DATA REQUIREMENTS FOR OBTAINING
PRODUCT REGISTRATION AND FOR LABEL AMENDMENTS
A. INTRODUCTION TO DATA REQUIREMENTS
C. GOOD LABORATORY PRACTICE (GLP)
1. Data Submitted to USEPA
2. Acute Toxicology
3. Product Chemistry
4. Residue Chemistry (discontinued for most in 2004)
5. Fish and Wildlife (and Aquatic Organisms)
6. Worker and User Safety
7. Efficacy
8. Phytotoxicity
9. Environmental Fate Data for First Agricultural Use
10. Chronic Toxicology Data for New Active Ingredients
11. Adverse Effects Data
E. DATA REQUIREMENTS FOR RENEWAL OF CERTAIN REGISTRATIONS
1. Adverse Effects Disclosure with Application for Renewal
2. Conditional Registration Data for Renewal
3. Interim Registration Data for Renewal
4. Emergency Registration Data for Renewal
______________________________________________________________
Appendix VI-1 ANTIMICROBIAL PRODUCT EFFICACY DATA REQUIREMENTS
EFFICACY DATA FOR ANTIMICROBIAL PRODUCTS
Basic Requirements
Confirmatory Data Requirement (discontinued in 2006)
Sanitizer and Disinfectant Label Requirements
pH Control Buffers
Aquatic or Industrial Use Antimicrobial ProductsANTIMICROBIALS, REQUIREMENT FOR IN-USE TESTS CONDUCTED UNDER CALIFORNIA CONDITIONS
Appendix VI-2 PRODUCT CHEMISTRY SUMMARIES
Chapter VI
DATA REQUIREMENTS FOR OBTAINING
PRODUCT REGISTRATION AND FOR LABEL AMENDMENTS
A. INTRODUCTION TO DATA REQUIREMENTS
This section contains data requirements for obtaining product registrations and label amendments. All studies except certain product chemistry, must be submitted in full. In lieu of submitting data, the Department may rely upon the evaluations of previously submitted data, regardless of data ownership, to support the registration or amendment of a pesticide product.
Federal data requirements are found in 40CFR Part 158. Guidelines for conducting the tests are found in OPPTS Series 810 through 885 and U.S. EPA's Pesticide Assessment Guidelines. DPR data requirements are found in the California Code of Regulations Sections 6159, and 6170 through 6200.
Please note that data are not required to be submitted for a product being registered as identical to a currently registered product. See Chapter V Identical Registrations for instructions.
The data requirements for biopesticides such as microbial and biochemical products are in Chapter VIII.
Study reports must be written to include all necessary information. The format used in scientific report writing (with introduction, procedures and methods, results, conclusion, and discussion) is the style most preferred. The information must be presented in a clear and concise manner. For a report to be acceptable, it must be dated and signed by the person responsible for the study, and should include information on when, where, how the study was conducted, and the results of the study.
A brief report or testimonial letter only, stating that a study was conducted with favorable results, is usually not acceptable.
C. GOOD LABORATORY PRACTICE (GLP)
U.S. EPA requires GLP for studies submitted to support federal registration. GLP refers to the specific methods to document a study and how the study was conducted. GLP is encouraged, but not required by DPR. If asked about this issue, inform the applicant that if they intend to submit the study to U.S. EPA, conducting the study with GLP is advisable.
The basic data requirements for all products, including currently registered active ingredients and new active ingredients, are listed in the following sections. All studies except certain product chemistry, must be submitted in full. Summaries are not acceptable. In lieu of submitting data, the Department may rely upon the evaluations of previously submitted data, regardless of data ownership, to support the registration or amendment of a pesticide product.
Title 3 of the California Code of Regulations (CCR) provides that data required by U.S. EPA regulations (40 CFR, Part 158) substantially meet California data requirements except for the additional data required in CCR Sections 6176-6193.5.
During scientific evaluation, an evaluator may recommend conditional registration for certain types of data. See Chapter III for instructions.
If the applicant does not believe a required study is applicable to their product's use patterns, the applicant can request the data be waived and must provide reasons for the waiver request. The adequacy of submitted data is determined during the scientific evaluation process.
Unique requirements for the following are in Chapter VII:
Interim Registration (AB771)
Emergency Registration (SB283)
Section 5 EUP
Research Authorization
Section 18
Section 24(c)
Section 25(b)
Spray Adjuvants
Unique requirements for Microbial and Biochemical products are in Chapter VIII.
