Document ID: EPA-HQ-OPP-2011-0741-0002
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2011-10-05T04:00Z

EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER  

EPA Registration Division contact: Gene Benbow, 703-347-0235 or benbow.gene@epa.gov 

Cytec Industries Inc.

Petition # 1F7887

	EPA has received a pesticide petition (#1F7887) from Cytec Industries Inc., 5 Garret Mountain Plaza, Woodland Park, NJ 07424, requesting, pursuant to section 408(d) of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a(d), to amend 40 CFR part 180  by establishing a tolerance of 0.01 ppm for residues of phosphine in or on the raw agricultural commodities:  asparagus; cherimoya; dates, fresh; figs, fresh; globe artichokes; pawpaws; pineapple, water chestnuts and watercress, and for all fresh fruit and vegetable crop groups (including Berry and Small Fruit; Citrus Fruit; Pome Fruit; Stone Fruit; Herbs and Spices; Brassica Leafy vegetables;  Leafy Vegetables; Bulb Vegetables; Cucurbits; Fruiting Vegetables except Cucurbits; Legume vegetables, except soybeans; Foliage of Legume Vegetables; Root and Tuber Group; and Root and Tuber Leaves Group).  Individually listed members of fresh fruit and vegetable crop groups for which tolerances are already established are requested to be included in their respective crop groups and no longer listed separately.  
  
EPA has determined that the petition contains data or information regarding the elements set forth in section 408 (d)(2) of  FDDCA; however, EPA has not fully evaluated the sufficiency of the submitted data at this time or whether the data supports granting of the petition. Additional data may be needed before EPA rules on the petition.

A. Residue Chemistry

	1. Plant metabolism.

Based on the limited use pattern (indoor use/sealed spaces) of cylinderized phosphine gas and phosphine-generating metallic phosphide products, plant and animal metabolism data were not required. The residue of concern is phosphine. The Agency has determined that decomposition products of phosphine are toxicologically insignificant at the levels found in treated commodities.

	2. Analytical method. 

The Pesticide Analytical Manual (PAM) Vol. II  lists, under aluminum phosphide, a colorimetric method (LOD = 0.01) and a GLC method with a flame photometric detection (LOD = 0.001 ppm) as Method A and B, respectively, for the enforcement of tolerances. The residue of concern is phosphine. It is noted that Method A remains a lettered method because of variable recoveries observed in an Agency method try-out. However, the method has been determined to be acceptable for enforcement because phosphine is highly reactive, and finite residues are not expected. Data submitted in support of the established tolerances were collected by one of these two methods.
      
Because phosphine is an inorganic compound, recovery of residues using FDA Multiresidue Protocols is not expected, and the requirement for such data has been waived by the Agency.

	3. Magnitude of residues. 

Residue data reflecting registered post-harvest treatments of stored raw agricultural and processed commodities under ambient temperatures were reviewed in the 1998 Aluminum and Magnesium Phosphide Registration Eligibility Decision and indicate that, with adequate aeration or further processing after treatment, residues of phosphine dissipate to non-detectable levels (all <0.01 ppm). Residue data also indicate that the phosphine release from registered aluminum and magnesium phosphide products and cylinderized phosphine gas are not significantly different. The established tolerances of 0.01 ppm for various fresh fruits and vegetables, and 0.1 ppm for dried fruit, nuts and cereals reflect a 48-hour aeration period.

Cytec Industries Inc. is proposing a new use of cylinderized phosphine to treat fresh fruits and vegetables in cold storage.  A new study was completed on six representative commodities (apples, grapes, peaches, strawberries, broccoli, squash) to determine whether commodities with high water content (fresh fruits and vegetables) that are fumigated and aerated under cold storage conditions have detectable residues after proper aeration.  In the study, residues were not detected (LOQs ranging from 0.9 to 2.4 ppb) 24 and 48 hours after aeration (6 and 12 hours after aeration for strawberries) in any of the six commodities tested.  

The study confirms that the tolerance of 0.01 ppm (the limit of detection) established for currently registered fresh fruits and vegetables and is also appropriate for fresh fruits and vegetables treated under cold storage conditions with cylinderized phosphine gas following appropriate aeration.  The study also supports the establishment of a tolerance for residues of phosphine in all fresh fruits and vegetables, because residues were not detected in any commodity tested, confirming all previous residue work that indicates residues of phosphine are not detectable following aeration according to label directions.  In addition, because residues are not detectable under cold treatment conditions, it is reasonable to assume that residues will not be present following treatment in warmer ambient conditions since phosphine is volatile fumigant.  For this reason, Cytec Industries Inc. is requesting the establishment of a tolerance of 0.01 ppm for all fresh fruits and vegetables.

B. Toxicological Profile

EPA has evaluated the available toxicity data and considered its validity, completeness, and reliability as well as the relationship of the results of the studies to human risk (see the June 9, 1999 Federal Register p. 30939).  The Agency does not normally use inhalation studies for oral (dietary) risk assessments. However, inhalation studies were used for phosphine because: (1) Use of an inhalation "dose" provides a conservative approach for oral risk assessments; (2) these studies enable the Agency to quantify the dosage of phosphine exposed to laboratory animals; (3) the Agency required inhalation studies (rather than oral studies) for this chemical because exposure to this chemical via inhalation is much more likely for those individuals who would have occupational exposure.

