UNITED STATES ENV I RONMENTAL PROTECTION AGENCY

WASH INGTON

, D

. C. 20460



### MEMORANDUM

Date: Final

- September 11, 2013



### SUBJECT: Phosphide (AI, Mg) and Phosphine: OFFICE OF CHEMICAL SAFETY AND

POLLUTION PREVENTION

Hum an-Hea l th Assessment Scoping Document Supporting Registration Review.

PC Code: Phosphide PC Code: 066500,

Aluminum Phosphide PC Code : 06650 I, Magnesium Phosphide PC Code: 066504

Decisi on No.: 476795 DP Barcode: 0410399

Registration No.: N / A

Petition No.: N / A

Risk Assessment Type: Scoping

TXRNo.: N / A . Regulatory Action: N / A

Case No. : CAS No.: Phosph ine: 7803-51-2, Aluminum Phosphide: 20859-73-

8

, Magnesium Phosphide: 12-057-74-8

MRID No.: N / A



### FROM: 40 CFR: 180.151

Marquea D

. K ing, Ph.D., T oxico l ogist,**Ris}Rl~~~ ~~~** **+-./** James S Miller, Environmental Scientist II

Thurston Morton, Senio r Chemist 

# -;Z:

Risk Assessment Branch IV

He a l th Effects Division (7509P)

### d.-~??-- 9ht.lt3 

### THROUGH: Elissa Reaves, Ph.D., Branch Chief**c;~---** ?- !"I '

Risk Assessment Branch IV

Heal th Effects Division (7509P)



### TO: Dana Friedman, Risk Manager Reviewer

Risk Management and Implementation Branch

Pesticide Re-Evaluation Di vis ion (7508P)

Attached is HED's hum an-hea lth risk assessment scoping document for phosphide (Aland Mg)

and phosphine to support registration review.

Page 1 of29Page 2 of 29 1.0 Executive Summary

Phosphine is marketed in se veral physical forms including me talized solids (aluminum and magnesium phosphide) that emit phosphine after c ontact with atmospheric moisture through a chemical process and as a cylinderized fumigant. Phosphine is a colorless gas effective against stored-product insect pests and vertebrate pests, mainly rodent s, and in addition to being an active ingredient as cylinderized phosphine, is the active ingredient for the metal phosphides.

The registered formulations of aluminum and magnesium phosphide incl ude the pellets/tablets (P/T), gasbags and impregnated materials such as belts. For the registered formulations of phosphine gas, cylinderized cannisters with varying active ingredient concentrations are used for fumigation purposes. Phosphine may be used as a space fumigant (mills, food plants, warehouses); as a vehicle fumigant (railcars, trucks, vans, contai ners); as a commodity fumigant (raw agricultural, processed foods, non-food durable goods); as a grain fumigant (silos, farm storage, flat storage); and as a vessel or ship fumigant.

The Health Effects Division (HED ) has evaluated the status of the human-health assessments for aluminum phosphide, magnesium phosphide, and phos phine to determine whether sufficient data are available to support Registratio n Review. HED has considered the most recent human health risk assessments for aluminum phosphide, magnes ium phosphide, and phosphine with respect to toxicity, exposure, and usage databases, and th e most updated Agency science policy and risk assessment methodologies to determine the scop e of work necessary to support Registration Review. The 1997 Reregistration Eligibility De cision (RED); the 1998 HIARC revised report on Aluminum and Magnesium Phosphide; the 1998 Re registration Eligibility Decision (RED); and the 1998 revised Reregistration Eligibility De cision (RED were reviewed for the scoping

document.

Inhalation exposure to phosphine gas represents the primary route of exposure for all three compounds. While the Agency also assessed poten tial oral exposures to phosphine residues in fumigated foods, this is not considered a major exposure pathway. The physiochemical properties of phosphine make significant dermal exposure unlikely and the quantification of potential low-level exposures difficult; therefore, a quantitative dermal exposure assessment will not been conducted. Personal protective equipment (PPE) for dermal protect ion will continue to be based on the acute toxicity of the end-use product, as desc ribed in the Worker Protection Standard and mitigation measures for dermal exposure described in PR Notice 93-7.

Phosphine is a highly reactive gas and is rapidly taken up via the lungs. It is highly toxic and classified under Toxicity Category I for acute in halation toxicity. The target organ for phosphine is the respiratory tract. In humans, symptoms of phosphine gas intoxication include shortness of breath, coughing, pulmonary irrita tion, nausea, headache, jaundi ce, fatigue, convulsions, and

death

The toxicity database for phosphine is not comple te. A special acute inha lation toxicity study in rats and an extended one-generation reproductive t oxicity study in rats via the inhalation routePage 3 of 29 are required. In the 1998 RED, a combination of guideline and literature studies was used to assess phosphine hazards. All submitted toxici ty data to support the metal phosphides and phosphine were generated for phosphine gas and ar e by the inhalation route of exposure. The

most recent risk assessment relied on the O ccupational Safety and Health Administration (OSHA) permissible exposure limit (PEL) as the point of departur e for inhalation risk assessments. Acute and chronic dietary endpoi nts were selected from guideline inhalation studies and the FQPA Safety factor was reduced to 1X. Given that additional toxicity data have been required, the Agency will need to re-evalu ate the points of departure (PoDs) and safety factors (SFs)/uncertainty factors (UFs) for risk assessment purposes as part of registration

review.

The residue chemistry and dietary exposure data base are complete and no additional data are required to support the registrati on review of the metal phosphide s and phosphine. There are no drinking water concerns associ ated with phosphine based on its limited use as a commodity fumigant. Dietary (food only) risks of concern have not b een identified for these active ingredients, however, if toxici ty endpoints change an updated dietary risk assessment may be required which incorporates updated consumption information.

The occupational/residential exposure databases are considered incomplete. An inhalation exposure study for applicators, product use info rmation, post-application inhalation studies, and monitoring data for phosphine ar e required. No residential scen arios have been previously assessed for the metal phosphides or phosphine. Ho wever, there is the potential for bystander exposures, which can occur from emissions duri ng treatment and aeration of commodities and structures. For registration review, these exposures will need to be addressed.

The 1998 RED did not identify risk concerns fo r workers equipped with appropriate PPE. However, a new occupational handler risk reassess ment will likely need to be completed during registration review to consider newly submitte d data, to incorporate a human equivalent concentration calculated for fumigators and post- application workers that will be exposed to previously treated goods (based on 8 hours of expos ure). Also, to the extent that they are available, consider policies currently under development rega rding assessment of fumigant

chemicals.

In summary, the following data defici encies were identified for Phosphine:

Toxicology:

 extended one-generation repr oduction study (inhalation)

 a special acute inhalation t oxicity study is required fo r Phosphine at this time based on current testing policy appli cable to all commodity fumigants (Attachment 5: Justification for Special Acute Inhalation Toxicity Study with Phosphine; Rury K., 5/14/13, TXR No. 0056638)

Residue Chemistry: NonePage 4 of 29 Dietary Exposure: None

Occupational/Residen tial Exposure:

 875.1400 Inhalation Exposure Study for Applicators . These studies are required to assess exposures for applicators i nvolved in fumigating commodities/materials

and/or structural facilities.