The following are the types of data which are submitted in support of various types of registrations and various types of uses. This section includes only a description of the types of data. See also California Notice to Registrants 2002-3. For more instruction on the routing of the data, see Chapter III Appendix III-1 on Selection of Evaluation Stations.
New product containing currently registered active ingredient
The following data are required to register a new product containing a currently registered active ingredient. Each data requirement, and the exceptions, are outlined in this chapter.
Acute Oral LD50
Acute Dermal (skin) LD50.
Eye Irritation.
Dermal (skin) Irritation.
Acute Inhalation LC50, if applicable.
Skin sensitization, if applicable.
Dermal absorption, if applicable.
Indoor exposure, if applicable.
Mixer, loader, applicator, if applicable.
New product containing a new active ingredient
To obtain registration of a product containing a new active ingredient, the following data are required to be submitted. Each type of data, and the exceptions, are more fully outlined in this chapter.
Products which do not require the data specific to a new active ingredient are Spray Adjuvants and Section 25(b) U.S. EPA-exempt products.
For products requiring federal registration, the applicant must submit all data that was submitted by the applicant to the U.S. EPA in support of federal registration of their product. Data waived by U.S. EPA must be submitted unless the Director makes a written finding that such data are not required to meet the purposes of the Food and Agricultural Code.
The applicant should also submit any written U.S. EPA documentation of data waivers. If U.S. EPA data waivers are granted, include the documentation when entering the package into evaluation.
2. Acute Toxicology - Reviewed by the Medical Toxicology
Branch
Acute toxicology studies must be complete; summaries are not acceptable.
For label amendments to decrease the signal word and/or the precautionary statements, the applicable acute toxicology study is required.
Overlabeling of the signal word is allowed if approved by U.S. EPA. The term overlabeling refers to a signal word or precautionary statement which is mor restrictive than that required by 40CFR. If all hazards identified by acute toxicology studies are mitigated by precautionary statements and the signal word (and the overlabeling does not cause an identified specific imminent hazard to the user), the labeling will be acceptable.
Acute toxicology data are not required for 100% sodium carbonate or 100% sodium bicarbonate when the following criteria are met:
Use OPPTS Series 870 (formerly Subdivision F) for conducting acute toxicology studies.
3. Product Chemistry - Reviewed by the Chemistry evaluation station
Summaries of certain product chemistry data are allowed as outlined in Appendix VI-2.
Guidelines for conducting product chemistry studies are in OPPTS Series 830 (formerly Subdivision D).
4. Residue Chemistry - Reviewed by the Chemistry evaluation station
(Note: This requirement was discontinued for most submissions, except Section 18s, in 2004 by California Notice to Registrants 2004-7)
(Note: This requirement was discontinued in 2004 by Ca Notice 2004-7) For Section 5 EUPs, residue data was required if a temporary or time-limited or interim tolerance has been set by U.S. EPA. EUPs are issued to allow limited use of products to accumulate data necessary for registration under Section 3 of FIFRA. If use of the EUP product may result in residues in or on food or feed, and U.S. EPA has not established a time-limited tolerance or exemption from tolerance, the food or feed derived from the experimental program must be destroyed or fed only to experimental animals.
Residue data are not required for the following (Note: This requirement was discontinued in 2004 by California Notice to Registrants 2004-7):
Guidelines for conducting residue chemistry studies are in OPPTS Series 860 (formerly Subdivision I).
5. Fish and Wildlife (and Aquatic Organisms) - Reviewed
by Fish and Wildlife evaluation station.
Fish and Wildlife data is required for products labeled for the following:
Fish and wildlife data are not required for indoor or home use or for spray adjuvants.
Note: Data requirements for each package should be confirmed in advance with the Fish and Wildlife evaluator.
Use U.S. EPA Pesticide Assessment Guidelines Subdivision E for conducting the studies.
First Tier
The following data are required on the active ingredient and are referred to as first tier studies.
Second Tier
The second tier studies may not be required depending on the type of use and results of the first tier studies. Any of these following studies that are received will be routed to the Fish and Wildlife evaluation station.
Wildlife Mammal Toxicity:
This requirement is generally waived since the other studies on safety of products to humans and domestic animals generally provide adequate characterization of toxic potential to mammals. However, if other studies demonstrate a wide variation in toxicity between species or if exposure to wild mammals is predicted to be high as a result of the nature of the use, a wild mammal LD50 study may be required.
Avian Reproduction Test:
A test which measures potential reproductive effects of a compound in the diet of birds may be required of a compound which as a result of use, is likely to cause prolonged or repeated exposure to birds; or which is persistent in the environment and therefore may persist in avian feed; or which tends to bioaccumulate in plants or animals as predicted by the octanol-water partition coefficient; or which bears a structural similarity to chemicals known to bioaccumulate.
