Iron (Present as ferric phosphate) and Its Associated End-use Products

Transcription

1 Proposed Re-evaluation Decision PRVD Iron (Present as ferric phosphate) and Its Associated End-use Products Consultation Document (publié aussi en français) 24 November 2017 This document is published by the Health Canada Pest Management Regulatory Agency. For further information, please contact: Publications Internet: Pest Management Regulatory Agency Health Canada Facsimile: Riverside Drive Information Service: A.L D or Ottawa, Ontario K1A 0K9 pmra.infoserv@hc-sc.gc.ca

2 ISSN: (print) (online) Catalogue number: H113-27/ E (print) H113-27/ E-PDF (PDF version) Her Majesty the Queen in Right of Canada, represented by the Minister of Health Canada, 2017 All rights reserved. No part of this information (publication or product) may be reproduced or transmitted in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, or stored in a retrieval system, without prior written permission of the Minister of Public Works and Government Services Canada, Ottawa, Ontario K1A 0S5.

3 Table of Contents Proposed Re-evaluation Decision... 1 Outcome of Science Evaluation... 1 Proposed Regulatory Decision for Ferric Phosphate... 2 International Context... 2 Next Steps... 2 Additional Scientific Information... 3 Science Evaluation Introduction Use Description of Ferric Phosphate The Technical Grade Active Ingredient: Its Properties and Uses Identity of the Technical Grade Active Ingredient Human Health Toxicological Summary Occupational Exposure and Risk Residential Exposure and Risk Dietary Exposure and Risk Aggregate Exposure Assessment Cumulative Assessment Environment Environmental Fate and Toxicology Environmental Exposure and Risk Assessment Terrestrial Organisms Aquatic Organisms Value Pest Control Product Policy Considerations Toxic Substances Management Policy Considerations Contaminants and Formulants of Health or Environmental Concern Incident Reports Conclusion List of Abbreviations Appendix I Registered Ferric Phosphate Products as of 25 August Appendix II Toxicity Effects of Ferric Phosphate to Terrestrial and Aquatic Organisms Appendix III Label Amendments for Products Containing Iron (present as ferric phosphate) 19 References Proposed Re-evaluation Decision PRVD

4 Proposed Re-evaluation Decision Under the Pest Control Products Act, all registered pesticides must be regularly re-evaluated by Health Canada s Pest Management Regulatory Agency (PMRA) to ensure that they continue to meet current health and environmental safety standards and continue to have value. The reevaluation considers data and information from pesticide manufacturers, published scientific reports, and other regulatory agencies. The PMRA applies internationally accepted risk assessment methods as well as current risk management approaches and policies. Iron (present as ferric phosphate) is used as a molluscicide to control snails and slugs in greenhouse crops, food crops, outdoor ornamentals, and turf in both residential and commercial settings. It is a naturally occurring mineral and used as a micronutrient in fertilizer, and is approved for food fortification use. 1 Ferric phosphate products are formulated as granules which are applied to the soil around plants. This consultation document 2 presents the proposed regulatory decision for the re-evaluation of ferric phosphate including the proposed updates to the label directions to further protect human health and the environment, as well as the science evaluation on which the proposed decision was based. All products containing ferric phosphate (as a molluscicide) registered in Canada are subject to this proposed re-evaluation decision. The PMRA will accept written comments on this proposal up to 90 days from the date of publication of this document. Please forward all comments to PMRA Publications (please see contact information on the cover page of this document). The final re-evaluation decision will be published taking into consideration the comments and information received. Outcome of Science Evaluation Ferric phosphate is the only slug bait available to organic growers. As such, ferric phosphate plays a vital role in both organic and non-organic food and ornamentals production. It also has value in resistance management for slugs and snails. Ferric phosphate naturally occurs in the environment, is used as a micronutrient in fertilizer, and is approved for food fortification use. With respect to human health, ferric phosphate has a low toxicity profile in humans, and there is no evidence of carcinogenicity or concerns for developmental and reproductive toxicity. Residential exposures are not of concern for homeowners and bystanders from use of ferric phosphate as a molluscicide (to control snails and slugs) when current label directions are observed. Similarly, occupational exposures are also not of concern when the current label directions are followed. Ferric phosphate granules are applied to soil around plants. 1 Canadian Food Inspection Agency, Reference Database for Hazard Identification, Nutrition Hazard. 2 Consultation statement as required by subsection 28(2) of the Pest Control Products Act. Page 1

