United States Chemical Safety December 2012 Environmental Protection and Pollution Prevention Agency (7510P)



# Aliphatic Alcohols, C1-C5 Registration Review: Final Work Plan December 2012Docket Number: EPA-HQ-OPP-2012-0340 www.regulations.gov

3 of 11 Aliphatic Alcohols, C1-C5 Registration Review Team

Human Health & Environmental Effects Jonathan Chen Steven Malish Srinivas Gowda David Bays James Breithaupt

Risk Management Wanda Henson Lance Wormell

Office of General Counsel Philip Ross

________________________________________ Supporting documents for the Aliphatic Alcohols, C1-C5 Case may be found in the registration review docket EPA-HQ-OPP-2012-0340 located on the internet at www.regulations.gov

.Docket Number: EPA-HQ-OPP-2012-0340 www.regulations.gov

4 of 11 Introduction

This is the Final Work Plan (FWP) of the Environmental Protection Agency (EPA or “the Agency”) for the registration review of Alipha tic alcohols, C1-C5 (Case 4003). The work plan includes the expected registration review time line. The work plan also addresses public comments received concerning the Preliminary Wo rk Plan (PWP) in the Summary Document which was posted in the Aliphatic alcohols, C1 -C5 registration review docket, and any other comments concerning the initial docket postings. The Summary Do cument provided information on what EPA knows about the pesticide and what additional risk analyses and data or information the Agency believes are needed to make a registration review decision.

The Agency is implementing the registration revi ew program pursuant to Section 3(g) of the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) and will review each registered pesticide every 15 years to determine whether it continues to meet th e FIFRA standard for registration. Changes in science, public policy an d pesticide use practices will occur over time. The registration review program is intended to ma ke sure that, as the ability to assess risk evolves and as policies and practi ces change, all registered pestic ides continue to meet that statutory standard. The public pha se of registration review begins when the initial docket is opened for each case. Information on this program is provided at: http://www.epa.gov/oppsrrd1/ registration_review/.

The Aliphatic Alcohols, C1-C5 Ca se contains two active ingred ients: ethanol (PC Code 001501) and isopropyl alcohol (PC Code 047501). The Pr eliminary Work Plan was published on July 6, 2012 and the 60-day comment period ended on Se ptember 10, 2012. The Preliminary Work Plan document is available on www.regulati ons.gov docket number EPA-HQ-OPP-2012-0340.

The first product containing ethano l was registered in the United States on April 21, 1948, and is registered for use as a glassware sanitizer in eating establishments and hard non-porous surface disinfectant and bacteriocide in eating estab lishments and institutional premises. There are currently 51 registered active products containing the active ingredient et hanol. End use products containing the chemical ethanol are registered for use as surface disinfectants in use sites such as agricultural premises and equipment, medical premises and equipment, industrial areas and residential and public access areas. Ethanol is also registered for use in an tifouling paints for use on boats bottoms and boat running gear below the water line. End us e products are also registered for use in aquatic industrial processe s and water systems such as cooling towers as well as pulp and paper mill process water systems. In addition to being registered for use in human drinking water systems, ethanol is also regi stered for use as an ingredient in products used in pools, hot tubs and spas. In addition, etha nol containing products are also used in aquatic areas such as commercial fishery water systems and fish containing lakes, ponds and reservoirs. There are two registered food contact uses for this chemical. One is for the sanitiza tion of food eggs and the other is as a post harvest trea tment for specific fruits and vegetables.

Ethanol also is registered for use as a plant growth regulator (a ripe ner). There is also a registered use of ethanol with ARCO Ethyl ene Generators (catalytic gene ration of ethylene gas) involving EPA Reg. No.# 58502-1, a product that is registered for use as a ripe ning agent for citrus fruits, pear, avocado, banana, papaya, melons, tomato, flue-cured tobacco/cigar/cigar wrapping. The receptors in fruits and vegetables absorb free at mospheric ethylene molecules, and this in turnDocket Number: EPA-HQ-OPP-2012-0340 www.regulations.gov

5 of 11 accelerates the ripening process. Due to the produc t based conversion of ethanol to ethylene gas, there are no expected exposures to ethanol on the raw agricultural commodity, (RAC) and residual ethylene gas is not expe cted. Fruits and vegetables produce ethylene gas naturally, and reabsorb the gas to stimulate th e production of more; as this is the process by which ripening occurs. Ethanol is converted to ethylene gas, and the gas is pumped into ripening rooms.

