Docket Number; EPA

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



# Calcium Oxide Registration Review:
Final Work Plan
June 2011Docket Number; EPA

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## Calcium Oxide Registration Review:
Final Work Plan
June 2011

Case # 

## 5104

Approved By:

# ~~**l ~**  Harri g an

- Farrelly Director, Antimicrobials Division

Date :

I 

### I

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3 Calcium Oxide Registration Review Team

Michelle Centra Human Health & Environmental Effects

Najm Shamim

Rebecca von dem Hagen Risk Management

Lance Wormell

Phil ip Ross Office of General Counsel

________________________________________ Supporting documents for the Calcium Oxide Case may be found in the registration review docket EPA

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4 This is the Final Work Plan (FWP) of the Environmental Protection Agency (EPA or “the Agency”) for the registration review of the C alcium O xide C ase (Case 5104 ). 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 C alcium O xide C ase registration review doc ket, 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 registrat ion 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 co ntinues 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 an d 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/oppsrrd 1/registration_review/.

Calcium oxide (PC Code 075601) is a bacteriocide/bacteriostat contained in a product registered
for use in the treatment of medical waste. C alcium hydroxide (PC Code 075604) , created by the mixing of calcium oxide and water, is a b acteriocide/bacteriostat contained in a manufacturing use product (MUP) registered for use for the manufacture of or fabrication into antimicrobial products to be used as coatings on or components of the following hard, inanimate surfaces and products: wa lls, floors, ceilings, tile, fixtures, tools, appliance exteriors, pipe exteriors, heating cooling ventilation (HVAC) equipment, duct work and related equipment (other than motors, fans and similar mechanical moving parts) interiors and exteriors, and conc rete, stone, ceramic, plaster, wood, drywall substrates in residential dwellings, schools, day care centers, professional offices, commercial and industrial buildings, factories, animal housing facilities (barns, corrals, fences) and healthcare facilities (hospitals, medical office, nursing homes).

Both calcium oxide and calcium hydroxide were new active ingredients in products registered in 1976. In 1989 all of the registered products containing calcium oxide or calcium hydroxide were voluntarily canc elled; therefore, these active ingredients were not evaluated under reregistration. In 2002 and 2004 EPA registered new products containing calcium oxide and calcium hydroxide, respectively.

The Calcium Oxide Preliminary Work Plan (PWP) was published on December 22, 2010 and the
60

- day comment period ended on February 22, 2011 . The Preliminary Work Plan is available on www.regulations.gov docket number EPA

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.Docket Number; EPA

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5 Comments Received on the Preliminary Work Plan

The Agency received one comment f rom the Physicians Committee for Responsible Medicine (PCRM) 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. One comment , described below, was received during the public comment period concerning structure activity relationships

.

Comment : PCRM encourages the registrant to use existing information and (Q)SAR to determine if an acute threshold or “limit test” approach can be used to fulfill data requirement 850.1075 Acute Fish Toxicity Study. If this approach is determined to be appropriate and utilized, it wil l reduce the number of animals used.

Response : As stated on page 11 of the calcium oxide summary document (available at regulations.gov in docket ID EPA

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- 0693) , “If stakeholders believe that submission of predicted data can fulfill one of the d ata needs for the calcium oxide case, then the Agency invites submission of this information. The submitter would be expected to supply a rationale describing the utility of the information and provide documentation on the scientific validity of the infor mation. The determination that the predicted data fulfills the data requirement would be at the sole discretion of the Agency.
Pre

- submission consultation with the Agency is encouraged.”

The Agency has considered and will continue to consider possible ac ceptance of SAR/(Q)SAR information/data to fulfill its data requirements on a case

- by

- case basis. The Agency supports a tiered testing framework for data requirements, providing for greater efficiency of testing resources while assuring data development a s warranted for an assessment. As part of this scheme all available information, including use patterns, exposure, existing toxicity and SAR/(Q)SAR information if applicable, should be used to
inform the decision as to where within the tiered framework te sting should be initiated and to inform the test design when testing is required. The Agency will consider a tiered testing framework based on the information and the supporting rational e submitted by the registrant.

