[Federal Register Volume 69, Number 23 (Wednesday, February 4, 2004)]
[Notices]
[Pages 5340-5344]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 04-2157]


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ENVIRONMENTAL PROTECTION AGENCY

[OPP-2003-0360; FRL-7334-4]


Carbamate Cumulative Assessment Group; Availability

AGENCY: Environmental Protection Agency (EPA).

ACTION: Notice.

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SUMMARY: Section 408(b)(2)(D)(v) and (vi) of the Federal Food Drug and 
Cosmetic Act (FFDCA), as amended by Food Quality Protection Act of 1996 
(FQPA), specifies that when determining the safety of a pesticide 
chemical, EPA shall base its risk assessment on aggregate exposure and 
available information concerning the cumulative effects to human health 
that may result from exposure to pesticides and other substances that 
have a common mechanism of toxicity. EPA has determined that certain 
substances in the carbamate class of pesticides share a common 
mechanism of toxicity. This notice announces EPA's determination 
regarding the specific substances which will be included within this 
cumulative assessment group (CAG) for the N-methyl carbamate pesticide 
cumulative risk assessment.

DATES: EPA expects a preliminary cumulative assessment will be 
available for public comment by the Spring of 2005. EPA will announce 
its availability and request public comments in a future Federal 
Register Notice.

FOR FURTHER INFORMATION CONTACT: Technical issues: David Miller, Health 
Effects Division (7509C), Office of Pesticide Programs, Environmental 
Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460-
0001; telephone number: (703) 305-5352; e-mail address: 
<a href="/cdn-cgi/l/email-protection#b8d5d1d4d4ddca96dcd9ced1dcd2f8ddc8d996dfd7ce"><span class="__cf_email__" data-cfemail="89e4e0e5e5ecfba7ede8ffe0ede3c9ecf9e8a7eee6ff">[email protected]</span></a>.
    General issues: John Leahy, Special Review and Reregistration 
Division (7508C), Office of Pesticide Programs, Environmental 
Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460-
0001; telephone number: (703) 305-6703; e-mail address: 
<a href="/cdn-cgi/l/email-protection#0b676e6a637225616463654b6e7b6a256c647d"><span class="__cf_email__" data-cfemail="274b42464f5e094d484f496742574609404851">[email protected]</span></a>.

SUPPLEMENTARY INFORMATION:

I. General Information

A. Does this Action Apply to Me?

    This notice is directed to the public in general; however, persons 
may be interested who work in agricultural settings or persons who are 
concerned about implementation of the Federal Insecticide, Fungicide, 
and Rodenticide Act (FIFRA); the Federal Food, Drug, and Cosmetic Act 
(FFDCA); and the amendments to both of these major pesticide laws by 
the Food Quality Protection Act (FQPA) of 1996. Since other entities 
may also be interested, the Agency has not attempted to describe all 
the specific entities that may be affected by this action. If you have 
any questions regarding the applicability of this action to a 
particular entity, consult the person listed under FOR FURTHER 
INFORMATION CONTACT. Potentially affected entities may include but are 
not limited to: Agricultural workers and farmers; pesticide industry 
and trade associations; environmental, consumer and farmworker groups; 
pesticide users and growers; pest consultants; State, local and Tribal 
governments; academia; public health organizations; food processors; 
and the public.

B. How Can I Get Copies of this Document and Other Related Information?

    1. Docket. EPA has established an official public docket for this 
action under docket identification (ID) number OPP-2003-0360. The 
official public docket consists of the documents specifically 
referenced in this action, any public comments received, and other 
information related to this action. Although a part of the official 
docket, the public docket does not include Confidential Business 
Information (CBI)

[[Page 5341]]

