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OFFICE OF CHEMICAL SAFETY
AND POLLUTION PREVENTION
                 UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
                            WASHINGTON, D.C.  20460

      	
      
      
                                                                               




MEMORANDUM

DATE:		September 6, 2012

SUBJECT:	Toxicology Scoping Document for the Registration Review of Phosphoric Acid Salts (iron phosphate, potassium phosphate, & dipotassium phosphate).

				Registration Review Case #: 	6027
				PC Code: 					034903, 076413, 176407			
				CAS #:						10045-86-0, 7778-77-0,  7758-11-4
				Chemical Class: 				Biochemicals

FROM:		Sadaf Shaukat, Biologist 	
            Biochemical Pesticides Branch
            Biopesticides & Pollution Prevention Division (7511P)
            				
TO:			Leonard Cole, Senior Regulatory Specialist
				Biochemical Pesticides Branch
            Biopesticides & Pollution Prevention Division (7511P)

ACTION REQUESTED

The following scoping document contains the human health assessment for the biopesticides Phosphoric acid salts
in support of the development of the Registration Review Work Plan.  
 
Executive Summary

Based on the available data and information, the Agency does not foresee the need for new data or for new risk assessments for phosphoric acid salts.  Hazard and exposure information as well as Agency risk assessments on these chemicals were evaluated against current safety standards established by the Agency's scientific policies and regulations and it was determined that there is no need to conduct additional risk assessments.  The active ingredients naturally occurring, have a non-toxic mode of action, and are of low toxicity.  There is reasonable certainty of no harm to the general population from exposure to these chemicals in pesticide products when they are used according to label instructions. 






I. Background

Phosphoric Acid Salts

As a pesticide, iron (ferric) phosphate is used in controlling snails and slugs on food crops and ornamentals at outdoor and indoor sites. Iron phosphate is a common chemical with a variety of uses, including as a human nutritional supplement and as an ingredient in fertilizer. It is applied to soil as part of a pellet that also contains bait to attract snails and slugs. When the pests eat the pellets, the iron phosphate interferes with calcium metabolism in their gut, causing the snails and slugs to stop eating almost immediately. They die three to six days later. (Iron Phosphate Fact Sheet, 2001)

The chemical was first registered by the Agency in 1997. There are currently four registered products containing the active ingredient. All four products are end-use products (EPs). Iron phosphate is the sole active ingredient in three of the products. Spinosad is an additional active ingredient for one of the products. There are no currently approved uses for this chemical as an inert ingredient in pesticide products. 

As a pesticide, potassium phosphate is used as a fungicide against powdery mildew on food crops. It does have a toxic mode of action, so is therefore not classified as a biochemical. However, it is eligible for reduced data requirements because of its simple structure and natural occurrence. (Potassium Phosphate Fact Sheet, 2009)

The chemical was first registered by the Agency in 1998.  There are currently four registered products containing the active ingredient. All four products are EPs. Potassium phosphate is not the sole active ingredient in these products. Mono- and di- potassium salts of phosphorous acid or sulfur are additional active ingredient for the products. There are no currently approved uses for this chemical as an inert ingredient in pesticide products. 

As a pesticide, dipotassium phosphate is also used as a fungicide against a broad spectrum of diseases including powdery mildew, leaf spot, root dot, downy mildew, etc. on turf, ornamentals, and non-bearing fruit and nut tree crops. It appears to have a mixed mode of action involving direct toxicity to the pathogen, aided by a boosting of the plant's defense mechanisms due to the fertilizing properties of the compound. (Dipotassium Phosphate Fact Sheet, 2002)

The chemical was first registered by the Agency in 2002.  There is currently one registered product containing the active ingredient. This product is an EP. Diotassium phosphate is not the sole active ingredient in this product. Mono- and di- potassium salts of phosphorous acid are the additional active ingredients for the product. There are no currently approved uses for this chemical as an inert ingredient in pesticide products. 

