UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

MEMORANDUM 

Date: Final - September 11, 2013 

SUBJECT: Phosphide (AI, Mg) and Phosphine: 

OFFICE OF CHEMICAL SAFETY AND 

POLLUTION PREVENTION 

Human-Health Assessment Scoping Document Supporting Registration Review. 

PC Code: Phosphide PC Code: 066500, 

Aluminum Phosphide PC Code: 06650 I, 

Magnesium Phosphide PC Code: 066504 

Decision 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.: Phosphine: 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. King, Ph.D., Toxicologist, Ris}Rl~~~~~~+-./ 

James S Miller, Environmental Scientist II 

Thurston Morton, Senior Chemist -;Z: 

Risk Assessment Branch IV 

Health Effects Division (7509P) 

d.-~??-- 9ht.lt3 THROUGH: Elissa Reaves, Ph.D., Branch Chief c;~--- ?- !"I' 

Risk Assessment Branch IV 

Health Effects Division (7509P) 

TO: Dana Friedman, Risk Manager Reviewer 

Risk Management and Implementation Branch 

Pesticide Re-Evaluation Division (7508P) 

Attached is HED's human-health risk assessment scoping document for phosphide (Aland Mg) 

and phosphine to support registration review. 

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Page 2 of 29

1.0 Executive Summary 

Phosphine is marketed in several physical forms including metalized solids (aluminum and 

magnesium phosphide) that emit phosphine after contact 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 rodents, 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 include 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, containers); 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 phosphine to determine whether sufficient data 

are available to support Registration Review. HED has considered the most recent human health 

risk assessments for aluminum phosphide, magnesium phosphide, and phosphine with respect to 

toxicity, exposure, and usage databases, and the most updated Agency science policy and risk 

assessment methodologies to determine the scope of work necessary to support Registration 

Review. The 1997 Reregistration Eligibility Decision (RED); the 1998 HIARC revised report on 

Aluminum and Magnesium Phosphide; the 1998 Reregistration Eligibility Decision (RED); and 

the 1998 revised Reregistration Eligibility Decision (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 potential 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 protection will continue to 

be based on the acute toxicity of the end-use product, as described 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 inhalation toxicity. The target organ for phosphine 

is the respiratory tract. In humans, symptoms of phosphine gas intoxication include shortness of 

breath, coughing, pulmonary irritation, nausea, headache, jaundice, fatigue, convulsions, and 

death 

The toxicity database for phosphine is not complete. A special acute inhalation toxicity study in 

rats and an extended one-generation reproductive toxicity study in rats via the inhalation route 
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are required. In the 1998 RED, a combination of guideline and literature studies was used to 

assess phosphine hazards. All submitted toxicity data to support the metal phosphides and 

phosphine were generated for phosphine gas and are by the inhalation route of exposure. The 

most recent risk assessment relied on the Occupational Safety and Health Administration 

(OSHA) permissible exposure limit (PEL) as the point of departure for inhalation risk 

assessments. Acute and chronic dietary endpoints 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-evaluate 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 database are complete and no additional data are 

required to support the registration review of the metal phosphides and phosphine. There are no 

drinking water concerns associated with phosphine based on its limited use as a commodity 

fumigant. Dietary (food only) risks of concern have not been identified for these active 

ingredients, however, if toxicity 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 information, post-application inhalation studies, and 

monitoring data for phosphine are required. No residential scenarios have been previously 

assessed for the metal phosphides or phosphine. However, there is the potential for bystander 

exposures, which can occur from emissions during 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 for workers equipped with appropriate PPE. 

However, a new occupational handler risk reassessment will likely need to be completed during 

registration review to consider newly submitted 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 exposure). Also, to the extent that they are 

available, consider policies currently under development regarding assessment of fumigant 

chemicals. 

In summary, the following data deficiencies were identified for Phosphine: 

Toxicology: 

 extended one-generation reproduction study (inhalation) 

 a special acute inhalation toxicity study is required for Phosphine at this time 

based on current testing policy applicable 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: None 
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Dietary Exposure: None 

Occupational/Residential 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 use 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 rates 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 for Phosphine during 

Registration Review: 

Toxicology: 

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

necessary. 

Residue Chemistry: None 

Dietary Exposure: 

 A new dietary exposure and risk assessment may be required during Registration 

Review to incorporate potential changes to the phosphine toxicological PODs. In 

addition, the assessment should include updated consumption information and 

utilize the newest version of DEEM-FCID. 