 875.1700 Product Use Information . This study is required to assess product use information parameters by major us e region, frequency, and application equipment.

 875.2500 Post-Application Inhalation Exposure Study. This study is required to assess post-application exposures for workers near fumigation facilities/operations or who work directly with previously treated

commodities/materials.

o Special Study – Ambient air monitoring. This study is required to assess ambient air concentrations for communities in proximity to treated facilities.

 Special Studies - Monitoring data on fumigated commodities . Special studies are required to evaluate emission ra tes for phosphine from treated commodities/materials and the potential for occupational exposure due to those emissions in the channels of trade after fumigation activities are complete.

EPA anticipates conducting the following ri sk assessment updates for Phosphine during Registration Review:

Toxicology:

 Reevaluation of the toxicity endpoints/ dose selection/uncertain ty factors may be

necessary.

Residue Chemistry: None

Dietary Exposure:

 A new dietary exposure and risk assessm ent may be required during Registration Review to incorporate potent ial changes to the phosphine toxicological PODs. In addition, the assessment should include updated consumption information and

utilize the newest ve rsion of DEEM-FCID.

Occupational/Residen tial Exposure:

 Revised HED occupational handler and post application risk assessments may be necessary based on the most recent expos ure data, Agency policies, or if the toxicological reevalua tion results in change s to the endpoints.Page 5 of 29  Additional or revised HED residential bystander risk assessments may be necessary based on the most recent expos ure data, Agency policies, or if the toxicological reevalua tion results in change s to the endpoints.

2.0 Introduction

The HED phosphide and phosphine Registration Review Team has evaluated the human health

risk assessments and the available informati on for phosphide and phosphine to determine what new data and risk assessments may be needed for registration review . Aluminum phosphide (AlP) was first registered in the U.S. in 1958, followed by magnesium phosphide (Mg 3 P 2 ) in 1979. In 2010, cylinderized phosphine (Ph 3 ) was first registered in the U.S. The Re-registration Eligibility Decision (RED) for aluminum and magnesium phosphide was signed in June 1998. Furthermore, in December of 1998, an addendum to the (1998 June RED) was issued to provide dietary exposure and risk estimated using DEEM TM (Dietary Exposure Evaluation Model)

.

Recently, HED reviewed and commented on a risk characterization document for phosphine authored by the Medical Toxicol ogy Branch of the Department of Pesticide Regulation for the State of California (Cal. DPR) (J, Housenge r, 25 April 2013). On March 21, 2013, the Agency accepted a label amendment submitted in Febr uary of 2013, to increased use rate and add certain food and non-food commodities currently on the phosphide (Al, and Mg.) labels to the current phosphine labels VAPORPH3OS ® (EPA Reg.: 68387-8); and ECO 2 FUME ® (EPA Reg.: 68387-7). Lastly, a new study authored by Spen cer Walse in conjunction with the USDA (S, Walse, MRID 49066801, 26 February 2013) was submitted to the Agency and is currently in the review process.

Phosphine is marketed in seve ral physical forms including meta lized solids that emit phosphine

after contact with moisture th rough a chemical process and as a cylinderized fumigant. The active ingredient of al l three products (AlP, Mg 3 P 2 and Ph 3 ) is phosphine, per se, which is a colorless gas effective against stor ed-product insect pests and verteb rate pests, mainly rodents. The registered formulations of aluminum and magnesium phosphide incl ude the pellets/tablets (P/T), gasbags and impregnated materials such as belts. For the registered formulation of phosphine gas, cylinderized cannisters with varying active ingredient concentrations are used for fumigation purposes. Phosphine may be used as a space fumigant (mills, food plants, warehouses); as a vehicle fumigant (railcars, trucks, vans, contai ners); as a commodity fumigant (raw agricultural, processed foods, non-food durable goods); as a grain fumigant (silos, farm storage, flat storage); and as a vessel or ship fumigant.

3.0 Hazard Identification/ToxicologyPage 6 of 29 The toxicology database for phosphi ne is not complete. A specia l acute inhalation toxicity study in rats and an extended one-generation reproductive toxicity study in rats via the inhalation route are required at this time. A de velopmental toxicity study in rabb its is not required at this time (HASPOC, TXR- 0056345). The requirement for a guideline im munotoxicity study was waived (HASPOC, TXR- 0056661).

Phosphine is a highly reactive gas and is rapidly taken up via the lungs. It is highly toxic and classified under Toxicity Category I for acute in halation toxicity. The target organ for phosphine is the respiratory tract. In humans, symptoms of phosphine gas intoxication include shortness of breath, coughing, pulmonary irrita tion, nausea, headache, jaundi ce, fatigue, convulsions, and

death.

Inhalation exposure to phosphine gas represents the primary route of exposure for all three compounds. While the Agency also assessed poten tial dermal exposures to phosphine residues in fumigated foods, this is not considered a majo r exposure pathway. Dermal exposure to metal phosphides is not a significant route of expos ure given the personal protective equipment (gloves) that applicators are require d to wear when using these products.

A possible mode of action (MOA) for phosphine is likely to be related to the inhibition of mitochondrial respiration. This e ffect has been seen in insects, rodents, and humans, and the commonality across species supports the data derived from non-hum an studies. Phosphine is a

reductant and reacts with iron heme and the metals of metal-dependent enzymes. This reductive capability allows for the inhibition of mitochondrial respiration (Pepelko, et al. , 2004). Kinetic analysis indicated that phosphine inhibits only one site (cytochr ome c oxidase) and does so in a noncompetitive manner. The induction of oxidative damage occurs in the brain, lung, and liver of rats. Specifically, phosphine significantly decreases glutathi one (GSH) concentrations in the above-mentioned organs. Since GSH is a key co mponent within the cellular defense cascade when injury occurs, the level of GSH in tissues is an initial indicator of oxidative stress.

All phosphine toxicity testing in laboratory an imals was conducted via th e inhalation route. Available and acceptable guideline studies in clude a 90-day rat study (using only a 15-day exposure period); developmental ra t study; and a chronic oncogenicity study. Also submitted but found to be unacceptable, but upgradeable was an acute neurotoxicity (ACN) study. Lethality is the primary adverse effect after acute phosphine exposure in experiment al toxicology studies with laboratory animals. Literature studies report the dose response for phosphine as a steep nonlinear threshold, consistent with Haber’s La w and time as a constant (C x T). This relationship holds true for multiple species: rats, mice, cats, rabbits, guinea pigs, turkeys, and chickens (Pepelko, et al. , 2004). The dose response relationshi p is consistent across species and there is no evidence for toxicity or mortality be low 5 ppm in an acute exposure scenario in laboratory animals. The LOAELs for phosphi ne reach low doses of 7 ppm for exposure

durations of 30-80 hours in la boratory animals. At 30 hours and beyond, LOAELs do not

decline with continued e xposure indicating that phosphine is short acting with a very steep dose response via inhalation exposure and does not accumulate in the body.Page 7 of 29 The 1998 (RED) relied on the OSHA permissible exposure limit (PEL) as the point of departure

for inhalation risk assessments. The Occupational Safety and Health Administration (OSHA) have established a Permissible Exposure Lim it (PEL) for phosphine gas at 0.3 ppm based on an epidemiologic study of grain fumigators wher e no adverse effects were observed at a concentration of 0.3 ppm. Based on limited info rmation presented in the study, the 0.3 ppm was

considered to be the NOEL.

