UNITED STATES ENVIRONMENTAL PROTECTION AGE CY

WASHINGTON, D.C. 20460

OFFICE OF CHEMICAL SAFETY

AND POLLUTIO~ PREVENTiON

February 18, 2011

MEMORANDUM

SUBJECT: Summary of Human Health Effects Data for the p-Chloro-m-cresol

and Sodium p-Chloro-m-cresolate Registration Review Decision

Document.

PC Coders): 064205, 064206 DP Bareode(sYNo(s): D383015

Registration No(s): PCMC

33967-8,33967-9,33967-12,49403-19

Decision No.: 440820 NaPCMC

39967-21,39967-22,39967-25,39967-26,39967-27,

39967-46

Petition No(s).: NA Regulatory Action: Human Health Registration

Review

Risk Assess Type: Multiple Chemicals Case No(s).: 3046,5011

CAS No(s): 59-50-7, 15733-22-9

TXRNo.:NA p-Chloro-m-Cresol, Sodium p-Chloro-m-Cresolate

MRID Nors).: NA 40 CFR: None

FROM:

TO:

THRU:

Nathan Mottl, Biologist

Team Two

Risk Assessment and Science Support Branch (RASSB)

Antimicrobials Division (751 OP)

Seiichi Murasaki, Chemical Review Manager

Regulatory Management Branch II

Antimicrobials Division (7510P)

Lance Wannell, Team Leader

Regulatory Management Branch n

Antimicrobials Division (751 OP)

Nader Elkassabany. Branch Chief

Risk Assessment and Science Support Branch (RASSB)

Antimicrobials Division (751 OP)

Page 1 of20
EXECUTIVE SUMMARY 

 The Antimicrobials Division (AD) Registration Review Team has evaluated the status 

of the human health assessments for p-chloro-m-cresol (case 3046, PC Code 064206) and 

sodium p-chloro-m-cresolate (case 5011, PC Code 064205) for the purpose of registration 

review. p-Chloro-m-cresol (PCMC) was first registered as a pesticide in the U.S in 1968 

and sodium p-chloro-m-cresolate (Na PCMC) was first registered in 2000. 

 PCMC is formulated in two manufacturing use products (MUPs) as a >99.9% active 

ingredient (a.i.) and as a dilutable concentrate (e.g., 29.6% a.i.) that is also mixed with ophenyl phenol at 12.5% a.i. Na PCMC is manufactured as a formulating intermediate (71 

% ai) and as ready-to-use soluble concentrates in five end-use products (31.9 to 71% ai). 

In addition, two of the Na PCMC end-use products contain other active ingredients such 

as o-phenyl phenol, octhilinone, and sodium pyrithione. 

A reregistration eligibility decision (RED) document for PCMC was conducted in 

1997. Since Na PCMC was registered in 2000, it was not included in the Registration 

Eligibility Decision (RED) document or the original PCMC case. A RED is not required 

for chemicals registered after November 1, 1984. The PCMC RED indicated that PCMC 

is a microbicide used to control slime-forming bacteria, yeasts and fungi as an industrial 

preservative in 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 exemption 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 preservative in 

lubricants at levels not to exceed 1 percent (FCN 560). It should be noted that PCMC has 

been recently registered for industrial, hospital, household, institutional, and hard surface 

disinfection. During registration review, the Agency may have to determine if any 

tolerances or exemptions from the requirement of a tolerance are needed for the 

disinfectant use. 

 Na PCMC has the same uses as PCMC and also has similar application rates. Past 

risk assessments submitted for registration have utilized much of the same toxicity, 

chemistry and exposure data used for PCMC. During registration the Agency concluded 

that much of the data for PCMC could be bridged to Na PCMC, since Na PCMC is 

rapidly protonated in water to form PCMC. EPA did not identify any FDA clearances for 

the Na PCMC active ingredient even though the uses were practically identical to PCMC. 

 The Agency did not identify a dietary risk assessment for PCMC/Na PCMC that 

assesses indirect food additive uses, and based on review of the current labeled uses, 

anticipates developing dietary assessments for the following use patterns: 

 

• Adhesives, 

• Cements, 

• Coatings, 

• Food contact paper, 

Page 2 of 20 
• Lubricant oils, 

• Detergents, and 

• Cleaning solutions. 

 

 The purpose of this review is to examine and characterize the existing hazard and 

exposure databases for PCMC and to determine whether new data and risk assessments 

are expected to be needed. Based on this review of the Agency data, existing risk 

assessments, reviews and the existing use pattern , the Agency expects that data and 

additional risk assessments will be needed to assess occupational, residential, dietary, and 

drinking water exposures. In addition, the Agency anticipates that additional toxicity and 

exposure studies may be needed to assess the hazards of PCMC. 

 

Page 3 of 20 
 

Section 1. Chemical Identity

Tables 1 and 2 identify the chemical identification of the two active ingredients covered 

in this registration review. 

Table 1. Chemical Identity 

Common 

Name 

p-Chloro-m-cresol 

Synomyms 4-Chloro-3-cresol, 4-Chloro-3-

methylphenol, Parachlorometacresol 

PC Code 064206 

CAS registry 

number 

59-50-7 

Registration 

Review Case 

No. 