5 When used according to label directions, residues of ferric phosphate in food and drinking water are expected to be minimal. Therefore, risks from dietary exposure in food and drinking water are not of concern for all populations. Ferric phosphate is a compound commonly found in soil. Ferric phosphate is nontoxic to birds, fish, and aquatic invertebrates. Based on the use pattern, potential exposure to non-target organisms is not expected to be of concern. Proposed Regulatory Decision for Ferric Phosphate Under the authority of the Pest Control Products Act and based on the evaluation of currently available scientific information, Health Canada is proposing that products containing ferric phosphate (used to control snails and slugs) are acceptable for continued registration for use and sale in Canada, provided that the updates to label directions are in place. Registered pesticide product labels include specific instructions for use. Directions include risk mitigation measures to protect human health and the environment that must be followed by law. As a result of the re-evaluation of iron (present as ferric phosphate), no additional risk mitigation measures are proposed by the PMRA. To meet current labelling standards, the following label updates are proposed (refer to the details in Appendix III): Environmental hazard label statements to both commercial and domestic products; Storage label statements; and Statement to keep out of reach of pets International Context Ferric phosphate is currently acceptable for use in other Organisation for Economic Co-operation Development (OECD) member countries, including the European Union, Japan, and the United States. As of 21 August 2017, no decision by an OECD member country to prohibit all uses of ferric phosphate for health or environmental reasons has been identified. Next Steps The public including the registrants and stakeholders are encouraged to submit comments during the 90-day public consultation period 3 upon publication of this proposed re-evaluation decision. All comments received during the 90-day public consultation period will be taken into consideration in preparation of re-evaluation decision document, 4 the re-evaluation decision document will include the final re-evaluation decision, the reasons for it and a summary of comments received on the proposed re-evaluation decision with the PMRA s responses. 3 Consultation statement as required by subsection 28(2) of the Pest Control Products Act. 4 Decision statement as required by subsection 28(5) of the Pest Control Products Act. Page 2

6 Additional Scientific Information No additional data are required. Page 3

7 Page 4

8 Science Evaluation 1.0 Introduction Iron (present as ferric phosphate) is a pesticide for control of snails and slugs. The registrant has indicated support for the re-evaluation of all products containing ferric phosphate, and currently registered products containing ferric phosphate are listed in Appendix I. 2.0 Use Description of Ferric Phosphate Ferric phosphate, as a molluscicide, is used in greenhouse crops, food crops, outdoor ornamentals, and turf (lawns and grass grown for seed) in both residential and commercial areas. Ferric phosphate interferes with the calcium metabolism in the gut causing the snail or slug to stop eating. It is formulated into granular or pellet baits that are to be applied in the evening when the ground is moist. Applied granules are expected to rapidly degrade under moist conditions, and as such, the product is re-applied as needed. Ferric phosphate is applied using ground application equipment (spreaders) or hand dispersion. The rate of application varies depending on the site used and ranges from g/container for greenhouse crops and ornamentals and from 33.6 to 150 g ferric phosphate / ha for food crops, lawns and grasses, and outdoor ornamental plants. Ferric phosphate is a naturally occurring mineral, is used as a micronutrient in fertilizer, and is approved for food fortification use The Technical Grade Active Ingredient: Its Properties and Uses 3.1 Identity of the Technical Grade Active Ingredient. Common name Function Chemical Family Chemical name 1 International Union of Pure and Applied Chemistry (IUPAC) 2 Chemical Abstracts Service (CAS) Iron (present as ferric phosphate) Molluscicide Inorganic salt Iron(III) phosphate CAS Registry Number Phosphoric acid, iron(3+) salt (1:1) 5 Canadian Food Inspection Agency, Reference Database for Hazard Identification, Nutrition Hazard. Page 5