 

Occupational/Residential Exposure: 

 Revised HED occupational handler and post application 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. 
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 Additional or revised HED residential bystander 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. 

2.0 Introduction 

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

risk assessments and the available information 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 (Mg3P2) in 

1979. In 2010, cylinderized phosphine (Ph3) 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 DEEMTM (Dietary Exposure Evaluation Model). 

Recently, HED reviewed and commented on a risk characterization document for phosphine 

authored by the Medical Toxicology Branch of the Department of Pesticide Regulation for the 

State of California (Cal. DPR) (J, Housenger, 25 April 2013). On March 21, 2013, the Agency 

accepted a label amendment submitted in February 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 ECO2FUME® (EPA Reg.: 

68387-7). Lastly, a new study authored by Spencer 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 several physical forms including metalized solids that emit phosphine 

after contact with moisture through a chemical process and as a cylinderized fumigant. The 

active ingredient of all three products (AlP, Mg3P2 and Ph3) is phosphine, per se, which is a 

colorless gas effective against stored-product insect pests and vertebrate pests, mainly rodents. 

The registered formulations of aluminum and magnesium phosphide include 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, containers); 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/Toxicology 
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The toxicology database for phosphine is not complete. A special 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 developmental toxicity study in rabbits is not required at this time 

(HASPOC, TXR- 0056345). The requirement for a guideline immunotoxicity 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 inhalation toxicity. The target organ for phosphine 

is the respiratory tract. In humans, symptoms of phosphine gas intoxication include shortness of 

breath, coughing, pulmonary irritation, nausea, headache, jaundice, fatigue, convulsions, and 

death. 

Inhalation exposure to phosphine gas represents the primary route of exposure for all three 

compounds. While the Agency also assessed potential dermal exposures to phosphine residues in 

fumigated foods, this is not considered a major exposure pathway. Dermal exposure to metal 

phosphides is not a significant route of exposure given the personal protective equipment 

(gloves) that applicators are required 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 effect has been seen in insects, rodents, and humans, and the 

commonality across species supports the data derived from non-human 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 (cytochrome 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 glutathione (GSH) concentrations in the 

above-mentioned organs. Since GSH is a key component 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 animals was conducted via the inhalation route. 

Available and acceptable guideline studies include a 90-day rat study (using only a 15-day 

exposure period); developmental rat 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 experimental toxicology studies 

with laboratory animals. Literature studies report the dose response for phosphine as a steep 

nonlinear threshold, consistent with Haber’s Law 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 relationship is consistent across species and 

there is no evidence for toxicity or mortality below 5 ppm in an acute exposure scenario in 

laboratory animals. The LOAELs for phosphine reach low doses of 7 ppm for exposure 

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

decline with continued exposure indicating that phosphine is short acting with a very steep dose 

response via inhalation exposure and does not accumulate in the body. 
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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 Limit (PEL) for phosphine gas at 0.3 ppm based on an 

epidemiologic study of grain fumigators where no adverse effects were observed at a 

concentration of 0.3 ppm. Based on limited information 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 since no treatment related effects 

were seen at a lower concentration (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 (decreased body temperatures and decreased 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 (cRfD) of 0.0113 mg/kg/day was derived from on 

an inhalation NOAEL of 3.0 ppm (HDT; a LOAEL was 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 children (as required by FQPA) should be reduced to 

1X based the following rationale: 

 

(A) There was no indication of increased susceptibility of rats to in utero and/or postnatal 

exposure to Aluminum/Magnesium Phosphide. 

(B) Exposure assessments do not indicate a concern 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 phosphine is not complete. A special acute inhalation toxicity study 

in rats is required. The special acute inhalation toxicity study should include the evaluation of 

the following: histopathology of the respiratory tract, including incidence and severity at 

multiple tested concentrations; GSH measurements (i.e., nose); pharmacokinetics/tissue 

dosimetry including time course; and sublethal portal of entry effects (i.e., within the respiratory 

tract) along with information on dose response, incidence, and severity. A protocol for this 

special acute inhalation study should be submitted for agency review, prior to study initiation. 