In the 1998 RED, the acute dietary endpoint was based upon the results of the 90-day inhalation study. The Point of Departure (POD) was 5 ppm = 0.007 mg/L = 1.8 mg/kg/day based on lack of treatment-related effects following 15 days of exposure in that study. Although there were no treatment-related effects seen, this dose/study was selected si nce no treatment related effects

were seen at a lower concentra tion (3 ppm) after long duration (13 weeks). The findings from the ACN study were used as co-critical. In that study, the NOAEL was <20 ppm for neurobehavioral findings (decreas ed body temperatures and decrea sed motor activity in males and females) and 40 ppm for the lack of systemic toxicity. The acute reference dose (aRfD) was 0.018 mg/kg/day. The chronic reference dose (cRf D) of 0.0113 mg/kg/day was derived from on an inhalation NOAEL of 3.0 ppm (HDT; a LOAEL wa s not established) that was based on the results of a 52-week interim report in rats.

At the time of the 1998 RED, the FQPA Safety Factor Committee concluded that the 10X factor for increased susceptibility of infants and child ren (as required by FQPA) should be reduced to 1X based the following rationale:

(A) There was no indication of increa sed susceptibility of rats to in utero and/or postnatal exposure to Aluminum/Magnesium Phosphide. (B) Exposure assessments do not indicate a concer n for potential risk to infants and children because: 1) residues of phosphine are not expected in food; 2) there is no concern for ground or surface water contamination from this use; 3) there are no registered residential uses.

3.1 Conclusions for Hazard Identification/Toxicology

The toxicology database for phosphi ne is not complete. A specia l acute inhalation toxicity study in rats is required. The speci al acute inhalation toxicity study should include the evaluation of the following: histopathology of the respirator y tract, including incide nce and severity at multiple tested concentrations; GSH measurements (i.e., nose); pharmacokinetics/tissue dosimetry including time course; and sublethal portal of entry effect s (i.e., within the respiratory tract) along with information on dose response, incidence, and se verity. A protocol for this special acute inhalation study should be submitted for agency review, prio r to study initiation. Additionally, an extended one-gener ation reproductive toxicity st udy in rats via the inhalation route is required at this time. The extended one -generation reproductive t oxicity study allows for the integrated evaluation of multiple organ sy stems (with an emphasis on the nervous, immune, and reproductive systems) acro ss several lifestages from con ception through adulthood. This study will be more useful to assess potential hazar d and risk than a rabbit developmental toxicity study. A study protocol for this study should be submitted for Agency review. Lastly, anPage 8 of 29 immunotoxicity study is not requir ed at this time for phosphine since the immunotoxicity studies with other fumigants did not provide a lower POD or result in a more sensitive endpoint than those already used for overall risk assessment.

Given that additional toxicity data have been re quired, the Agency will need to re-evaluate the points of departure (PoDs) and sa fety factors (SFs)/uncertainty f actors (UFs) for risk assessment purposes as part of registration review.

4.0 Residue Chemistry

The residue chemistry database for aluminum phosphide, magnesium phosphide, and phosphine gas is adequate for Registration Review. All three products produce phosphine gas which is the only residue of concern for both tolerance setting and risk assessment purposes. No additional plant and livestock metabolism data are require d for the purposes of registration review. The residue of concern is phosphine and the current tolerance expression is appropriate. Residue data reflecting registered postharvest treatment s of stored raw agricultural and processed commodities indicate that, with adequate aerati on or further processing after treatment, residues of phosphine dissipate to nondetectable leve ls. Acceptable methods are available for enforcement and data collection purposes for plant commodities. The Pesticide Analytical Manual (PAM) Vol. II lists, unde r aluminum phosphide, a colorimetric method (LOD 0.01 ppm) and a GLC method with flame photometric dete ction (LOD = 0.001 ppm) as Methods A and B, respectively, for the enforcemen t of tolerances. Both methods determine the level of phosphine

residues. Residues in livestock commodities are not anticipated from the currently registered uses of the metal phosphides and phosphine gas.

Tolerances for residues of phosphine gas resultin g from fumigation using either aluminum or magnesium phosphide have been reassessed at 0.01 ppm and 0.1 ppm. These tolerances were set based on a determination that the fumigation of foods is a food use, despite the absence of quantifiable residues in fumigated foods. The tolerance level of 0.01 pp m was established for

those commodities for which direct treatment is not permitted. Tolerances of 0.1 ppm were recommended for those commodities for which fumigation is allowed.

4.1 Conclusions for Residue Chemistry

The residue chemistry database for aluminum phosphide, magnesium phosphide, and phosphine gas is adequate for Registration Review. No additi onal data are required fo r registration review.

5.0 Dietary Exposure

The dietary risk assessment for phosphine includes residues in food only. EFED has determined that given the proposed use pattern (commodity fumigation) and the physical/chemical propertiesPage 9 of 29 of phosphine, there is a low exposure potential for contaminating ground and surface water. A drinking water assessment will not be conducted for registration review.

The most recent phosphine/phosphide dietary exposure and risk assessment was performed as an addendum to the June 1998 assessment conducted by HED. In the most current dietary exposure assessments, HED had made the co nservative assumption that all foods contained in the DEEM consumption database (except meat/milk/poultry/ eggs) will have residues of phosphine gas at 0.006 ppm, the highest reported detection limit. A ll food items were considered to bear residues

because there is a tolerance of 0.01 ppm for residues of phosphine gas resulting from the use of either magnesium or aluminum phosphide on all processed foods (40 CFR 185.380 and 185.200). Additionally the conservative assumption was made that 100% of all commodities included in the DEEM database (except meat/milk/poultry/eggs) would contain residues at that anticipated

residue level.

Acute dietary (food) exposure does not exceed HED’s level of concern. The percent of the aPAD occupied at the 99.9% tile was <30 % for all po pulation subgroups. These estimates of acute dietary exposure are partially re fined, yet still conservative in that was assumed that all food (except meat/milk/poultry/eggs) co nsumed by an individual woul d contain phosphine gas residues at 0.006 ppm. This anticipated residue level is based on the highest limit of detection reported in tolerance petitions. HED again not es that all tolerances are ba sed upon non-detectable residues in residue field trials. Because phosphi ne 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.

Chronic dietary (food) exposure doe s not exceed HED’s level of c oncern. The percent of the cPAD occupied was <10 % for all population subgroups.

5.1 Conclusions for Dietary Exposure

The dietary-exposure database is adequate to support the existing regi strations. Previously conducted assessments did not indicate any acute or chronic risks of concern. However, a new dietary exposure and risk assessment may be re quired during Registration Review to incorporate potential changes to the phosphine toxicologi cal PODs. In addition, the assessment should include updated consumption information and utilize the newest version of DEEM-FCID.