EPA has also considered available information concerning the variability of the sensitivities of major identifiable subgroups of consumers, including infants and children. The nature of the toxic effects caused by phosphine are discussed below.

	1. Acute toxicity.  

A rat acute inhalation study on phosphine indicated an LC50 greater than 11 ppm, the highest dose tested (HDT). This puts phosphine in Toxicity Category I, i.e., Highly Toxic. Given the use patterns and chemical characteristics of metallic phosphide and cylinderized phosphine gas products,  the other acute toxicity 81-series guideline studies used to establish precautionary labeling were waived for these chemicals as they would not change the Toxicity Category or affect protective clothing requirements. The material of concern is phosphine gas which is the material with pesticidal properties, when either metallic phosphides or cylinderized phosphine gas is used.

 The acute dietary endpoint is based upon the results of the 90-day inhalation study. The dose and endpoint for risk assessment was 5 ppm or 1.8 milligrams/kilogram/day (mg/kg/day) based on the lack of treatment-related effects following 15 days of exposure. The acute reference dose (RfD) is 0.018 mg/kg/day, including a 100-fold uncertainty factor (UF) to account for inter- and intra species variation.  The agency determined that an FQPA safety factor was not needed for the protection of infants and children.

	2. Genotoxicity. 

In a Salmonella typhimurium reverse gene mutation assay, the test was negative with hydrogen phosphide (PH3) in all strains up to cytotoxic concentrations (488 ppm/plate +- S9).

  i. Chromosome aberrations. In an in vitro cytogenetic assay with Chinese hamster ovary (CHO) cells phosphine was positive at 2,500 and 5,000 ppm without S9 activation. This resulted in a significant but not dose-related increase in the frequency of cells with structural chromosome aberrations. Significant clastogenic effects were also noted at 2,500 ppm with S9 activation but not at the HDT (5,000 ppm).
        
  ii. Other genotoxic mechanisms. In an in vivo unscheduled DNA Synthesis (UDS) in primary rat hepatocytes, the test was negative in male Fischer rats exposed via inhalation to PH3 doses of 0, 4.8, 13, 18 or 23 ppm (equiv. to 0, 11.4, 30.8, 42.6 or 54.5 mg/m3, respectively) for 6 hours. Overt toxicity (i.e., difficulty in breathing) but no target cell cytotoxicity was observed at the HTD.

        Based on the findings reported by Garry et al., (1989) that pesticide applicators exposed to phosphine had increased levels of chromosome damage, the USEPA sponsored a series of acute (Kligerman et al.,1994a) and subacute (Kligerman et al., 1994b) inhalation cytogenetic studies with phosphine. A summary of these studies are as follows:
        
      (a) Phosphine was negative for the induction of micronucleated polychromatic erythrocytes (MPE) in bone marrow cells and splenocytes and negative for the induction of sister chromatid exchange or chromosomal aberrations in splenocytes of CD-1 male mice exposed by inhalation to 0, 5, 10 or 15 ppm for 6 hours. Overt toxicity, manifested as lethargy and shallow breathing was seen at the HDT. There was a dose-related and significant reduction of splenocyte cell cycling at all levels, which indicates that phosphine was cytotoxic to splenocytes. There was, however, no adverse effect on bone marrow cells (Kligerman, et al., 1994).
         
      (b)  Male B6C3F1 mice and male F344 rats were exposed by inhalation to 0, 1.25, 2.5 or 5.0 ppm phosphine, 6 hours/day, 5 days/week over an 11-day period. Bone marrow cells and/or peripheral blood lymphocytes were harvested and examined for sister chromatid exchanges and chromosomal aberrations (mouse and rat peripheral blood lymphocytes) and for MPEs (rat bone marrow and mouse bone marrow and peripheral blood lymphocytes). In addition, B6C3F1 males were exposed via inhalation to 0 or 5 ppm as above over a 12-day period and mated with untreated females in a dominant lethal assay. Results show that phosphine was not genotoxic at any endpoint.

  iii. Additional in vivo data summarized below were available for review:
        
      (a) Following subchronic inhalation exposure (0, 0.3, 1.0 or 4.5 ppm, 6 hours/ day, 5 days/week for 13 weeks) but not acute inhalation exposure (0 or 5.5 ppm, 2 weeks, 6 hours/day, 5 days/week for 2 weeks), phosphine at 4.5 ppm caused a statistically significant increase in micronucleus induction in the spleen lymphocytes and bone marrow cells of Balb-c male and female mice. There was, however, no increase in gene mutations at the hypoxanthine guanine phosphoribosyl transferase locus in the recovered spleen lymphocytes.
         