II. Tolerances
40 CFR § 180.1191: Ferric phosphate; exemption from the requirement of a tolerance.
An exemption from the requirement of a tolerance is established for residues of the biochemical pesticide, ferric phosphate (FePO4, CAS No. 11045 - 86 - 0) in or on all food commodities. [62 FR 56105, Oct. 29, 1997].
40 CFR § 180.1193: Potassium dihydrogen phosphate; exemption from the requirement of a tolerance.
Potassium dihydrogen phosphate is exempted from the requirement of a tolerance in or on all food commodities when applied as a fungicide in accordance with good agricultural practices. [63 FR 43085, Aug. 12, 1998]

III. Incidents

According to the Incident Data System, there have been no reports of incidents resulting from the use of pesticide products containing potassium phosphate and dipotassium phosphate as active ingredients from January 1, 1992 to October 27, 2011.

There have been 50 reported incidents resulting from the use of pesticide products containing iron phosphate as the active ingredient.

IV. Toxicity Profile

Iron Phosphate

Sufficient data have been provided to fulfill the biochemical pesticide data requirements under 40 CFR 158.2050 for the current use patterns for iron phosphate.  The data available to the Agency are summarized in Table 1 below.

Table 1. Human Health Assessment Data Requirements for iron phosphate* (40 CFR § 158.2050)
                           Study/OCSPP Guideline No.
                                    Results
                         Toxicity Category/Description
                                     MRID
                           Acute oral toxicity (rat)
                                  (870.1100)
                                       
                             LD50 > 5,000 mg/kg
                                       
                                      IV
                                   44042704
                        Acute dermal toxicity (rabbit)
                                  (870.1200)
                                       
                  LD50 > 5,000 g/kg for males and females
                                       
                                      IV
                                   44042705
                       Acute inhalation toxicity	 (rat)
                                  (870.1300)
                                       
Waived. FDA regards iron phosphate as GRAS; it is abundant in nature, has low toxicity, is used as a nutritional supplement, and has low water-solubility.
                                       
                                       
                                       
                        Primary eye irritation (rabbit)
                                  (870.2400)
Minimally  irritating. Minimal irritation of the conjunctivae, resolved within 48 hours.
                                      III
                                   44042706
                      Primary dermal irritation (rabbit)
                                  (870.2500)
No irritation observed
                                      IV
                                   44042407
                  Dermal sensitization  (Buehler-guinea pig)
                                  (870.2600)
Waived. FDA regards iron phosphate as GRAS; it is abundant in nature, has low toxicity, is used as a nutritional supplement, and has low water-solubility.
                                       
                                       
                                       
                          Dermal sensitization (LLNA)
                                  (870.2600)
Waived. FDA regards iron phosphate as GRAS; it is abundant in nature, has low toxicity, is used as a nutritional supplement, and has low water-solubility.
                                       
                                       
                                       
                             90-Day oral toxicity
                                  (870.3100)
Waived. FDA regards iron phosphate as GRAS; it is abundant in nature, has low toxicity, is used as a nutritional supplement, and has low water-solubility.

                                       
                                       
                            90-Day dermal toxicity
                                  (870.3250)
Waived. FDA regards iron phosphate as GRAS; it is abundant in nature, has low toxicity, is used as a nutritional supplement, and has low water-solubility.

                                       
                                       
                          90-Day inhalation toxicity
                                  (870.3465)
Waived. FDA regards iron phosphate as GRAS; it is abundant in nature, has low toxicity, is used as a nutritional supplement, and has low water-solubility.

                                       
                                       
                                 Mutagenicity 
                  (Bacterial reverse mutation test; 870.5100)
 Waived. FDA regards iron phosphate as GRAS; it is abundant in nature, has low toxicity, is used as a nutritional supplement, and has low water-solubility.

                                       
                                       
                                 Mutagenicity 
           (Unscheduled DNA synthesis in mammalian cells; 870.5550)
Waived. FDA regards iron phosphate as GRAS; it is abundant in nature, has low toxicity, is used as a nutritional supplement, and has low water-solubility.

                                       
                                       
                                       
Waived. FDA regards iron phosphate as GRAS; it is abundant in nature, has low toxicity, is used as a nutritional supplement, and has low water-solubility.