6.0 Residential Exposure

No residential scenarios have been pr eviously assessed for phosphide (AlP, Mg 3 P 2 ) or phosphine (Ph 3 ). As previously noted, the active ingredient fo r the phosphine and phosphide products is phosphine gas. The Agency has historically assumed that, provided ad equate aeration of dwellings is completed prior to re -entry, exposure to owners of fumi gated structures is expected to be negligible given proper aera tion procedures are in place; ho wever, there is the potential for bystander exposures, which can occur from em issions during treatment and aeration of commodities and structures. For registration review and as per other fumi gants, these exposures will need to be addressed, including th e use of computer modeling analyses ( e.g. , PERFUM) and estimation of potential buffer zones (J. Dawson and C. Smith, D353906, 6 November 2008).Page 10 of 29 There is sufficient information to comple te such analyses for phosphide (AlP, Mg 3 P 2 ) and phosphine (Ph 3 ). However, in the event that the available information (MRID 49066801) suggests that there may be bystander risks of con cern, a more refined analysis would be possible if additional data were available. Types of info rmation that could be used to refine the bystander

assessment include information on treatment conditi ons such as building/st ructure types, volumes treated, concentration/time schedul es used, release height, air ex change rates, and historical

emissions data. To the extent that these subm itted data show potential for bystander exposure, residential assessments may be n eeded during regi stration review.

6.1 Conclusions for Residential Exposure

Bystander risk to phosphine emissions from treated commodities and structures will need to be evaluated based label prescribed use conditions , and if the points of departure (PODs) or uncertainty factors (UFs) change based on acute toxicological data required by HASPOC.

7.0 Aggregate-Risk Assessment

As per FQPA 1996, when there are pot ential residential exposures to the pesticide, aggregate risk assessment must consider exposures from thr ee major sources: oral, dermal and inhalation exposures. Potential routes of phosphine exposure include oral (food) and inhalation. Due to the vapor pressure and PPE for phosphine , dermal exposure is not likely.

7.1 Conclusions for Aggregate Risk Based on the use pattern for phosphine, an aggregate assessment will likely be performed during Registration Review.

8.0 Occupational Exposure

The HED occupational exposure databases for phosphide (AlP, Mg 3 P 2 ) and phosphine (Ph 3 ) are limited. The physiochemical properties of phosphine also make significant dermal exposure unlikely and the quantification of potential low-level exposures diffi cult; therefore, a quantitative dermal exposure assessment has not been complete d. Since HED does not have adequate data to quantify dermal risk, the personal-protective equipment (PPE) for dermal protection will continue to be based on the acute toxicity of the end-use product, as desc ribed in the Worker Protection Standard and mitigation measures for dermal expos ure described in PR Notice 93-7. Furthermore, since phosphine is a gas, human exposures are e xpected to occur primar ily through the inhalation

route

8.1 Occupational Handlers

There is potential for occupational handler i nhalation exposure to phosphine gas based on the registered HED uses of phosphide (AlP, Mg 3 P 2 ) and phosphine (Ph 3 ). Inhalation exposures are expected for acute, short- and intermediate-term durations.

Phosphide (AlP, Mg 3 P 2 ) Formulations: The 1998 (RED) (P. Lewis et al ., 22 December 1998) indicates that potential inhalation risks, due to the degradation of the AlP, and Mg 3 P 2 pellets into phosphine gas are acceptable when usedPage 11 of 29 according to label directions (e.g., use of SCBA for fumigators). These risks are based on the use of the OSHA/PEL as the point of departure, whic h could change based on newly required studies. MOEs were unacceptable (MOE < 100) at baseline conditions (no PPE/respir ators). The potential exists for workers who are not directly associat ed with the fumigation/aeration activities near areas where these operations are occurring or those who handle previously treated commodities (bystanders). Therefore, these ri sks also need to be addressed.

Cylinderized Phosphine (Ph 3 ): On February 4, 2013, the registrant submitted a la bel amendment (J. Miller, 7 March 2013) that

states that VAPORPH3OS ® (EPA Reg.: 68387-8); and ECO 2 FUME ® (EPA Reg.: 68387-7) are phosphine gas cannisters administered as a chambered gas fumigant for food and non-food commodities on March 21, 2013, the la bel amendment was accepted.

8.2 Occupational Post-Application Workers

Additional consideration will need to be given to post-application exposures pending future evaluation of the air monitoring data subm itted (S, Walse, MRID 49066801, 26 February 2013). As part of registration review, tasks for workers near fumigation facilities/operations need to be defined to properly assess post-ap plication activities (i.e . aerators, forklift operators, bystanders etc.). Potential exposures due to off gassing will be a ssessed for workers conducting postapplication activities near treatment operations.

As noted above, HED is curren tly reviewing an off gassing st udy conducted by Spenser Walse in conjunction with the USDA (S, Walse, MRID 49066801, 26 February 2013).

8.3 Conclusions for Occupational Exposure

The Agency believes that most applicator and post -application worker exposur es are likely to be of a shorter duration (i.e., acute or short-term by agency definition). A much smaller percentage of the overall user population is expected to ha ve longer duration exposur es (i.e., intermediateterm or chronic). A new occupational handler an d post-application risk reassessment needs to be completed during registration review. This r eassessment will incorporate recently submitted data; a human equivalent concen tration calculated for fumigators and post-application workers that will come into contact with previously tr eated goods (based on 8 hours of exposure), and to the extent that they are available, policies cu rrently under development regarding assessment of fumigant chemicals.

Occupational/Residential Exposure Studies Required The following additional studies are required to support the registrati on review of phosphine.

875.1400 Inhalation Exposure Study for Applicators . These studies are required to assess exposures for applicators involved in fumigating commodities/materials and/or structural
facilities.

875.1700 Product Use Information . This study is required to assess product use information parameters by major use region, fre quency, and application equipment.Page 12 of 29 875.2500 Post-Application Inhalation Exposure Study. This study is required to assess postapplication exposures for workers near fumigatio n facilities/operations or who work directly with previously treated commodities/materials.

Special Study – Ambient air monitoring. This study is required to assess ambient air

concentrations for communities in proximity to treated facilities.

Special Studies - Monitoring data on fumigated commodities . Special studies are required to evaluate emission rates for phosphine from treat ed commodities/materials and the potential for occupational exposure due to those emissions in th e channels of trade af ter fumigation activities are complete.

9.0 Public Health and Pesticide Incident Data

The OPP Incident Data System (IDS) was que ried from January 2008 to February 2013 and NIOSH SENSOR-Pesticides was queried from 1999-2009 and included reports of alleged human

health incidents from various sources.

Aluminum Phosphide

For the Main IDS, there were 3 incidents reported for single chemical only in the database. This incident was classified as major severity. In Aggregate IDS, there were 6 reported incidents involving aluminum phosphide. These incidents were classified as minor severity. A query of

SENSOR-Pesticides identifies 75 cases invol ving aluminium phosphide, stemming from 57

events.

Magnesium Phosphide

For the Main IDS, there was 1 inci dent reported in the database. Th is incident was classified as minor severity. In Aggregate IDS, there we re no reported incidents involving magnesium phosphide. A query of SENSOR-Pesticides id entifies 2 cases, stemming from 2 events, involving the single active ingr edient magnesium phosphide.