      (b) After 6 hours of inhalation exposure, phosphine, at the HDT (19 ppm) induced a significant increase in chromosomal aberrations in the bone marrow of Sprague Dawley male rats but not in the female rats. The effect is considered equivocal because increased chromosomal aberration frequencies were only seen in high-dose males with severely reduced mitotic indices (MIs). Females did not show increased chromosome aberrations and did not have decreased MIs. There was also no effect on peripheral lymphocytes.

      (c) In an Australian study of workers exposed to phosphine, 31 phosphine fumigators and 21 controls, all employed at the New South Wales Grain Corporation, were examined for micronucleus incidence in peripheral blood lymphocytes and their concentrated urine was assessed for mutagenicity in TA100 and TA98 strains of S. typhimurium. In addition, serum bile acids were measured. The subjects, all males, were matched for medication, X-ray exposure within the past year and smoking habits. There was no indication how often the fumigators were exposed, or the most recent exposure date or the length of the various fumigators employed. No individual data were presented to identify if certain individuals showed unusually high micronuclei incidence, or presence of mutagens in the urine.

         Urine samples were concentrated 75-fold and the procedure of Yamaski and Ames (1977) was used to test mutagenicity to TA100 and TA98 in the presence or absence of metabolic activation (S9). There was no increase in the mutagenicity of urine from the fumigators (N-27) vs controls  (N=-19) in this assay.
         
         Serum bile acids showed no changes related to phosphine exposure. Cholesterol and some liver enzymes (gamma-glutamyl transferase were elevated in the exposed group. Micronuclei formation was measured in isolated peripheral blood lymphocytes cultured for 44 hours in the presence of phytohemagglutinin to stimulate mitosis, arrested at metaphase with cytochalasin-B and harvested by cytocentrifugation after 72 hours in culture. The micronucleus incidence was comparable among the fumigators and the control groups (overall MI for fumigators = 6.9 vs 7.1 for controls).
         
         Phosphine is not mutagenic in bacteria but is clastogenic in vitro. Both the negative Ames test and the positive CHO cell chromosome assay are consistent with the in vitro test results for zinc phosphide. Studies conducted in vivo indicate that phosphine is not clastogenic in mice or rats and does not cause dominant lethal mutations in mice following acute exposures for up to 2 weeks. There is, however, evidence that inhalation exposures of phosphine for up to 13 weeks induced significant clastogenic and/or an euploidogenic effects in male and female mice. In a 2-year rat inhalation study, however, there were no treatment related effects and both the NOEL and LOEL for phosphine are > 3 ppm.

	3. Reproductive and developmental toxicity. 

   i. Developmental toxicity.      
         
         In a developmental study, CD-derived Sprague Dawley mated female rats (24-27/dosage group) were exposed in inhalation chambers to concentrations of phosphine gas at 0, 0.03, 0.3, 3.0, 5.0 and 7.5 ppm, 6 hours per day on gestation days 6 through 15. The highest dose group was terminated after 10 days of exposures due to high mortalities (14/24). The treated females were observed twice daily for toxicity, and body weights and food consumption were monitored throughout the study. At day 20 post-coitus, the females were sacrificed and examined for corpora lutea, implantations, live and dead fetuses and early and late resorptions. Pups were identified, sexed and examined for external malformations and visceral and skeletal defects. The females and their fetuses from the high dose group were not examined for developmental effects. The only abnormalities observed were increased resorptions in liters (16 litters, 76 pups). Increased resorptions were not seen in the 0.3, 3.0 or 5.0 ppm groups. All other observations were comparable to the control females and pups. The maternal NOAEL was 5 ppm and the maternal LEL was 7.5 ppm based on the high incidence of maternal deaths. The reproductive NOAEL is 5 ppm and the developmental NOAEL was 5 ppm.

   ii. Reproductive toxicity.  
         
         This study was not required for phosphine-producing products. The complete toxicology data requirements for food-use chemicals are not required for phosphine products since little phosphine exposure is expected from use on foods as a fumigant. In addition, the Agency does not routinely require the standard toxicological data base for a food use chemical for fumigants. Fumigants are gases, which dissipate rapidly and provide for no residual control. Phosphine diffuses rapidly through the stored product because it is a small molecule and does not absorb to most commodities. Dietary exposure to this gas is not expected, tolerances are established to prevent misuse of the fumigants. It is for this reason, lack of exposure, that the Agency does not routinely require the complete battery of testing required for a food-use chemical, for fumigants. The very nature of the chemicals used for fumigation (very high volatility) make dietary exposure an unlikely scenario. The Agency reevaluated all previously waived food- use data requirements while reassessing these fumigants and determined that, based on lack of expected exposure, the data were not required. The only exception to this is the 2-year combined cancer-chronic study because there were specific concerns regarding chronic effects from low level exposure in grain workers.