or other information whose disclosure is restricted by statute. The 
official public docket is the collection of materials that is available 
for public viewing at the Public Information and Records Integrity 
Branch (PIRIB), Rm. 119, Crystal Mall <greek-i>2, 1921 Jefferson Davis 
Hwy., Arlington, VA. This docket facility is open from 8:30 a.m. to 4 
p.m., Monday through Friday, excluding legal holidays. The docket 
telephone number is (703) 305-5805.
    2. Electronic access. You may access this Federal Register document 
electronically through the EPA Internet under the ``Federal Register'' 
listings at http://www.epa.gov/fedrgstr/.
    An electronic version of the public docket is available through 
EPA's electronic public docket and comment system, EPA Dockets. You may 
use EPA Dockets at http://www.epa.gov/edocket/ to submit or view public 
comments, access the index listing of the contents of the official 
public docket, and to access those documents in the public docket that 
are available electronically. Once in the system, select search, then 
key in the appropriate docket ID number.
    Certain types of information will not be placed in the EPA Dockets. 
Information claimed as CBI and other information whose disclosure is 
restricted by statute, which is not included in the official public 
docket, will not be available for public viewing in EPA's electronic 
public docket. EPA's policy is that copyrighted material will not be 
placed in EPA's electronic public docket but will be available only in 
printed, paper form in the official public docket. To the extent 
feasible, publicly available docket materials will be made available in 
EPA's electronic public docket. When a document is selected from the 
index list in EPA Dockets, the system will identify whether the 
document is available for viewing in EPA's electronic public docket. 
Although not all docket materials may be available electronically, you 
may still access any of the publicly available docket materials through 
the docket facility identified in Unit I.B. EPA intends to work towards 
providing electronic access to all of the publicly available docket 
materials through EPA's electronic public docket.

II. Background

    The Food Quality Protection Act (FQPA) of 1996 amended the laws 
under which EPA evaluates the safety of pesticide residues in food. 
Section 408(b)(2)(D)(v) and (vi) of the Federal Food Drug and Cosmetic 
Act, as amended by FQPA, specifies that when determining the safety of 
a pesticide chemical, EPA shall base its risk assessment on aggregate 
exposure (i.e., total dietary including water, residential, and other 
non-occupational) and available information concerning the cumulative 
effects to human health that may result from dietary, residential, or 
other non-occupational exposure to pesticides and other substances that 
have a common mechanism of toxicity. Further, in carrying out the FQPA 
tolerance reassessment provisions, EPA is instructed to give priority 
to review of the tolerances or exemptions that appear to pose the 
greatest risk to public health. (Section 408(q)(2))
    Both the organophosphorus and carbamate classes of pesticides have 
been given high priority by the Office of Pesticide Programs for the 
reassessment of their tolerances and the completion of cumulative risk 
assessments in accordance with the mandates of FQPA. A revised 
cumulative risk assessment for the organophosphorus pesticides has been 
completed and is available on the EPA website at http://www.epa.gov/pesticides/cumulative/ (Ref. 7). The carbamate class of pesticides have 
been given the next highest priority by OPP for the reassessment of 
tolerances in accordance with the mandates of FQPA, and OPP expects a 
preliminary cumulative risk assessment for the relevant 
acetylcholinesterase-inhibiting members of this class to be available 
to the public by spring of 2005.

A. Determining the Common Mechanism Group

    In order to assess the carbamate class for cumulative toxic 
effects, the Agency needed to first identify as a Common Mechanism 
Group (CMG) those carbamate pesticides that cause a common toxic effect 
by a common mechanism. The purpose of this notice is to:
    1. Describe the approach, process, and reasoning used by the Agency 
in identifying, categorizing, and selecting the N-methyl carbamate 
pesticides which have been designated as a common mechanism group; and
    2. Identify the N-methyl carbamate pesticides which OPP expects to 
be assessed and evaluated in the N-methyl carbamate cumulative risk 
assessment document.
As the cumulative assessment proceeds, the public and other interested 
parties will be provided the opportunity to comment and provide input 
concerning all aspects of the assessment.
    As had been done for the organophosphorus pesticides, OPP began its 
review of the carbamates by commissioning a report by the Risk Sciences 
Institute (RSI), part of the International Life Sciences Institute 
(ILSI), which considered whether the carbamate pesticides shared a 
common mechanism of toxicity. The RSI panel evaluated the potential for 
two or more carbamate pesticides to act by the same mechanism by 
applying three principles. The principles were:
    <bullet<ls-thn-eq> They cause the same critical effect(s)
    <bullet<ls-thn-eq> They act on the same molecular target at the 
same target tissue
    <bullet<ls-thn-eq> They act by the same biochemical mechanism of 
action perhaps because they share a common toxic intermediate (Ref. 2)
The RSI panel focused on cholinesterase (ChE) inhibition as a 
scientifically accepted mechanism of action for the carbamates and 
found that the three principles were met for the ChE-inhibiting 
carbamates. The panel issued its report, ``Common Mechanism of 
Toxicity: Evaluation of Carbamate Pesticides,'' to OPP in March 1999 
and concluded that the ChE-inhibiting carbamates should be considered 
to act by a common mechanism of toxicity. RSI also pointed out that 
some carbamates also produce effects that may not be related to ChE 
inhibition (Ref. 1).
    Subsequent to this ILSI report, OPP prepared its own report on this 
grouping and presented its analysis in a draft document entitled ``A 
Science Policy on a Common Mechanism of Toxicity: The Carbamate 
Pesticides And the Grouping of Carbamate with the Organophosphorus 
Pesticides'' to the FIFRA Scientific Advisory Panel (SAP) for review in 
September 1999 (Ref. 3). This draft document generally concluded that 
while all of the carbamate pesticides appeared to share a similar 
chemical structure, they differed in the types of toxic effects they 
caused and therefore it was appropriate to divide the group into three 
distinct subgroups: Carbamates, thiocarbamates, and dithiocarbamates. 
Subcategories of carbamates based on structural characteristics of the 
carbamate moiety and ChE inhibiting potential are described in this 
draft document. The report resulting from this September 22, 1999 SAP 
meeting endorsed OPP's position in that ``the Panel agreed unanimously 
with the Agency's conclusion that acetylcholinesterase provides a 
sufficient basis for determining a common mechanism of toxicity for 
grouping carbamate pesticides'' (Ref. 4). The SAP, however, also 
pointed out that other toxic effects (e.g., developmental, thyroid, 
neurotoxic) should be evaluated as endpoints for grouping the 
thiocarbamates and dithiocarbamates.