9 Molecular Formula FeO4P Structural Formula Fe 3+ O - Molecular Weight O - P O - O Registration No. of Technical Grade Active Ingredient Purity of Technical Grade Active Ingredient % 29.78% 4.0 Human Health Based on registered use pattern, exposure to ferric phosphate can occur through consuming food and drinking water, working as a commercial loader/applicator, handling the product in a residential setting, or by entering treated sites. Two key factors are considered when assessing health risks: the levels at which no health effects occur and the levels to which people may be exposed. The levels used to assess risks are established to protect the most sensitive human population (for example, children and nursing mothers). As such, sex and gender are taken into account in the risk assessment. Continued registration is only supported for uses that are determined as having no health risks of concern. 4.1 Toxicological Summary Iron is distributed throughout plants and animals, and it is an important biological trace metal. The toxicity of iron salts, such as ferric phosphate, depends on the amount of bioavailable iron, and for iron to be bioavailable, it must be present or reduced to the ferrous (Fe 2+ ) form. As such, iron salts are of low to high acute oral toxicity in mice and rats. Specifically, ferric (Fe 3+ ) phosphate is insoluble in water and has been shown to have poor bioavailability in humans and animals. Following oral exposure, ferric phosphate is not expected to be absorbed in large quantities from the gastrointestinal tract into systemic circulation, and it is unlikely to be resorbed through intact skin in any significant amount. On this basis, ferric phosphate has a low toxicity profile. Acute exposure to aerosols and mists of soluble iron salts were determined to be irritating to the skin and eyes. Iron compounds are not expected to be dermal sensitizers. In almost all of the long-term oral bioavailable (Fe 2+ ) iron exposure reports in humans, the liver, central nervous system, cardiovascular system, and gastrointestinal tract were identified as target organs. Long-term intake of absorbable / bioavailable (Fe 2+ ) iron is likely to present as a blood disorder and / or, in severe cases, liver cirrhosis. Page 6

10 Repeated, long-term inhalation of iron oxide in industry workers identified the lung as the target organ where benign pneumoconiosis, shortness of breath, and a tendency to cough were noted. There is no evidence of carcinogenicity from iron exposure. No concerns for developmental or reproductive toxicity were identified in the available information. Given the low toxicity profile of ferric phosphate, no toxicological endpoints have been established for quantitative risk assessment by the PMRA. As a result, the PMRA has used a qualitative approach to assess the potential risks to ferric phosphate. 4.2 Occupational Exposure and Risk Ferric phosphate molluscicide end-use products are ready-to-use granular formulations applied using hand scattering or granular spreaders in and/or around the perimeter of the area to be protected, between the rows of crops, or in the base of potted plants. Workers can be exposed to ferric phosphate through loading and/or applying the product as well as through clean-up and maintenance activities. Workers can also be exposed through soil residues when entering a treated site to conduct activities such as transplanting and/or harvesting. When loading and applying ferric phosphate, worker exposure is expected to be primarily via the dermal route, and current labels of commercial products require use of gloves during loading and application to minimize this exposure. Based on the low exposure from the current use pattern, low toxicity profile of ferric phosphate, and mitigative measures already on the label, the potential worker risk to loaders and applicators is not expected to be of concern. No additional mitigation measures are proposed. Given the application scenario of a granular pellet applied directly to soil around plants, residues on plant foliage are expected to be minimal. Consequently, dermal post-application exposure to ferric phosphate via plant foliage is expected to be minimal. Granules are to be applied in the evening, when the ground is moist, and applied granules are expected to rapidly degrade under moist conditions, resulting in minimal exposure via soil residues during re-entry activities. Based on the minimal exposure potential and low toxicity profile of ferric phosphate, potential risk during re-entry activities is not expected to be of concern. No additional mitigation measures are proposed. 4.3 Residential Exposure and Risk The ready-to-use domestic class ferric phosphate molluscicide end-use products used by residential handlers are applied using hand scattering or push-type spreaders in and/or around the perimeter of the residential area to be protected such as vegetable and flower gardens, ornamental plants, shrubs, trees, berry plants, and fruit. Page 7

11 Similar to professional workers, homeowners can be exposed to ferric phosphate when loading and applying the end-use products and from contact with soil following application. Residential exposure from use of the domestic products is expected to be equivalent to occupational exposure and is also not expected to be of concern with the current label directions and low toxicity profile of ferric phosphate. Exposure to toddlers and young children via oral ingestion of pellets (following application) via hand-to-mouth, object-to-mouth, and incidental soil ingestion was also considered. Current label directions specify to apply the product in the evening when young children and toddlers would not be accessing the treated area, and applied granules are expected to degrade quickly in the environment when exposed to soil moisture. On this basis, potential exposure to toddlers and young children is not expected to be of concern, especially when the low toxicity profile of ferric phosphate and the low concentration of ferric phosphate in the end use products are taken into account with current label directions. No additional mitigation measures are proposed. 4.4 Dietary Exposure and Risk Ferric phosphate is found naturally in the environment, and iron is a normal constituent of the human diet. Based on the current label directions, ferric phosphate granules are applied to soil around plants, and they do not contact the plant directly. Dietary residues in plants resulting from the use of ferric phosphate as a molluscicide are expected to be negligible. Ferric phosphate is insoluble in water, and it is expected to be strongly adsorbed to soil. As such, it is not expected to accumulate in drinking water sources from the registered use pattern. The use of ferric phosphate according to label directions is not expected to result in residues in food and drinking water, and dietary risk (food and drinking water) is not expected to be of concern for all populations. No additional mitigation measures are proposed. 4.5 Aggregate Exposure Assessment Aggregate exposure is the total exposure to a single pesticide that may occur from food, drinking water, residential, and other non-occupational sources from all known or plausible exposure routes (oral, dermal, and inhalation). For ferric phosphate, aggregate exposure includes residential use exposure and dietary exposure. However, given the limited exposure potential and the low toxicity profile of ferric phosphate, aggregate exposure is not expected to be of concern under the current conditions of use for all populations. 4.6 Cumulative Assessment The Pest Control Products Act requires that the PMRA consider the cumulative exposure to pesticides with a common mechanism of toxicity. While ferric phosphate may share a common moiety with other iron-based active ingredients, the potential risks from cumulative exposure to ferrous iron are not of concern given the low toxicity profile and the limited exposure potential. Page 8