Comment : PCRM believes that because calcium oxide compounds are known to be severely corrosive, the 28

- day inhalation toxicity (870.3465) and 21/28

- day dermal toxicity (870.3200) studies should not be required. In addition, PCRM argues that these
studies cannot be diluted because that would not be the article and the technical grade (TGAI ) is not a diluted substance as the final product is

.
Response : The Agency does not require the undiluted TGAI be used to conduct the 28

- day inhalation toxicity (870.3465) and 21/28

- day dermal toxicity (870. 3200) studies. According to EPA’s published OPPTS Health Effects Test Guidelines 870.3465 and 870.3200, “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. Doses should be spaced appropriately to produce test groups with a range of toxic effects.” The Agency anticipates submission of subchronic dermal and inhalation toxicity studies conducted with dilute concent rations ofDocket Number; EPA

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6 either calcium oxide or calcium hydroxide that demonstrate toxic effects at non

corrosive/non

- caustic levels.

For use in conduct ing a complete human health/exposure risk assessment for all registered pesticide uses of the calcium oxide chemica ls and to ensure that these chemicals meet the safety standards established by FFDCA, as amended by FQPA, the Agency anticipates requiring repeated dose dermal and inhalation toxicity studies as
outlined in the PWP.

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 Calcium O xide
Case registration review.

Risk Assessments and Anticipated Data Needs

**•** The Agency will conduct a comprehensive ecological risk assessment, including an endangered species risk assessment, for all uses of calcium oxide and calcium hydroxide

. The Agency also anti cipates the need to conduct human health risk assessments for the calcium oxide case including an occupational risk assessment for calcium oxide and occupational and residential risk assessments for calcium hydroxide. The Agency expects to require additi onal data for use in conduct ing the registration review of the calcium oxide

case

.
Ecological Risk Assessment Status and Data Needs

**•** No ecological risk assessment has been performed for the calcium oxide case.

**•** The Agency does not anticipate the need to c omplete an environmental fate risk assessment. Based on current use patterns no long term environmental impact is expected from calcium oxide or calcium hydroxide because once calcium enters the environment, it is expected to quickly reach background leve ls. No environmental fate data gaps exist for the present uses
of these chemicals.

**•** The Agency anticipates the need to require the following additional ecotoxicity data for use
in conduct ing an ecological risk assessment for the registration review of cal cium oxide and calcium hydroxide.

o GDLN 850.1075

– Acute Freshwater Fish Toxicity

o GDLN 850.5400

– Aquatic Growth, Tier II Green Algae

**•** For more information, please refer to Preliminary Plan for Registration Review of: Calcium Hydroxide/Calcium Oxide

, located in the docket.

Human Health Risk Assessment Status and Data Needs

**•** No human health risk assessment has been performed for the calcium oxide case.Docket Number; EPA

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7 Dietary Assessment

**•** Dietary (food and water) exposure is not expected from the registered use of calcium oxide
because the chemical is applied in a closed system and must be disposed of in a sanitary landfill. Dietary exposure (food and water) is not expected from the regis tered calcium hydroxide manufacturing use product because it is not for use in or on coating or other antimicrobial pesticides that will be used on food contact, food preparation or food processing surfaces. The U.S. Food and Drug Administration consider s calcium oxide and calcium hydroxide Generally Recognized as Safe (GRAS) for use in foods with no limitations except good manufacturing practices. Therefore, because non

- occupational exposure and hazard are expected to be minimal, the Agency does not ant icipate conducting dietary or aggregate risk assessments for the calcium oxide case.

Tolerances and International Harmonization

**•** Calcium hydroxide is exempt from the requirement of a tolerance when used as an inert ingredient as a solid diluent or carrier i n pesticide formulations applied to growing crops or to raw agricultural commodities (40 CFR 180.1001(c)).

Occupational and Residential Assessment and Risk

**•** The Agency anticipates conducting an occupational risk assessment for calcium oxide and occupationa l and residential risk assessments for calcium hydroxide based on current use patterns.

Aggregate and Cumulative Exposure and Risk

**•** In examining aggregate exposure, EPA takes into account the available and reliable information concerning exposures to pest icide residues in food and drinking water, as well as

non

- occupational pesticide exposures. An aggregate risk assessment has not been deemed necessary for the calcium oxide case because non

- occupational exposure and hazard are expected to be minimal.