	4. Subchronic toxicity. 

In a 90 day rat inhalation study, Fischer 344 rats (10/sex/dose) were exposed to phosphine 6 hours/day, 5 days/week for 13 weeks at levels of 0, 0.3, 1.0 or 3.0 ppm. Additional groups (3-5/sex/group) were exposed at 0 or 10 ppm starting at week 8, and 0 or 5 ppm starting at week 12. Recovery groups were included in the study at each dose level and sacrificed after 4 weeks of post-exposure observations. In the groups exposed at levels up to 3.0 ppm, there was a transient decrease in body weight gain accompanied by decreased food consumption. Red blood cell counts, hemoglobin concentration, and hematocrit values were slightly decreased in males exposed at 3.0 ppm (at 4 weeks only), but no effects were observed in these males at 13 weeks or in females at either interval. No exposure-related gross or histologic findings were observed at levels up to and including 3.0 ppm. Exposure at 10 ppm for 3 days caused 40% mortality in females but no mortality in males. Exposure at 10 ppm for 4 weeks caused 80% death in females. Both males and females exposed at 10 ppm had coagulative necrosis in the tubules of the kidneys and pulmonary congestion was observed in the females that died. No histologic findings related to dosing were apparent in the rats exposed for 2 weeks at 5 ppm; an increase in the BUN and alkaline phosphatase were observed in males but not females exposed at 5 ppm. An LEL for subchronic exposure (13 weeks) was not established in this study. The no-observed adverse effect level (NOAEL) for 13 weeks was 3 ppm (HDT). An LEL of 10 ppm for 4 weeks was based on lethality (4/5 deaths for females) due to the sharp dose-response curve.

Based on the use pattern and the fact that phosphine is a gas, an end-point and risk assessment were not conducted for short- and intermediate-term, oral or dermal exposures.

	5. Chronic toxicity. 

In a 2-year rat feeding study, diets were treated with Phostoxin pellets at 48 and 90 gm/metric ton, fumigated for 48 hours and 72 hours, mixed for 2 hours, and then aerated for one hour. The feed was then stored frozen in small sealed containers until used as laboratory rat feed. Sixteen separate batches of feed were treated utilizing this methodology over the 2-year period. Samples of diet were taken to determine phosphine at the time the feed was removed from the freezer. Phosphine levels ranged from 0.2 to 7.5 ppm and averaged approximately 1 ppm. The amounts of phosphine that remained in the feed offered to the rats as food was not measured (but would be expected to be less because of dissipation). Therefore, the actual dosages in this study are unknown. Two groups of 60 rats each (30 males and 30 females) were used, one as treatment group and other as controls. The rats were observed for the effects on growth, food consumption, survival, morbidity, hematology, blood chemistry and gross and microscopic pathology. No differences were seen between the controls and the treated animals for any toxicity parameter. No increased oncogenicity resulted from fumigation residues. The study was not considered guideline since toxicity, secondary to phosphine residues, is not possible when aeration is adequate. However, the study shows that toxic levels of residues were not achieved even with the excessive fumigation treatment rates.

In a chronic/oncogenicity study, Charles River Fischer CDF Rats (60/sex/group) were exposed, under dynamic chamber conditions, to 0, 0.3, 1 and 3 ppm of phosphine. The rats were kept under standard laboratory conditions, observed twice daily and sacrificed (10/sex/group) during week 52 of the study. Body weights; food consumption; routine hematologic, serum biochemical and urinary analyses were all comparable to control animals. There were no adverse effects observed for the initial 12 month period. Body weights; food consumption; routine hematologic, serum biochemical and urinary analyses were all comparable to control animals. Ophthalmological observations, gross pathology, organ weights and histopathology indicated no adverse effects from the phosphine exposures. The NOAEL for the 52 week period was 3.0 ppm, the HDT.

Chronic toxicity. EPA has established the chronic reference dose (RfD) for phosphine at 0.0113 mg/kg/day. This RfD is based on a 2-year chronic/oncogenicity inhalation toxicity study in rats. The dose for the risk assessment was a NOAEL=3 ppm = 0.004 mg/L=1.13 mg/kg/day. A 100 fold UF was applied to account for inter-and intra-species variation.

Carcinogenicity. The results of a non-guideline 2-year rat feeding study did not indicate a carcinogenic concern. Additionally, the results of a 2-year whole body inhalation study showed no treatment-related changes suggestive of a toxic or carcinogenic effect in rats.

	6. Animal metabolism. 

Based on the limited use pattern of phosphine fumigants, plant and animal metabolism data were not required. The residue of concern is phosphine. The Agency has determined that decomposition products of phosphine are toxicologically insignificant at the levels found in treated commodities.

	7. Metabolite toxicology. NA-REMOVE

	8. Endocrine disruption. NA-REMOVE

C. Aggregate Exposure

	1. Dietary exposure. 

In 1999, tolerances were revised and consolidated under 40 CFR 180.225 (a) and (b) for the residues of phosphine, in or on a variety of raw agricultural commodities at either 0.01 ppm or 0.1 ppm level, including food and feed tolerances (see the June 9, 1999 Federal Register p. 30939 and the December 29, 1999 Federal Register p. 72947). The tolerance expression was revised to eliminate references concerning how phosphine gas was generated, to ensure that phosphine gas delivered or generated via different technologies (e.g., cylinderized phosphine gas) was included. Tolerances are set at 0.01 ppm for those commodities for which direct treatment with a metallic phosphide product is not permitted. Tolerances of 0.1 ppm were established for commodities with which aluminum and magnesium are allowed to come into direct contact, e.g., tablets added directly to corn grain as it is stored in silos, or bulk stored nuts or dried fruit.  [Note that Cytec's cylinderized phosphine products are applied as a gas and this use pattern is not possible.] 