12 5.0 Environment Ferric phosphate will enter the environment through application to fields and residential gardens. There is a potential that non-target terrestrial and aquatic habitats may be exposed to the molluscicide as a result of application. 5.1 Environmental Fate and Toxicology Ferric phosphate is ubiquitous in nature. It is not volatile, and it does not readily dissolve in water. Iron salts, such as ferric phosphate, are expected to be strongly adsorbed to soil. These properties minimize dispersal of ferric phosphate beyond where it is applied in the terrestrial environment, and, as such, aquatic environments are also not expected to be significantly exposed to ferric phosphate. In general, the amount of ferric phosphate that would be released to the environment following use as a molluscicide is insignificant when compared to the iron and ferric phosphate naturally present in the environment. Ferric phosphate is relatively non-toxic to birds, fish and aquatic invertebrates. Relevant toxicity data from the review of ferric phosphate to non-target species is summarized in Appendix II. 5.2 Environmental Exposure and Risk Assessment The environmental risk assessment integrates the environmental exposure and ecotoxicology information to estimate the potential for adverse effects on non-target species. This integration is achieved by comparing exposure concentrations with concentrations at which adverse effects occur. Estimated environmental exposure concentrations (EECs) are concentrations of pesticide in various environmental media, such as food, water, soil and air. The EECs are estimated using standard models which take into consideration the application rate(s), chemical properties and environmental fate properties, including the dissipation of the pesticide between applications. Ecotoxicology information includes acute and chronic toxicity data for various organisms or groups of organisms from both terrestrial and aquatic habitats including invertebrates, vertebrates, and plants. Toxicity endpoints used in risk assessments may be adjusted to account for potential differences in species sensitivity as well as varying protection goals (such as, protection at the community, population, or individual level). Initially, a screening level risk assessment is performed to identify pesticides and/or specific uses that do not pose a risk to non-target organisms, and to identify those groups of organisms for which there may be a potential risk. The screening level risk assessment uses simple methods, conservative exposure scenarios (for example, direct application at a maximum cumulative application rate) and sensitive toxicity endpoints. A risk quotient (RQ) is calculated by dividing the exposure estimate by an appropriate toxicity value (RQ = exposure/toxicity), and the risk quotient is then compared to the level of concern (LOC). If the screening level risk quotient is below the level of concern, the risk is considered negligible and no further risk characterization is necessary. If the screening level risk quotient is equal to or greater than the level of concern, then a refined risk assessment is performed to further characterize the risk. A refined assessment Page 9

13 takes into consideration more realistic exposure scenarios (such as drift to non-target habitats) and might consider different toxicity endpoints Terrestrial Organisms The screening-level risk assessment was conducted based on the maximum application rate. Exposure to birds and mammals was assessed assuming direct oral consumption of the granular bait. The screening level risk assessment indicated that potential risk from ferric phosphate is not of concern for earthworms and terrestrial invertebrates. Based on the current use pattern, the potential risk to birds and mammals feeding on the bait granules is not expected to be concern. No additional risk mitigation measures are proposed Aquatic Organisms For the screening-level risk assessment, the potential exposure of ferric phosphate to the aquatic environment was assessed based on the direct application to water bodies of two different depths (80 cm and 15 cm). The 80-cm deep water body was chosen to represent a permanent body of water, and the 15-cm depth was chosen to represent a seasonal body of water. Based on the current use pattern, the existing screening level aquatic risk assessment indicated that the potential risk from ferric phosphate is not of concern to freshwater fish, aquatic invertebrates, and algae. Based on the current use pattern, the potential risk to amphibians is not expected to be concern. No additional risk mitigation measures are proposed. Updates to labels to meet the current standard are proposed (Appendix III). 6.0 Value Ferric phosphate has value in that it is one of only three registered active ingredients in Canada used for the control of molluscs, and it is the only slug bait available to organic growers. Combined with integrated and cultural pest management of slugs and snails, ferric phosphate plays a vital role in both organic and non-organic foods and ornamentals production. Ferric phosphate also has value as in resistance management for slugs and snails: it uses a different mode of action to kill slugs and snails when compared to other registered products. As a result, they can be applied in a rotational manner to help delay the development of resistance. Page 10