[[Page 5342]]

    Upon consideration of the ILSI report, the SAP comments, and 
reviews by OPP, it has been concluded by OPP that the pesticides that 
comprise the subgroup of N-methyl carbamates, based on their structural 
characteristics and similarity and their shared ability to inhibit 
acetylcholinesterase by carbamylation of the serine hydroxyl group 
located in the active site of the enzyme, should be designated as a 
Common Mechanism Group. (Ref. 5).
    The thiocarbamates and dithiocarbamates are not included in the CMG 
for cholinesterase-inhibiting carbamates. The thio- and dithio- 
carbamate subgroups were the subject of a separate FIFRA SAP meeting, 
September 7, 2001 - Common Mechanism of Action of Thiocarbamates and 
Dithiocarbamates, in which it was determined that acetylcholinesterase 
inhibition was not their principal mechanism of toxicity\1\ (Ref. 6). 
As pointed out in the Cumulative Guidance, ``refined quantitative 
estimates should generally focus on common effects that represent the 
principal toxicities for the CMG'' ...so that cumulative risk 
assessments are efficient and protect public health (Ref. 8). Thus, 
neither the thiocarbamates nor the dithiocarbamates are included in the 
cumulative assessment of N-methyl carbamates since they do not share 
ChE inhibition as a common principal mechanism of toxicity.
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    \1\For example, the thiocarbamates and dithiocarbamate 
pesticides are the sulfur analogs of carbamates, and are not used as 
insecticides but rather as herbicides or fungicides because these 
carbamates generally do not appear to be effective cholinesterase 
inhibitors. Neuropathology is the primary effect of concern for 
these chemicals.
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B. Determining the Cumulative Assessment Group

