United States Chemical Safety July 2011 Environmental Protection and Pollution Prevention Agency (7510P) 

# p - chloro - m - cresol & sodium p - chloro - m - cresolate Registration Review : Final Work Plan July 2011Docket Number: E PA-HQ-OPP-2011 - 0071, EPA - HQ - OPP-2011 - 0073 www.regulations.gov 

## p-chloro-m-cresol & 

## sodium p-chloro-m-cresolate Registration Review: Final Work Plan September 2011 

## Case # 

## 3046 & 

## 5011

an Harrigan - Farrelly Director, Antimicrobials Division Date:

# 1/**'Z1J (1**  2 of IIDocket Number: EPA - HQ - OPP - 2011 - 0071 , EPA - HQ - OPP - 2011 - 0073 www.regulations.gov

3 of 11 p - chloro - m - cresol and sodium p - chloro - m - cresolate Registration Review Team Nathan Mottl Human Health & Environmental Effects Srinivas Gowda Seiichi Murasaki Risk Management Lance Wormell Philip Ross Office of General Counsel

________________________________________ S upporting documents may be found in the registration review docket EPA - HQ - OPP - 2011 - 0071 for the p - chloro - m - cresol Case and in the registration review docket EPA - HQ - OPP - 2011 - 0073 for the sodium p - chloro - m - cresolate Case, both located on the internet at www.regulations.gov .Docket Number: EPA - HQ - OPP - 2011 - 0071 , EPA - HQ - OPP - 2011 - 0073 www.regulations.gov

4 of 11 This is the Final Work Plan (FWP) of the Environmental Protection Agency (EPA or “the Agency”) for the registration review of p - c hloro - m - cresol (Case 3046 ) and sodium p - chloro - m cresolate (Case 5011) . The work plan includes the expected registration review timeline . The work plan also addresses public comments received concerning the Preliminary Work Plan (PWP) in the Summary Document which was posted in the p - c hloro - m - cresol and sodium p chloro - m - cresolate registration review docket s , and any other comments concerning the initial docket postings . The Summary Document 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. Introduction

The Agency is implementing the registration review 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 the FIFRA standard for registration. Changes in sc ience, public policy and pesticide use practices will occur over time. The registration review program is intended to make sure that, as the ability to assess risk evolves and as policies and practices change, all registered pesticides continue to meet tha t statutory standard. The public phase 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 p - c hloro - m - c resol and sodium p - chloro - m - cresolate Preliminary Work Plan (PWP) (PC Code s 064206 and 064205 ) was published on March 30, 2011 and the 6 0 - day comment period ended on May 31, 2011 . The Preliminary Work Plan document is available on www.regulati ons.gov docket number s EPA - HQ - OPP - 2011 - 0071 and EPA - HQ - OPP - 2011 - 0073 . The current registration review cases include two chemicals: p - chloro - m - cresol ( C ase 3046, PC Code 064206) and its salt, sodium p - chloro - m - cresolate ( C ase 5011, PC Code 064205). Because sodium p - chloro - m - cresolate rapidly protonates in water to form p - chloro - m - cresol, data will be bridged between sodium p - chloro - m - cresolate products and the technical product for p - chloro mcresol. The first product containing 4 - Chloro - 3 - cresol ( p - chloro - m - cresol or PCMC ) (PC Code 064206 ) as an active ingredient was registered in the United States in 1968 . Currently, there are three products registered with EPA. PCMC is used to control slime - forming bacteria, yeasts, and fungi in industrial preservatives inc luding oil recovery drilling muds/packer fluids, adhesives, coatings, emulsions, leather processing liquors and leather products, metal working fluids, and paints. PCMC has a use classification as a material preservative and currently does not have a pesti cide tolerance or exemptions from the requirement of a tolerance. PCMC is cleared by the Food and Drug Administration (FDA) as an indirect food additive and formulated into adhesives (21 CFR 175.105), and paper and paperboard components (176.180, 176.200, 176.210). In addition, it has a food contact notification (FCN) as a lubricant at levels not to exceed 1 percent (FCN 560). PCMC has recently been registered for disinfectant uses for industrial, hospital, household, institutional, and hard surface disi nfection. A reregistration eligibility decision (RED) for p chloro - m - cresol was completed in 1996 .Docket Number: EPA - HQ - OPP - 2011 - 0071 , EPA - HQ - OPP - 2011 - 0073 www.regulations.gov