14 7.0 Pest Control Product Policy Considerations 7.1 Toxic Substances Management Policy Considerations In accordance with the PMRA Regulatory Directive DIR , the assessment of ferric phosphate against Track 1 criteria of Toxic Substances Management Policy (TSMP) under Canadian Environmental Protection Act was conducted. It determined that: Ferric phosphate does not meet all the Track 1 criteria. 7.2 Contaminants and Formulants of Health or Environmental Concern During the re-evaluation of ferric phosphate, contaminants in the technical were compared against the List of Pest Control Product Formulants and Contaminants of Health or Environmental Concern maintained in the Canada Gazette. 7 The list is used as described in the PMRA Notice of Intent NOI and is based on existing policies and regulations including DIR99-03 and DIR , and taking into consideration the Ozone-depleting Substance Regulations, 1998, of the Canadian Environmental Protection Act (substances designated under the Montreal Protocol). The PMRA has reached the following conclusion: Ferric phosphate products do not contain any contaminants of health or environmental concern. End-use products contain wheat, which is considered as a formulant of concern (as allergen). Current labels contain adequate warning statement related to the allergen wheat. 8.0 Incident Reports Since 26 April 2007, registrants have been required by law to report incidents, including adverse effects to health and the environment, to the PMRA within a set time frame. As of 19 July 2017, there have been no human or environmental incident reports received by the PMRA; however, ten domestic animal incidents have been reported. Causality to ferric phosphate was determined in eight of the ten cases (7 dogs, 1 cat), and accidental oral ingestion of a granular ferric phosphate product around the home was the exposure route in all incidents. Briefly, three ingested the product directly from the container, three had access to the treated area, and in two cases, it was unclear how the product was accessed. Most animals had gastrointestinal symptoms such as vomiting or drooling, and one animal was reported as not feeling well. 6 DIR99-03, The Pest Management Regulatory Agency s Strategy for Implementing the Toxic Substances Management Policy. 7 Canada Gazette, Part II, Volume 139, Number 24, pages : List of Pest Control Product Formulants and Contaminants of Health or Environmental Concern and in the order amending this list in the Canada Gazette, Part II, Volume 142, Number 13, pages Part 1 Formulants of Health or Environmental Concern, Part 2 Formulants of Health or Environmental Concern that are Allergens Known to Cause Anaphylactic-Type Reactions and Part 3 Contaminants of Health or Environmental Concern. Page 11

15 Overall, the assessment of incident data involving ferric phosphate did not identify any significant health or environmental risk. However, there are currently no standard precautionary statements on the end-use labels for exposure to domestic animals, and a statement is proposed to be added to the labels (Appendix III). All relevant information received through the PMRA incident reporting program were considered in the re-evaluation of ferric phosphate. 9.0 Conclusion Ferric phosphate is the only slug bait available to organic growers. As such, ferric phosphate plays a vital role in both organic and non-organic food and ornamentals production. It also has value in resistance management for slugs and snails. Ferric phosphate naturally occurs in the environment, is used as a micronutrient in fertilizer, and is approved for food fortification use. With respect to human health, ferric phosphate has a low toxicity profile in humans, and there is no evidence of carcinogenicity or concerns for developmental and reproductive toxicity. Residential exposures are not of concern for homeowners and bystanders from use of ferric phosphate as a molluscicide when current label directions are followed. Similarly, occupational exposures are also not of concern when the current label directions are followed. Ferric phosphate granules are applied to soil around plants. When used according to label directions, residues of ferric phosphate in food and drinking water are expected to be minimal. Therefore, risks from dietary exposure in food and drinking water are not of concern for all populations. Ferric phosphate is a compound commonly found in soil. Ferric phosphate is nontoxic to birds, fish, and aquatic invertebrates. Based on the use pattern, potential exposure to non-target organisms is not expected to be of concern. Updates to label directions are being proposed to meet the current labeling standards. Page 12