Phosphine

For the Main IDS, there was 1 inci dent reported in the database. Th is incident was classified as moderate severity. In Aggregate IDS, there were no reported incidents involving phosphine. A query of SENSOR-Pesticides identifies 22 cases, stemming from 9 events, involving phosphine.

9.1 Conclusions for Public Health and Pesticide Incident Data

For magnesium phosphide and phosphine there is relatively low frequency and severity of incident cases reported both IDS and NIOSH SENS OR-Pesticides, there does not appear to be a

concern at this time that would warrant further investigation. The Agency will continue to

monitor the incident information and if a con cern is triggered, additional analysis will be

included in the risk assessment.Page 13 of 29 Although aluminum phosphide had a low frequency of incidents in IDS, there was one incident

that resulted in two deaths. In NOISH SE NSOR-Pesticides, aluminum phosphide had a moderately high frequency of inci dents that were mostly moderate or low in severity. EPA has recently (2010) expanded and clarified the outdo or use restrictions for all phosphine products used against burrowing rodents. Considering th e newly required safety measures, the Agency

will continue to monitor the incident informa tion and provide an updated review of incidents during registration review.

10.0 Tolerance Assessment and International Harmonization

Tolerances are established for residues of the fumigants aluminum phosphide, magnesium phosphide and phosphine gas in 40 CFR §180.225. Compliance with the tolerance levels specified in this paragraph is to be determ ined by measuring phosphine, when used as a postharvest fumigant, pre-harvest treatment of pe st burrows, fumigation of processed food, or fumigation of animal feed. Tolerances ra nge from 0.01 ppm to 0.1 ppm on a number of

commodities.

There was no Mexican or CODEX MRLs fo r phosphine. However, there are numerous Canadian MRLs for phosphine. On commodities where Canadian and US MRLs exist, there is harmonization of MRLs. However, there are in stances where Canada has MRLs on commodities

and the US does not and vice versa. In these instances, harmonization is not an issue.

11.0 Environmental Justice

Potential areas of environmental ju stice concerns, to the extent po ssible, were considered in the most recent phosphide/phosphine human health ri sk assessment, in accordance with U.S. Executive Order 12898, “Federal Actions to Ad dress Environmental Justice in Minority Populations and Low-Income Populations,” (http://www.hss.energy.gov/nuclearsafety /env/guidance/justic e/eo12898.pdf). The OPP typically considers the highest potential exposures from the legal use of a pesticide when conducting human-health risk assessments , including, but not limited to, people who obtain drinking water from sources near agricultural areas, the va riability of diets within the U.S., and people who may be exposed when harv esting crops. Should th ese highest exposures indicate potential risks of concern, OPP further refines the risk assessm ents to ensure that the risk

estimates are based on the best available information.

12.0 Cumulative

Unlike other pesticides for which EPA has fo llowed a cumulative risk approach based on a common mechanism of toxicity, EPA has not made a common mechanism of toxicity finding as to phosphide/phosphine and any other substances. For the purposes of this assessment, therefore, EPA has not assumed that phosphi de/phosphine has a common mechan ism of toxicity with other substances. For information regarding EPA’s ef forts to determine which chemicals have a common mechanism of toxicity and to evaluate th e cumulative effects of such chemicals, see the policy statements released by EPA’s Office of Pesticide Programs concerning commonPage 14 of 29 mechanism determinations and proc edures for cumulating effects from substances found to have

a common mechanism on EPA’s website at http://www.epa.gov/pest icides/cumulative/

.

13.0 Endocrine Disruption

As required by FIFRA and FFDCA, EPA reviews num erous studies to asse ss potential adverse outcomes from exposure to chemicals. Collectiv ely, these studies includ e acute, subchronic and chronic toxicity, including asse ssments of carcinogenicity, ne urotoxicity, developmental, reproductive, and general or systemic toxicity. These studies include e ndpoints, which may be susceptible to endocrine influe nce, including effects on endocri ne target organ histopathology, organ weights, estrus cyclicity, sexual maturatio n, fertility, pregnancy rates, reproductive loss, and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and chronic studies that assess gr owth, developmental and reprod uctive effects in different taxonomic groups. As part of its most recent registration decision for potassium and sodium nitrate, EPA reviewed these data and selected the most sensitive endpoints for relevant risk assessment scenarios from the existing hazard database. However, as required by FFDCA section 408(p), potassium and sodium nitrate are s ubject to the endocrine screening part of the Endocrine Disruptor Screening Program (EDSP).

EPA has developed the EDSP to determine whet her certain substances (including pesticide active and other ingredients) may have an effect in humans or wildlife similar to an effect produced by a “naturally occurring estrogen, or ot her such endocrine effect s as the Administrator may designate.” The EDSP employs a two-tiered approach to making th e statutorily required

determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a chemical substance to interact with the estrog en, androgen, or thyroid (E, A, or T) hormonal systems. Chemicals that go th rough Tier 1 screening and are found to have the potential to interact with E, A, or T hormonal systems will proceed to the next stag e of the EDSP where EPA will determine which, if any, of th e Tier 2 tests are necessary base d on the available data. Tier 2 testing is designed to identify a ny adverse endocrine-related eff ects caused by the substance, and establish a dose-response relationship between the dose and the E, A, or T effect.

Under FFDCA section 408(p), the Agency must screen all pesticide chemicals. Between October 2009 and February 2010, EPA issued test orders/data call-ins for the first group of 67 chemicals, which contains 58 pest icide active ingredients and 9 inert ingredients. A second list of

chemicals identified for EDSP scr eening was published on June 14, 2013 a and includes some pesticides scheduled for Registration Review and chemicals found in water

. For further information on the status of the EDSP, the policies and procedures, the lists of chemicals, future lists, the test guidelines and the Tier 1 screening battery, pleas e visit our website. b

In the interim, EPA is making no human health or environmental safety findings associated with the EDSP screening of [insert chemical/case]. Before completing this Registration Review, the Agency will make an EDSP FFDCA section 408(p) determination.

a See http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPPT-2009-0477-0074 for the final second list of

chemicals.

b http://www.epa.gov/endo/Page 15 of 29 14.0 Human Studies

Human Studies

Phosphide and phosphine occupation al risk assessments relied in part on data from a study in which adult human subjects were involved (Jaquith, D., D229345, 12 December 2000). This study appears be an “observational” study and, th erefore, not subject to the need for Human Studies Review Board (HSRB) evaluation. Furthe rmore, the chemical specific studies used to develop the previous occupationa l handler assessment were not reviewed for compliance with required ethical standards for conducting human studies. Many such studies, involving exposure to many different pesticides, comprise ge neric pesticide exposure databases such as the Pesticide Handlers Exposure Database (PHED) and the Agricultural Reentry Task Force (ARTF)

Database. EPA has reviewed all the studies supporting these multi-pesticide generic exposure databases, and has found no clear and convincing ev idence that the conduct of any of them was either fundamentally unethical or significantly deficient relati ve to the ethical standards prevailing at the time the research was conducted. All applicable requirements of EPA’s Rule for the Protection of Human Subjects of Research (40 CFR Part 26) have been satisfied, and there is no regulatory barrier to c ontinued reliance on these studies.