    Once the constituents of a CMG are identified, a necessary follow-
on step in assessing the cumulative risk of a common mechanism group 
(here, the N-methyl carbamates) involves selecting a subset of these 
CMG chemicals as a Cumulative Assessment Group (CAG) (see Ref. 8). As 
described in the Cumulative Guidance (Ref. 8), this subset of CMG 
chemicals is selected because not all chemicals grouped by common 
mechanism of toxicity should necessarily be included in a quantitative 
cumulative risk assessment. For example, initial cumulative assessments 
should not attempt to quantify risk resulting from chemicals with low 
hazard potential or from minor exposure scenarios, but should instead 
focus on those chemicals that are likely to be risk contributors. 
Specifically (and again as detailed in the cumulative guidance 
document), the CAG--and consequently the cumulative risk assessment--
should exclude those chemicals, those chemical uses, and those exposure 
scenarios/routes/pathways for which risk and exposure does not 
contribute in any meaningful or substantive ways to the total 
cumulative risk picture\2\.
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    \2\As stated in the Cumulative Guidance (USEPA 2002), ``This 
focus on likely risk contributors is important ... since a large 
number of chemicals may increase the complexity and uncertainty with 
no substantial change in total exposure. Additionally, including a 
large number of chemicals in the refined quantitation of risk also 
may confound the interpretation and utility of the assessment 
results for risk management decisions'' (Ref. 8).
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    OPP began the process of determining the members of the CAG by 
identifying those carbamates which contained the N-methyl structural 
moiety. These are listed in the upper rows of Table 1 and identified as 
such by an X in the second column. Next, OPP further narrowed the list 
of the potential CAG-candidates by reviewing OPP databases to determine 
those CMG members that have active food or residential registrations. 
This information is summarized in columns 3 and 4 of Table 1 which 
lists those carbamates which have one or more active food/feed or 
residential registrations, respectively. Those carbamates which have 
neither food nor residential (non-food) current registrations were 
eliminated from further consideration for inclusion in the CAG.
    Next, OPP investigated the presence, pattern, and magnitudes of 
residues in the USDA's Pesticide Data Program (PDP) database through 
2002. Those carbamates for which PDP has collected data and those for 
which detectable residues were found in the PDP database through 2002 
are listed via an X in the 5\th\ and 6\th\ columns of Table 1. Those 
chemicals for which PDP did collect residue data but did not detect any 
residues were eliminated from consideration from the CAG if there were 
no residential uses. Thus, those chemicals without residential 
registrations were eliminated for further consideration if an X is 
present in Column 5 and absent from Column 6. No chemicals were 
excluded from the CAG as a result of this analysis.
    Finally, the 7\th\ column of Table 1 lists those that are currently 
undergoing phase-out or cancellation. As was done with the OP 
assessment, chemicals currently undergoing phase-out or cancellation 
are not included in the CAG since exposures are expected to be zero at 
some point in the near future.
    Based on the above information, N-methyl carbamates which OPP 
expects to include in the cumulative risk assessment for the carbamate 
pesticides is as follows: Aldicarb, aldoxycarb, carbaryl, carbofuran, 
formetanate HCl, methiocarb, methomyl, oxamyl, pirimicarb, propoxur, 
and thiodicarb.
    These carbamates all display ChE-inhibiting activity, have current 
active registrations, and are expected to contribute to the carbamate 
cumulative risk assessment through quantitatively meaningful exposure 
scenarios.

                                           Table 1.--Summary of Selection Criteria for Carbamate CAG Grouping
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                                                                   Registration                              PDP Data
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                                                                             Non-Food Use
                                                           Food Use          Registration        Any PDP Data                            Phase Out or
                                      N-methyl?        Registration\a\?   (e.g., Residential      Available?       Any PDP Detects?      Cancellation?
                                                                                Uses)?
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Aldicarb                         X                   X                                        X                   X
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Aldoxycarb                       X                   X                                        X                   X
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Carbaryl                         X                   X                    X                   X                   X
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Carbofuran                       X                   X                                        X                   X
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[[Page 5343]]

 
Formetanate HCl                  X                   X                                        X                   X
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Methiocarb                       X                                        X                   X                   X
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Methomyl                         X                   X                                        X                   X
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Oxamyl                           X                   X                                        X                   X
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Pirimicarb                       X                   X                                        X                   X
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Propoxur                         X                   X                    X                   X
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Thiodicarb\d\                    X                   X                                        X                   X
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Aminocarb (Matacil)              X                                                                                                    X
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Bendiocarb                       X                                                            X                                       X
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Bufencarb (bux)                  X                                                                                                    X
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Carbosulfan                      X                                                                                                    X
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Cloethocarb (Lance)              X                                                                                                    X
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Dimetilan (Elecron, Famid)       X                                                                                                    X
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Ethiofencarb                     X                                                            X                                       X
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Isolan (Primin)                  X                                                                                                    X
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Isoprocarb (Etrofolan, MIPC)     X                                                                                                    X
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Mexacarbate (Zectran)            X                                                                                                    X
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Promecarb (Carbamult)            X                                                                                                    X
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Trimethacarb (Broot, Landrin)    X                                                                                                    X
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Asulam                                               X
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Barban                                                                                        X                                       X
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Chlorpropham                                         X                                        X                   X
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Desmidapham                                          X                                        X                   X
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2-EEEBC\b\                                                                                                                            X
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Fenoxycarb (torus)                                   X
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IPBC\c\                                                                   X
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Karbutilate                                          X
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Phenmediphan                                         X                                        X                   X
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Propamocarb                                          X
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Propham                                                                                                                               X
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Thiophanate (methyl)                                 X                    X
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Butylate                                             X                                        X
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Cycloate                                                                                      X
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EPTC                                                                                          X
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[[Page 5344]]