                                       
                                       
                                 Mutagenicity 
          (In vivo mammalian erythrocyte micronucleus test; 870.5395)
Waived. FDA regards iron phosphate as GRAS; it is abundant in nature, has low toxicity, is used as a nutritional supplement, and has low water-solubility.

                                       
                                       
                                 Mutagenicity
            (In vitro mammalian cell gene mutation test; 870.5300)
Waived. FDA regards iron phosphate as GRAS; it is abundant in nature, has low toxicity, is used as a nutritional supplement, and has low water-solubility.

                                       
                                       
                       Developmental toxicity (rabbits)
                                  (870.3700)
Waived. FDA regards iron phosphate as GRAS; it is abundant in nature, has low toxicity, is used as a nutritional supplement, and has low water-solubility.

                                       
                                       
[*]Results taken from studies performed on EPs; No data available on TGAI.

Potassium Phosphate

Sufficient data have been provided to fulfill the biochemical pesticide data requirements under 40 CFR 158.2050 for the current use patterns for potassium phosphate.  The data available to the Agency are summarized in Table 2 below.
Table 2. Human Health Assessment Data Requirements for Potassium Phosphate (40 CFR § 158.2050)
                           Study/OCSPP Guideline No.
                                    Results
                         Toxicity Category/Description
                                     MRID
                           Acute oral toxicity (rat)
                                  (870.1100)
                                       
         LD50 > 5,000 mg/kg for males and > 500 g/kg for females
                                       
                                      III
                                   44234202
                        Acute dermal toxicity (rabbit)
                                  (870.1200)
                                       
                  LD50 > 2,000 g/kg for males and females
                                       
                                      III
                                   44234203
                       Acute inhalation toxicity	 (rat)
                                  (870.1300)
                                       
 Waived. Low acute mammalian toxicity, exempt from requirement of a tolerance 
                                       
                                       
                                       
                        Primary eye irritation (rabbit)
                                  (870.2400)
Practically non-irritating. No corneal opacity or iritis was noted during the study. One hour after test substance instillation, all animals exhibited conjunctivitis with clearance by 48 hours.
                                      III
                                   44234204
                      Primary dermal irritation (rabbit)
                                  (870.2500)
Non-irritant
                                      IV
                                   44234205
                  Dermal sensitization  (Buehler-guinea pig)
                                  (870.2600)
 Waived. Low acute mammalian toxicity, exempt from requirement of a tolerance 
                                       
                                       
                                       
                             90-Day oral toxicity
                                  (870.3100)
 Waived. Low acute mammalian toxicity, exempt from requirement of a tolerance 
                                       
                                       
                            90-Day dermal toxicity
                                  (870.3250)
 Waived. Low acute mammalian toxicity, exempt from requirement of a tolerance 
                                       
                                       
                          90-Day inhalation toxicity
                                  (870.3465)
 Waived. Low acute mammalian toxicity, exempt from requirement of a tolerance 
                                       
                                       
                                       
                                 Mutagenicity 
                  (Bacterial reverse mutation test; 870.5100)
 Waived. Low acute mammalian toxicity, exempt from requirement of a tolerance 
                                       
                                       
                                       
                                 Mutagenicity 
           (Unscheduled DNA synthesis in mammalian cells; 870.5550)
 Waived. Low acute mammalian toxicity, exempt from requirement of a tolerance 
                                       
                                       
                                       
                                 Mutagenicity 
          (In vivo mammalian erythrocyte micronucleus test; 870.5395)
 Waived. Low acute mammalian toxicity, exempt from requirement of a tolerance 
                                       
                                       
                                 Mutagenicity
            (In vitro mammalian cell gene mutation test; 870.5300)
 Waived. Low acute mammalian toxicity, exempt from requirement of a tolerance 
                                       
                                       
                       Developmental toxicity (rabbits)
                                  (870.3700)
 Waived. Low acute mammalian toxicity, exempt from requirement of a tolerance 
                                       
                                       
                                       

Dipotassium Phosphate

Sufficient data have been provided to fulfill the biochemical pesticide data requirements under 40 CFR 158.2050 for the current use patterns for dipotassium phosphate.  The data available to the Agency are summarized in Table 2 below.

