[Federal Register Volume 65, Number 183 (Wednesday, September 20, 2000)]
[Notices]
[Pages 56895-56901]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 00-24210]


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ENVIRONMENTAL PROTECTION AGENCY

[PF-946; FRL-6588-8]


Notice of Filing a Pesticide Petition to Establish an Exemption 
from The Requirement of a Tolerance for a Certain Pesticide Chemical in 
or on Food

AGENCY: Environmental Protection Agency (EPA).

ACTION: Notice.

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SUMMARY: This notice announces the initial filing of a pesticide 
petition proposing the establishment of regulations to provide an 
exemption from the requirement of a tolerance for residues of a certain 
pesticide chemical in or on various food commodities.

DATES: Comments, identified by docket control number PF-946, must be 
received on or before October 20, 2000.

[[Page 56896]]


ADDRESSES: Comments may be submitted by mail, electronically, or in 
person. Please follow the detailed instructions for each method as 
provided in Unit I.C. of the ``SUPPLEMENTARY INFORMATION.'' To ensure 
proper receipt by EPA, it is imperative that you identify docket 
control number PF-946 in the subject line on the first page of your 
response.

FOR FURTHER INFORMATION CONTACT:  By mail: Marshall Swindell, 
Antimicrobial Division (7510C), Office of Pesticide Programs, 
Environmental Protection Agency, 1200 Pennsylvania Ave., NW., 
Washington, DC 20460; telephone number: (703) 308-6341; e-mail address: 
[email protected].

SUPPLEMENTARY INFORMATION:

I. General Information

A. Does this Action Apply to Me?

    You may be affected by this action if you are an agricultural 
producer, food manufacturer or pesticide manufacturer. Potentially 
affected categories and entities may include, but are not limited to:

 
------------------------------------------------------------------------
                                                          Examples of
           Categories                    NAICS            potentially
                                                       affected entities
------------------------------------------------------------------------
Industry                          111                 Crop production
                                  112                 Animal production
                                  311                 Food manufacturing
                                  32532               Pesticide
                                                       manufacturing
------------------------------------------------------------------------

    This listing is not intended to be exhaustive, but rather provides 
a guide for readers regarding entities likely to be affected by this 
action. Other types of entities not listed in the table could also be 
affected. The North American Industrial Classification System (NAICS) 
codes have been provided to assist you and others in determining 
whether or not this action might apply to certain entities. If you have 
questions regarding the applicability of this action to a particular 
entity, consult the person listed under ``FOR FURTHER INFORMATION 
CONTACT.''

B. How Can I Get Additional Information, Including Copies of this 
Document and Other Related Documents?

    1. Electronically. You may obtain electronic copies of this 
document, and certain other related documents that might be available 
electronically, from the EPA Internet Home Page at http://www.epa.gov/. 
To access this document, on the Home Page select ``Laws and 
Regulations'' and then look up the entry for this document under the 
``Federal Register--Environmental Documents.'' You can also go directly 
to the Federal Register listings at http://www.epa.gov/fedrgstr/.
    2. In person. The Agency has established an official record for 
this action under docket control number PF-946. The official record 
consists of the documents specifically referenced in this action, any 
public comments received during an applicable comment period, and other 
information related to this action, including any information claimed 
as confidential business information (CBI). This official record 
includes the documents that are physically located in the docket, as 
well as the documents that are referenced in those documents. The 
public version of the official record does not include any information 
claimed as CBI. The public version of the official record, which 
includes printed, paper versions of any electronic comments submitted 
during an applicable comment period, is available for inspection in the 
Public Information and Records Integrity Branch (PIRIB), Rm. 119, 
Crystal Mall #2, 1921 Jefferson Davis Highway, Arlington, VA, from 8:30 
a.m. to 4 p.m., Monday through Friday, excluding legal holidays. The 
PIRIB telephone number is (703) 305-5805.