Acute LC50 Estuarine and Marine:
Studies on estuarine and marine organisms are required when direct application to such sites is specified by label direction or when significant concentrations may enter estuarine or marine environments due to the nature of the use or predicted mobility and persistence of the compound.
Fish Early Life Stage and Aquatic Invertebrate Life Cycle Studies:
These are required when the compound is to be applied directly to water; or when the compound is expected to be transported to water as a result of use, or if the use is likely to result in continuous or recurrent exposure to water; or if any LC50 or EC50 to an aquatic organism is less than 1.0 ppm, or if the estimated environmental concentration is predicted to equal or exceed 0.01 times any LC50 or EC50 for an aquatic organism; or reproductive effects, cumulative effects or persistence in water (half-life more than 4 days) are indicated from any other study.
An Aquatic Organism Accumulation Test:
This test may be required if residues are likely to occur in the aquatic environment and if the product or its principal degradation products has a water solubility less than 0.5 ppm and an octanol-water partition coefficient greater than 1000; and the product is relatively persistent in water (half-life more than 4 days); or if the compound or its metabolites has demonstrated a tendency to accumulate in organs and tissues of mammals or avian species.
Third tier (and fourth)
Tier three (and four) tests may be required when the results of tier two (and three) tests indicate that additional data is needed to assess potential fish and wildlife hazards:
Simulated or Actual Field Testing: On mammals and birds these tests may be required by USEPA on a case by case basis if data from the first tier studies indicate that a product is highly toxic to wildlife; and/or the product is persistent in the environment as determined by environmental fate studies; and/or the compound is retained or accumulated in food; and/or the use pattern is likely to result in exposure to toxic concentrations.
Life Cycle Tests: Tests on fish may be required if the compound is to be applied directly to water or is expected to be transported to water; or if the estimated environmental concentration is expected to exceed 0.1 of the no effect level in an early life stage test; or if other studies suggest that reproductive physiology of fish may be affected.
Simulated or Actual Field Tests: For aquatic organisms, may be required when data from other studies indicate a potential to cause adverse short term or long term effects in fish or aquatic invertebrates and where such a study is determined useful in assessing risk of exposure.
Non-target bee toxicity
Bee toxicity data is required for pesticides which are likely to contact commercial apiaries or foraging bees. Test procedures are described by UC laboratory studies in Leaflet 2287 or by equivalent procedures.
6. Worker and User Safety Related to Exposure - Reviewed by the Worker Health and Safety Branch
Guidelines for conducting worker reentry studies are in OPPTS Series 875 (formerly Subdivision K).
7. Efficacy Data - reviewed by various evaluation stations
Each request for product registration or an applicable label amendment must include data supporting efficacy claims. The term efficacy refers to a product's performance.
Efficacy data is not required for Section 5 EUPs, RAs, manufacturing-use only (formulating into pesticides) products, or if selected as a deferred study for an Interim registration.
Tests must address factors normally encountered in the use patterns claimed for the product. These factors depend on the type of pests and site to be treated, and may include the following:
Efficacy reviews are done by the following evaluation stations.
Tests may include the following information:
Comparison tests conducted with various pesticides.
Tests conducted with various pests, diseases and plants.
Tests with different application rates.
Tests for dose response.
Tests conducted with pre-treatment, post-treatment, untreated control, or standard product counts.
Data on application methods - foliar spray, dust, fumigation, tree injection, irrigation water.
Field, greenhouse and lab tests.
Effect on beneficial and non-target organisms.
The Plant Physiology station evaluates efficacy data for herbicides, plant growth regulators, adjuvants, and agriculture-related algaecides.
The Microbiology station evaluates all antimicrobial products for efficacy. This includes pesticidal claims for disinfection, sanitizing, surface fungicides (wood preservatives), antimicrobial washes for fruits and vegetables, and algaecides for industrial and residential uses. Refer to Appendix VI-1 for specific Antimicrobial Efficacy Data requirements.
The Fish and Wildlife station reviews efficacy data for vertebrate control products such as rodenticides, for antifouling boat paints or coatings, fish control agents, aquatic amphibian control agents, terrestrial amphibian and reptilian control agents, avian toxicants, and vertebrate repellents.
The Chemistry station reviews efficacy for spray adjuvants.
Note: Although U.S. EPA requires the generation of efficacy data, they often waive submission of efficacy data, except for products labeled to control microorganisms posing a threat to human health.