3046 

Structure 

According to the RED, PCMC is a white crystalline solid that is moderately soluble 

in water (4 gm/L), and very soluble in organic solvents (500 gm/L ethanol). PCMC is 

lipophilic with a log Kow of 3. The melting point of the solid is 63-65oC and the boiling 

point is 239oC. The molecular weight is 142.6. The solution in water acts as an organic 

weak acid with a pH of 5.6 and a dissociation constant of 9.4. The vapor pressure is 0.25 

mm Hg at 25oC. 

Table 2. Chemical Identity 

Common 

Name 

Sodium p-Chloro-m-cresolate 

Synomyms p-Chloro-m-cresol, sodium salt; 

Parachlorometacresolate, sodium salt; 

Sodium Parachlorometacresolate; Sodium 

4-chloro-3-cresolate; Sodium 4-chloro-3-

methylphenolate; Sodium p-chloro-mmethylphenate; 

PC Code 064205 

CAS registry 

number 

15733-22-9 

Page 4 of 20 
Registration 

Review Case 

No. 

5011 

Structure 

Section 2. Toxicology 

 The Agency has reviewed the existing toxicity assessments and toxicity data for 

PCMC and Na PCMC. The Agency reviewed the historical toxicological database 

supporting the reregistration of PCMC and Na PCMC. Based on the use pattern, the 

Agency expects that additional toxicity data will be needed. 

 It appears that the Agency decided to rely on the same toxicity information taken 

from the Registration Eligibility Decision (RED) for p-Chloro-m-cresol to support the 

registration of sodium p-chloro-m-cresolate (Na PCMC) (D331570, D331571, D331573, 

D331575). The Agency identified only one acute oral toxicity study that is unique for Na 

PCMC. 

Acute Toxicity

PCMC 

 For registration review, the Agency will rely on the existing acute toxicity database 

developed during reregistration. According to Agency documentation (D011751), 

PCMC has an acute oral toxicity category of III based on an oral LD50 of 3,636 mg/kg 

for female rats and 5,129 mg/kg for male rats. An acute dermal toxicity category of IV 

was based on a dermal LD50 of >5,000 mg/kg from a dermal rat study. PCMC was 

identified as corrosive to the eye and skin on rabbits (acute toxicity category I). However, 

it was not a dermal sensitizer in guinea pigs. The rat inhalation study was waived since 

PCMC is corrosive on skin. 

Na PCMC 

 According to Agency documentation (D280484), the registrant submitted an acute 

toxicity test for Na PCMC. The data indicated that Na PCMC had an acute oral toxicity 

category of III based on an oral LD50 of >2000 mg/kg for male rats and 1,272 mg/kg for 

female rats. This study was reviewed as acceptable. Since there is no technical product, 

the acute data requirements are bridged to the technical product PCMC. 

Mutagenicity

 The Agency does not anticipate the need for additional mutagenicity data based on 

review of the existing mutagenicity data submitted during reregistration of PCMC. In the 

Page 5 of 20 
database of mutagenicity studies, no evidence of gene mutation was identified in two 

acceptable in vitro bacterial reverse gene mutation (Ames) assays (MRID 00078838 and 

MRID 42199901). No forward gene mutations were seen in an in vitro study Chinese 

hamster ovary (HGRPT) study with and without metabolic activation (MRID 41548601). 

No chromosome aberrations were seen in an acceptable in vivo mammalian cytogenetics 

bone marrow micronucleus assay in mice (MRID 41598101 and MRID 42005201). 

PCMC was tested in rat primary hepatocytes in an unscheduled DNA synthesis study 

(UDS) assay and did not cause DNA damage or inducible repair under the conditions of 

the study (MRID 41598101 and MRID 42163201). 

Subchronic Toxicity 

Oral 

One subchronic feeding study in 20/sex male and female Wistar rats at dose levels 

of 0, 150, 500 or 1500 ppm for 13 weeks (0, 12, 41, or 120 mg/kg/day for males and 0, 

17, 54, or 167 mg/kg/day for females) was found in the existing literature. Clinical signs, 

body weights, food consumption, clinical biochemistry, urinalysis, organ weights, gross 

pathology and microscopic pathology were measured. At 500 and 1500 ppm, a decrease 

in body weight gain was observed in males but not females (5-6% less than controls). No 

other effects were observed. The decreases in body weight gain are not of toxicological 

significance. The NOEL is greater than 1500 ppm which was the highest dose tested 

(MRID 00124844). 

Dermal 

A 21-day dermal study using a TGAI of 99.9% PCMC was tested in a 21-day 

dermal study in New Zealand White rabbits (10/sex/dose group) at the following dose 

levels: 0, 10, 40 or 160 mg/kg/day. The animals were dosed 5 days/week for a total of 15 

applications. It appears that the test material was applied without a vehicle. Dermal 

irritation was observed in all treated groups, which ranged from slight erythema and very 

slight edema (10 mg/kg/day) to severe erythema and slight edema (160 mg/kg/day). 