C. How and to Whom Do I Submit Comments?

    You may submit comments through the mail, in person, or 
electronically. To ensure proper receipt by EPA, it is imperative that 
you identify docket control number PF-946 in the subject line on the 
first page of your response.
    1. By mail. Submit your comments to: Public Information and Records 
Integrity Branch (PIRIB), Information Resources and Services Division 
(7502C), Office of Pesticide Programs (OPP), Environmental Protection 
Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460.
    2. In person or by courier. Deliver your comments to: Public 
Information and Records Integrity Branch (PIRIB), Information Resources 
and Services Division (7502C), Office of Pesticide Programs (OPP), 
Environmental Protection Agency, Rm. 119, Crystal Mall #2, 1921 
Jefferson Davis Highway, Arlington, VA. The PIRIB is open from 8:30 
a.m. to 4 p.m., Monday through Friday, excluding legal holidays. The 
PIRIB telephone number is (703) 305-5805.
    3. Electronically. You may submit your comments electronically by 
e-mail to: ``[email protected],'' or you can submit a computer disk as 
described above. Do not submit any information electronically that you 
consider to be CBI. Avoid the use of special characters and any form of 
encryption. Electronic submissions will be accepted in Wordperfect 6.1/
8.0 or ASCII file format. All comments in electronic form must be 
identified by docket control number PF-946. Electronic comments may 
also be filed online at many Federal Depository Libraries.

D. How Should I Handle CBI That I Want to Submit to the Agency?

    Do not submit any information electronically that you consider to 
be CBI. You may claim information that you submit to EPA in response to 
this document as CBI by marking any part or all of that information as 
CBI. Information so marked will not be disclosed except in accordance 
with procedures set forth in 40 CFR part 2. In addition to one complete 
version of the comment that includes any information claimed as CBI, a 
copy of the comment that does not contain the information claimed as 
CBI must be submitted for inclusion in the public version of the 
official record. Information not marked confidential will be included 
in the public version of the official record without prior notice. If 
you have any questions about CBI or the procedures for claiming CBI, 
please consult the person identified under FOR FURTHER INFORMATION 
CONTACT.

E. What Should I Consider as I Prepare My Comments for EPA?

    You may find the following suggestions helpful for preparing your 
comments:
    1. Explain your views as clearly as possible.
    2. Describe any assumptions that you used.
    3. Provide copies of any technical information and/or data you used 
that support your views.
    4. If you estimate potential burden or costs, explain how you 
arrived at the estimate that you provide.
    5. Provide specific examples to illustrate your concerns.
    6. Make sure to submit your comments by the deadline in this 
notice.
    7. To ensure proper receipt by EPA, be sure to identify the docket 
control number assigned to this action in the subject line on the first 
page of your response. You may also provide the name, date, and Federal 
Register citation.

II. What Action is the Agency Taking?

    EPA has received a pesticide petition as follows proposing the 
establishment and/or amendment of regulations to

[[Page 56897]]

provide an exemption from the requirement of a tolerance for residues 
of a certain pesticide chemical in or on various food commodities under 
section 408 of the Federal Food, Drug, and Comestic Act (FFDCA), 21 
U.S.C. 346a. EPA has determined that this petition contains data or 
information regarding the elements set forth in section 408(d)(2); 
however, EPA has not fully evaluated the sufficiency of the submitted 
data at this time or whether the data support granting of the petition. 
Additional data may be needed before EPA rules on the petition.

List of Subjects

    Environmental protection, Agricultural commodities, Feed additives, 
Food additives, Pesticides and pests, Reporting and recordkeeping 
requirements.

    Dated: September 5, 2000.
Frank Sanders,
Director, Antimicrobial Division, Office of Pesticide Programs.

Summary of Petition

    The petitioner summary of the pesticide petition is printed below 
as required by section 408(d)(3) of the FFDCA. The summary of the 
petition was prepared by the petitioner and represents the view of the 
petitioners. EPA is publishing the petition summary verbatim without 
editing it in any way. The petition summary announces the availability 
of a description of the analytical methods available to EPA for the 
detection and measurement of the pesticide chemical residues or an 
explanation of why no such method is needed.