Effectiveness and usefulness of the product are proven through field tests, laboratory tests, in-use tests, or simulated-use tests by procedures which closely approximate actual use and which employ typically used application equipment. The data must be obtained under California or similar environmental use conditions to demonstrate the product's effectiveness as labeled.
Use OPPTS Series 810 (formerly Subdivision G) for conducting product performance studies.
8. Phytotoxicity - Reviewed by Plant Physiology evaluation station
Note: U.S. EPA does not require phytotoxicity data except during reevaluation or special review. Guidelines for conducting studies are in Subdivision J.
9. Environmental Fate Data (Chemistry) for First Agricultural
Use - reviewed by Chemistry evaluation station
The following environmental fate (groundwater protection) studies are required for the first agricultural use of an active ingredient and for all products containing new active ingredients that have agricultural use patterns. Some of these data are required as part of the AB2021 data call-in.
For aquatic use patterns, the following additional tests are required:
For forestry use patterns, a forestry field dissipation study is required (two sites if only forestry use patterns exist for the active ingredient).
Field dissipation studies are conducted using a typical end use product. All others use either pure active ingredient or radiolabeled active ingredient. Finally, an anaerobic aquatic metabolism study may be freely substituted for the anaerobic soil metabolism study.
Use OPPTS Series 835 (formerly Subdivision N) for assistance in conducting the environmental fate studies.
For Interim Registrations, up to three specified studies may be deferred for up to 3 years. See Chapter VII for Interim Registration criteria.
10. Chronic Toxicology and Mutagenicity Data for a New Active Ingredient - Reviewed by the Medical Toxicology Branch.
This data is required for new active ingredients and is also required as part of the SB950 data call-in. Chronic toxicology data includes the following:
Use OPPTS Series 870 (formerly Subdivision N) for conducting the studies.
Microbial and biochemical products. Chronic toxicology data may not be required for microbial or biochemical pesticides depending on results of subchronic studies and labeled use patterns. For details on microbial and biochemical products see Chapter VIII.
Antimicrobial new active ingredients. Chronic toxicology data may not be required for these products. Refer to U.S. EPA Data Call-In Notice for Antimicrobial Pesticide Active Ingredients, dated January 1987, for requirements.
For Section 5 EUP's. Only the first year of a chronic feeding study, a first generation interim report on a two-generation reproduction study, a teratology study with one species, and gene mutation studies (see above) are required for a food use product. See details in Chapter VII.
11. Adverse Effects Disclosure Data - routed to the designated Registration Specialist and evaluated by the applicable evaluators.
If during the registration process (or anytime thereafter), an applicant or registrant has factual or scientific data or evidence of any adverse effect or risk to human health or the environment from a pesticide product including ambient air quality, the applicant or registrant must immediately submit such evidence, including all information required under Section 6 (a)(2) of FIFRA.
E. DATA REQUIREMENTS FOR RENEWAL OF CERTAIN REGISTRATIONS
Before a pesticide registration can be renewed, certain data must be submitted as follows:
1. Adverse Effect Disclosure with Application for Renewal
Each application for renewal includes a statement that the applicant has complied with the adverse effects disclosure requirements.
If adverse effects disclosure information or data is received with the renewal application, the data or information is forwarded to the designated Registration Specialist for processing. See details of the procedure and criteria in Chapter IX.
2. Conditional Registration Data for Renewal
The registrant of any conditionally registered pesticide must submit the specified data within the specified time frames. An annual report detailing the progress towards development of each item of data is required for annual renewal of the registration. The conditional registration may not be renewed unless this report is submitted with the renewal application.
To route additional data received to meet specified conditions, follow procedures in the "Intake through Archiving" guidance document.
3. Interim Registration Data for Renewal
The registrant of an Interim Registration must submit the deferred data within the specified time frames, not to exceed three years. The Interim registration cannot be renewed if the time frames for data submission have been exceeded. For details on processing Interim Registrations, see Chapter VII.
To route the deferred studies as additional data when they are received, follow procedures in the "Intake through Archiving" guidance document.
4. Emergency Registration Data for Renewal
An Emergency Registration is allowed by Section 12833. An Emergency Registration can be issued for only one year, with a one year renewal allowed if the scientific evaluation process is not yet completed. The registrant must submit evidence that the emergency pest problem continues. This information must be reviewed before the registration can be renewed. For details on processing Emergency Registrations, see Chapter VII.
Appendix VI-1
ANTIMICROBIAL PRODUCT EFFICACY DATA REQUIREMENTS
"Antimicrobial" means those pesticides used to control, prevent, destroy, or mitigate bacteria, fungi, or viruses in any environment except those on or in living animals (including man), living plants, processed food, beverages, pharmaceuticals, and cosmetics.