Other dermal effects included skin thickening, scaling, blanching, raw areas, necrosis, 

brown scab-like areas, and sloughing. Fissuring occurred in one mid-dose female and in 

two high dose males. The NOAEL for dermal irritation is less than 10 mg/kg/day lowest 

dose tested. No systemic effects were observed at either 10 mg/kg/day or 40 mg/kg/day. 

At 160 mg/kg/day, a compound related enhancing effect on nonsupporative 

pericholangitis (both sexes) and bile duct proliferation (females) in the liver were 

observed. The systemic NOEL is 40 mg/kg/day and the LOEL is 160 mg/kg/day based on 

enhanced liver pathology in both sexes (MRID 00062905). 

Inhalation 

 No inhalation toxicity tests are available. 

Developmental Toxicity

Page 6 of 20 
 EPA reviewed a rat developmental study on PCMC (D179265) in which PCMC 

was administered to Wistar rats at dose levels of 0, 30, 100, and 300 mg/kg/day during 

days 6-15 of gestation. At 300 mg/kg, 6 dams died and treatment-related clinical signs of 

toxicity included audible breathing sounds, gasping breathing, reduced motility and high 

stepping gait, lying on side, somnolence, abdominal position, spastic convulsions, rough 

coat, sunken flanks and bloody muzzle. At 100 mg/kg, labored breathing was observed 

in two rats, and decrease in body weight gain. The NOAEL for maternal toxicity is 30 

mg/kg/day and the LOAEL is 100 mg/kg/day based on clinical signs of toxicity and 

decreases in body weight gain (100 mg/kg/day and above) and death, decreases in food 

consumption and increases in total resorptions (300 mg/kg/day). The NOAEL for 

developmental toxicity is 100 mg/kg/day and the LOAEL is 300 mg/kg/day based on a 

significant decrease in the mean fetal weight per litter at 300 mg/kg/day when compared 

to the control group and a slight increase in the number of microphthalmias or 

anophthalmias at this dose level (MRID 42292901). 

Chronic Toxicity/Carcinogenicity

Technical PCMC (99.9 to 99.97 % a.i.) was tested in a chronic/carcinogenicity 

feeding study for male and female Wistar rats. Fifty rats per sex were tested per dose 

level at 24 months with an additional ten per sex scheduled to be sacrificed at 53 weeks. 

The following dose levels were administered: 0, 400, 2000, or 10,000 ppm (0, 21, 103.1, 

or 558.9 mg/kg/day for males and 0, 27.7, 134.3, or 743.5 mg/kg/day for females). The 

systemic NOAEL is less than 400 ppm and the systemic LOAEL is 400 ppm based on 

poor general condition, decreased body weight and food efficiency, increased water 

intake, decreased urinary protein, changes in organ weights and histopathology of the 

kidney, brain (400 ppm and above), testes and epididymides (2000 ppm and above) 

(MRID 42784801). 

In this study, pituitary tumors were found in females, and male rats had a 

significant increasing trend in testicular interstitial cell tumors (p <0.05). The incidences 

of these tumors, however, were within the historical control range. Therefore, the 

increased incidence of tumors seen in this study was not related to treatment with PCMC. 

Based on the results of the study, the Agency concluded that PCMC is not classifiable as 

a human carcinogen and is assigned to Group D. 

Reproductive Toxicity 

 Since the Agency expects that there will be chronic effects as a result of the uses 

(e.g., metalworking fluid use), the Agency anticipates the need for a rodent reproduction 

and fertility effects study. This study examines the reproductive and neurotoxicity effects 

in the maternal rat and developing offspring. It may also provide a toxicity endpoint 

applicable for human health risk assessment to women (15-49 years of age), infants and 

children. 

Summary of Toxicity Data 

 The Agency reviewed the existing toxicity database, the acute toxicity and 

mutagenicity, subchronic (oral and dermal), developmental, chronic, and carcinogenicity 

Page 7 of 20 
studies. Based on the review, the Agency expects the need to conduct risk assessments 

based on inhalation exposures (e.g., aerosols resulting from application of paint using 

airless sprayer and aerosol exposure to metal working fluids) and reproductive effects 

(e.g. chronic exposure to metalworking fluid. Thus, the Agency anticipates that a 90-day 

inhalation and reproductive effect studies will be needed for registration review. In 

addition chronic exposure to metal working fluids would also trigger the need for a 

rodent reproduction and fertility study. 

 In addition, the Agency also anticipates the need for at least a non-rodent (e.g., rabbit) 

developmental study to identify the susceptibility of different species. It is a wellrecognized scientific fact that species responses to developmental insult can vary widely 

as a result of pharmacokinetic or pharmacodynamic differences. The dose at which 

maternal or prenatal developmental toxicity is observed may not be the same across 

species, and the severity of the response in dams or fetuses may also differ. 

Section 3. Dietary Assessment 

Although categorized as a non-food use, AD anticipates that there may be indirect 

dietary exposure to PCMC and Na PCMC. Since PCMC and Na PCMC are both used in 

adhesives, paper and paperboard, and lubricants as a preservative against bacteria, mold, 

and fungi, it is possible that these chemicals could indirectly migrate into food exposed to 

the treated paper and adhesives. 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) to preserve lubricant at levels not to exceed 1 percent (FCN 

560). This use has not yet been codified under FDA guidelines (as per 21 CFR). It should 

be noted that Agency did not identify an FDA clearance for Na PCMC. 