Additionally, an extended one-generation reproductive toxicity study in rats via the inhalation 

route is required at this time. The extended one-generation reproductive toxicity study allows for 

the integrated evaluation of multiple organ systems (with an emphasis on the nervous, immune, 

and reproductive systems) across several lifestages from conception through adulthood. This 

study will be more useful to assess potential hazard and risk than a rabbit developmental toxicity 

study. A study protocol for this study should be submitted for Agency review. Lastly, an 
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immunotoxicity study is not required 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 required, the Agency will need to re-evaluate the 

points of departure (PoDs) and safety factors (SFs)/uncertainty factors (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 required for the purposes of registration review. The 

residue of concern is phosphine and the current tolerance expression is appropriate. Residue 

data reflecting registered postharvest treatments of stored raw agricultural and processed 

commodities indicate that, with adequate aeration or further processing after treatment, residues 

of phosphine dissipate to nondetectable levels. Acceptable methods are available for 

enforcement and data collection purposes for plant commodities. The Pesticide Analytical 

Manual (PAM) Vol. II lists, under aluminum phosphide, a colorimetric method (LOD 0.01 ppm) 

and a GLC method with flame photometric detection (LOD = 0.001 ppm) as Methods A and B, 

respectively, for the enforcement 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 resulting 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 ppm 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 additional data are required for 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 properties 
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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 conservative 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. All 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 population subgroups. These estimates of acute 

dietary exposure are partially refined, yet still conservative in that 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. HED 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. 

Chronic dietary (food) exposure does not exceed HED’s level of concern. 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 registrations. Previously 

conducted assessments did not indicate any acute or chronic risks of concern. However, a new 

dietary exposure and risk assessment may be required during Registration Review to incorporate 

potential changes to the phosphine toxicological 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 previously assessed for phosphide (AlP, Mg3P2) or phosphine 

(Ph3). As previously noted, the active ingredient for the phosphine and phosphide products is 

phosphine gas. The Agency has historically assumed that, provided adequate aeration of 

dwellings is completed prior to re-entry, exposure to owners of fumigated structures is expected to 

be negligible given proper aeration procedures are in place; however, there is the potential for 

bystander exposures, which can occur from emissions during treatment and aeration of 

commodities and structures. For registration review and as per other fumigants, these exposures 

will need to be addressed, including the use of computer modeling analyses (e.g., PERFUM) and 

estimation of potential buffer zones (J. Dawson and C. Smith, D353906, 6 November 2008). 
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There is sufficient information to complete such analyses for phosphide (AlP, Mg3P2) and 

phosphine (Ph3). However, in the event that the available information (MRID 49066801) 

suggests that there may be bystander risks of concern, a more refined analysis would be possible 

if additional data were available. Types of information that could be used to refine the bystander 

assessment include information on treatment conditions such as building/structure types, volumes 

treated, concentration/time schedules used, release height, air exchange rates, and historical 

emissions data. To the extent that these submitted data show potential for bystander exposure, 

residential assessments may be needed during registration 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 potential residential exposures to the pesticide, aggregate risk 

assessment must consider exposures from three 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, Mg3P2) and phosphine (Ph3) are 

limited. The physiochemical properties of phosphine also make significant dermal exposure 

unlikely and the quantification of potential low-level exposures difficult; therefore, a quantitative 

dermal exposure assessment has not been completed. 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 described in the Worker Protection 

Standard and mitigation measures for dermal exposure described in PR Notice 93-7. Furthermore, 

since phosphine is a gas, human exposures are expected to occur primarily through the inhalation 

route 

8.1 Occupational Handlers 

There is potential for occupational handler inhalation exposure to phosphine gas based on the 

registered HED uses of phosphide (AlP, Mg3P2) and phosphine (Ph3). Inhalation exposures are 

expected for acute, short- and intermediate-term durations. 

Phosphide (AlP, Mg3P2) Formulations: 

The 1998 (RED) (P. Lewis et al., 22 December 1998) indicates that potential inhalation risks, due 

to the degradation of the AlP, and Mg3P2 pellets into phosphine gas are acceptable when used 
Page 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, which could change based on newly required studies. 

MOEs were unacceptable (MOE < 100) at baseline conditions (no PPE/respirators). The potential 

exists for workers who are not directly associated with the fumigation/aeration activities near 

areas where these operations are occurring or those who handle previously treated commodities 

(bystanders). Therefore, these risks also need to be addressed. 

Cylinderized Phosphine (Ph3): 

On February 4, 2013, the registrant submitted a label amendment (J. Miller, 7 March 2013) that 

states that VAPORPH3OS® (EPA Reg.: 68387-8); and ECO2FUME® (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 label 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 submitted (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-application activities (i.e. aerators, forklift operators, bystanders 

etc.). Potential exposures due to off gassing will be assessed for workers conducting postapplication activities near treatment operations. 