16 List of Abbreviations List of Abbreviations bw cm EC50 EEC Fe 2+ Fe 3+ g ha kg L LC50 LOC mg MRL nm Pa OECD ph PMRA RQ λ Body weight Centimetre(s) Effective Concentration, half-maximal response Expected environmental concentration Ferrous ion Ferric ion Gram(s) Hectare Kilogram(s) Litre(s) Lethal Concentration, 50% death Level of concern Milligram(s) Maximum Residue Limit Nanometer(s) Pascal(s) Organization for Economic Co-operation and Development -log10 hydrogen ion concentration Pest Management Regulatory Agency Risk quotient Wavelength Page 13

17 Page 14 List of Abbreviations

18 Appendix I Registered Ferric Phosphate Products as of 25 August 2017 Reg No. Marketing Class Technical W. Neudorff GmbH KG Domestic W. Neudorff GmbH KG Manufacturing W. Neudorff GmbH KG Commercial W. Neudorff GmbH KG Commercial Omex Agriculture Inc Domestic Scotts Canada Ltd Domestic Gardens Alive Inc Commercial Engage Agro Corporation Technical Scotts Canada Ltd Domestic Scotts Canada Ltd. Appendix I Registrant Product Name Formulation Guarantee FERRIC PHOSPHATE TECHNICAL ACTIVE INGREDIENT SLUGGO SLUG & SNAIL BAIT FOR GARDENS NEU1165M MANUFACTURING CONCENTRATE FERRAMOL SLUG AND SNAIL BAIT SLUGGO SLUG AND SNAIL BAIT SCOTTS ECOSENSE SLUG-B-GON SLUG & SNAIL BAIT ESCAR-GO SLUG AND SNAIL BAIT SLUGGO PROFESSIONAL SLUG AND SNAIL BAIT SCOTTS FERRIC PHOSPHATE TECHNICAL SCOTTS ECOSENSE SLUG B GON SLUG AND SNAIL BAIT II solid 29% granular 0.28% granular 0.28; granular 0.28% granular 0.28% granular 0.28% granular 0.28% granular 0.28% solid 29.78% pellets % Page 15

19 Page 16 Appendix I

20 Appendix II Appendix II Toxicity Effects of Ferric Phosphate to Terrestrial and Aquatic Organisms Category Species Toxicity Invertebrate, Acute Earthworm 14 d LC 50 > 7.6 mg ferric phosphate/kg soil Avian, Acute Oral Bobwhite Quail 14 d LD 50 > 20 mg ferric (Colinus virginianus) phosphate/kg bw Rat, Acute Sprague-Dawley 14 d LD 50 > 50 mg ferric phosphate/kg bw Freshwater Fish, Acute, Freshwater Invertebrate, Acute Freshwater algae Rainbow trout (Onchorhynchus mykiss) Daphnia magna Green alga (Pseudokirchneriella subcapitata) 96 h LC 50 > 1.2 mg ferric phosphate/l 48 h EC 50 >1.2 mg ferric phosphate/l 96 h- EC 50 = 0.39 mg ferric phosphate/l (cell density) Page 17

21 Page 18 Appendix II

22 Appendix III Appendix III Label Amendments for Products Containing Iron (present as ferric phosphate) The label amendments presented below do not include all label requirements for individual enduse products, such as first aid statements, disposal statements, precautionary statements, and supplementary protective equipment. Information on labels of currently registered products should not be removed unless it contradicts the label statements provided below. A submission to request label revisions will be required within 90 days of finalization of the reevaluation decision. I) The following statements MUST BE REMOVED from all sections of the label. Commercial and Domestic Class Products: WILL NOT HARM PETS, BIRDS, OR WILDLIFE KEEP OUT OF REACH OF CHILDREN II) The following principal display panel statements must be added: Commercial and Domestic Class Products: KEEP OUT OF REACH OF CHILDREN AND PETS III) Under PRECAUTIONS, the following statements must be added: Commercial Class Products: KEEP OUT OF REACH OF CHILDREN AND PETS Domestic Class Products: KEEP OUT OF REACH OF CHILDREN AND PETS IV) The following statements must be included in a section entitled ENVIRONMENTAL HAZARDS. Commercial Class Products: To reduce runoff from treated areas into aquatic habitats avoid application to areas with a moderate to steep slope, compacted soil, or clay. Avoid application when heavy rain is forecast. Page 19