The Agency does not expect finite residues on the consumer's dinner plate, even for those commodities with a 0.1 ppm tolerance. This is because these commodities are aerated for 48 hours, cooked, shelled, washed, or otherwise prepared in some other way before they are actually consumed. For example, nuts are shelled and further processed before reaching the consumer. Other commodities such as dates are washed and graded for packaging which would remove any unreacted phosphine residue (from metallic phosphide products). The Agency has residue data from numerous studies on a wide variety of commodities and processed foods that confirm, with adequate aeration (48 hours is required) there will not be finite residues in or on food commodities. 

The residue studies submitted in support of the raw agricultural commodities currently on phosphine product labels were conducted with metallic phosphides.  Aluminum or magnesium phosphide treatment is phytotoxic to some fresh fruits and vegetables because of the ammonium carbamate in metallic phosphides, therefore, tolerances were not established for susceptible fruits and vegetables.  Metallic phosphides are formulated with ammonium carbamate to aid in the breakdown of the pellets and tablets.  Ammonium carbamate itself breaks down to carbon dioxide and ammonia.  Ammonia is very phytotoxic, causing a great deal of damage to fresh fruit.       

Cylinderized phosphine gas (first registered in 1999) does not cause damage to fresh commodities.  Cytec Industries Inc. is proposing to add cold storage fumigation to its cylinderized phosphine product labels, with higher treatment rates, shorter treatment times, and forced air aeration to ensure that fresh commodities are quickly aerated in order to maintain quality.  A study was completed on six representative commodities (apples, grapes, peaches, strawberries, broccoli, squash) to determine whether commodities with high water content that are fumigated and aerated under cold conditions have detectable residues after proper aeration.  Residues were not detected (LOQs ranging from 0.9 to 2.4 ppb) 24 and 48 hours after aeration (6 and 12 hours after aeration for strawberries) in any of the six commodities tested.  The study supports the conclusion that the tolerance of 0.01 ppm (the limit of detection) established for currently registered fresh fruits and vegetables is sufficient for cold storage treatment with cylinderized phosphine gas following appropriate aeration.  In addition, the study confirms that fumigation and aeration according to label directions will not result in detectable phosphine residues in fresh fruits and vegetables.

Risk assessments were conducted by EPA in 1999 (see the June 9, 1999 Federal Register p. 30939) to assess dietary exposures and risks from phosphine as detailed below.

	i. Food. 

        a.          Acute exposure and risk. 

The acute exposure analysis conducted at the time tolerances were reassessed (64 Fed. Reg. p. 72947, December 29, 1999) included all foods, and therefore included the additional commodities for which tolerances are now being proposed.  The results of the Agency's risk assessment are reported in this section.

Acute dietary risk assessments are performed for a food-use pesticide if a toxicological study has indicated the possibility of an effect of concern occurring as a result of a one day or single exposure. Dietary exposure to phosphine can potentially occur via residues of phosphine gas remaining in treated commodities. A large number of studies involving numerous types of raw and processed commodities and processed commodities submitted to the Agency for establishment of food tolerances indicate that residues of phosphine gas will be non-detectable with adequate aeration. One of these studies involved the analysis of 49 different processed foods, with all residues being <0.004 ppm (limit of detection for this study). There are many studies cited in the Registration Standard (PB87-117172) and Reregistration Eligibility Decision (RED) (EPA-738-R-98-018) that support  the conclusion that residues will typically be non-detectable with adequate aeration, i.e., <0.004 ppm. Tolerances were established based on the limits of quantification of the analytical method for phosphine gas for those commodities that may not come into direct contact phosphine during the fumigation procedure. Tolerances of 0.1 ppm were established for those commodities for which aluminum and magnesium phosphide tablets or pellets are allowed to come in direct contact. This tolerance level allows for any small amount of unreacted product compound left in the food or feed that would be removed later during processing. Direct addition (with its 0.1 ppm tolerance) is not allowed for processed commodities, and is strictly prohibited by the product use manuals. In addition, cold storage fumigations of the new commodities for which tolerances are being proposed cannot be accomplished by direct treatment with metallic phosphides because the gas has to be free of ammonia and must be added quickly in order to preserve the quality of the commodity under fumigation.