5 of 11 The first product containing sodium p - chloro - m - cresolate (Na PCMC) (PC Code 064205) as an active ingredient was registered in the United States in 2000. Curr ently, there are six active products registered with EPA. Registered uses for Na PCMC are the same as uses of PCMC (i.e., Na PCMC is registered for use as a disinfectant for industrial, hospital, household, institutional, and hard surface disinfection and as a material preservative to control slimeforming bacteria, yeasts, and fungi in oil recovery drilling muds/packer fluids, adhesives, coatings, emulsions, leather processing liquors and leather products, metal working fluids, and paints). Na PCMC currentl y does not have a pesticide tolerance or exemptions from the requirement of a tolerance. The Agency will determine if any tolerances or exemptions from the requirement of a tolerance are needed for registered uses of Na PCMC during registration review. The Agency did not identify any FDA clearances for Na PCMC. A RED was not completed for sodium p - chloro - m cresolate because it was registered after November 1, 1984. The Agency received two comments during the pu blic comment period on the initial docket, described below. In the PWP, the Agency solicited comments on specifi c topics: environmental justice, water body impairment , trade irritants , and structure activity relationships . No comments or information were r eceived during the public comment period concerning these issues. Comments Received on the Preliminary Work Plan

Comment: The FIFRA Endangered Species Task Force (FESTF) submitted a comment noting that it has data that will assist the Agency in conducting an endangered species risk assessment for PCMC and Na PCMC, and requesting that any technical registrant for M - Cresol who is not a member of the FESTF (or a company having met its data compensation obligations) be asked to provide a formal offer - to - pay to FESTF for reliance on their data. Response: The Agency thanks FESTF for its comment and will consider this information as it conducts the registration review and makes its registration review decisions. Comment: In the comment, PCRM ass erts that “[b]ecause the original materials are corrosive, they must be diluted to prevent potentially confounding and painful portal - of - entry injuries in the test animals. Therefore, the study is not effectively modeling the material to which handlers and others are exposed.” The Physicians Committee for Responsible Medicine (PCRM) submitted a comment regarding the 90 - day inhalation toxicity study (GLN 870.3465).

Furthermore, PCRM believes results from the study would likely lead to a more certain, but less conservative, risk assessment since the original risk assessment assumed 100% respiratory absorption. Response: The Agency does not requi re the undiluted TGAI be used to conduct the 90 - day inhalation toxicity (870.3465). According to EPA’s published OPPTS Health Effects Test Guidelines 870.3465, “it is desirable to have a concentration - response relationship as well as a NOEL. Therefore, at least three concentration levels plus a control and, where appropriate, a vehicle...shall be used. Concentrations should be spaced appropriately to produce test groups with a range of toxic effects.” The AgencyDocket Number: EPA - HQ - OPP - 2011 - 0071 , EPA - HQ - OPP - 2011 - 0073 www.regulations.gov

6 of 11 anticipates submission of subchronic inhalation toxicity studies conducted with dilute concentrations of PCMC or Na PCMC that demonstrate toxic effects at non corrosive/non - caustic levels. In the absence of these data, the Agency may assume 100% respiratory absorption and, if risks of concerned are id entified, impose unnecessary mitigation measures through future risk assessment and decision - making. For future decisions, the 90 - day inhalation study will allow the Agency to conduct human - health risk assessments using real - world, chemical - specific inputs and minimize the potential for underestimating or overestimating risk. The comments received during the initial public comment period did not affect the anticipated data needs, work plan and timeline described in the PWP and they remain as they were prese nted initially in the PWP. Further, this document makes final the work plan for the p - c hloro - m - cresol and sodium p - chloro - m - cresolate registration review process. The Agency will conduct a comprehensive ecologica l risk assessment, including an endangered species risk assessment, for all uses of p - chloro - m - cresol and sodium p - chloro - m - cresolate . The Agency will conduct a human health risk assessment. The Agency will require additional data for use in conducting the registration review for p - chloro - m - cresol and sodium p - chloro - m cresolate . Risk Assessments and Anticipated Data Needs

Ecological Risk Assessment Status and Data Needs **•** No ecological risk assessments were performed for p - chloro - m - cresol or sodium pchloro - m cresolate due to limited indoor use pa tterns and low likelihood of environmental exposure. Because of the potential for environmental exposure if material preservatives pass through waste water treatment plants (WWTPs) and are discharged into terrestrial and aquatic environments, the Agency wi ll conduct ecological and environmental fate risk assessments for material preservative uses . **•** The Agency has not conducted risk assessments that support a complete endangered species determination for p - chloro - m - cresol or sodium p - chloro - m - cresolate. The ecological risk assessments planned during registration review will allow the Agency to determine whether the use of p - chloro - m - cresol or sodium p - chloro - m - cresolate has 'no effect' or 'may affect' federally listed threatened or endangered species (listed species) or their designated critical habitats. When an assessment concludes that a pesticide’s use 'may affect' a listed species or its designated critical habitat, the Agency will consult with the U.S. Fish and Wildlife Service and/or National Marine Fis heries Services (the Services), as appropriate. **•** The Agency anticipates the need to require the following additional ecological data for use in conducting the registration review of p - chloro - m - cresol and sodium p - chloro - m - cresolate . 850.5400 -- Algal Toxicity Tier II using freshwater green alga, Selenastrum capricornutumDocket Number: EPA - HQ - OPP - 2011 - 0071 , EPA - HQ - OPP - 2011 - 0073 www.regulations.gov