**•** EPA does not have, at this time, available data to determine whether calcium oxide and calcium hydroxide have a common mechanism of toxicity with other substances or how to include this pesticide in a cumulative risk assessment.

**•** For the purposes of this Registration Review, EPA has assumed that calcium oxide and calcium hydroxide do not have a common mechanism of toxicity with other substances when used as an antimicrobial as registered.

Human Health Data Needs

**•** The Agency intends to reevaluate the existi ng submitted, cited and published data and evaluate anticipated toxicology data for calcium oxide and calcium hydroxide during the registration review risk assessment in order to better characterize hazard and potential human
health risks.Docket Number; EPA

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8 **•** The Agency anti cipates the need to require the following additional human health data for
use in conduct ing the registration review of the calcium oxide case

.
Toxicology Data for Calcium Hydroxide or Calcium Oxide

o 870.3200 21/28

- day Dermal Toxicity

o 870.3465 28

- day In halation Toxicity

o 870.5100 Bacterial Reverse Mutation Test

o 870.5300 In vitro Mammalian Cell Gene Mutation Test or 870.5375 In vitro Mammalian Chromosome Aberration Test

o 870.5385 Mammalian Bone Marrow Chromosomal Aberration Test or 870.5395
Mammalian Erythrocyte Micronucleus Test

Exposure Data for Calcium Oxide (Occupational Applicator

– Medical Waste; Loading; Open Pour)

o 875.1300 Inhalation Exposure

- Outdoor

o 875.1400 Inhalation Exposure

- Indoor

o 875.1600 Data Reporting and Calculations

o 875.1700 Product Use Information

Exposure Data for Calcium Hydroxide (Occupational/Residential Applicator

– Paints/Coatings; Brush, Roller, Spray

- on)

o 875.1100 Dermal Exposure

- Outdoor

o 875.1200 Dermal Exposure

- Indoor

o 875.1300 Inhalation Exposure

- Outdoor

o 875.1400 Inhalati on Exposure

- Indoor

o 875.1600 Data Reporting and Calculations

o 875.1700 Product Use Information

**•** For more information, please refer to Calcium Oxides (Calcium Oxide and Calcium Hydroxide): Human Health Assessment Scoping Document in Support of Registration
Re view , 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.

**•** For more information, please refer to Preliminary Plan for Registrati on Review of: Calcium Hydroxide/Calcium Oxide , located in the docket.

Incidents:

Ecological:

**•** No calcium oxide or calcium hydroxide ecological incidents have been reported in the OPP
incident database.Docket Number; EPA

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9 Human Health:

**•** The Agency has reviewed the OPP Incident Data Systems (IDS) and one incident associated with calcium hydroxide exposure was reported in which dermal and eye irritation were the associated symptoms. No incidents associated with calcium oxide exposure have been reported.

Endangered Species

The Agency has not conducted a risk assessment that supports a complete endangered species determination for calcium oxide or calcium hydroxide. The ecological risk assessment planned during registration review will allow the Agency to determine whether c alcium oxide or calcium hydroxide’s uses have '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, repro ductive 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. A human health risk assessment identifyin g the most sensitive endpoints has
not been conducted for the Calcium Oxide C ase. As required by FFDCA section 408(p),
calcium oxide and calcium hydroxide are subject to the endocrine screening part of the Endocrine Disruptor Screening Program (EDSP).

EP A 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 a s 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 estroge n, 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

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10 chemicals, which contains 58 pesticide active ingredients and 9 inert ingr edients. Calcium oxide and calcium hydroxide 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 calcium
oxide and calcium hydroxide

. 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.go v/endo/

.