Anticipated residues were used for both the chronic and acute dietary exposure analysis. The Agency conducted a Dietary Exposure Evaluation Model (DEEM) analysis, for both acute and chronic exposure scenarios, making the very conservative assumption (protective of human health) that all food contained in the DEEM consumption database (except meat/milk/poultry/eggs), i.e., the food consumed by an individual in a given day, would contain residues of phosphine gas at the anticipated residue level of 0.006 ppm.  This was the highest limit of detection for any of the residue studies in the Agency's tolerance petition files and was used for both the acute and chronic analysis.  [Note that the highest limit of detection was 0.0024 ppm in the new study conducted by Cytec Industries Inc.] The Agency considers this to be a "worst-case"' scenario. Acute dietary exposure from food does not exceed the Agency's level of concern. The percent of the acute RfD (0.018 mg/kg/day) occupied, at the 99.9th percentile, is less than 30% for the population subgroups examined (see Table 1). The Agency again notes that tolerances are based upon non-detectable residues in residue field trials. Because phosphine gas will dissipate into the atmosphere, especially as foods are cooked (heated) or prepared, residues are unlikely to be found on food at the time of consumption.  In addition, the acute dietary endpoint is based on a NOAEL which is the highest dose in the study. The true NOAEL may well be higher than that observed in the study. Therefore, the Agency concludes that there is a reasonable certainty of no harm from acute dietary exposure.

Table 1.  Acute Dietary (Food) Exposure at the 99.9th Percentile

Population Subgroup

Exposure (mg/kg/day)

Percent Acute RfD

U. S. Population

0.003872

22

Non-nursing Infants (< 1 yr old) 

0.004943

27

Children (1-6 Yr old)

0.004440

25

        b.          Chronic exposure and risk. 
           
 The chronic exposure analysis conducted at the time tolerances were reassessed included all foods, and therefore included the commodities for which tolerances are now being proposed.  The results of the Agency's risk assessment are reported in this section.

The results of the DEEM chronic exposure analysis for exposure are summarized in Table 2.  Chronic exposure does not exceed the Agency's level of concern. The percent of the chronic RfD (0.113 mg/kg/day) occupied is less than 1% for the population subgroups examined.    These estimates of exposure are partially refined, yet still conservative in that it was assumed that all food (except meat/milk/poultry/eggs) consumed by an individual would contain phosphine gas residues at 0.006 ppm. This anticipated residue level is based on the highest limit of detection reported in tolerance petitions. The Agency again notes that all tolerances are based upon non-detectable residues in residue field trials. Because phosphine gas will dissipate into the atmosphere, especially as foods are cooked (heated) or prepared, residues are unlikely to be found on food at the time of consumption.

Table 2.  Chronic Dietary (Food) Exposure

Population Subgroup

Exposure (mg/kg/day)

Percent Chronic RfD

U. S. Population

0.000261

2

Non-nursing Infants (< 1 yr old)

0.001004
9

Children (1-6 Yr old)

0.000474

4

Chronic aggregate dietary exposure (food and water) does not exceed HED's level of concern. Using conservative assumptions, chronic risk estimates from exposure in food were less than 1% for all population subgroups examined. In fact, due to the rapid dissipation of gaseous phosphine, the Agency does not expect finite residues on treated commodities at all if used according to label directions. Therefore, the Agency concludes that there is a reasonable certainty of no harm from chronic dietary exposure.

Cytec Industries conducted an updated tolerance assessment using DEEM-FCID 2.16. In the new analysis, all commodities were assumed to contain 0.01 ppm phosphine, except for cereal grains, nuts and dried dates.  The raw agricultural commodity forms of cereals (for example, wheat grain) were assumed to contain 0.1 ppm phosphine, and processed forms (for example, wheat flour) were assigned a residue value of 0.01 ppm, which is the established tolerance for processed food commodities.  Meat, milk, poultry and eggs were not included because secondary residues are not expected and tolerances for direct treatment of these commodities have not been established.  Default processing factors were set to 1.0, because phosphine will dissipate rather than concentrate during processing.  A summary of the results is provided below:

  									
       Table 3.  Acute Dietary (Food) Exposure at the 99.9th Percentile
Population Subgroup
Exposure (mg/kg/day)
Percent Acute RfD
(acute RfD=0.018 mg/kg/day)
	U. S. Population
                                   0.001339
                                     0.07
Non-nursing Infants (< 1 yr)
                                   0.002197
                                     0.12
Children 1-2 Years
                                   0.002074
                                     0.12

                   Table 4.  Chronic Dietary (Food) Exposure
Population Subgroup
Exposure (mg/kg/day)
Percent Chronic RfD
(chronic RfD=0.0113 mg/kg/day)
U. S. Population
                                   0.000180
                                      0.2
Non-nursing Infants (< 1 yr)
                                   0.000263
                                      0.2
Children 1-6 Years
                                   0.000414
                                      0.4

These exposure and risk estimates based on tolerance level residues and using the updated version of the DEEM-FCID exposure model support EPA's previous conclusion that there is a reasonable certainty of no harm from acute and chronic dietary exposure to phosphine if a tolerance of 0.01 ppm is established for crop groups representing all fresh fruits and vegetables, and a tolerance of 0.1 ppm is established for dried fruit and the cereal grain and tree nut crop groups.  

	ii. Drinking water. 

Phosphine degrades in days (half-life is estimated to be 5 hours) and has a low exposure potential for contaminating ground and surface water because it is a gas. Therefore, these uses are unlikely to result in any exposure through ground or surface water and aggregate exposure is limited only to food.