7 of 11 **•** The Agency anticipates the need to require the following additional environmental fate data for use in conducting the registration review of p - chloro - m - cresol and sodium p - chloro - m cresolate . 835.2120 -- Hydrolysis 835.2240 -- Photodegradation in water 850.6800 -- Modified activated slud ge, respiration inhibition test 835.1110 -- Activated Sludge Sorption Isotherm 835.3110 -- Ready Biodegradability **•** F or more information , please refer to Summary of Product Chemistry, Environmental Fate, and Ecotoxicity Data for the p - Chloro - m - Cresol and Sodium p - Chloro - m - Cresolate Registration Review Decision Document , located in the docket . Human Health Risk Assessment Status and Data Need s **•** Assessments to support sodium p - chloro - m - cresolate’s initial registration in 2000 utilized the same toxicity, chemistry, and exposure data used in support of the p - chloro - m - cresol RED in 1996. Because the PCMC RED was pre - FQPA, the Agency expects new ris k assessments will be necessary. Furthermore, risk assessments must be performed for the disinfectant and leather product uses for both p - chloro - m - cresol and sodium p - chloro - mcresolate.

**•** Although categorized for non - food use, the Agency anticipates the need to conduct dietary exposure and risk assessments because of possible indirect dietary exposure resulting from migration of residues from pesticidal sources (e.g., adhesives, cements, coatings, food contact paper, and lubricant oils) in to food. Dietary Assessment

**•** The Agency will also assess potential acute and chronic indirect ingestion exposure estimates resulting from kitchen surface disinfectant and detergent uses. **•** The Agency will determine the need for a dietary drinking water risk assessment follow ing the submission and review of required environmental fate data.

**•** PCMC has a use classification as a material preservative and currently does not have a pesticide tolerance or exemptions from the requirement of a tolerance. PCMC is cleared by the Food and Drug Administration (FDA) as an indirect food additive and formulated into adhesives (21 CFR 175.105), and paper and paperboard components (176.180, 176.200, 176.210). Tolerances and International Harmonization

**•** Na PCMC currently does not have a pesticide tolerance or exemptions from the requirement of a tolerance. The Agency did not identify any FDA clearances for Na PCMC.Docket Number: EPA - HQ - OPP - 2011 - 0071 , EPA - HQ - OPP - 2011 - 0073 www.regulations.gov

8 of 11 **•** During registration review, the Agency will determine if any tolerances or exemptions from the requirement of a tolerance are needed for the registered uses of PCMC/Na PCMC.

**•** Assessments of occupational risk are planned for registration review because potential exposure is expected through dermal and inhalation routes during open - pour and mixing for materials preservation, oil recovery, leather production, and textile production. Dermal and inhalation exposure are also expected to result from the use of treated paints, disinfectants, and metal - working fluids. Occupational and Residential Assessment and Risk

**•** Assessments of r esidential risk are planned for registration review because potential exposure is expected through dermal, inhalation, and incidental ingestion routes resulting from the use of treated paints, leather, and household disinfectants.

**•** An aggregate risk assessment for PCMC/Na PCMC is needed to assess aggregate exposures from dietary sources (food and water), residential handler, and post - application exposures for paint. Aggregate and Cumulative Exposure and Risk

**•** EPA does not have, at this time, available data to determine whether PCMC/Na PCMC ha ve common mechanism s of toxicity with other substances or how to include th e s e pesticide s in a cumulative risk assessment. **•** For the purposes of this Registration Review, EPA has assumed that PCMC/Na PCMC do not have common mechanism s of toxicity with other substances when used as antimicrobial s as registered.

**•** The Agency anticipates the need to require the following additional human health data for use in conducting the registration review of p - chloro - m - cresol and sodium p - chloro - m cresolate . Human Health Data Needs

870.3465 -- 90 - day inhalation toxicity (rat) 870.3700 -- D evelopmental toxicity study (rabbit ) 870.3800 -- Reproduction and fertility effects 875.1100 -- Dermal outdoor exposure 875.1200 -- Dermal indoor exposure 875.1300 -- Inhalation outdoor exposure 875.1400 -- Inhalation indoor exposure 875.1600 -- Application exposure data reporting and calculations 875.1700 -- Product use information 875.2300 -- Indoor surface residue dissipation 875.2500 -- Inhalation exposure 875.2700 -- Product use informationDocket Number: EPA - HQ - OPP - 2011 - 0071 , EPA - HQ - OPP - 2011 - 0073 www.regulations.gov