23 Appendix III Contamination of aquatic areas as a result of runoff may be reduced by including a vegetative strip between the treated area and the edge of the water body. V) The following statements must be included in a section entitled DIRECTIONS FOR USE: Commercial Class Products: DO NOT contaminate irrigation or drinking water supplies or aquatic habitats by cleaning of equipment or disposal of wastes. As this product is not registered for the control of pests in aquatic systems, DO NOT use to control aquatic pests. DO NOT apply by air. Domestic Class Products: DO NOT contaminate irrigation or drinking water supplies or aquatic habitats by cleaning of equipment or disposal of wastes. VI) The following statements must be included in a section entitled STORAGE: Commercial and Domestic Class Products: To prevent contamination, store this product away from food or feed. VII) The following must be included in a section entitled DISPOSAL: Domestic Class Products: DO NOT reuse the empty containers. Dispose in household garbage. Unused or partially used products should be disposed at provincially or municipally designated hazardous waste disposal sites. Page 20

24 References References I) LIST OF STUDIES/INFORMATION SUBMITTED BY REGISTRANT(S) UNPUBLISHED PMRA Reference Document Number , [Privacy removed] FeP [CBI removed] Analysis 19Dec14, DACO: 2.13,2.13.1, CBI , [Privacy removed] Iron and Phosphorus Analyses Report 3Dec14, DACO: 2.13,2.13.1, CBI , Iron Phosphate CoAs [Privacy removed] 2013, DACO: , , FeP TGAI [Privacy removed] Chemistry Volume 12Mar14, DACO: 2.0,2.1,2.11,2.11.1,2.11.2,2.11.3,2.11.4,2.12,2.12.1,2.13,2.13.1,2.13.2,2.13.3, ,2.14,2.14.1, , , , , ,2.14.2,2.14.3,2.14.4,2.14.5,2.14.6,2.14.7,2.14.8,2.14.9,2.2,2.3,2.3.1,2.4,2.5,2.6,2.7,2.8,2.9 CBI , [Privacy removed] Impurities Analysis Batch 1 annotated, DACO: CBI , [Privacy removed] Impurities Analysis Batch 2 annotated, DACO: CBI , [Privacy removed] Impurities Analysis Batch 3 annotated, DACO: CBI , [Privacy removed] Impurities Analysis Batch 4 annotated, DACO: CBI , [Privacy removed] Impurities Analysis Batch 5 annotated, DACO: CBI , [Privacy removed] Chemistry for Ferric Phosphate. DACO: 2.1, 2.10, , , , 2.12, 2.13, , , , , , , , , , , , , , , 2.2, 2.3, 2.4,2.5, 2.6, 2.7, 2.8, 2.9, CBI , Analyses of ferric phosphate, DACO: CBI , Additional Impurities Analyses FeP, DACO: CBI , FeP TGAI Product Chemistry, DACO: 2.11,2.13.3, CBI , Dissociation constants of phosphates and a number of related salts, DACO: CBI , Iron orthophosphate: DETERMINATION OF MELTING/FREEZING TEMPERATURE AND WATER SOLUBILITY, DACO: ,2.14.2,2.14.4, CBI Page 21

25 , Iron orthophosphate: DETERMINATION OF MELTING/FREEZING TEMPERATURE AND WATER SOLUBILITY, DACO: ,2.14.2,2.14.4, CBI , Iron orthophosphate: DETERMINATION OF MELTING/FREEZING TEMPERATURE AND WATER SOLUBILITY, DACO: ,2.14.2,2.14.4, CBI , Chemical Safety Report, DACO: CBI References , IP 27 Iron orthophosphate: DETERMINATION OF RELATIVE DENSITY, DACO: CBI , Ferric Orthophosphate Production, DACO: ,2.11.3, CBI , Not applicable, DACO: , CBI , Not applicable, DACO: , CBI , Safety Data Sheet E B, DACO: CBI , Description of starting materials + Suppliers SDS TDS, DACO: CBI , Detailed Production Process Description + flow chart / Ferric Orthophosphate Production, DACO: CBI , Discussion of Formation of Impurities, DACO: CBI ,DACO: CBI , DACO: CBI , DACO: CBI , DACO: CBI , DACO: CBI RESPONSE TO PRELIMINARY REVIEW,TOX,SUMMARY OF EVALUATIONS PERFORMED BY THE JOINT FAO/WHO EXPERT COMMITTEE ON FOOD ADDITIVES,EVALUATION OF CERTAIN FOOD ADDITIVES AND CONTAMINANTS,BIOAVAILABILITY OF IRON SOURCES&THEIR UTILIZATION IN FOOD ENRICHMENT,VOL1OF1, SUBN # (FERRIC PHOSPHATE), DACO: RESPONSE TO PRELIMINARY REVIEW, ACUTE/SKIN, EYE AND RESPIRATORY IRRITATIONS, TOXICOLOGY OF THE EYE, ENCYCLOPEDIA OF CHEMICALS, DRUGS, PLANTS, TOXINS, AND VENOMS, THIRD EDITION, VOL 1 OF 1, W.M. GRANT, ( ; ; ) SUBN. # (FERRIC PHOSPHATE), DACO: 4.2.2,4.2.3, RESPONSE TO PRELIMINARY REVIEW, SHORT TERM TOXICITY, HANDBOOK ON THE TOXICOLOGY OF METALS, SECOND EDITION, VOL 2: SPECIFIC METALS, VOL 1 OF 1, L. FRIBERG ET AL, 1986 ( ) SUBN. # (FERRIC PHOSPHATE), DACO: Page 22