3M

0F6124

    EPA has received a pesticide petition (0F6124) from 3M, St. Paul, 
MN 55144-1000, proposing, pursuant to section 408(d) of the Federal 
Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a(d), to amend 40 
CFR part 180 to establish an exemption from the requirement of a 
tolerance in raw agricultural commodities and food for residues of zinc 
2-pyridinethiol-oxide, used as a preservative in sponges (zinc-chitosan 
modified cellulose sponges). EPA has determined that the petition 
contains data or information regarding the elements set forth in 
section 408(d)(2) of the FFDCA. EPA has completed a preliminary 
evaluation of the aggregate exposure and risk in reviewing an 
assessment provided by 3M. EPA's findings have been made part of this 
notice, with attribution. However, EPA has not completed its evaluation 
of the sufficiency of the submitted data at this time or whether the 
data support granting of the petition. Additional data may be needed 
before EPA rules on the petition.

A. Residue Chemistry

    1. Sample extract preparation. The amount of zinc pyrithione that 
can be extracted from a 3M sponge in typical use was determined as a 
preliminary step in estimating exposure and risk. The mean level of 
zinc pyrithione bound into the 3M sponge is 0.35% on a dry weight 
basis. New sponges measuring 114 x 71 x 20 millimeters (mm) were 
removed from their packages and rinsed a total of 10 times by 
completely saturating the sponges under running 43  deg.C tap water 
with hand wringing between saturations. Samples were then filled with 
tap water one final time and passed through a zero clearance wringer 
with rubber rolls having a Shore gage A hardness of 20-25. These 
preconditioning rinses were carried out to insure removal of softening 
agents from the sponge manufacturing process and to bring all samples 
to an equal final moisture content.
    Each preconditioned sponge was placed in a separate pint size 
ziplock polyethylene plastic bag. Fifty milliliters (mL) of extraction 
solution were added and the bag sealed. Extraction solutions were 
deionized water and dilute solutions of dishwashing detergent. Three 
sponges were tested for each set of extraction conditions. Each bag was 
thoroughly agitated by repeated hand squeezing to insure uniform 
distribution of the extraction liquid throughout the sponge sample. For 
elevated temperatures, samples were then placed in an agitated 
temperature controlled water bath for an extraction period of 10 
minutes. Room temperature samples were placed on the lab bench in a 
horizontal position for 10 minutes.
    Following the 10 minute extraction period, the extraction liquid 
was recovered by hand squeezing liquid from the sponge back into its 
sample bag. The recovered liquid was then transferred into a clean 125 
mL high density polyethylene sample bottle with screw top lids. The 
bottle was sealed until the sample was analyzed.
    2. Analysis of extracts. Extract samples were analyzed for zinc ion 
using a Thermo Jarrell Ash model 61 E inductively coupled plasma (ICP) 
atomic emission spectrometer.
    Each extract sample was transferred to a beaker and weighed to the 
nearest milligram (mg). The beaker was then placed on a hot plate and 
carefully evaporated to dryness. Then 2-3 mL of concentrated sulfuric 
acid was added to the beaker to digest any organic material in the 
sample. Concentrated nitric acid was added dropwise to oxidize any 
resulting charred organic matter. The acid solution was carefully 
transferred to a 50 mL volumetric flask and the beaker washed several 
times with deionized water which was added to the flask. The solution 
was diluted to the mark with deionized water and analyzed directly for 
zinc ion. Fresh zinc standards were prepared in the same acid matrix as 
the samples.
    Although the analysis measures only zinc ion, it is assumed that 
the full zinc pyrithione moiety is removed from the sponge by the 
extraction solution. The zinc ion forms a coordination complex with the 
cellulose, as shown above, thereby binding the pyrithione anion into 
the cellulose structure. Loss of a zinc cation (2+) is, therefore, 
necessarily accompanied by loss of two pyrithione anions (1-).
    3. Magnitude of residues. The mean level of zinc pyrithione found 
using deionized water at 65  deg.C was 9.4 parts per million (ppm). In 
dish detergent solutions at the same temperature, mean levels were 12.4 
ppm (0.1% detergent) and 26.8 ppm (1% detergent). For comparison 
purposes, certain samples were put through the sample preparation and 
extraction process three times. The amount of zinc pyrithione recovered 
was comparable in all three cycles. For ``worst case'' risk assessment 
purposes, the upper bound (95% probability) of highest mean value found 
for detergent extract solutions at 65  deg.C is used, i.e., 
30 parts per million (ppm). This extract solution contains 
1% by weight dish detergent. A level of 0.1% or less is normally used 
for dishwashing.
    The solubility of zinc pyrithione in water is known to increase 
with increasing detergent concentration. It has a very low solubility 
in pure water (15 to 20 ppm) but its solubility increases by complex 
formation with organic amines to near 300 ppm in very concentrated 
detergent such as shampoo base.