Antimicrobial agents include disinfectants, sanitizers, non-liquid sterilants, virucides, bacteriostats, algaecides, fungicides, and fungistats used on inanimate surfaces and in aquatic environments. Also included are pH adjusters and modifiers.
Liquid chemical sterilants (except ethylene oxide) labelled for use on medical instruments introduced directly into the human body or in contact with intact mucuous membranes are not considered pesticides.
The efficacy of most antimicrobial agents cannot be predicted on the basis of their chemical composition or formulation. It can be determined only by adequate microbiological testing.
Depending upon the type of antimicrobial agent, target microorganisms, and site to be treated, all tests should be designed to include those factors normally encountered in the use pattern intended for the product; e.g., presence or absence of organic soil or other interfering conditions, temperature, exposure period, and the number of times, or duration that the use solution can be used or reused. The actual test procedure will vary according to the characteristics of the product, the target organism(s) and the pattern of use intended.
A variety of standardized laboratory test methods for evaluating the efficacy of antimicrobial agents has been adopted by AOAC International (formerly the Association of Official Analytical Chemists). It is recommended that these standard methods be employed whenever applicable for determining the efficacy of antimicrobial pesticides and developing the efficacy data necessary for California registration. In some cases, modification of these standard methods will be necessary to reflect use conditions applicable to the particular product.
If an applicable AOAC method is not available for a particular product type or use, it is recommended that an applicable standard or established method adopted by USEPA be used, e.g. standard methods from the American Society for Testing and Materials (ASTM). It should be noted, however, that the applicant is responsible for the validity of the results and the applicability of the test method selected.
If no established method is available, or if major modification to a standard method is required, the applicant may submit a proposed protocol for review. This protocol is routed into the evaluation process with an EP suffix on the tracking ID#.
Test Substance
Tests involving antimicrobial pesticides should be conducted with the formulation to be offered for sale. The test results must demonstrate the effectiveness of the product's formulation when used according to the proposed label's directions for which registration is sought.
Exposure Period (Contact Time)
Claimed exposure times must be substantiated with data from appropriate tests. If the labeling of a product contains directions for use at exposure periods shorter or longer than those specified in the applicable test method, the test method should be modified to conform to the exposure period described in the label directions. When no exposure period is referenced on the label, it is assumed by the evaluation scientist to be 10 minutes for disinfectants and 30 seconds for sanitizers.
Hard Water Claims
If effectiveness in hard water is claimed on the product label, the product must be tested by the appropriate method in water at the claimed hardness level. Water hardness should be expressed in terms of ppm of calcium carbonate.
Organic Soil
If a product is intended for use as a one-step cleaner-disinfectant, cleaner-sanitizer, or in the presence of organic soils, the product must be tested by the appropriate method in the presence of a representative organic soil normally associated with the site of use, such as five percent blood serum for use in medical environments, chicken manure in a poultry house, or horse manure in a stable.
Soap Scum
If the product claims effectiveness as a disinfectant or sanitizer in the presence of soap scum, the study must be conducted in the presence of representative soap residue, eg. 0.005% sodium stearate.
Reuse of Product
If the product label claims reuse of the use solution for a period of time more than one day, such claims must be substantiated with efficacy data demonstrating how many times a prepared use solution of the product can be used and reused before a fresh solution should be prepared. The data must demonstrate the claimed effectiveness of the use solution that has undergone simulated re-use stressing with cumulative bioburden over the period of time specified in the directions.
If a product label claims use to disinfect barber and beauty salon equipment, re-use data derived from samples that are stressed for seven days, are required even if the label does not recommend re-use. This data requirements is waived if the label instructs users to change the solution at least daily. This requirement is due to the California Board of Barbering and Cosmetology regulation Section 979, allowing disinfecting solutions to be used for up to one week without changing.
Adverse Effects
Data describing the nature and extent of any adverse effects observed on treated materials or surfaces resulting from treatment with the antimicrobial pesticides (e.g., staining, discoloration, corrosion, etc.) must be provided as part of the efficacy report. Laboratory reports on failure of the tests should also be included in the submission.
Systematic and complete descriptions of the test employed and the results obtained are essential for proper review and evaluation of product performance by DPR. All test reports must include identification of the testing laboratory or organization, when and where the tests were conducted, and the name(s) and signature(s) of the person(s) responsible for conducting the test.