The first product containing isopropyl alcoho l (isopropanol) was registered on March 5, 1948 and is registered for use as a glassware saniti zer in eating establishments and hard non-porous surface disinfectant and bacteriocide in househol d, commercial and institutional premises. There are currently 32 registered produc ts containing the active ingredie nt isopropyl alcohol. Products containing isopropyl alcohol are al so registered for use in sp ray, ready to use solution and impregnated wipe forms. End use products co ntaining the chemical isopropyl alcohol are registered for use as porous (f abrics, mattresses, etc.) and non- porous surface disinfectant in use sites such as agricultu ral premises and equipment, industr ial areas and residential and public access areas. Products containing isopropyl alcoho l are also registered for use in/on medical premises and equipment and veterinary premises as well as in/on salon a nd barber shop areas and utensils as well as ultra sonic cleaners and fo r pre-cleaning of medical instruments prior to disinfection. In addition, isopropyl alcohol containing products are also used in non-pesticidal products as a deodorizer in air fresheners. It is al so registered for use in retail and institutional food establishments, food processing plants and other health department regulated food facilities.

There are no EPA established tolerances or exemptions from tolerances identified for isopropanol; however, there are se veral FDA established tolerances for isopropanol in modified hop extract (21 CFR 172.560) and in foods for human consumption (21 CFR 173.240). Ethanol has three inert exemptions from the requirement of a tolerance in 40 CFR 180.910, -.930, and - .940. Both ethanol and isopropanol also have a wide range of non-pesticidal uses. For example, ethanol is contained in some be verages, and isopropanol is th e major ingredient in rubbing alcohol.

Ethanol is listed in 21 CFR 184.1293 as generally recognized as safe (GRAS). Additionally, as defined in 21 CFR 170.3(o)(2), it may be used as an antimicrobial agent on pizza crusts prior to final baking at levels not to exceed 2.0% active by product weight.

The Agency completed a Reregistration Eligibil ity Decision (RED) for Aliphatic Alcohols, C1- C5, in 1995. When the aliphatic alcohols, C1-C 5 (ethanol andisopropyl alcohol) registration review case was established, it wa s considered that C1-5 alcohol s are all very water-soluble and are expected to be similar. The remaining al cohol groups, C6-16, which were in reregistration case 4004 for which a RED was completed in 2007, will be addressed under a separate registration review case.

Comments Received on the Preliminary Work Plan

The Agency received one comment during the p ublic comment period on the initial docket, described below. In the PWP, the Agency soli cited comments on specific topics: environmental justice, water body impairment, trade irritants, an d structure activity relati onships. No comments or information were received during the public comment period con cerning these issues.Docket Number: EPA-HQ-OPP-2012-0340 www.regulations.gov

6 of 11 Comment:

Delta Analytical believes that EPA has approved isopropyl alcohol (IP A) as an inert ingredient in products at percentages much hi gher than the 30% and 5% (for quat products) and requests that EPA review and provide an explanation of the pe rcentages in this paragraph. Delta Analytical questions whether the percentages listed for IPA as an active ingredient or an inert ingredient are current and requests information on the supporting scientific rationale. Information received from an EPA reviewer stated that below 50% isopropanol in quaternary ammonium compound products is an inert ingredient. Therefore, ar e ethanol and isopropyl alcohol when present in quaternary ammonium compound products at percenta ges greater than 50% are considered to be active ingredients?