9 of 11 875.2900 -- Data reporting and calculations 875.3000 -- Nondietary ingestion exposure **•** For more information, please refer to Summary of Human Health Effects Data for the p Chloro - m - cresol and Sodium p - Chloro - m - cresolate Registration Review Decision Document , located in the docket . Product Chemistry Data Needs **•** The Agency does not anticipate the need to require additional product chemistry data for th is registration review at this time. **•** F or more informa tion , please refer to Summary of Product Chemistry, Environmental Fate, and Ecotoxicity Data for the p - Chloro - m - Cresol and Sodium p - Chloro - m - Cresolate Registration Review Decision Document , located in the docket . Ecological: Incidents:

**•** No p - chloro - m - cresol or sodium p - chloro - m - cresolate ecological incidents have been reported in the Ecological Incident Information System (EIIS), maintained by EPA’s Environmental Fate and Effects Division (EFED). Human Health: **•** No p - chloro - m - cresol or sodium p - chloro - m - cresolate human poisoning incidents have been reported in the OPP Incident Data System (IDS). Endangered Species The Agency has not conducted risk assessments that support a complete endangered species determination for p - chloro - m - cresol or sodi um p - chloro - m - cresolate. The ecological risk assessments planned during registration review will allow the Agency to determine whether the use of p - chloro - m - cresol or sodium p - chloro - m - cresolate has 'no effect' or 'may affect' federally listed threatened o r endangered species (listed species) or their designated critical habitats. When an assessment concludes that a pesticide’s use 'may affect' a listed species or its designated critical habitat, the Agency will consult with the U.S. Fish and Wildlife Servi ce and/or National Marine Fisheries Services (the Services), as appropriate. Endocrine Disruptor Screening Program As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potential adverse outcomes from exposure to chemicals. Collectively, t hese studies include acute, subchronic and chronic toxicity, including assessments of carcinogenicity, neurotoxicity, developmental, reproductive, and general or systemic toxicity. These studies include endpoints which may be susceptible to endocrine influ ence, including effects on endocrine target organ histopathology, organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, reproductive loss,Docket Number: EPA - HQ - OPP - 2011 - 0071 , EPA - HQ - OPP - 2011 - 0073 www.regulations.gov

10 of 11 and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests a nd chronic studies that assess growth, developmental and reproductive effects in different taxonomic groups. As part of its most recent registration decision , EPA reviewed these data and selected the most sensitive endpoints for relevant risk assessment sc enarios from the existing hazard database. However, as required by FFDCA section 408(p), p - chloro - m - cresol and sodium p - chloro - m - cresolate are subject to the endocrine screening part of the Endocrine Disruptor Screening Program (EDSP). EPA has developed t he EDSP to determine whether 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 other such endocrine effects as the Administrat or may designate.” The EDSP employs a two - tiered approach to making the 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 estrogen, androgen, or t hyroid (E, A, or T) hormonal systems. Chemicals that go through Tier 1 screening and are found to have the potential to interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA will determine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2 testing is designed to identify any adverse endocrine - related effects 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 screen 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 pesticide active ingredients and 9 inert ingredients. P - chlo ro - m - cresol and sodium p - chloro - m - cresolate are not among the group of 58 pesticide active ingredients on the initial list to be screened under the EDSP. Accordingly, as part of registration review, EPA will issue future EDSP orders/data call - ins, requirin g the submission of EDSP screening assays for p chloro - m - cresol and sodium p - chloro - m - cresolate . For further information on the status of the EDSP, the policies and procedures, the list of 67 chemicals, future lists, the test guidelines and the Tier 1 screening battery, please visit our website: http://www.epa.gov/endo/ . EPA has created the following estimated timeline for the completion of the p - chloro - m - cresol and sodium p - chloro - m - cresolate registration review: Timeline Anticipated Schedule Activitie s Estimated Month/Year Phase 1: Opening the docket Open Public Comment Period for Docket Completed March 2011 Close Public Comment Period for Docket Completed May 2011 Phase 2: Case Development Develop Final Work Plan (FWP) Completed July 2011 Issue DCI September 2012Docket Number: EPA - HQ - OPP - 2011 - 0071 , EPA - HQ - OPP - 2011 - 0073 www.regulations.gov

11 of 11 Data Submission September 2016 Open Public Comment Period for Preliminary Risk Assessments March 2018 Close Public Comment Period for Preliminary Risk Assessments June 2018 Phase 3: Registration Review Decision Open Public Comment Period for Proposed Reg. Review Decision September 2018 Close Public Comment Period for Proposed Reg. Review Decision December 2018 Final Decision and Begin Post - Decision Follow - up March 2019 Total (years) 8 Next Steps A DCI will be developed regarding the data needs listed under the “Risk Assessments and Data Needs” section of this document. The Agency expects to issue the DCI in September 2012 . Human health and environmental fate and ecological hazard assessments will be conducted for all uses.