If the methods employed to develop efficacy data are standard methods (such as standard AOAC test), certain minimal information must be provided in the test report. The report must include, but is not limited to, the following:
If standard methods are significantly modified to support specific claims and/or patterns for a product, the protocol modifying the test must be provided in specific detail with the test report.
If standard methods, or modification thereto, are not employed to develop efficacy data (such as actual in-use or many kinds of simulated-use testing), complete testing protocols must be submitted with the test reports. All materials and procedures employed in testing should be described. (Note: The format of the report may be modelled after original research reports published in technical or scientific journals).
Where references to published reports or papers are made, copies or reprints of such references should be provided with test reports.
In reporting the results of in-use tests or simulated in-use tests, data on adverse effects, including the nature
and extent of such effects, should also be included in the report.
EFFICACY DATA REQUIREMENTS FOR ANTIMICROBIAL PRODUCTS
For reference, use U.S. EPA Pesticide Assessment Guidelines, Subdivision G.
Specific efficacy data requirements, testing protocols, test methods and standards for antimicrobial agents are those adopted by U.S. EPA and published in the Pesticide Assessment Guidelines, Subdivision G (Product Performance), Sections 91-1 through 91-97, dated October 1982.
Categories of products for uses not covered by the guidelines shall be supported by appropriate data developed from tests using scientific methods and procedures acceptable to the Director. When in doubt, the applicant may contact the Department to discuss the type of data that would be required and acceptable test methods applicable to their product. Written protocols of proposed tests for efficacy may be submitted for review before initiating the test.
Following are examples of products or uses not presently covered by U.S. EPA guidelines:
Antimicrobial Products Requiring Confirmatory Data Only (Discontinued
in 2006)
Confirmatory efficacy data are required for certain antimicrobial products labelled for use only as a disinfectant or sanitizer.
There are two commonly encountered situations in which an applicant is permitted to use previously submitted basic efficacy data another registrant's basic efficacy data and submit only confirmatory data (supplemental to the basic reference data) to support the registration of their antimicrobial product. These two specific situations and the required confirmatory data are described on the following page. Confirmatory data are required on the applicant's own finished product, as offered for sale, to demonstrate their ability to produce an effective product.
When the test methodology utilized in deriving the original supporting efficacy data were modified to include additional elements not specified in the recommended method, such as organic soil, hard water, longer or shorter contact time, etc., the confirmatory data must also be produced under similarly modified conditions. The specified confirmatory data are required to be developed at the dilution and condition which represents the highest level of efficacy and most stringent condition claimed on the label.
The formulation for the product proposed for registration is the same as for one which the cited data were derived from, but which is manufactured or packaged by a different company. In addition, the label claims and directions for use for both products should be basically identical.
Confirmatory data are required in most cases with minor formulation changes. However, there are exceptions to the rule. For example, substituting different kinds of dyes and fragrances, in most situations, will not require confirmatory data.
The following are confirmatory tests and performance standards for the various types of disinfectants and sanitizers:
Disinfectants (limited efficacy)
Confirmatory test standard:
Ten carriers on each of two samples representing two different batches must be tested against either Staphylococcus aureus or Salmonella choleraesuis, depending upon the microorganisms against which the activity of the product is limited. The AOAC Use-Dilution Method for liquids or the AOAC Germicidal Spray Products Test for spray products should be used. (Note: Products with claims against Gram positive bacteria should be tested against S.aureus; products with claims against Gram negative bacteria should be tested against S. cholerasuis.)
Confirmatory performance standard:
Killing on all carriers is required.
Disinfectants (general or broad spectrum efficacy)
Confirmatory test standard:
Ten carriers on each of two samples representing two different batches tested against both Staphylococcus aureus and Salmonella choleraesuis using the AOAC Use-Dilution Method for liquid products, or the AOAC Germicidal Spray Products Test for spray products are required.
Confirmatory performance standard:
Killing on all carriers is required.
Disinfectants (hospital or medical management efficacy)
Confirmatory test standard:
Ten carriers on each of two samples representing two different batches tested against Salmonella choleraesuis, Staphylococcus aureus and Pseudomonas aeruginosa. The AOAC Use-Dilution Method for liquid products, or the AOAC Germicidal Spray Products Test for spray products should be used.
Confirmatory performance standard:
Killing on all 100% carriers is required.
Sanitizer for previously cleaned food-contact surfaces
Confirmatory tests standard:
One test on one sample, with or without hard water (depending on label claims), is required using either the AOAC Germicidal and Detergent Sanitizer Test against Escherichia coli for quaternary ammonium compounds, chlorinated trisodium phosphate and anionic detergent-acid formulations, or the AOAC Available Chlorine Germicidal Equivalent Concentration Test against Salmonella typhi for iodophor, mixed halides, and chlorine-bearing chemicals.