15.0 Risk Assessment Updates, Data Deficiencies, and Label Revisions

The following data deficiencies were identified for phosphine:

Toxicology:

 extended one-generati on reproduction study

 special acute inhalation study

Residue Chemistry: None

Dietary Exposure: None

Occupational/Residen tial Exposure:

 875.1400 Inhalation Exposure Study for Applicators . These studies are required to assess exposures for applicators involved in fumigating commodities/materials

and/or structural facilities.

 875.1700 Product Use Information . This study is required to assess product use information parameters by major us e region, frequency, and application equipment.

 875.2500 Post-Application Inhalation Exposure Study. This study is required to assess post-application exposures for workers near fumigation facilities/operations or who work directly with previously treated

commodities/materials.

o Special Study – Ambient air monitoring. This study is required to assess ambient air concentrations for communities in proximity to treated facilities.Page 16 of 29  Special Studies - Monitoring data on fumigated commodities . Special studies are required to evaluate emission ra tes for phosphine from treated commodities/materials and the potential for occupational exposure due to those emissions in the channels of trade after fumigation activities are complete.

EPA anticipates conducting the following risk assessment updates during Registration Review: Toxicology:

 Reevaluation of the toxicity endpo int/dose selection may be necessary.

Residue Chemistry: None

Dietary Exposure:

 A new dietary exposure and risk assessm ent may be required during Registration Review to incorporate potent ial changes to the phosphine toxicological PODs. In addition, the assessment should include updated consumption information and

utilize the newest ve rsion of DEEM-FCID

Occupational/Residen tial Exposure:

 Revised HED occupational handler risk assessments may be necessary based on the most recent exposure data, Agency policies, or if the toxicological

reevaluation results in changes to the endpoints.

 Additional or revised HED residential bystander risk assessments may be necessary based on the most recent expos ure data, Agency policies, or if the toxicological reevaluatio n of results in changes to the endpoints.Page 17 of 29 16.0 References

Memoranda Relevant to Registration Review.

Author Barcode Date Title

J. Rowland D012640 6/10/1998 ALUMINUM/MAGNESIUM PHOSPHIDE

- REVISED REPORT of the Hazard Identification

Ass es sment Review Committee.

P. Lewis D357118 6/22/1998 HED Chapter of the Registration Eligibility Document (RED) PC Code No 66501

P. Lewis D 12/22/1998 REVISED HED Chapter of the Registration Eligibility Document (RED) PC Code No 66501

J. Housenger memo 4/25/2013 U.S. EPA Comments - DPR Phosphine Risk

Assessment

Dawson, J. and Smith, C. D353906 11/06/2008 Data Evaluation Records for the Mill Emissions Study, Historical Emissi ons Data Evaluation, and Modeling Analysis Completed By the Methyl Bromide Industry Panel

Rury, K. TXR No.

0056661 5/22/2013 Phosphine

- Report of the Hazard and Science Policy Council (HASPOC) Meeting of May 9, 2013: Waiver for the Immunotoxicity Study (870.7800).

Rury, K. TXR No.

0056345 3/5/2013 Phosphine

- Report of the Hazard and Science Policy Council (HASPOC) Meeting of June 7,

2012: Waiver for the recommendation on need for additional studies to support increased use

rate

D. Hrdy D236017 5/28/1997 Aluminum Phosphide and Magnesium Phosphide. Case 0025 and 0645. Chemical No.

066501 and 066504. Product and Residue Chemistry Chapters for the Aluminum Phosphide and Magnesium Phosphide Reregistration Eligibility Decision

J. Miller D400996 3/7/2013 Label Amendment to add existing crops to phosphine from phosphides

S. Walse MRID

49066801 2/26/2013 Off-gassing study conducted in conjunction with the USDA. Phosphine and Methyl Bromide comparison.Page 18 of 29 Attachments

Attachment 1: Chemical Identity Table Attachment 2: Phosphine Ac ute Toxicity Profile Table Attachment 3: Aluminum and Magnesium P hosphide/Phosphine Endpoint Selection Table

Attachment 4: International Residue Limits Table

Attachment 5: Justificati on for Studies for PhosphinePage 19 of 29 Attachment 1: Chemical Identity Table

Aluminum Phosphide Magnesium Phosphide Phosphine

Empirical formula AlP Mg 3 P 2 PH 3

Molecular weight 57.96 134.9 33.9

CAS registry number 20859-73-8 12-057-74-8 7803-51-2

PC Codes 066501 066504 066500 IUPAC Phosphane

MeltingPoint/range oC -132.8 °C

Boiling Point oC -87.7 °C

Density at 20 oC (g/cm3) 1.379 g/l

Water Solubility (20oC) 31.2 mg/100 ml

Attachment 2: Phosphine Ac ute Toxicity Profile Table

Guideline

No. Study Type MRID Results Toxicity Category

81-1 Acute Oral No study

-- NA

81-2 Acute Dermal No study

-- NA

81-3 Acute Inhalation 41377001 LC 50> = 11 ppm (HDT) I

81-4 Primary Eye

Irritation No study

-- NA

81-5 Primary Skin

Irritation No study

-- NA

81-6 Dermal Sensitization No study

--Page 20 of 29 Attachment 3: Aluminum and Magnesium P hosphide/Phosphine Endpoint Selection Table

Dose and Endpoints for Risk Assessment- Phosphine All of the previous hazard and risk assessmen ts use phosphine gas as the agent of concern. Aluminum (Al) Phosphide and Magnesium (Mg) Phosphide are pellets but act as fumigants by releasing phosphine gas. Th erefore, the previous phosphine dietary exposure and risk assessment was also conducted for Al and Mg Ph osphide since they are registered to control insects primarily by indoor fumigation of raw agricultural commodities (RACs), animal feeds, processed food commodities, and non-food commodities in sealed containers or structures. Summary of Aluminum and Magnesium Phos phide Endpoints for Risk Assessments are presented below:

Exposure

Scenario Concentration Endpoint Study

Acute Dietary 1.18 mg/kg/day

converted from 5 ppm No treatment-related effects after exposure for 15 days. 15- Day exposure regiment in a 90- day inhalation -

Rat.

UF=100 Acute RfD =0.018

Chronic Dietary 1.13 mg/kg/day

converted from 3 ppm No treatment-related eff ects after chronic (52 weeks) inhalation exposure. Chronic Toxicity

Inhalation-Rat

UF=100 Chronic RfD =0.0113

Short-Intermediate or Long-Term (Dermal) None The use pattern does not indicate potential exposure via the dermal route. Therefore, dermal risk assessments are not required.