EPA did not identify a dietary risk assessment for the indirect food additive uses for 

PCMC in the RED. As a result, EPA anticipates the need to conduct dietary exposure 

and risk assessments for the following use patterns: 

• Adhesives, 

• Cements, 

• Coatings, 

• Food contact paper, and 

• Lubricant oils. 

 In addition, PCMC and Na PCMC are used in detergents and cleaning solutions 

used for industrial, hospital, household, institutional, and hard surface disinfection. The 

Agency will need to assess potential acute and chronic indirect ingestion exposure 

estimates resulting from the use of disinfectants on kitchen surfaces in the home and also 

an assessment for detergents. 

 All registered use sites for PCMC /Na PCMC are indoors. Although expected to be 

infrequent, dietary exposures via drinking water may occur in the event a discharge of 

contaminated waste water occurs from a facility manufacturing preservatives for paints, 

metal working fluids, adhesive, cements, coatings, etc. The contaminated water may then 

Page 8 of 20 
pass through wastewater treatment facilities and into drinking water. However, there are 

no environmental fate data to determine whether PCMC/Na PCMC can pass through 

wastewater treatment facilities into drinking water or migrate into residential 

groundwater wells as a result of its current use patterns. Upon receipt and review of the 

environmental fate data the Agency anticipates requiring (hydrolysis, photolysis, and 

ready biodegradability), the need for a drinking water exposure assessment for PCMC/Na 

PCMC will be determined. Therefore, the need for a dietary drinking water assessment 

will be revisited upon submission and review of the needed environmental fate data. 

Section 4. Aggregate and Cumulative Exposure 

 In examining aggregate exposure, EPA takes into account the available and reliable 

information concerning exposures to pesticide residues in food and drinking water, and 

non-occupational pesticide exposures. Dietary (food and drinking water) exposures of 

concern are anticipated for PCMC/Na PCMC. 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. 

 Section 408(b)(2)(D)(v) of FFDCA requires that, when considering whether to 

establish, modify, or revoke a tolerance, the Agency consider "available information” 

concerning the cumulative effects of a particular pesticide's residues and "other 

substances that have a common mechanism of toxicity.” EPA has not yet determined 

whether PCMC/Na PCMC have common mechanisms with other compounds, 

consequently a cumulative assessment will not be performed at this time. 

Section 5. Occupational/Residential Exposure 

 An occupational and/or residential exposure assessment is required for an active 

ingredient if (1) certain toxicological criteria are triggered and (2) there is potential 

exposure to handlers (mixers, loaders, applicators, etc.) during use or to persons entering 

treated sites after application is complete. There are potential occupational and 

residential handler and post application exposures to persons entering treated sites (e.g., 

painting, metal working,etc.). The Agency expects that new risk assessments are needed. 

PCMC/Na PCMC are antimicrobial pesticides used on indoor nonfood uses as a 

preservative for oil recovery drilling muds/packer fluids, adhesives, coatings, emulsions, 

leather processing liquors and leather products, metal working fluids, and paints. The 

label does not specify specific mixing or loading systems; therefore, the Agency assumes 

that workers could be exposed during mixing/loading (both open and closed mixing and 

loading systems). Additionally, occupational workers could also experience dermal and 

inhalation exposure while applying preservatives using brush/roller, low pressure and 

airless sprayers. The exposures expected are presented in bulleted format below: 

• Occupational dermal and inhalation handler exposure to PCMC and Na 

PCMC during the open pour /closed mixing for materials preservation, oil 

recovery, leather production and textile production. 

Page 9 of 20 
• Occupational dermal and inhalation handler exposures to treated metal 

working fluids (MWFs), treated paints (brush/roller, low pressure and airless 

sprayer), and disinfectant uses (mopping and wiping). 

• Residential dermal and inhalation handler exposure to during the use of 

treated paints (brush/roller, low pressure and airless sprayer). 

• Residential postapplication incidental ingestion and dermal exposure (e.g. 

exposure to leather and household use of disinfectants of countertops). 

• Postapplication inhalation exposure to treated paints and MWFs. 

The label specifies that personal protective equipment (PPE) [e.g. chemical resistant 

gloves, long sleeved shirt, socks, shoes, and pants] will be used for occupational handling 

exposures from mixing or loading. However, since this chemical is used as preservative 

in paints, label restrictions for applicators using preservatives in paint are not applicable 

(e.g. cannot label paint on cans). Based on Agency concerns to open mixing/loading, as 

well as potential applicator exposures (e.g. airless sprayer) the Agency anticipates that 

new risk assessments will be needed. The Agency will need both inhalation and dermal 

exposure data to conduct these risk assessments. In addition, description of human 

activity data (GDLN 875.2300 are needed for uses including material preservatives used 

in paint, and metal working fluids. The Agency relies on professional judgments for 

many of the use parameters used (e.g., amount handled and duration of use) in the 

exposure assessments. The Agency will need this data to understand to conduct postapplication inhalation exposure assessments. 