Confirmatory performance standard:
For halide products, test results must show product concentration equivalent in activity to 50, 100, and 200 ppm of available chlorine (the reference standard sodium hypochlorite). For other chemical products, acceptable results must demonstrate a 99.999% reduction in the number of each test microorganism within 30 seconds contact time, or the length of contact time as specified on the label. The results must be reported according to actual count and percentage reduction over the control.
Reference U.S. EPA's Confirmatory Efficacy Data Requirements DIS/TSS-5 dated September 22, 1982.
Antimicrobial Products NOT Requiring Confirmatory Data
Confirmatory efficacy data are not required for antimicrobial products not labelled as a disinfectant or sanitizer for use on food contact surfaces. Confirmatory efficacy data are not required for products which are merely repackaged, relabeled, or simple aqueous dilutions of a product already registered for which there are data on file to support product registration.
Disinfectants and sanitizers with formulations and claims identical to a registered product and manufactured by the same formulator as the registered product, do not require confirmatory data.
Disinfectants and sanitizers that do not require confirmatory data must be accompanied by the following documents:
All documentation submitted must be verified.
Sanitizer and Disinfectant Label Requirements
Reference U.S. EPA Pesticide Assessment Guidelines, Subdivision H, available on microfiche.
Labels for sanitizer and disinfectants often lack certain basic elements in the directions for use. Following are some of these elements which are most often neglected, along with the recommended action:
Potable water rinse after sanitizing food contact surfaces is no longer allowed on the label. Refer to the USEPA Label Improvement notice for sanitizers issued July 25, 1986, to registrants of antimicrobial products used as food contact surface sanitizer. This Notice was issued in accordance with the Label improvement Program, PR Notice 80-1. For other label requirements, refer to DIS/TSS-11.
Use directions should indicate a minimum contact time with the disinfectant and should clearly indicate the method of application, e.g. wiping, mopping, or spraying. For reference, see DIS/TSS-15.
If wiping off or rinsing after treatment is to be recommended, a minimum contact time with the disinfectant or the sanitizer should be specified on the label.
Use directions should require removal of all animals from premises, litter and manure from floors, and emptying of all feeding and watering troughs prior to treatment. For label reference, see DIS/TSS-18.
If removal of people or animals before releasing the air sanitizer in a closed area is required or recommended, a minimal reentry period should be specified on the label and such a reentry period should be supported by adequate data. For other label requirments, refer to DIS/TSS-11.
Data must show how much product is required to buffer 100 gallons of water, having hardness equivalent to 175 ppm as calcium carbonate, to the pH recommended on the label, except for swimming pool products. If no pH is recommended on the label, then pH may be used as the criteria, except for swimming pools. Buffering capacity for other pHs may be requested in some cases. pH control buffers are registered as spray adjuvants in California.
Aquatic Use Antimicrobial Products
Antimicrobial products for use in aquatic conditions include disinfectants, bactericides, fungicides, and algaecides for use in various aquatic sites such as swimming pools, spas, fountains, decorative ponds, reservoirs, waterways, water cooling systems, air washers, brewery pasteurizers, retort systems, pulp and papermill water systems, secondary oil recovery systems, waterbeds, drip irrigation systems, etc.
Except for a few uses, such as pulp and papermill water systems and secondary oil recovery systems, the data requirements for these types of products are as follows:
1. Presumptive laboratory data derived from the product tested against representative problem-causing organisms normally found in the target water systems and any other additional organisms claimed on the proposed label. These data should demonstrate the minimum biocidal and/or biostatic concentrations of the product against the tested organisms under a defined contact time. The AOAC Use Dilution Test method and other methods used to determine the minimum inhibitory concentrations are acceptable for determining the presumptive data.
2. In-use or simulated in-use data derived from a minimum of two different units of each type of water system claimed on the proposed label. In-use studies should be conducted at test rates, frequencies of treatement, and other specified use conditions according to the directions for use and for a defined period of time appropriate for the specific use sites.
In general, disinfectants for use in swimming pools need to be tested for the duration of the entire swimming season; algaecides for use to winterize swimming pools need to be tested for the duration of the entire off season, i.e. from late autumn to early spring; and algaecides for use in swimming pools and most water cooling systems need to be tested for a minimum period of 30 days in systems with existing algae problems.
The duration of the studies may also be lengthened or shortened to conform with specific label directions on the duration of the effective period per dose regimen. For example, if a biocide used in treating the condensation drip pans in refrigeration units claim effectiveness for at least 3 months, each unit/dose must be tested for a period of 3 months. Depnding on the protocol used, untreated control units may be required in order to demonstrate by comparison the effectiveness of the treated units.