B. Toxicological Profile

    In January 1996, EPA published its Reregistration Eligibility 
Decision (RED) for Sodium Omadine in which no observed adverse effect 
levels (NOAELs) and a reference dose (RfD) are formally selected. 
Sodium and zinc pyrithione have very similar toxicology profiles. The 
pyrithione anion is the biologically active moiety in either active 
ingredient. The pertinent toxicology endpoints are described below for 
zinc pyrithione

[[Page 56898]]

when studies on this test material are available. Otherwise endpoints 
were used from studies where sodium pyrithione was the test material. 
EPA, in its risk assessment for the 3M product, calculated RfD, given 
below, by applying various safety factors to the NOAELs.
    1. Acute toxicity. Acute oral LD50 (rat) = 269 
milligrams/kilograms (mg/kg) (male/female) for sodium pyrithione and 
630 mg/kg (males) and 460 mg/kg (females) for zinc pyrithione. Acute 
dermal LD50 (rabbit) > 2,000 mg/kg for both sodium and zinc 
pyrithione. Acute inhalation LD50 (rat) = 0.61 milligram/
liter (mg/L) (4-hour) for sodium pyrithione and > 0.61 mg/L for zinc 
pyrithione. Sodium pyrithione is a mild irritant to skin and eyes, and 
it is not a sensitizer. Zinc pyrithione is corrosive to skin and eyes, 
and it is not a sensitizer.
    2. Genotoxicty. In vitro and in vivo tests indicate that sodium and 
zinc pyrithione are not genotoxic.
    3. Reproductive and developmental toxicity. Technical grade zinc 
pyrithione active ingredient was administered by gavage at doses of 0, 
7.5 and 15 mg/kg to Charles River albino rats. Maternal body weight 
gain depression was observed. A lowest observed adverse effect level 
(LOAEL) of 7.5 mg/kg was found. There was an increased incidence of 
skeletal abnormalities at the maternally toxic high dose level (15 mg/
kg). In a separate study using sodium pyrithione, NOAEL = 5 mg/kg/day.
    In a study using 30 pregnant Sprague-Dawley rats per group, zinc 
pyrithione was administered by oral gavage on days 6-15 of gestation at 
0, 0.75, 3, and 15 mg/kg/day. One dam died on gestation day 16. 
Developmental toxicity was observed as an increase in postimplantation 
loss at mid and high dose levels. The high dose group was significantly 
different than controls (p  0.01). An increase in early 
resorptions (3.6%/dam) was observed with whole litter resorption 
occurring in 3 high dose dams. In the 15 mg/kg/day group, the number of 
live fetuses per litter was significantly reduced (p  0.05), 
mean fetal weights were reduced (16%), and gravid uterine weights were 
reduced (16%; p  0.01) when compared to controls.
    A significant number of fetuses were found to have external, 
visceral, or skeletal malformations at the 15 mg/kg/day group: digit 
anomalies at p  0.05; dilated renal pelvis at p  
0.05; and a verbal/rib anomaly at p  0.01. Dose-related 
fused ribs were observed at 3.0 and 15 mg/kg/day levels. The maternal 
toxicity NOAEL for the study was 0.75 mg/kg/day, based on excessive 
salivation during the dosing period, and the developmental toxicity 
NOAEL was 0.75 mg/kg/day based on increased incidences of fused ribs.
    Another study used 20 white New Zealand rabbits per groups and oral 
gavage doses of 0, 0.5, 1.5, and 3.0 mg/kg/day of zinc pyrithione on 
gestation days 6-18. A significant decrease in body weight (p 