26 References RESPONSE TO PRELIMINARY REVIEW,LONG TERM TOX,BODY IRON STORES&RISK OF COLONIC NEOPLASIA,PHARMACOLOGICAL BASIS THERAPEUTICS,DRUGS EFFECTIVE IRON-DEFICIENCY&OTHER HYPOCHROMIC ANEMIAS,HANDBOOK TOX OF METALS,VOL1OF1,R.L.NELSON ET AL, (86: ; ; );SUBN (FERRIC PHOSPHATE), DACO: RESPONSE TO PRELIMINARY REVIEW, GENOTOXICITY, IRON- INDUCED DNA DAMAGE AND SYNTHESIS IN ISOLATED RAT LIVER NUCLEI, BIOCHEM. J., EXPERIENTIA 34, VOL 1 OF 1, T.K. SHIRES, 1982 (205: ;8: ) SUBN. # (FERRIC PHOSPHATE), DACO: RESPONSE TO PRELIMINARY REVIEW,REPRODUCTIVE/DEVELOPMENTAL TOXICITY,FATAL INTOX IN LATE PREGNANCY,CONTROL POISONINGS,CLINICAL PATH CONFERENCE,CONSEQUENCES IRON OVERDOSE,MATERNAL IRON POISONING, VOL1OF1, M.OLENMARK, 1987 (25(4): ; ; ;10: ;19: ) SUBN (FERRIC PHOSPHATE), DACO: RESPONSE TO PRELIMINARY REVIEW,PHARMACOKINETICS,CASARETT AND DOULL'S TOXICOLOGY THE BASIC SCIENCE OF POISONS,PHARMACOLOGICAL BASIS OF THERAPEUTICS,DRUG EVALUATIONS,PATTY'S INDUSTRIAL HYGIENE AND TOX, M.O.AMDUR ET AL, 1991 (623; ; ; ;1493; ) SUBN (FERRIC PHOSPHATE), DACO: RESPONSE TO PRELIMIN REVIEW,RISE TOTAL IRON-BINDING CAPACITY AFTER IRON OVERDOSE,DIRECT EVIDENCE IN VIVO,IRON OXIDE/SALTS,DRINKING WATER REGULATIONS,TISSUE CHANGES IN RATS,K.K.BURKHART ET AL(20: ;88: ;III ; ; ;822-B ;77: )SUBN (FERRIC PHOSPHATE), DACO: SUMMARIES-TOX PROFILE,DATA,TOX IRON PHOSPHATE,IRON SALTS/OXIDE,PATTY'S INDUSTRIAL HYGIENE&TOX,COMPREHENSIVE REVIEW TOX,MEDICAL TOX,DIAGNOSIS&TREAT.HUMAN POISONINGS,CONDENSED CHEMICAL DICTIONARY, ( ; ; ; ; LG )SUBN (FERRIC PHOSPHATE), DACO: 4.1, WAIVERS: ENVIRONMENTAL CHEMISTRY AND FATE, FERRIC PHOSPHATE, IRON (III) PHOSPHATE FERRIC ORTHOPHOSPHATE, SUBN. # , DACO: 8.1, , , , , , , , , , , , , , , Page 23

27 References PUBLISHED PMRA Reference Document Number REREGISTRATION ELIGIBILITY DOCUMENT (RED), IRON SALTS, EPA, R.E.D. FACTS, APPENDICES AND ATTACHMENTS, REPORT, (738-S ;738-F ;CASE 4058) (FERRIC PHOSPHATE), DACO: REREGISTRATION ELIGIBILITY DOCUMENT (RED): IRON SALTS. U.S. EPA "EPA R.E.D.FACTS-IRON SALTS".(EPA-738-F ;H-7508W), DACO: 5.14 II) ADDITIONAL INFORMATION CONSIDERED PUBLISHED PMRA Reference Document Number Evaluation Report for Category B, Submission Number Page 24