For pulp and papermill water systems, if the ASTM Standard Test Method for Efficacy of Slimicides for the Paper Industry - Bacterial and Fungal Slime (E 599 and E600, or E1839-96) is used, no in-use studies are required unless the laboratory studies are inconclusive.
For secondary oil recovery water systems, no in-use studies are required. The bacteriostatic and time-kill tests in the American Petroleum Institute (API) Recommended Practice for Biological Analyses of Subsurface Injection Water Tests are acceptable methods and should be carried out in duplicate.
Antimicrobial Preservatives or Industrial Processing
Antimicrobial products are also used as preservatives, especially during industrial processing. Some examples of the materials to be preserved are paints and stains (in-can preservatives), paint films, metal working fluids, fuel, drilling muds, adhesives, latex emulsions, caulks and sealants, polishes, cleansers, cosmetics, pesticides, sponges.
The data requirements for this type of product generally include in-use or simulated in-use data tested on representative samples of the materials to be preserved at the lowest label recommended use rate for the longest period of time claimed on the label. Untreated control samples are required. The inocula used may either be spoiled materials or isolates from spoiled materials. Tests against bacteria and fungi must be conducted separately for the data to be acceptable.
Presumptive laboratory data are also required for certain uses such as in fuel additives and additives for sugar mills. For most other uses, presumptive laboratory data are not strictly necessary, but may be used as the basis for establishing antimicrobial activities of the products as grounds for requesting conditional registration.
For additional reference and specific tests for specific uses, see the U.S. EPA Pesticide Assessment Guidelines, Subdivision G.
ANTIMICROBIALS, REQUIREMENT FOR DATA FROM IN-USE TESTS CONDUCTED UNDER CALIFORNIA CONDITIONS
Testing conducted under California conditions is not usually a concern for antimicrobial products. Products, such as many of the antimicrobials, intended for indoor use are not affected by climatic or environmental conditions. Furthermore, because California is a large state with a wide range of climatic and environmental conditions, data generated in locations that are not in extreme climate conditions, will in general be bridgeable to California conditions.
DPR would request repetition of in-use studies, if the submitted studies were generated in extreme environmental conditions not normally encountered in California.
EFFICACY DATA REQUIREMENTS - PRODUCTS FOR USE ON HARD SURFACES
|
Level of Activity |
Test Method, AOAC |
Test Microorganisms |
Total No.of Carriers |
Performance Standard |
| STERILIZERS | Sporicide Test Method | Bacillus subtilis
(ATCC 19659) and Clostridiam sporogenes (ATCC 3584) |
720 (a) | Killing on all 720 carriers |
| DISINFECTANTS - Limited Efficacy |
Use-Dilution (solids & liquids) or Germicidal Spray (sprays) | Salmonella choleraesuis (ATCC 1078) for gram-negative or Staphyloccus aureus (ATCC 6538) for gram-positive | 180 (b) | Must kill 59 out of each 60 carriers |
| - General or Broad Spectrum Efficacy | Use-Dilution (solids & liquids) or Germicidal Spray (sprays) |
Salmonella choleraesuis
(ATCC 1078) and
Staphylococcus aureus (ATCC 6538) |
360 (c) | Must kill 59 out of each 60 carriers |
| - Hospital or Medical Environment Efficacy | Use-Dilution (solids & liquids) or Germicidal Spray (sprays) |
Salmonella choleraesuis (ATCC 1078) and Staohylococcus aureus (ATCC 6538) and Pseudomonas aeruginosa (ATCC 15442) | 540 (d) | Must kill 59 out of each 60 carriers |
| SANITIZERS - For Nonfood Contact Surfaces |
USEPA's Test Method (91-30,D8) | Staphylococcus aureus (ATCC 6538) and Klebsiella pneumoniae (ATCC 4352) (e) | one test on each representative surface | 99.9% reduction compared to control within 5 minutes |
| - For Food Contact Surfaces | ||||
|
* For Halides |
Available Chlorine Germicidal Equivalent Concentration Method | Salmonella typhi (ATCC 6539) | one test on each of 3 samples | concentration equivalent to 50, 100 and 200 ppm available chlorine |
|
* For Other Products |
Germicidal and Detergent Sanitizers Method | Escherichia coli (ATCC 11229) and Staphylococcus aureus (ATCC 6538) | one test on each of 3 samples | 99.999% reduction in each test organism within 30 seconds |