Response:

The percentages listed for isopropy l alcohol as an active or an in ert ingredient are current as written in the Preliminary Work Plan and s upport documents. As stated in the 1995 aliphatic alcohols RED, inert ingredient determinations are made on a case-by-case basis. While the 1995 RED provides some general information on alipha tic alcohols, each product is individually assessed. Normally the applicant submitting the registration application will make the initial determination on whether an ingredie nt in the product is active or inert. The Agency, as a part of its review, will then determine whether the ingredie nt by itself has the capability to function as a pesticide, whether the ingredient has the abil ity to enhance a pesticide effect in another compound whose pesticidal activity may be substantia lity increased due to the interaction of the compounds, or whether the substance is indeed an inert ingredient. Addi tional factors including the concentration (dosage, intensity ) of the agent, the mode of action of the agent, contact time, the number of microorganisms, the nature of the microorganisms in the population, the presence of solvents, interfering organic matter and inhibition may also fact or into EPA’s determination. If the Agency’s initial evaluation is inconclusive as to whether an i ngredient is active or inert, the Agency will ask the company to submit efficacy data with and without the i ngredient in question. At that point, the efficacy data will determine th e classification of the ingredient. The Agency is open to answering additional questions regarding classification of active ingredients and inerts and encourages the registrant to contact the EPA Product Manager with additional questions as appropriate.

The comments received during the initial public co mment period did not affect the data needs, work plan and timeline described in the PWP and th ey remain as they were presented initially in the PWP. Further, this document makes final th e work plan for the Aliphatic alcohols, C1-C5 registration review process.

Risk Assessments and Anticipated Data Needs

The Agency will not conduct an ecological risk assessment. The Agency will not conduct a human health risk assessment. The Agency will not require additional data for use in conducting the registration review for Ethanol and Isopropanol.Docket Number: EPA-HQ-OPP-2012-0340 www.regulations.gov

7 of 11 Ecological Risk Asse ssment Status and Anticipated Data Needs

 The most recent qualitative ecological risk asse ssment was performed for aliphatic alcohols, C1-C5 (ethanol and isopropyl alcoho l) in support of the 1995 RED.

 The Agency does not anticipate the need to require additional ecologi cal data for use in registration review for aliphati c alcohols, C1-C5 (ethanol and isopropyl alcohol) Case at this time. The use pattern is restricted to indoor uses (listed above), and its use will lead to little, if any, exposure to non-target organisms.

 The Agency does not anticipate the need to requi re additional environmental fate data for use in the aliphatic alcohols, C1-C5 (ethanol and isopropyl alcohol) registration review case at this time. There is sufficient information in the public literature on the fate of aliphatic alcohols in the environment. Aliphati c alcohols chemistry is well known and well documented in the open literature. Although the a liphatic alcohols are exp ected to be stable in water under typical use conditions, the co mpounds are not hazardous to the environment because they are readily biodegradable, a nutrient for microbes, and a metabolite of microbes.

For more information, please refer to Product Chemistry, Environmental Fate, and Ecological Effects Scoping Document in Support of Regist ration Review of Aliphatic Alcohols, C1-C5 (Ethanol and Isopropyl Alcohol). EPA-HQ-OPP-2012-0340, loca ted in the docket.

Human Health Risk Assessment Status and Anticipated Data Needs

 No human health risk assessment has been perf ormed for aliphatic alcohols, C1-C5 (ethanol and isopropyl alcohol). Human health risk assessments were not needed at the time of the RED, because the Agency determined that toxico logical criteria were not triggered and that the exposure and risk from the active ingredient s were not significant when compared to the frequent intentional human exposures re sulting from non-pesticidal uses.

 The Agency does not anticipate the need to re quire additional human health data for use in this registration review for ali phatic alcohols, C1-C5 (ethanol a nd isopropyl alcohol) at this time.