Timeline

EPA has created the following estimated timeline for the completion of the C alcium O xide C ase registration review :

Anticipated Schedule
Activities Estimated Month/Year

Phase 1 : Opening the docket Open Public Comment Period for Docket Completed
December 2010
Close Public Comment Period for Docket Completed February 2011
Phase 2 : Case Development Develop Final Work Plan (FWP) Completed
June 2011
Issue DCI June 2012

Data Submission June 2 014 Open Public Comment Period for Preliminary Risk Assessments September 2015 Close Public Comment Period for Preliminary Risk Assessments December 2015

Phase 3 : Registration Review Decision Open Public Comment Period for Proposed Reg. Review Decision June 2016 Close Public Comment Period for Proposed Reg. Review Decision September 2016 Final Decision and Begin Post

- Decision Follow

- up December 2016 Total (years) 6

Next Steps

A DCI will be developed regarding the anticipated data needs listed under the “Risk Assessments
and Anticipated Data Needs” section of this document. The Agency expects to issue the DCI in
June 2012

. Human health and ecological hazard assessments will be conducted for all registered

uses of calcium oxide and calcium hydroxide

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11 V. GLOSSARY of TERMS & ABBREVIATIONS

ai Active Ingredient
AR Anticipated Residue
ASTM American Society for Testing and Materials
AWPA American Wood Preserver’s Association
CBI Confidential Business Information
CFR Code of Federal Regulations
cPAD Chronic Population Adjusted Dose
CSF Confidential Statement of Formula
CSFII USDA Continuing Surveys for Food Intake by Individuals
DCI Data Call

- In
DEEM Dietary Exposure Evaluation Model
DFR Dislodgeable Foliar Residue
DNT Developmental Neurotoxicity
DWLOC Drinking Water Level of Comparison
EC Emulsifiable Concentrate Formulation
EDWC Estimated Drinking Water Concentration
EEC Estimated Environmental Concentration
EP End use Product
EPA Environmental Protection Agency
EUP End

- Use Product
FDA Food and Drug Administration
FIFRA Federal Insecticide, Fungicide, and Rodenticide Act
FFDCA Federal Food, Drug, and Cosmetic Act FQPA Food Quality Protection Act
FOB Functional Observation Battery
GENEEC Tier I Surfac e Water Computer Model
IR Index Reservoir
LC 50 Median Lethal Concentration. A statistically derived concentration of a substance that can be expected to cause death in 50% of test animals. It is usually expressed as the weight of substance per weight or volume of water, air or feed, e.g., mg/l, mg/kg or ppm.
LD 50 Median Lethal Dose. A statistically derived single dose that can be expected to cause death in 50% of the test animals when administered by the route indicated (oral, dermal, inhalation). It i s expressed as a weight of substance per unit weight of animal, e.g., mg/kg.
LOC Level of Concern
LOAEL Lowest Observed Adverse Effect Level μg/g Micrograms Per Gram μg/L Micrograms Per Liter mg/kg/day Milligram Per Kilogram Per Day mg/L Milligrams P er Liter
MOE Margin of Exposure
MRID Master Record Identification (number). EPA's system of recording and tracking
submitted studies.
MUP Manufacturing

- Use Product
NA Not Applicable NAWQA USGS National Ambient Water Quality Assessment
NPDES National Pollutant Discharge Elimination System
NR Not Required
NOAEL No Observed Adverse Effect Level
OPP EPA Office of Pesticide Programs
OPPTS EPA Office of Prevention, Pesticides and Toxic Substances
PAD Population Adjusted Dose
PAIRA Pure Active Ingredi ent RadiolabelledDocket Number; EPA

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12 PCA Percent Crop Area
PDP USDA Pesticide Data Program
PHED Pesticide Handler's Exposure Data
PHI Preharvest Interval phr Pounds Per Hundred ppb Parts Per Billion
PPE Personal Protective Equipment

ppm Parts Per Million
PRZM/EXAMS Tier II Surface Water Computer Model Q 1 * The Carcinogenic Potential of a Compound, Quantified by the EPA's Cancer Risk Model
RAC Raw Agriculture Commodity
RED Reregistration Eligibility Decision
REI Restricted Entry Interval
RfD Reference Dose RQ R isk Quotient
RTU Ready to Use
SCI

- GROW Tier I Ground Water Computer Model
SAP Science Advisory Panel
SF Safety Factor
SLN Special Local Need (Registrations Under Section 24©) of FIFRA)
TGAI Technical Grade Active Ingredient
TEP Typical End

- Use Product
USDA United States Department of Agriculture
UF Uncertainty Factor
WPS Worker Protection Standard