 The Agency will also need some data to clarify some labeled use patterns. Product 

use data (GDLN 875.1700 and GDLN 875.2500) will help the Agency to determine and 

refine the exact handler and post-application scenarios applicable for risk assessment. A 

complete description of product use would ensure that the risk assessment is inclusive of 

the types of exposures occurring during residential and occupational use. The listing of 

the end use consumer products would be used to define the exposure scenarios to be 

assessed in the risk assessment. The Agency identified some specific scenarios where the 

product use was not clear. For example, there was a leather use for PCMC, but it was 

unclear if the leather was actually used to make clothes. There is also a disinfectant 

product that could be used on household hard surfaces (i.e., countertops and floors). 

Based on the disinfectant product use on household countertops and floors, the 

Agency also anticipates that indoor residue data (GDLN 875.2300) is needed to 

accurately account for the amount of residues found on countertops and floors from 

wiping or mopping activities. This data is needed to conduct post-application assessment 

for the disinfectant product use. 

Based on the uses as a preservative in leather products and the use as a disinfectant 

found on hard surfaces sprayed with disinfectant, the Agency expects that non-dietary 

ingestion data (GDLN 875.3000) will be needed. This data will help the Agency to 

examine the residue transfer from leather products and contact from hard surfaces (e.g., 

counter tops and floors). Without this data, the Agency would need to assume worst case 

assumptions. 

Section 6. Anticipated Data Needs 

Page 10 of 20 
 The Antimicrobial Division (AD) anticipates the need for additional human health 

data for PCMC. The Agency expects to need the following toxicology study (utility and 

rationale provided in Appendix A) and exposure data (utility and rationale provided in 

Appendix B). 

Toxicity

• 90-day inhalation toxicity study (GDLN 870.3465) 

• Developmental toxicity study (rabbit) (GDLN 870.3700) 

• Reproduction and Fertility Effects study (GDLN 870.3800) 

Occupational and Residential Handler Exposure Data Needs

• Dermal Exposure (Outdoor and Indoor) (GDLN 875.1100 and 875.1200) 

• Inhalation Exposure (Outdoor and Indoor) (GDLN 875.1300 and 875.1400) 

• Data Reporting and Calculations (GDLN 875.1600) 

• Product Use Information (GDLN 875.1700) 

Occupational and Residential Post Application Exposure Data Needs

• Indoor Surface Residue Dissipation Data (GDLN 875.2300) 

• Inhalation Exposure (GDLN 875.2500) 

• Product Use (GDLN 875.2700) 

• Description of Human Activity (GDLN 875.2800) 

• Data Reporting and Calculations (GDLN 875.2900) 

• Non-Dietary Ingestion (GDLN 875.3000) 

Section 7. Tolerances 

 There are no pesticide tolerances or exemptions from the requirement of tolerance for 

PCMC or Na PCMC. 

 

Section 8. Endocrine Disruption 

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, 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 reregistration decision, EPA reviewed these data and selected the most sensitive 

endpoints for relevant risk assessment scenarios from the existing hazard database. 

Page 11 of 20 
However, as required by FFDCA section 408(p), PCMC/Na PCMC is 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. PCMC/Na PCMC is 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 PCMC/Na PCMC. 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/. 

Section 9. Human Incident Data 

There have been no human incidents reported in any of the OPP databases associated 

with exposure to PCMC and Na PCMC. 

Section 10. Overall Conclusions 

 The Agency reviewed the hazard and exposure databases for PCMC/Na PCMC and 

anticipates that additional studies will be needed for registration review. Although a RED 

has been completed, the Agency expects to conduct any additional risk assessments 

(occupational, residential, dietary, and drinking water) for this chemical since the RED 

did not cover all the existing uses for registration review, did not complete a dietary 

assessment for the indirect food uses, and the Agency will need additional toxicity and 

exposure data to develop a risk assessment and characterize the hazard database. 

Section 11. References 

p-Chloro-m-cresol Reregistration Eligibility Decision Document (RED), January 1997. 

http://www.epa.gov/pesticides/reregistration/status.htm

Page 12 of 20 
Appendix A: Toxicity Guideline Study Justifications 

Guideline Numbers: 870.3465 

Study Titles: 90-day Inhalation Toxicity Study 

Rationale for Requiring the Data 

The Agency does not have a full picture of the potential effects which PCMC/Na PCMC 

could occur as a result of exposure via the inhalation route. The needed study which was 

not previously available would provide insight into concerns regarding toxicity via the 

inhalation route. It may also provide a toxicity endpoint applicable to an inhalation risk 

assessment. The Agency previously used an oral toxicological endpoint from a maternal 

toxicity endpoint from a developmental study and assumed 100% absorption. Inhalation 

exposure is high for workers who apply paint through airless sprayers and brushes. 

These applicators would likely to be exposed to aerosols from paint applications. In 

addition, an inhalation study is required to address uncertainties around the inhalation 

toxicity to refine the Agency’s risk assessment. Currently for inhalation exposures an 

extra 10 X uncertainty factor is added for a lack of an inhalation toxicity endpoint. The 

study may result in a change in how risks are quantified and removal of a 10X 

uncertainty. The data would allow the Agency to conclude more definitively whether or 

not there would be any concerns for inhalation toxicity in the rat. This would provide a 

more complete hazard characterization of PCMC and Na PCMC in regards to the 

potential risks to the U.S. general population. 