 
Molinate                                                                                      X                                       X
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Pebulate                                                                                      X
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Vernolate                                                                                     X
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Diallate                                                                                                                              X
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Triallate                                            X                                        X
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Thiobencarb                                          X                                        X
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Mancozeb                                             X                    X
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Maneb                                                X                    X
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Metiram                                              X                    X
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Zineb                                                                                                                                 X
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Metam Na, K                                          X                    X
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Thiram                                               X                    X
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Ferbam                                               X                    X
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Ziram                                                X                    X
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 \a\ This includes Food Handling Establishment use for carbaryl and propoxur
\b\ 2-2(ethoxyethoxy)ethyl 2-bensimidazole carbamate
\c\ 3-iodo-2-propynyl butlcarbamate (aka Trotsan polyphase)
\d\Thiodicarb is a dimer of methomyl and is analyzed as methomyl by the PDP program
Note: The following carbamate pesticides were excluded from the above table since they are not N-methyl carbamates, they do not possess current U.S.
  registrations for food or non-food uses, there exist no detections in the USDA PDP program, and there is no indication that these have been actively
  phased out or cancelled: Alanycarb, allyxycarb, benfuracarb, butacarb, butocarboxim, butoxycarboxim, carbanolate, carboxazole, chlorprocarb,
  decarbofuran, dichlormate, dicresyl, dimetan, dioxacarb, EMPC, fenasulam, fenethacarb fenobucarb furathiocarb, hyquincarb, nitrilacarb, promacyl
  tazimcarb, terbucarb thiocarboxime, thiofanox, XMC, xylycarb, and NaDMDTC.

D. References

    1. International Life Sciences Institute (ILSI). 1999 Common 
Mechanism of Toxicity: Evaluation of Carbamate Pesticides, 
International Life Science Institute Report, Washington DC.
    2. Mileson, B., JE Chambers, WL Chen, W Dettbarn, M Ehrich, AT 
Eldefrawi, DW Gaylor, K Hammernik, E Hodgson, AG Karczmar, S Padilla, 
CN Pope, RJ Richardson, DR Saunders, LP Sheets, LG Sultatos and KB 
Wallace. Common Mechanism of Toxicity: a case study of organophosphorus 
pesticides. Toxicological Sciences 41, pp.8-20.
    3. USEPA, 1999a. A Science Policy on a Common Mechanism of 
Toxicity: The Carbamate Pesticides And the Grouping of Carbamate with 
the Organophosphorus Pesticides; draft document. August 30, 1999. 
http://www.epa.gov/scipoly/sap/1999/september/carbam.pdf.
    4. USEPA, 1999b. SAP Report No. 99-05. November 18, 1999.http://www.epa.gov/scipoly/sap/1999/september/finalrpt.pdf.
    5. USEPA, 2001a. Memorandum from Marcia Mulkey to Lois Rossi. 
Implementation of the Determinations of a Common Mechanism of Toxicity 
for N-Methyl Carbamate Pesticides and for Certain Chloroacetanilide 
Pesticides. July 12, 2001.http://www.epa.gov/oppfead1/cb/csb_page/updates/carbamate.pdf.
    6. USEPA, 2001b. Memorandum from Paul Lewis to Marcia Mulkey. SAP 
Report 2001-11. November 1, 2001.http://www.epa.gov/scipoly/sap/2001/september7/september2001finalsapreport.pdf.
    7. USEPA, 2002a. Organophosphate Pesticides; Availability of the 
Revised Organophosphate Cumulative Risk Assessment. (67 FR 41993; June 
20, 2002)
    8. USEPA, 2002b. Guidance on Cumulative Risk Assessment of 
Pesticide Chemicals That Have a Common Mechanism of Toxicity. January 
14, 2002. (67 FR 2210; January 16, 2002)http://www.epa.gov/pesticides/trac/science/cumulative_guidance.pdf.

List of Subjects

    Environmental protection.


    Dated: January 20, 2004.
James Jones,
Director, Office of Pesticides Program.
[FR Doc. 04-2157 Filed 2-3-04; 8:45 am]
BILLING CODE 6560-50-S


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