	2. Non-dietary exposure. 

Phosphine is a restricted use pesticide that is used to fumigate raw agricultural commodities, processed foods, and non-food commodities in sealed spaces.  Phosphine is also used to control rodents in burrows. It has no residential uses. Residential exposure is not expected; therefore, no risk assessment for these scenarios were conducted.

D. Cumulative Effects

Section 408(b)(2)(D)(v) requires that, when considering whether to establish, modify, or revoke a tolerance, the Agency consider "available information" concerning the cumulative effects of a particular pesticide's residues and "other substances that have a common mechanism of toxicity."  The Agency believes that "available information" in this context might include not only toxicity, chemistry, and exposure data, but also scientific policies and methodologies for understanding common mechanisms of toxicity and conducting cumulative risk assessments.

EPA does not have, at this time, available data to determine whether phosphine has a common mechanism of toxicity with other substances or how to include this pesticide in a cumulative risk assessment. Unlike other pesticides for which EPA has followed a cumulative risk approach based on a common mechanism of toxicity, phosphine does not appear to produce a toxic metabolite produced by other substances. For the purposes of this tolerance action, therefore, EPA has not assumed that phosphine has a common mechanism of toxicity with other substances.

E. Safety Determination

	1. U.S. population. 

         a. Acute risk. The aggregate acute risk reflects food source risk only, therefore an additional aggregate risk assessment is not needed. The use patterns associated with cylinderized phosphine gas and aluminum and magnesium phosphide are not expected to impact water resources through labeled uses; therefore, exposure to humans through drinking water is not expected. In addition, all phosphine products are restricted use pesticides, which have no indoor residential uses; therefore, residential exposure is not expected for these restricted use products. The acute risk from food exposure to phosphine is < 1% of the acute RfD at the 99.9th percentile of exposure, which indicates an adequate margin of safety.
         
         b. Chronic risk. Using tolerance level residues, default concentration factors set to 1.0, and 100% crop treated exposure assumptions, aggregate exposure to phosphine from food will utilize less than 1% of the chronic RfD for the U.S. population and all population subgroups, including infants and children.  EPA generally has no concern for exposures below 100% of the RfD because the RfD represents the level at or below which daily aggregate dietary exposure over a lifetime will not pose appreciable risks to human health. The potential residues in drinking water are considered to be zero; therefore, the combined exposure of chronic food and drinking water exposure to phosphine would be less than 1% of the RfD for children or the general U.S. Population. Due to the nature of the non-dietary use, EPA believes that the commercial use of phosphine as a fumigant and in pest burrows will not result in any significant residential exposure. Therefore the chronic risk is based on food only.  
            
         c. Short- and intermediate-term risk. Short- and intermediate- term risks are assessed in tolerance actions where a pesticide has the potential for residential exposure through a route other than the diet. No such potential exists for phosphine. The acute and chronic risk assessments fully capture the risks associated with this tolerance action.

         d. Aggregate cancer risk for U.S. population. EPA has determined that there is no evidence of carcinogenicity in the available studies. Based upon this determination it can be concluded that phosphine does not pose a cancer risk.

         e. Conclusion. The Agency concludes that there is reasonable certainty that no harm will result from aggregate exposure to phosphine residues.
         

	2. Infants and children. 

FFDCA section 408 provides that EPA shall apply an additional ten-fold margin of safety for infants and children in the case of threshold effects to account for pre-and post-natal toxicity and the completeness of the database unless EPA determines that a different margin of safety will be safe for infants and children. Margins of safety are incorporated into EPA risk assessments either directly through use of a MOE analysis or through using uncertainty (safety) factors in calculating a dose level that poses no appreciable risk to humans. EPA believes that reliable data support using the standard MOE and uncertainty factor (usually 100 for combined inter- and intra-species variability) and not the additional tenfold MOE/uncertainty factor when EPA has a complete data base under existing guidelines and when the severity of the effect in infants or children or the potency or unusual toxic properties of a compound do not raise concerns regarding the adequacy of the standard MOE/safety factor.

The phosphine data base is considered complete, with respect to the usual data requirements for fumigants. There are no data gaps. In assessing the potential for additional sensitivity of infants and children to residues of phosphine, EPA considered data from a prenatal inhalation developmental toxicity study in rats. The results of developmental toxicity and reproductive toxicity studies are discussed above in Section B. 3. The toxicity data for phosphine does not indicate increased susceptibility in utero or postnatal. Exposure assessments do not indicate a concern of potential risk to children because phosphine residues are not expected in food or drinking water or near residential sites, i.e., control of rodents in burrows. In addition, the Agency conducted a very conservative exposure assessment, i.e., protective of human health. It is for all these reasons that the Agency concludes that the additional safety factor of 10 can be removed.

Based on these risks EPA concludes that there is reasonable certainty that no harm will result to infants and children or the general population from aggregate exposure to phosphine residues.