As noted above, HED is currently reviewing an off gassing study 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 exposures 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 have longer duration exposures (i.e., intermediateterm or chronic). A new occupational handler and post-application risk reassessment needs to be 

completed during registration review. This reassessment will incorporate recently submitted 

data; a human equivalent concentration calculated for fumigators and post-application workers 

that will come into contact with previously treated goods (based on 8 hours of exposure), and to 

the extent that they are available, policies currently under development regarding assessment of 

fumigant chemicals. 

Occupational/Residential Exposure Studies Required 

The following additional studies are required to support the registration 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, frequency, 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 fumigation 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 treated commodities/materials and the potential for 

occupational exposure due to those emissions in the channels of trade after fumigation activities 

are complete. 

9.0 Public Health and Pesticide Incident Data 

The OPP Incident Data System (IDS) was queried 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 involving aluminium phosphide, stemming from 57 

events. 

Magnesium Phosphide

For the Main IDS, there was 1 incident reported in the database. This incident was classified as 

minor severity. In Aggregate IDS, there were no reported incidents involving magnesium 

phosphide. A query of SENSOR-Pesticides identifies 2 cases, stemming from 2 events, 

involving the single active ingredient magnesium phosphide. 

Phosphine

For the Main IDS, there was 1 incident reported in the database. This 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 SENSOR-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 concern 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 SENSOR-Pesticides, aluminum phosphide had a 

moderately high frequency of incidents that were mostly moderate or low in severity. EPA has 

recently (2010) expanded and clarified the outdoor use restrictions for all phosphine products 

used against burrowing rodents. Considering the newly required safety measures, the Agency 

will continue to monitor the incident information 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 determined by measuring phosphine, when used as a postharvest fumigant, pre-harvest treatment of pest burrows, fumigation of processed food, or 

fumigation of animal feed. Tolerances range from 0.01 ppm to 0.1 ppm on a number of 

commodities. 

There was no Mexican or CODEX MRLs for 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 instances 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 justice concerns, to the extent possible, were considered in the 

most recent phosphide/phosphine human health risk assessment, in accordance with U.S. 

Executive Order 12898, “Federal Actions to Address Environmental Justice in Minority 

Populations and Low-Income Populations,” 

(http://www.hss.energy.gov/nuclearsafety/env/guidance/justice/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 variability of diets within the 

U.S., and people who may be exposed when harvesting crops. Should these highest exposures 

indicate potential risks of concern, OPP further refines the risk assessments to ensure that the risk 

estimates are based on the best available information. 

12.0 Cumulative 

Unlike other pesticides for which EPA has followed 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 phosphide/phosphine has a common mechanism of toxicity with other 

substances. For information regarding EPA’s efforts to determine which chemicals have a 

common mechanism of toxicity and to evaluate the cumulative effects of such chemicals, see the 

policy statements released by EPA’s Office of Pesticide Programs concerning common 
Page 14 of 29

mechanism determinations and procedures for cumulating effects from substances found to have 

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

13.0 Endocrine Disruption 

As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potential adverse 

outcomes from exposure to chemicals. Collectively, these studies include acute, subchronic and 

chronic toxicity, including assessments of carcinogenicity, neurotoxicity, developmental, 

reproductive, and general or systemic toxicity. These studies include endpoints, which may be 

susceptible to endocrine influence, including effects on endocrine target organ histopathology, 

organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, reproductive loss, 

and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and 

chronic studies that assess growth, developmental and reproductive 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 subject to the endocrine screening part of the 

Endocrine Disruptor Screening Program (EDSP). 

EPA has developed the EDSP to determine whether 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 other such endocrine effects as the Administrator 

may designate.” The EDSP employs a two-tiered approach to making the 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 estrogen, androgen, or thyroid (E, A, or T) hormonal 

systems. Chemicals that go through Tier 1 screening and are found to have the potential to 

interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA 

will determine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2 

testing is designed to identify any adverse endocrine-related effects 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 pesticide active ingredients and 9 inert ingredients. A second list of 

chemicals identified for EDSP screening was published on June 14, 2013a

 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, please 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 occupational 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, therefore, not subject to the need for Human 

Studies Review Board (HSRB) evaluation. Furthermore, the chemical specific studies used to 

develop the previous occupational 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 generic 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 evidence that the conduct of any of them was 

either fundamentally unethical or significantly deficient relative 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 continued 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-generation reproduction study 

 special acute inhalation study 

Residue Chemistry: None 

Dietary Exposure: None 

Occupational/Residential 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 use 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 rates 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 endpoint/dose selection may be necessary. 