Dietary Assessment

 The registered uses of the aliphatic alc ohols, C1-C5, are not expected to result in contamination of surface water or ground water. Based on the antimicrobial use patterns of these chemicals as well as the fate property of ra pid volatilization from the treated surface. It has been determined that residues of et hanol, along with byproducts resulting from degradation, are not expected to migrate through wastewater tr eatment facilities into drinking water or migrate into residentia l groundwater wells. In the even t that the treated surface is rinsed after pesticidal applic ation and subsequently, the ra pid volatilization supports that ethanol is not expected to be present in the drinking water.Docket Number: EPA-HQ-OPP-2012-0340 www.regulations.gov

8 of 11 Tolerances and Intern ational Harmonization

 There are no EPA established tolerances or exemptions from tolerances identified for isopropanol; however, there are several FDA es tablished tolerances for isopropanol in modified hop extract (21 CFR 172.560) and in foods for human consumption (21 CFR 173.240). Ethanol has three inert exemptions from the requireme nt of a tolerance in 40 CFR 180.910, -.930, and -.940. Both ethanol and isopr opanol also have a wide range of nonpesticidal uses. For example, ethanol is contai ned in some beverages, and isopropanol is the major ingredient in rubbing alcohol.

 Ethanol is listed in 21 CFR 184.1293 as generall y recognized as safe (GRAS). Additionally, as defined in 21 CFR 170.3(o)(2), it may be used as an antimicrobial agent on pizza crusts prior to final baking at levels not to exceed 2.0% active by product weight.

Occupational and Residen tial Assessment and Risk

 Based on frequent intentional human exposures to ethanol along with th e rapid volatilization of the active ingredient from the treated surf aces, it is not expected that there will be measurable residues available to trigger the need for a residential exposure assessment.

 Based on frequent intentional human exposures to isopropyl alcohol along with the rapid volatilization of the active ingredient from the tr eated surfaces, it is not expected that there will be measurable residues available to trigger the need for a residential exposure

assessment.

Aggregate and Cumulative Exposure and Risk

 In examining aggregate exposure, EPA take s into account the available and reliable information concerning exposures to pesticide re sidues in food and drinking water, as well as non-occupational pesticide exposures. An aggreg ate risk assessment has not been deemed necessary for ethanol and isopr opyl alcohol because a human h ealth risk assessment is not required.

EPA does not have, at this time, available da ta to determine whether ethanol has a common mechanism of toxicity with other substances or how to include this pesticide in a cumulative risk

assessment.

 For the purposes of this Registration Review , EPA has assumed that isopropyl alcohol does not have a common mechanism of toxicity w ith other substances when used as an antimicrobial as registered.

Human Health Anticipated Data Needs

 The Agency does not anticipate the need to require additional human health data for the registration review at this time.

For more information, please refer to Aliphatic Alcohols, C1-C5: Human Health Effects Scoping Document for the Registration Review Decision , located in the docket.Docket Number: EPA-HQ-OPP-2012-0340 www.regulations.gov

9 of 11 Product Chemistry Anticipated Data Needs

 The Agency does not anticipate the need to re quire additional product chemistry data for the registration review at this time.

For more information, please refer to Product Chemistry, Environmental Fate, and Ecological Effects Scoping Document in Support of Regist ration Review of Aliphatic Alcohols, C1-C5 (Ethanol and Isopropyl Alcohol). , located in the docket.

Incidents:

Ecological:

 No ethanol ecological incidents have been re ported in the Agency’s Ecological Incident Information System (EIIS).

 No isopropyl alcohol ecol ogical incidents have been reported in the Agency’s Ecological Incident Information System (EIIS).

Human Health:

 No ethanol alcohol human poisoni ng incidents have been reported in the OPP Incident Data System (IDS).

 No isopropyl alcohol human poisoning incidents have been reported in the OPP Incident Data System (IDS).

Endangered Species

EPA has made a “No Effect” determination for endangered species for ethanol and isopropyl alcohol and further environmental risk a ssessments will not be conducted unless public comments or other submissions pr ovide new information or data that warrant such assessment. Based on ethanol and isopropyl alco hol’s use patterns, volatility, ready biodegradability, and low toxicity, and the use of these compounds as a nutrient source by microbes, the Agency has determined that the registered uses of ethanol and isopropyl alcohol will have “no effect” (NE) on endangered or threatened terrestrial or aquatic species, or their designated critical habitats, as listed by the U.S. Fish and Wildlife Serv ice (USFWS) and the National Oceanic and Atmospheric Administration (NOAA) . As a result, no further risk assessment is anticipated unless new information warrants such action.