Practical Utility of the Data 

How will data be used? 

An inhalation study may result in changes to the endpoints and how the risks are quantified. 

How could the data impact the Agency’s future decision-making? 

The study would form the foundation for hazard characterization and toxicity endpoints selection 

for risk assessment through all exposure routes (oral, inhalation, and dermal). The data would 

allow the Agency to conclude more definitively whether or not there would be any concerns for 

inhalation toxicity in rodent species. It is possible that the database uncertainty factor be reduced 

or removed, resulting in different magnitude of the value of the endpoint used for regulation. . In 

many cases, toxicity observed via the inhalation route is higher than toxicity observed via oral 

exposure, which means that the route-to-route extrapolation used in the RED risk assessment 

could have resulted in an underestimation of risks from inhalation. It is particularly important to 

properly assess inhalation risks for PCMC and Na PCMC because there is high inhalation 

exposure for workers applying paints. 

Guideline Number: 870.3700 

Data Requirement: Rabbit Developmental 

Rationale for Requiring the Data 

The Agency does not have a full picture of the developmental toxicity of PCMC/Na 

PCMC. The needed study would provide insight into concerns regarding pre- and/or 

postnatal toxicity as needed by FQPA. It may also provide a toxicity endpoint applicable 

to risk assessment. 

Practical Utility of the Data 

Page 13 of 20 
1. How will the data be used? 

The study may result in a change in how risks are quantified. The data would allow the 

Agency to conclude more definitively whether or not there are any concerns for preand/or postnatal toxicity in the rabbit. This would provide a more complete hazard 

characterization of PCMC and Na PCMC in regards to the potential risk of 

developmental toxicity. 

2. How could the data affect the risk assessment? 

The study may result in a change in how risks are quantified. It is possible that the 

database uncertainty factor may be reduced or removed, resulting in different magnitude 

of the value of the endpoint used for regulation. The difficulty of predicting real world 

human exposure via oral route with limited data and no developmental toxicity data in 

rabbit or other alternative information, triggered the need for a developmental (guideline) 

toxicity study in the rabbit, in order to adequately evaluate real world human exposure to 

PCMC and Na PCMC, particularly women in the 15-49 years of age and infants and 

children. 

Guideline Number: 870.3800 

Data Requirement: Reproduction and Fertility Effects - rodent 

Rationale for Requiring the Data 

The needed study would provide insight into concerns regarding the potential risks of 

reproductive toxicity in the rat as well as potential neurotoxicity in developing offspring. It may 

also provide a toxicity endpoint applicable to risk assessment. 

Practical Utility of the Data 

1. How will the data be used? 

The data would allow the Agency to conclude more definitively whether or not there are any 

concerns for potential reproductive toxicity in the rat and it would also provide some information 

regarding potential neurotoxicity in developing offspring exposed to PCMC and Na PCMC. 

Data was not available previously. The Agency needs a chronic oral toxicological endpoint to 

assess MWF uses. A reproductive study is needed to determine the chronic oral toxicological 

endpoint.

2. How could the data impact the Agency’s future decision-making? 

The study may result in a change in how risks are quantified. The needed study may provide a 

chronic toxicity endpoint applicable to risk assessment. It is possible that the database 

uncertainty factor be reduced or removed, resulting in a different magnitude of the value of the 

endpoint used for regulation. It is particularly important to properly assess chronic risks for 

PCMC and Na PCMC because there is chronic exposure for workers who use MWFs. 

Appendix B: Exposure Guideline Study Justifications 

Guideline Numbers: 875.1100 and 875.1200 

Study Titles: Dermal Exposure (Indoor and Outdoor) 

Rationale for Requiring the Data 

Note: Dermal exposure data are needed for both residential and occupational uses. The selection 

of an outdoor versus an indoor site is based on the high end exposure scenario. In almost all 

cases, repeating an exposure study for the same scenario outdoors and indoors is not necessary. 

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The potential for dermal exposure is very likely for exposure scenarios involving metal working 

fluids and paints. The existing CMA data base and PHED for these scenarios are limited in scope 

for QA/QC and number of monitoring units. EPA presented the need for additional handler 

exposure data to the January 2007 Science Advisory Panel (SAP) as well as to the April 2007 

Human Studies Review Board (HSRB) and both groups agreed that additional data are warranted. 

The criteria for the dermal exposure data are based on the potential for dermal exposure from the 

labeled uses (e.g., occupational workers using paints and leather working fluids) and evidence of 

toxicity. If the toxicological endpoints from PCMC/Na PCMC are used to assess the risks, there is 

an endpoint selected for the dermal route

Practical Utility of the Data 

1. How will the data be used? 

The dermal exposure data will be used to assess dermal exposures from application of paints. For 

occupational uses, the dermal exposure data will be used to assess the short-, and intermediateterm exposures. The dermal exposure data will be used to determine the accuracy of the dermal 

risks to both residence and occupational workers. 