Residue Chemistry: None 

Dietary Exposure: 

 A new dietary exposure and risk assessment may be required during Registration 

Review to incorporate potential changes to the phosphine toxicological PODs. In 

addition, the assessment should include updated consumption information and 

utilize the newest version of DEEM-FCID 

Occupational/Residential 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 exposure data, Agency policies, or if the 

toxicological reevaluation 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 

Assessment 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 Emissions 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 Acute Toxicity Profile Table 

Attachment 3: Aluminum and Magnesium Phosphide/Phosphine Endpoint Selection Table 

Attachment 4: International Residue Limits Table 

Attachment 5: Justification for Studies for Phosphine 

 
Page 19 of 29

Attachment 1: Chemical Identity Table 

Aluminum 

Phosphide 

Magnesium 

Phosphide 

Phosphine 

Empirical formula AlP Mg3P2

PH3

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 Acute 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 LC50> = 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 Phosphide/Phosphine Endpoint Selection Table 

Dose and Endpoints for Risk Assessment- Phosphine 

All of the previous hazard and risk assessments 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. Therefore, the previous phosphine dietary exposure and risk 

assessment was also conducted for Al and Mg Phosphide 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 Phosphide 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 effects 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 level 

 
Page 21 of 29

Attachment 4: International Residue Limits Table 

Summary of US and International Tolerances 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 oranges 
Page 22 of 29

Summary of US and International Tolerances 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 Tolerances 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 finished 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 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 

MRLs With No US Equivalent 

Triticale 0.1 

 

Completed: : M. Negussie; 05/20/2013 

 
Page 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 assessment for Phosphine, the Agency will need to 

conduct an acute worker and an acute bystander assessment. Several other fumigants have a 

special acute inhalation study in rats which evaluates histopathology of the respiratory tract 

including incidence and severity at multiple tested concentrations, GSH measurements (i.e. nose), 

pharmacokinetics/tissue dosimetry including time course, 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 

LC50 values, and do not have additional respiratory 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 endpoint, which was obtained from a developmental 

toxicity study and used to evaluate acute worker 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 calculated using the monitoring data collected for 

almond/walnut fumigation workers exceed the 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 departure 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 uncertainty around the acute endpoint. These data will 

allow the Agency to fully characterize the effects that occur following acute exposure. In 

addition, more precise information will allow the Agency to refine its previous 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 fumigation of commodities, other 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 has the most accurate 

information possible to assess exposures for those involved in the fumigation process. In addition, 

these data will be used during registration review 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 Agency’s future decision-making? 

The inhalation exposure data will be used to determine the accuracy of the inhalation risks to 

occupational applicators during fumigation activities based on modern fumigation practices. If 

future risk assessments are performed without these data, the Agency will have to factor a 

significant degree of uncertainty into its regulatory decision-making process and that the current 

mitigation measures (i.e., personal protective equipment) 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 registrants with respect to the 

ability to evaluate risks associated with the modern use practices associated with phosphine. It 

will also allow the Agency to refine its previous risk assessment and could be used to defend 

challenges to the phosphine decision and to consider 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 and usage is limited to the directions found 

on pesticide labels and estimates of the amounts used to treat certain commodities or structures. 

The Agency, believes that the current understanding of the phosphine usage pattern is not 

sufficient to assess the full range of potential exposure 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 phosphine 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, maximum 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 exposures 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 consequence 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 commodity/material fumigation and/or structural 

fumigations. The existing data for exposure to phosphine are limited in terms of the variety of 

post-application activities and the potential exposures due to off-gassing from treated structural 

facilities and commodities. 

The original data requirements were not broad 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-application 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 inhalation exposure to phosphine for workers conducting a 

variety of post-application activities near fumigated 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 will 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. These 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 multiple fumigated structures and/or commodities 

during the season of use in high areas of use which can result in community based exposures 

from multiple sources. The existing data for ambient 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-application exposure for communities near commodity 

fumigation facilities and treated structures 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 evaluate: (1) post-application inhalation exposure to phosphine for 

communities near fumigated facilities/commodities, (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 will 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 concentrations, (2) determine post-application 

inhalation exposure to phosphine for communities 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 associated with commodity fumigation were not 

quantitatively assessed when these uses were established. The Agency did not have monitoring 

data to directly measure emissions of phosphine from fumigated commodities/materials. 

These data will ensure that the Agency has the most accurate information 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 level 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 characterize 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 the exposure models could be used to refine the 

previous risk assessment and to defend challenges to the phosphine decision.