Endocrine Disruptor Screening Program

As required by FIFRA and FFDCA, EPA reviews num erous studies to asse ss potential adverse outcomes from exposure to chemicals. Collectiv ely, these studies includ e acute, subchronic and chronic toxicity, including asse ssments of carcinogenicity, ne urotoxicity, developmental, reproductive, and general or systemic toxicity. These studies include e ndpoints which may be susceptible to endocrine influe nce, including effects on endocri ne target organ histopathology, organ weights, estrus cyclicity, sexual maturatio n, fertility, pregnancy rates, reproductive loss,Docket Number: EPA-HQ-OPP-2012-0340 www.regulations.gov

10 of 11 and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and chronic studies that assess gr owth, developmental and reprod uctive effects in different taxonomic groups. A human health risk assessment identifying the most sensitive endpoints has not been conducted for the aliphatic alcohols, C1 -C5 (ethanol and isopropyl alcohol) registration review case. However, as required by FFDCA sec tion 408(p), aliphatic alcohols, C1-C5 (ethanol and isopropyl alcohol) are subjec t to the endocrine screening pa rt of the Endocrine Disruptor Screening Program (EDSP).

EPA has developed the EDSP to determine whet her certain substances (including pesticide active and other ingredients) may have an effect in humans or wildlife similar to an effect produced by a “naturally occurring estrogen, or ot her such endocrine effect s as the Administrator may designate.” The EDSP employs a two-tiered approach to making th e statutorily required determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a chemical substance to interact with the estrog en, androgen, or thyroid (E, A, or T) hormonal systems. Chemicals that go th rough Tier 1 screening and are found to have the potential to interact with E, A, or T hormonal systems will proceed to the next stag e of the EDSP where EPA will determine which, if any, of th e Tier 2 tests are necessary base d on the available data. Tier 2 testing is designed to identify a ny adverse endocrine-related eff ects caused by the substance, and establish a dose-response relationship between the dose and the E, A, or T effect.

Under FFDCA section 408(p), the Agency must scre en all pesticide chemicals. Between October 2009 and February 2010, EPA issued test orders/data call-ins for the first group of 67 chemicals, which contains 58 pesticid e active ingredients and 9 inert ingredients. Ethanol was included on that list and has been issued an order to conduc t the Tier 1 testing. Once all required Tier 1 and Tier 2 data have been received and reviewed, the endpoints and safety factors used for risk assessment purposes will be examined and a new risk assessment performed if necessary. For further information on the status of the EDSP, the policies and procedur es, the list of 67 chemicals, future lists, the test guidelines and the Tier 1 screening ba ttery, please visit our website: http://www.epa.gov/endo/.

Timeline

EPA has created the following estimated timeline for the completion of the Aliphatic alcohols, C1-C5 registration review:

Anticipated Schedule 1

Activities Estimated Month/Year Phase 1: Opening the docket Open Public Comment Period for Docket Completed July 2012
Close Public Comment Peri od for Docket Completed September 2012 Phase 2: Case Development Develop Final Work Plan (FWP) Completed December 2012
Issue DCI N/ADocket Number: EPA-HQ-OPP-2012-0340 www.regulations.gov

11 of 11 Data Submission N/A Open Public Comment Period for Preliminary Risk Assessments N/A Close Public Comment Period for Preliminary Risk Assessments N/A Phase 3: Registration Review Decision Open Public Comment Period for Propos ed Reg. Review Decision December 2013 Close Public Comment Period for Proposed Reg. Review Decision February 2013 Final Decision and Begin Post-Decision Follow-up June 2014 Total (years) 2

Next Steps

EPA will complete a proposed registration revi ew decision for - Aliphatic Alcohols, C1-C5 (Case 4003), to be issued in Fiscal Year 2013.

1 The anticipated schedule will be revised as necessary base d, for example, on any need arising under the Endocrine Disruptor Screening Program with respect to the active ingredients in this case.