F. International Tolerances

The following tolerances for phosphine residues have been established by the CODEX Alimentary Commission: Cereal grains, 0.1 ppm; cocoa beans, 0.01 ppm; dried fruits, 0.01 ppm; dried vegetables, 0.01 ppm; peanuts, 0.01 ppm; spices, 0.01 ppm; tree nuts, 0.01 ppm. These tolerance levels are at or below the equivalent U.S. tolerances levels. 

This tolerance proposal would result in harmonization with international tolerances by replacing individual cereal grain tolerances with a 0.1 ppm tolerance for the Cereal Grain crop group and replacing the individual spice tolerances with a 0.01 ppm tolerance for the Herbs and Spices crop group.  Replacing individual tree nut tolerances with a 0.1 ppm tolerance for the Tree Nut Crop Group would assist in harmonization by establishing the crop group, even though the U.S. tolerance for unprocessed tree nuts (raw agricultural commodities) is higher.  The only other remaining tolerance that would not be harmonized with CODEX would be the U.S. tolerances of 0.1 ppm for dried dates.  However, the U.S. tolerance for processed foods is 0.01 ppm, therefore the tolerance for processed forms of tree nuts and dried dates are harmonized with CODEX. 

PART 180  -  [AMENDED]

Section 180.225 is proposed to be amended as follows:

§ 180.225  Phosphine; tolerances for residues.

(a) General.  (1) Tolerances are established for residues of the insecticide phosphine in or on the following raw agricultural commodities resulting from post-harvest fumigation:

Commodity
                            Parts Per Million (PPM)
Alfalfa
                                     0.01
Artichoke, Globe
                                     0.01
Asparagus
                                     0.01
Almonds
                                      0.1
Avocado
                                     0.01
Banana/Plantain
                                     0.01
Barley, grain
                                      0.1
Brazil nuts
                                      0.1
Cacoa Beans, dried bean
                                      0.1
Cashews
                                      0.1
Cherimoya
                                     0.01
Coffee Bean, green
                                      0.1
Corn, field, grain
                                      0.1
Corn, pop, grain
                                      0.1
Corn, sweet, fresh
                                     0.01
Cotton undelinted seed
                                      0.1
Dates, dried fruit
                                      0.1
Dates, fresh fruit
                                     0.01
Figs, fresh fruit
                                     0.01
Filberts
                                      0.1
Fruit, Berry and Small Fruit, Group 13-07
                                     0.01
Fruit, Citrus Fruit, Group 10
                                     0.01
Fruit, Pome Fruit, Group 11
                                     0.01
Fruit, Stone Fruit, Group 12
                                     0.01
Herbs and Spices, Group 19
                                     0.01
Mango
                                     0.01
Millet, grain
                                      0.1
Oat, grain
                                      0.1
Papaya
                                     0.01
Pawpaws
                                     0.01
Peanuts
                                      0.1
Pecans
                                      0.1
Persimmon
                                     0.01
Pineapple
                                     0.01
Pistachios
                                      0.1
Rice, grain
                                      0.1
Rye, grain
                                      0.1
Safflower seed
                                      0.1
Sorghum, grain
                                      0.1
Soybean, seed
                                      0.1
Sunflower seed
                                      0.1
Triticale, grain
                                      0.1
Vegetables, Brassica (Cole) Leafy Vegetables, Group 5
                                     0.01
Vegetables, Bulb Vegetables, Group 3
                                     0.01
Vegetables, Cucurbits, Group 9
                                     0.01
Vegetables, Fruiting Vegetables (except Cucurbits), Group 8
                                     0.01
Vegetables, Leafy Vegetables (except Brassica), Group 4
                                     0.01
Vegetables, Legume Vegetables Foliage, Group 6
                                     0.01
Vegetables, Root and Tuber Group 1
                                     0.01
Vegetables, Root and Tuber Leaves Group 2
                                     0.01
Wheat, grain
                                      0.1
Walnut
                                      0.1
Water Chestnut
                                     0.01
Watercress
                                     0.01
                                       
                                       
(2) ...no change

(3) ...no change

(4) ...no change

(5) To assure safe use of this pesticide, it must be used in compliance with the labeling conforming to that registered by the U.S. Environmental Protection Agency (EPA) under FIFRA.  Labeling shall bear a restriction for ambient temperature fumigations to aerate the finished food/feed for 48 hours before it is offered to the consumer, unless the airborne phosphine levels are tested and found to be less than the TLV of 0.3 ppm, or unless EPA specifically determines that a different time period is appropriate.

For cold storage fumigations, cold storage chambers must be aerated quickly with forced air to ensure that the commodity stays cold.  Labeling shall bear a restriction to aerate the commodity until the aerated chamber is tested and found to have phosphine concentrations less than the TLV of 0.3 ppm

Where appropriate, a warning shall state that under no condition should any formulation containing aluminum or magnesium phosphide be used so that it will come in contact with any processed food, except processed brewer's rice, malt, and corn grits stored in breweries for use in the manufacture of beer.

(b) Section 18 emergency exemptions [Reserved]
(c) Tolerances with Regional registrations [Reserved]
(d) Indirect or inadvertent residues.  [Reserved]