Short Term (Inhalation) 0.007 mg/L No treatment-related effects after exposure for 15 days. 15- Day exposure regiment in a 90- day inhalation -

Rat. UF=100

Intermediate (Inhalation) NOAEL= 0.004 mg/L No evidence of toxicity at the highest tested

concentration. 90-Day Inhalation -

Rat

UF=100

Long-Term (Inhalation) NOAEL= 0.004 mg/L No evidence of toxicity at the highest tested

concentration. Chronic Toxicity

Inhalation - Rat

0.004 mg/L
NOAEL = no observed adverse effect level; LOAEL = low observed adverse effect levelPage 21 of 29 Attachment 4: International Residue Limits Table

Summary of US and International Tole rances and Maximum Residue Limits

Residue Definition:

US Canada Mexico

1 Codex

40 CFR 180.225: 1). Tolerances are established for residues of phosphine in or on the following raw agricultural commodities (RACs) resulting from post-harvest fumigation for the control of insects with phosphine gas or phosphide compounds that produce phosphine gas Phosphine None

Commodity Tolerance (ppm) /Maximum Residue Limit (mg/kg)

US Canada Mexico

1 Codex

Almond 0.1 0.1

Avocado 0.01 0.01

Banana 0.01 0.01 Barley, grain 0.1 0.1 Cabbage, Chinese, bok choy 0.01 0.01

Cabbage, Chinese, napa 0.01 0.01
Cacao bean, dried bean 0.1 0.1

Cashew 0.1 0.1
Citron, citrus 0.01 0.01 Coffee, bean, green 0.1 0.1 Corn, field, grain 0.1 0.1 Corn, pop, grain 0.1 0.1
Cotton, undelinted seed 0.1
Date, dried fruit 0.1 0.1 dates
Dill, seed 0.01 0.01 Eggplant 0.01 0.01

Endive 0.01 0.01 Grapefruit 0.01 0.01

Hazelnut 0.1 0.1 Kumquat 0.01 0.01

Lemon 0.01 0.01

Lettuce 0.01 0.01

Lime 0.01 0.01 Mango 0.01 0.01 Millet, grain 0.1 0.1 pearl millet, proso millet

Mushroom 0.01
Nut, brazil 0.1 0.1 Oat, grain 0.1 0.1

Okra 0.01 0.01 Orange, sweet 0.01 0.01 orangesPage 22 of 29 Summary of US and International Tole rances and Maximum Residue Limits

Residue Definition:

US Canada Mexico

1 Codex

Papaya 0.01 0.01

Peanut 0.1 0.1

Pecan 0.1 0.1

Pepper 0.01 0.01 bell peppers, non-bell peppers, pepper hybrids

Persimmon 0.01 0.01

Pistachio 0.1 0.1 Rice, grain 0.1 0.1 Rye, grain 0.1 0.1
Safflower, seed 0.1 0.1 Salsify, tops 0.01 0.01
Sesame, seed 0.1 0.1 Sorghum, grain 0.1 0.1 Soybean, seed 0.1 0.1 dry soybeans
Sunflower, seed 0.1 0.1 Sweet potato, roots 0.01 0.01 Tangelo 0.01 0.01 Tangerine 0.01 0.01

Tomato 0.01 0.01

Vegetable, legume, group 6, except soybean 0.01 0.01 Dry (adzuki beans, beans, blackeyed peas, broad beans, catjang seeds, chickpeas, cowpea seed, field peas, guar seeds, kidney beans, lablab beans, lentils, lima beans, moth beans, mung beans, navy beans, pigeon peas, pink beans, pinto beans, rice beans, southern peas, tepary beans, urd beans) 0.01 edible podded (dwarf peas, jackbeans, moth beans, peas, pigeon peas, runner beans, snap beans, snow peas, soybeans, sugar snap peas, sword beans, wax beans, yardlong beans) 0.01grain lupin 0.01 succulent shelled ( blackeyed peas, broad beans, cowpeas, english peas, garden peas, green peas, lima beans, peas, pigeon peas, southern peas)

Walnut 0.1 0.1 black walnuts, English walnuts,Page 23 of 29 Summary of US and International Tole rances and Maximum Residue Limits

Residue Definition:

US Canada Mexico

1 Codex

Wheat, grain 0.1 0.1 US [40 CFR §180.225(a)(2)] Canada Mexico

1 Codex

Tolerances are established for residues of the fumigant in or on all RACs resulting from preharvest treatment of pest burrows in agricultural and non-crop land areas. Phosphine None

Commodity Tolerance (ppm) /Maximum Residue Limit (mg/kg)

US Canada Mexico

1 Codex

All raw agricultural commodities resulting from preharvest treatment of pest

burrows 0.01

US [40 CFR §180.225(a)(3)] Canada Mexico

1 Codex

Residues resulting from fumigation of processed

food Phosphine None

Processed food 0.01 0.01 all processed foods US [40 CFR §180.225(a)(4)] Canada Mexico

1 Codex

Residues resulting from fumigation of animal

feed Phosphine None

Animal feed 0.1 US [40 CFR §180.225(a)(5)] (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 to aerate the fi nished food/feed for 48 hours before it is offered to the consumer, unless EPA specifically determines that a different time is appropriate. Where appropriate, a wa rning 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 f ood, except processed brewer's rice, malt, and corn grits stored in breweries fo r use in the manufacture of beer MRLs With No US Equivalent

Triticale 0.1

Completed: : M. Negussie; 05/20/2013Page 24 of 29 Attachment 5: Justification for Studies with Phosphine

Special Study: Special Acute Inhalation Toxicity Study in Rodents with Phosphine

Rationale for Requiring the Data

Like other fumigants, as part of the risk asse ssment for Phosphine, the Agency will need to conduct an acute worker and an acute bystande r assessment. Several other fumigants have a special acute inhalation study in rats which ev aluates histopathology of the respiratory tract including incidence and severity at multiple test ed concentrations, GSH measurements (i.e. nose), pharmacokinetics/tissue dosimetry including time c ourse, and sublethal portal of entry effects (i.e. within the respiratory tract) along with information on dose response, incidence and severity. The currently available acute inhalation toxicity studies for Phosphine only provide

LC 50 values, and do not have additional respirat ory tract histopathology information. This special study has been shown to be useful in fumigant risk assessment. Available inhalation studies have shown that the nasal cavity is a target organ for Phosphine. Therefore, there is a reasonable likelihood that a special acute inhalation toxicity study would identify a more sensitive endpoint than the current acute endpoi nt, which was obtained from a developmental toxicity study and used to evaluate acute wo rker and acute bystander exposure to Phosphine. Practical Utility of the Data

How will the data be used?

There is a potential for exposure and risk for non-occupational/residential bystanders as a result of commodity fumigations. The MOEs calcula ted using the monitoring data collected for almond/walnut fumigation workers exceed th e Agency’s level of concern for acute, short/intermediate term and long-term exposure via the inhalation route. These data will be used to reevaluate the current point of depart ure for the acute worker and acute bystander

assessments.

How could the data impact the Agency’s future decision-making?

The absence of the special acute inhalation toxicity study with comprehensive evaluations of the respiratory tract may result in increased uncertain ty around the acute endpoint. These data will allow the Agency to fully characterize the eff ects that occur following acute exposure. In addition, more precise information will allow the Ag ency to refine its pr evious risk assessment and to defend challenges to the phosphine decision.Page 25 of 29 Guideline Number: 875.1400 Study Title: Inhalation Exposure Study for Applicators Rationale for Requiring the Data
The inhalation exposure route is very important for exposure scenarios such as fumigation activities where gases will be generated. However, very limited worker exposure monitoring data

are available for workers involved in the fumiga tion of commodities, othe r materials, and/or

structural facilities . These data do not address the breadth of possible activities associated with phosphine uses that are of potential risk concern. Traditional sources of worker exposure information (e.g., Pesticide Handlers Exposure Database or PHED) have not been used to supplement the existing data and do not apply because of the highly volatile nature of phosphine.