Table 3. Human Health Assessment Data Requirements for Dipotassium Phosphate* (40 CFR § 158.2050)
                           Study/OCSPP Guideline No.
                                    Results
                         Toxicity Category/Description
                                     MRID
                           Acute oral toxicity (rat)
                                  (870.1100)
                                       
                  LD50 > 5,050 mg/kg for males and females
                                       
                                      IV
                                   44815005
                        Acute dermal toxicity (rabbit)
                                  (870.1200)
                                       
                  LD50 > 5,050 g/kg for males and females
                                       
                                      IV
                                   44815006
                       Acute inhalation toxicity	 (rat)
                                  (870.1300)
                                       
                                 >2.97 mg/L
                                       
                                      IV
                                   44815007
                        Primary eye irritation (rabbit)
                                  (870.2400)
No corneal opacity; positive conjunctival irritation
                                      IV
                                   44815008
                      Primary dermal irritation (rabbit)
                                  (870.2500)
Very slight erythema on 2/6 rabbits one hour after patch removal with resolution by 24 hours
                                      IV
                                   44815009
                  Dermal sensitization  (Buehler-guinea pig)
                                  (870.2600)
                               Not a sensitizer
                                       
                                       
                                   44815010
                             90-Day oral toxicity
                                  (870.3100)
              Waived. Low acute mammalian toxicity; non-food use
                                       
                                       
                            90-Day dermal toxicity
                                  (870.3250)
Waived. Low acute mammalian toxicity; proposed use pattern will not result in prolonged exposure at concentrations that are likely to be toxic
                                       
                                       
                          90-Day inhalation toxicity
                                  (870.3465)
Waived. Low acute mammalian toxicity; proposed use pattern will not result in prolonged exposure at concentrations that are likely to be toxic 
                                       
                                       
                                 Mutagenicity 
                  (Bacterial reverse mutation test; 870.5100)
Waived. Low acute mammalian toxicity; very low nticipated human exposure, not structurally related to a mutagen
                                       
                                       
                                 Mutagenicity 
           (Unscheduled DNA synthesis in mammalian cells; 870.5550)
Waived. Low acute mammalian toxicity; very low anticipated human exposure, not structurally related to a mutagen 
                                       
                                       
                                 Mutagenicity 
          (In vivo mammalian erythrocyte micronucleus test; 870.5395)
Waived. Low acute mammalian toxicity; very low anticipated human exposure, not structurally related to a mutagen 
                                       
                                       
                                 Mutagenicity
            (In vitro mammalian cell gene mutation test; 870.5300)
Waived. Low acute mammalian toxicity; very low anticipated human exposure, not structurally related to a mutagen 
                                       
                                       
                       Developmental toxicity (rabbits)
                                  (870.3700)
Waived. Low acute mammalian toxicity; very low anticipated human exposure, not structurally related to a mutagen 
                                       
                                       
*All acute tox requirements were waived for the TGAI; Results taken from studies performed on EP












VI. References

U.S. EPA Biochemical Fact Sheet for Iron Phosphate. Issued January, 2001. <http://www.epa.gov/opp00001/chem_search/reg_actions/registration/fs_PC-034903_01-Mar-01.pdf >

U.S. EPA Biochemical Fact Sheet for Potassium Phosphate. Issued January, 2001. <http://www.epa.gov/opp00001/chem_search/reg_actions/registration/fs_PC-076413_25-Nov-09.pdf >

U.S. EPA Biopesticides Registration Action Document (BRAD) for Dipotassium Phosphate.  Issued March, 2003.
      <http://www.epa.gov/opp00001/chem_search/reg_actions/registration/decision_PC-176407_23-Mar-03.pdf>





cc:  S. A. Shaukat, L. Cole, BPPD Science Review File, IHAD/ARS
 	  S. A. Shaukat, FT, PY-S: 09/06/12