2. How could the data impact the Agency’s future decision-making? 

If risks warrant mitigation, the dermal exposure data will provide the types of mitigation necessary 

such as chemical resistant gloves or closed systems for commercial uses, or potential removal of 

uses from the label.

Guideline Numbers: 875.1300 and 875.1400 

Study Titles: Inhalation Exposure (Indoor and Outdoor) 

Rationale for Requiring the Data 

Note: Inhalation exposure data are needed for both residential and occupational uses. The 

selection of an outdoor versus an indoor site is based on the high end exposure scenario (for 

inhalation the selection is typically indoors). In almost all cases, repeating an exposure study for 

the same scenario outdoors and indoors is not necessary. 

The inhalation exposure route is very important for exposure scenarios such application of paints or 

metalworking fluids where aerosols would be generated. In addition, inhalation exposures from 

application are evident in exposure studies in the Pesticide Handlers Exposure Database (PHED). 

The significance of these exposures is directly affected by the severity of the inhalation 

toxicological endpoint of concern. At this point in time, no toxicological data are available to 

assess the inhalation risk. The existing Chemical Manufacturer Association (CMA) data base and 

PHED for these scenarios are limited in scope for QA/QC and number of monitoring units. EPA 

presented the need for additional handler exposure data to the January 2007 Science Advisory 

Panel (SAP) as well as to the April 2007 Human Studies Review Board (HSRB) and both groups 

agreed that additional data are warranted. 

The criteria for the inhalation exposure data are based on the potential for respiratory exposure 

from the labeled uses (e.g., exposure to application of paints) and evidence of toxicity. If no 

toxicological endpoints of concern were identified, then the inhalation exposure data would not be 

needed.

Practical Utility of the Data 

1. How will the data be used? 

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The inhalation exposure data would be used to assess the residential short-term duration of painting 

with a paint brush/roller and an airless sprayer. For occupational uses, the inhalation exposure data 

would be used to assess the short- and intermediate-term as well as pouring PCMC (e.g., poured 

into paint as a preservative in manufacturing settings, and preservation of leather preservative 

solutions). 

 

2. How could the data impact the Agency’s future decision-making? 

If risks warrant mitigation, the inhalation exposure data will provide the types of mitigation 

necessary such as dust mist respirators, full face respirators or closed systems for commercial uses, 

or potential removal of uses from the label.

Guideline Numbers: 875.1600

Study Title: Data Reporting and Calculations 

Rationale for Requiring the Data

For all exposure studies this data need is needed to facilitate the review of the data. 

The study report and all raw data/calculations would be reviewed for the adequacy of the 

data. 

Practical Utility of the Data

1. How will the data be used? 

The data are needed to interpret the dermal and inhalation exposure data collected. 

2. How could the data impact the Agency’s future decision-making? 

This data need is triggered if an exposure study is conducted. It would aid the Agency to 

make accurate interpretations of the studies to develop an accurate and refined risk 

assessment and refined mitigation.

Guideline Numbers: 875.1700

Study Title: Product Use Information

Rationale for Requiring the Data

Product use information is a description of how the product is actually applied; it is not a 

field study. A description of how this product is used would provide for a comprehensive 

realistic assessment of its potential applications. The description of the application 

techniques would be used to define the exposure scenarios to be assessed in the risk 

assessment. 

Practical Utility of the Data

1. How will the data be used? 

A complete description of product use would ensure that the risk assessment is inclusive of 

the types of exposures occurring during residential and occupational use. 

2. How could the data impact the Agency’s future decision-making? 

The need for a risk assessment as needed under Registration Review would require that the 

risk assessor understands how the product is applied. 

Guideline Number: 875.2300 

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Study Title: Indoor Surface Residue Dissipation 

Rationale for Requiring the Data 

Based on the use of PCMC and Na_PCMC as a hard surface disinfectant for countertops and 

floors, human contact to treated countertops and floors may occur. There are no data available to 

estimate exposure to adults and children from exposure to treated floors and countertops with 

PCMC and Na PCMC.

Practical Utility of the Data 

1. How will the data be used? 

Without data, the Agency will conduct a screening level assessment using a conservative surface 

residue value of 1 mg/cm2 . Currently, there are no data that can be used to estimate exposure to 

adults or to children exposed to treated wood. These data will be used to refine the Agency’s risk 

assessment and to confirm or refute the Agency’s screening level assessment. 

2.How could the data impact the Agency’s future decision-making? 

Depending on the results of the dislodgeable residue study, the Agency may pursue risk mitigation 

measures regarding the use of formulated products containing PCMC and Na PCMC as the active 

ingredient in occupational and residential scenarios. 

Guideline Number: 875.2500 

Study Title: Inhalation Exposure 

Rationale for Requiring the Data 

The post application inhalation exposure may be required if it is determined that the use of these 

products have the potential to release PCMC and Na PCMC during the product use conditions (e.g., 

open systems, and vapor/mists from MWFs). 

Practical Utility of the Data

1. How will the data be used? 

The post application inhalation exposure data will be used to assess the residential and/or 

occupational inhalation risks to PCMC and Na PCMC if released based on product use. 