To protect workers from inhalation exposure to pesticides, the Agency requires inhalation exposure monitoring data. These data will ensure that the Agency h as the most accurate information possible to assess exposures for those i nvolved in the fumigation process. In addition, these data will be used during registration re view to evaluate the potential for phosphine occupational exposure to fumigators who treat structural facilities, commodities, and other materials, and will inform the Agency as to how to manage any risks which may be identified based on these data which will reflect the current use practices for phosphine. Practical Utility of the Data

How will the data be used?

The inhalation exposure data will be used to assess occupational risks for workers involved in fumigation activities during treatment of commodities, materials and/or structural facilities.

How could the data impact the Ag ency’s future decision-making?

The inhalation exposure data will be used to de termine the accuracy of the inhalation risks to occupational applicators during fumigation activ ities based on modern fumigation practices. If future risk assessments are performed without th ese data, the Agency will have to factor a significant degree of uncertainty into its regulat ory decision-making process and that the current mitigation measures (i.e., personal protective equipm ent) may not provide adequate protection for workers applying phosphine in structural facilities and/or during the treatment of commodities and

other materials.

The lack of these data will limit the flexibility of the Agency and registrant s with respect to the ability to evaluate risks associated with the mode rn use practices associated with phosphine. It will also allow the Agency to refine its previ ous risk assessment and c ould be used to defend challenges to the phosphine decision and to cons ider additional sources of exposure to those involved in the fumigation process.Page 26 of 29 Guideline Number: 875.1700 Study Title: Product Usage Information Rationale for Requiring the Data
The Agency’s understanding of phosphine products a nd usage is limited to the directions found on pesticide labels and estimates of the amounts u sed to treat certain commodities or structures. The Agency, believes that the current unders tanding of the phosphine usage pattern is not sufficient to assess the full range of potential expos ure associated with its use because how it is applied, how much is applied, and associated fumigation practices (e.g., aeration methods) can impact exposures and these data are not available in a systematic manner.

Additional data are necessary to understand p hosphine usage in terms of both commodity and facility fumigations and the potential exposures as a result of these uses. These data will ensure that the Agency has the most accurate information possible to assess product usage parameters by major use region, frequency, season, maximu m and typical rates, and application equipment/procedures. In addition, these data will be used during registration review to evaluate the potential exposure for workers and the general public. Practical Utility of the Data

How will the data be used?

This information will be used to confirm the end-use products, use patterns, usage assumptions and parameters to determine e xposures to phosphine for humans or provide the basis for possible refinements to the process based on a more thorough understanding of modern fumigation practices.

How could the data change the Agency’s decision?

Additional precautions and/or restrictions may be necessary to protect workers and the general public from exposures to phosphine as a consequen ce of commodity/material fumigations and/or fumigation of structural facilities. These data will allow the Agency to refine its previous risk

assessment and could be used to defend challenges to the phosphine decision.Page 27 of 29 Guideline Number: 875.2500 Study Title: Post-Application Inhalation Exposure Study Rationale for Requiring the Data

Post-application inhalation exposure to phosphine is predicted to occur as a result of the registered uses of phosphine, including comm odity/material fumigation and/or structural fumigations. The existing data for exposure to phos phine are limited in terms of the variety of post-application activities and the potential expos ures due to off-gassing from treated structural

facilities and commodities.

The original data requirements were not broa d enough to assess risks to occupational workers near fumigated facilities treated with phosphine or who have to work directly with phosphine

treated commodities/materials that could result in post-application exposures which may be a concern. These data will ensure that the Agency has the most accurate information possible to assess post-application exposures for workers near fumigation structural facilities/operations or

who work with treated commodities/materials. In addition, these data will be used in registration review to determine if the potential for post-a pplication occupational exposure for workers near fumigation facilities/operations is below the Agency ’s level of concern or establish further risk management needs that would apply to the use of phosphine. Practical Utility of the Data

How will the data be used?

These data will be used to determine inhalati on exposure to phosphine for workers conducting a variety of post-application activities near fumiga ted facilities/commodities or who work directly

with treated commodities/materials.

How could the data impact the Agency’s future decision-making?

The post-application inhalation exposure study w ill provide data to support and fully characterize and quantify the exposure and risks of workers exposed to this pesticide. Due to the lack of data, the Agency has used assumptions in developing the risk assessment. Th ese data will allow the Agency to refine its previous risk assessment and could be used to defend challenges to the phosphine decision.Page 28 of 29 Special Study : Ambient air monitoring

Rationale for Requiring the Data

Post-application inhalation exposure from ambient air to phosphine is predicted to occur as a result of the registered use of phosphine on mu ltiple fumigated structures and/or commodities during the season of use in high areas of use wh ich can result in community based exposures from multiple sources. The existing data for am bient air concentrations are limited for communities in proximity to areas where commodity /material fumigations may occur, as well as where facilities themselves may be treated.

These data will ensure that the Agency has the most accurate information possible to protect communities near fumigation facilities/operations. In addition, these data will be used to determine if the potential for post-applica tion exposure for communities near commodity fumigation facilities and treated structures is be low the Agency’s level of concern. Practical Utility of the Data

How will the data be used?

These data will be used to evaluate: (1) post-a pplication inhalation exposure to phosphine for communities near fumigated facilities/comm odities, (2) potential maximum peak air concentrations in areas of high seasonal use, and (3 ) potential community-level air concentrations in areas of high use.

How could the data impact the Agency’s future decision-making?

The post-application inhalation exposure study w ill provide data to support and fully characterize and quantify the exposure and risks of communities exposed to this pesticide. These data will allow the Agency to: (1) evaluate whether the mitigation measures such as good agricultural practices can effectively reduce ambient air c oncentrations, (2) determine post-application inhalation exposure to phosphine for communiti es near fumigated facilities/commodities, (3) refine its previous risk assessment, and (4) to defend challenges to the phosphine decision.Page 29 of 29 Special Study: Monitoring data on fumigated commodities

Rationale for Requiring the Data

The potential post-application exposures associ ated with commodity fumigation were not quantitatively assessed when these u ses were established. The Agency did not have monitoring data to directly measure emissions of phos phine from fumigated commodities/materials.

These data will ensure that the Ag ency has the most accurate in formation possible on exposure to evaluate emission rates from treated commodities. Post-application risks estimates will be calculated for workers exposed to phosphine and will be used to determine if the potential for occupational exposure due to those emissions (i.e ., for post-application workers who must handle or receive treated commodities) is below the Agency’s level of concern. Practical Utility of the Data

How will the data be used?

These data will be used to determine if the exposure to phosphine from handling treated commodities/materials is below the Agency’s leve l of concern. In addition, these data will be used to inform emissions factors and buffer zone estimates during the treatment and aeration phases of the fumigations for phosphine commodity uses.

How could the data impact the Agency’s future decision-making?

These monitoring data are needed to fully char acterize emissions from fumigated commodities. These data will allow the Agency to refine its previous risk assessment in terms of model parameterization (i.e., buffer zones, emissions and other factors). In addition, more precise information appropriate for parameterization of th e exposure models could be used to refine the previous risk assessment and to defend challenges to the phosphine decision.