BACKGROUND 

In a submission via Federal eRulemaking Portal dated August 24, 2009, Gowan Company 

submitted preliminary comments on several documents included in the June 2009 initial docket 

for the Registration Review of phosmet. This response is limited to comments on documents 

which are the purview of the Health Effects Division (HED). The specific comments for which 

HED is providing response were identified as comments 1.4, 1.5 and 2.1. 

RESPONSE TO COMMENTS 

Registrant Comment 1.4 

The FQPA safety factor of 10X was retained by the Agency for women of child-bearing age 

because of the lack of the gestational component of the comparative cholinesterase assay. 

Gowan points to the Agency’s previous conclusion that the guideline developmental toxicity 

study on phosmet did not identify any adverse fetal effect (2004 letter from EPA to Gowan 

Company), and that exposure to the fetus during gestation is less than to the dam. Gowan asserts 

that potential bioavailability of phosmet to the fetus following substantial maternal exposure is 

quite limited, and therefore, no additional FPQA safety factor for women of child-bearing age is 

warranted. 

Agency Response 

HED concurs that as stated in the referenced EPA letter, the developmental toxicity study did not 

identify any adverse fetal effects; however, HED notes that this study did not include an 

assessment of the endpoint of concern, cholinesterase inhibition, in either the dam or the fetus. 

Further, HED notes that the full context of the referenced 2004 EPA letter cited also includes 

EPA’s position that Gowan Company could defer initiation of the DNT until the Agency had 

completed an analysis of DNT studies conducted on other organophosphate chemicals. This 

deferral was additionally predicated on the submission of acute and repeat-dose relative 

sensitivity studies. 

Subsequent to the cited EPA letter, Gowan submitted acute (3/19/2007) and repeat-dose 

(3/6/2009) comparative cholinesterase assays on phosmet. Having reviewed the recently 

submitted acute and repeat-dose comparative cholinesterase sensitivity studies, the Agency 

concluded that the FQPA SF could be removed for infants and children since the new data 

adequately characterized the risk to that group. These data provided sufficient information to 

assure that selected endpoints are protective of adverse effects for these population subgroups. 

The Agency has reviewed epidemiological data from other organophosphates which indicates 

that the pregnant animal may be more sensitive than the non-pregnant animal. Therefore, the 

key issue which dictates retention of the FQPA SF for women of child bearing years is based on 

concern that the pregnant animal may be more sensitive to phosmet exposure. In the absence of 

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a DNT on phosmet which would have provided the gestational component needed to address the 

concern that pregnant animals and/or the fetus may be more sensitive, and in light of the 

information gleaned from the analysis of data on other organophosphates, the Agency maintains 

that there is not sufficient evidence to support removal of the FQPA safety factor for women of 

child bearing years at this time for phosmet. 

Registrant Comment 1.5

Gowan Company has cited an Agency comment that the results of recent epidemiology studies in 

mothers and children highlight the importance of considering gestational exposure, but notes that 

the Agency hasn’t provided rationale explaining why epidemiology studies with other 

compounds are relevant to phosmet, particularly to the assignment of phosmet-specific FQPA 

safety factor. 

Agency Response

The Agency considers the epidemiology studies on other organophosphate chemicals to be 

relevant to phosmet to the extent that they raise a potential concern that pregnant animals may be 

more sensitive to the adverse effects of organophosphates than non pregnant animals. Given the 

similar toxicity profile among the organophosphates this evidence suggests a concern. That 

concern must be addressed either through an uncertainty factor or with actual data since FQPA 

requires the Agency to retain the FQPA SF unless there is sufficient data to remove it. In light of 

the sensitivity seen in closely related compounds, and since the Agency is lacking data with a 

gestational component which would have come from a DNT, the Agency continues to maintain 

that an FQPA SF for females of child bearing years must be retained. 

Registrant Comment 2.1 

The registrant notes that additional information was requested in a meeting with HED and SRRD 

on August 3, 2009. Gowan requested these documents (see below) in order to prepare an 

adequate response to both the Human Health Assessment Scoping Document [EPA-HQ-OPP2009-0316-004] and to the Revision To the Occupational Postapplication Exposure and Risk 

Calculations for Phosmet [EPA-HQ-OPP-2009-0316-007]. 

Agency Response

The 2009 ToxSac meeting notes for phosmet were transmitted to Gowan on August 26, 2009. A 

formal and detailed response to the Gowan January 19, 2009 letter was completed on September 

1, 2009 (TXR No. 0055254) and transmitted to Gowan on September 18, 2009. The BMD 

analysis, which was part of the July 30 post-application risk assessment, was also transmitted to 

Gowan on September 18, 2009. 

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