392729

Page 15 of 16 Table A. 2.2 . Subchronic, Chronic and Other Toxicity Profile for Polybutene.

Guideline

No. Study Type MRID No. (year)/
Classification /Doses Results

870.3100 90

- Day oral toxicity (diet)

- rat 00117945 (1982) Acceptable/non

- guideline 2500 mg/kg/day, administered

in diet NOAEL = 2500 mg/kg/day LOAEL = not determined (>2500 mg/kg/day)

870.3150 90

- Day oral toxicity

- dog Not available.

870.3200 21

- Day dermal toxicity Not available.

Non

guideline

- inhalation 2

- week inhalation toxicity

-

rat Published article, Skyberg et al. (1990) Env. Res. 53:48

- 61.

Acceptability not determined

Whole

- body aerosol inhalation exposure of 6 male rats /dose

group for 7 hrs/day, 5 days/week for two weeks at 70 or 700 mg/m 3 NOAEL = 70 mg/m 3

LOAEL = 700 mg/m 3 , based on pulmonary edema and hyperemia, and mortality (exposure days 1 and 6)

.

870.3700a Prenatal developmental

- rat Not available.

870.3700b Prenatal developmental

-

rabbit Not available.

870.3800 Reproduction and fertility

effects

- rat Not available.

870.4100a Chronic toxicity

- rodent Not available.

870.4100b Chronic toxicity

- dog Not available.

870.4200b Carcinogenicity (mouse) Not available.

870.4300 Combined chronic

toxicity/carcinogenicity

- rat Not available.

870.5100 Bacterial Reverse Gene

Mutation Assay

( S. typhimurium strains TA97a, TA98, TA100, TA102 or TA1535) 43076602 (1993)

A cceptable/guideline ( analysis confirming test material
concentration not submitted but not required based on lack of genotoxicity in other studies and general lack of toxicity )

0.08, 0.1, 0.33, 0.8, 1.0, 3.3 or 5.0 mg/plate, tested with and
without S9 activation NEGATIVE

No evidence of induced mutant

colonies above background in S. typhimurium in the presence or absence of S9 activation. Tested up to limit dose (no cytotoxicity or precipitation observed).Polybutene Human Health Risk Assessment DP No. D392729

Page 16 of 16 Table A. 2.2 . Subchronic, Chronic and Other Toxicity Profile for Polybutene.

Guideline

No. Study Type MRID No. (year)/
Classification /Doses Results

870.5300 In Vitro Mammalian Cell

Forward Mutation Assay (TK locus), Chinese hamster ovary cells strain

AS52 43076603 (1993)

Acceptable/guideline

0.001, 0.003, 0.010, 0.033, 0.10, 0.33 or 1.0 μL/mL in

cultu re media, all tested with
and without S9 activation. NEGATIVE

There was no concentration

- related
increase in induced mutant colonies over background observed in the presence or absence of S9 activation. Cytotoxicity was not observed; insolubility was observed at 0.33 and 1.0 μL/mL.

870.5385 In vivo bone marrow

micronucleus assay, mouse 43076604 (1993)

Acceptable/guideline

1.25, 2.5 or 5 g/kg bw (intraperitoneal injection) with sacrifice at 24, 48 or 72 hr NEGATIVE

There was no evidence of a clastogenic and/or aneugenic effect up to the limit dose of 5 g/kg bw. No systemic toxicity observed.

870.7485 Metabolism and

pharmacokinetics (rat) Not available.

870.6200a Acute Neurotoxicity (rat) Not available.

870.6200b Subchronic Neurotoxicity

(rat) Not available.

870.7800 Immunotoxicity Not available.