For example, the use MWFs is expected to trigger an inhalation postapplication assessment 

2. How could the data impact the Agency’s future decision-making? 

The inhalation exposure data will be used to determine the accuracy of the post application 

inhalation risks to occupational bystanders. If risks warrant mitigation, the inhalation exposure 

data will provide the types of mitigation necessary such as respiratory protection from respirators or 

closed systems for commercial uses to potential removal of uses from the label. 

Guideline Number: 875.2700 

Study Title: Product Use

Rationale for Requiring the Data 

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A description of how products containing PCMC and Na PCMC are used will provide a 

comprehensive, realistic assessment of its potential applications. Product use information for the 

post application data is a description of what type of consumer products are treated; it is not a field 

study (guideline no. 875.2700). A description of what types of consumer products are treated, 

specifically what types of leather, disinfectant use and paints, will provide a comprehensive, 

realistic assessment of potential post application exposures. Therefore, these data are required. 

Product use information assists EPA to more accurately assess pesticide exposure to applicators by 

describing how the pesticide is actually used and applied. EPA requires this information because 

differences in use can translate to significant differences in exposure, and thus in risk. 

The guideline for post-application product use information was presented to the FIFRA Science 

Advisory Panel (SAP) in March 1998. (The draft guideline is available at 

http://www.epa.gov/scipoly/sap/meetings/1998/march/contents.htm.). The guideline for applicator 

product use information should be substantially similar to the one for post-application. 

Practical Utility of the Data 

1. How will the data be used? 

A complete description of product use would ensure that the risk assessment is inclusive of the 

types of exposures occurring during residential and occupational use. The listing of the end use 

consumer products would be used to define the exposure scenarios to be assessed in the risk 

assessment. For example, if the use for leather is used to make clothes or if the preservative is used 

in inks, or if the product is used on countertops then a postapplication assessment may need to be 

considered. 

2. How could the data impact the Agency’s future decision-making? 

A complete description of consumer products treated would ensure that the risk assessment is 

inclusive of the types of exposures occurring during residential use. The need for a risk assessment 

as needed under Registration Review would require that the risk assessor understands how the 

product is applied. 

Guideline Number: 875.2800 

Study Title: Descriptions of Human Activity 

Rationale for Requiring the Data 

Very limited worker activity data are available for antimicrobial pesticides, including material 

preservatives used in paint, and metal working fluids. Worker application parameters are generally 

defined by the physical nature of the formulation (e.g., formula and packaging), by the equipment 

required to deliver the chemical to the use site, and by the application rate required to achieve an 

efficacious dose. The risk assessment noted that many of the use parameters used (e.g., amount 

handled and duration of use) were based on professional judgments. These data are needed to fill 

this data gap and provide information needed to refine the risk assessment. 

Practical Utility of the Data 

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1. How will the data be used? 

These data will clearly identify the specific equipment used to deliver PCMC and Na PCMC to the 

use site, which in high exposure scenarios, such a metal working fluids and paint applications, will 

allow the Agency to refine its risk assessment. 

2. How could the data impact the Agency’s future decision-making? 

If review and evaluation of the descriptions of human activity data indicate that only closedsystems are used for mixing/loading and applying metal working fluids, then the need for a 

reproductivity study is negated. Therefore, submission of acceptable human activity data 

demonstrating the metal working fluid scenario for PCMC and Na PCMC is an enclosed system 

will eliminate a significant cost and burden for the registrant (specifically, the costs associated with 

generating the reproductivity and fertility study data). For the other use scenarios, descriptions of 

human activity data will allow the Agency to refine its risk assessment and make decisions using 

fewer assumptions and more reliable data. 

Guideline Number: 875.2900 

Data Requirement: Data Reporting and Calculations

Rationale for Requiring the Data 

For all exposure studies, these data are needed occupationally and in the residential setting to 

facilitate the review of the data. 

Practical Utility of the Data 

1. How will the data be used? 

The study report and all raw data/calculations will be reviewed for the adequacy of the data. 

2. How could the data impact the Agency’s future decision-making? 

The data are needed to define and interpret the inhalation and dermal exposure data collected. 

This data need is triggered any time an exposure study is conducted. It would aid the Agency to 

make accurate interpretations of the studies to develop an accurate and refined risk 

assessment and refined mitigation.

Guideline Number: 875.3000 

Data Requirement: Non-Dietary Ingestion 

Rationale for Requiring the Data 

The design of the non dietary ingestion exposure study can be combined with the Indoor Surface 

Residue Dissipation study (875.2300) to determine the available residue leaching from a child 

mouthing treated leather clothing articles as well as hand-to-mouth behavior on counter tops treated 

with PCMC disinfectant. 

Practical Utility of the Data

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1. How will the data be used? 

This product is used as a material preservative in leather products and as a disinfectant on counter 

tops and floors. The available residues from hard surfaces will be used to determine the magnitude 

of children’s incidental exposure from these uses.

2. How could the data impact the Agency’s future decision-making? 

The data are needed to refine the risk estimates if risks of concern are identified assuming 100% 

residue transfer from leather products and contact from hard surfaces (e.g., counter tops and floors). 

If risks of concern are not identified when 100% residue transfer is assumed, the data are not 

needed.