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 2011
Docket Number: EPA-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 

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Docket Number: EPA-HQ-OPP-2011-0071, EPA-HQ-OPP-2011-0073

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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

________________________________________

Supporting 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

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This is the Final Work Plan (FWP) of the Environmental Protection Agency (EPA or “the 

Agency”) for the registration review of p-chloro-m-cresol (Case 3046) and sodium p-chloro-mcresolate (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-chloro-m-cresol and sodium pchloro-m-cresolate registration review dockets, 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 science, 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 that 

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-chloro-m-cresol and sodium p-chloro-m-cresolate Preliminary Work Plan (PWP) (PC 

Codes 064206 and 064205) was published on March 30, 2011 and the 60-day comment period 

ended on May 31, 2011. The Preliminary Work Plan document is available on 

www.regulations.gov docket numbers EPA-HQ-OPP-2011-0071 and EPA-HQ-OPP-2011-0073.

The current registration review cases include two chemicals: p-chloro-m-cresol (Case 3046, PC 

Code 064206) and its salt, sodium p-chloro-m-cresolate (Case 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-chloromcresol.

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 including 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 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). 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 disinfection. A reregistration eligibility decision (RED) for pchloro-m-cresol was completed in 1996.
Docket Number: EPA-HQ-OPP-2011-0071, EPA-HQ-OPP-2011-0073

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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. Currently, 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 

currently 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-mcresolate because it was registered after November 1, 1984.

The Agency received two comments during the public comment period on the initial docket, 

described below. In the PWP, the Agency solicited comments on specific topics: environmental 

justice, water body impairment, trade irritants, and structure activity relationships. No comments 

or information were received 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 asserts 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 require 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 Agency 
Docket Number: EPA-HQ-OPP-2011-0071, EPA-HQ-OPP-2011-0073

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anticipates submission of subchronic inhalation toxicity studies conducted with dilute 

concentrations of PCMC or Na PCMC that demonstrate toxic effects at noncorrosive/non-caustic levels. 

In the absence of these data, the Agency may assume 100% respiratory absorption and, if 

risks of concerned are identified, 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 presented 

initially in the PWP. Further, this document makes final the work plan for the p-chloro-m-cresol

and sodium p-chloro-m-cresolate registration review process.

The Agency will conduct a comprehensive ecological 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-mcresolate.

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-mcresolate due to limited indoor use patterns 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 will 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 Fisheries 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 

capricornutum
Docket Number: EPA-HQ-OPP-2011-0071, EPA-HQ-OPP-2011-0073

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• 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-mcresolate.

835.2120 -- Hydrolysis

835.2240 -- Photodegradation in water

850.6800 -- Modified activated sludge, respiration inhibition test

835.1110 -- Activated Sludge Sorption Isotherm

835.3110 -- Ready Biodegradability

• For 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 Needs

• 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 risk 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) into 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 following 

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.
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• 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 residential 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 have

common mechanisms of toxicity with other substances or how to include these pesticides in a 

cumulative risk assessment.

• For the purposes of this Registration Review, EPA has assumed that PCMC/Na PCMC do 

not have common mechanisms of toxicity with other substances when used as antimicrobials

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-mcresolate.

Human Health Data Needs

870.3465 -- 90-day inhalation toxicity (rat)

870.3700 -- Developmental 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 information
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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 pChloro-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 this

registration review at this time.

• For 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.

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 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 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, these 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 influence, including effects on endocrine target organ histopathology, 

organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, reproductive loss, 
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and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and 

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 scenarios 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 the 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 Administrator 

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 thyroid (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-chloro-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, requiring the submission of EDSP screening assays for pchloro-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

Activities 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 2012
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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.