### Phosphoric Acid Salts PC Code: 034903, 076413, 176407 Ty pe of Review: Toxicology (Registration Review)

OFFICE OF CHEMICAL SAFETY AND POLLUTION PREVENTION 

### UNITED ST **AT ES ENVIRONMENT**  **AL PROTECTION A**  **GENCY**

WA SHINGTON, 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 **Che mi**  **cal Class:** Biochemical s 

## 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 scie ntific policies and regulations and it was determined that there is no need to conduct additional risk assessments. The active ingredients naturall y occurring, have a non

- toxic mode of action, and are of low toxicity

. There is reasonable certaint y of no harm to the general population from exposure to these chemicals in pesticide products when they are used according to label instructions.

### Phosphoric Acid Salts PC Code: 034903, 076413, 176407 Ty pe of Review: Toxicology (Registration Review) 2



## 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. Itis applied to soil as part of a pellet that als o 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 day s later. (Iron Phosphate Fact Sheet, 2001) The chemical was first registered b y 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. The re are no currentl y approved uses for this chemical as an inert ingredient in pesticide products. As a pesticide, **potassium phosphate** is used as a fungicid e 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 b y 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. The re 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 toxic ity 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 b y the Agency in 2002. There is currently one registe red 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. The re 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 (FePO 4 

## , CAS No. 11045

– 86

– 0) in or on all food commodities. [62 FR 56105, Oct. 29, 1997 ].

### Phosphoric Acid Salts PC Code: 034903, 076413, 176407 Ty pe of Review: Toxicology (Registration Review) 3


## 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 Sy s tem, 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 result ing 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.

### Phosphoric Acid Salts PC Code: 034903, 076413, 176407 Ty pe of Review: Toxicology (Registration Review) 4

**Table 1 . Hum**  **an 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) LD 50 > 5,000 mg/kg IV 44042704 Acute dermal toxicity (rabbit) (870.1200) LD 50 > 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; 870.555 0) 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.

### Phosphoric Acid Salts PC Code: 034903, 076413, 176407 Ty pe of Review: Toxicology (Registration Review) 5

**Table 1 . Hum**  **an Health Assessment**  **Data Requirements for iron phosphate**  ***** **(40 CFR § 158.2050) Study/OCSPP**  **Guideline No. Results**  **Toxicity Category/Description**  **MRID** 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.

### Phosphoric Acid Salts PC Code: 034903, 076413, 176407 Ty pe of Review: Toxicology (Registration Review) 6

**Table 2 . Hum**  **an 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) LD 50 > 5,000 mg/kg for males and > 500 g/kg for females III 44234202 Acute dermal toxicity (rabbit) (870.1200) LD 50 > 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; 870.555 0) 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.

### Phosphoric Acid Salts PC Code: 034903, 076413, 176407 Ty pe of Review: Toxicology (Registration Review) 7

**Table 3 . Hum**  **an Health Assessment**  **Data Requirements for Dip**  **otassium Phosphate** ***** **(40 CFR § 158.2050) Study/OCSPP**  **Guideline No. Results**  **Toxicity Category/Description**  **MRID** Acute oral toxicity (rat) (870.1100) LD 50 > 5,050 mg/kg for males and females IV 44815005 Acute dermal toxicity (rabbit) (870.1200) LD 50 > 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; 870.555 0) 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

### Phosphoric Acid Salts PC Code: 034903, 076413, 176407 Ty pe of Review: Toxicology (Registration Review) 8



## 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 D ocument (BRAD) for Dipotassium Phosphate . I ssued 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