 0.01) was observed for mid and high-dose groups, but the 
absolute body weight changes were small. Five high-dose does and one 
mid-dose doe had total resorption. One high-dose doe aborted on day 27. 
No statistically significant differences were observed in anomalies for 
treated groups compared to controls. The maternal/developmental NOAEL 
was 0.5 mg/kg/day.
    Based upon the above studies, EPA considers zinc pyrithione to be a 
frank developmental toxicant.
    4. Subchronic toxicity. Technical grade zinc pyrithione was 
administered in the diet to 20 male and 20 female Charles River CD 
albino rats per dose group at 5, 25 and 125 ppm for up to 93 days. No 
mortality occurred at 5 or 25 ppm; significant mortality at 125 ppm (39 
out of 40). Slight growth rate depression was observed in the 25 ppm 
group. No significant treatment-related biochemical or 
histopathological finding were made at 5 or 25 ppm. NOAEL = 25 ppm 
( 2.5 mg/kg/day).
    Six Rhesus monkeys per dose group were administered a 1% suspension 
in gum tragacanth by gavage at does of 0.5, 2.0 and 8.0 mg/kg for 90 
days. All animals appeared normal. Emesis was observed on days 1 and 2 
in intermediate and high dose groups and not again throughout the 
study. No treatment-related gross or microscopic pathology was 
observed. There was a statistically significant decrease in the weights 
of uteri in high dose females.
    Clinical signs, including hind limb weakness, motor incoordination 
and spinal kyphosus with muscle atrophy, were observed at the high dose 
in a neurotoxicity study in Charles River CD rats where zinc pyrithione 
was administered at 0 and 250 ppm for 9 or 14 days, followed by a 14- 
to 28-day recovery period. Clinical signs did not persist during the 
recovery period. Histopathology revealed dense granular axoplasmic 
deposits in the axons of sural and intramuscular lumbrical nerves. 
Normal muscle morphology was observed in the acutely affected rats. In 
a separate study using sodium pyrithione as a test material, 
neurotoxicity end points were as follows: lowest observed adverse 
effect level (LOAEL) = 2.0 mg/kg/day; NOAEL = 0.5 mg/kg/day.
    Male and female Crl:CD(SD)BR rats were treated with zinc pyrithione 
using occluded dermal doses at 0, 20, 100, and, 1,000 mg/kg/day for 6 
hours/day for 5/days/week for 13 weeks. Females in the high dose group 
exhibited decreased food consumption (91.6% of control), decreased body 
weight gain (48.9% of control), and decreased food efficiency (53.8% of 
control) for the period of treatment. The systemic NOAEL in females was 
100 mg/kg/day and in males 1,000 mg/kg/day.
    Groups of 15 male and 15 female Sprague-Dawley rats were tested in 
whole-body inhalation exposure chambers to zinc pyrithione aerosols at 
0.005, 0.0025, or 0.01 mg/L/for 6 hours/day, 5 days/week for 13 weeks. 
One animal of each sex died at the 0.0025 mg/L/day level. Three males 
and four females died at the 0.01 mg/L/day exposure level. Decreased 
body weights, food consumption and food efficiency were observed at the 
highest dose. Significantly increased lung weights were noted at the 
mid and high dose. Mild inflammation of the interstitial tissue of the 
lung and medial hypertrophy of pulmonary arteries was found at the high 
dose. The systemic NOAEL was 0.005 mg/L/day.
    5. Chronic toxicity. Zinc pyrithione was administered in the diet 
at doses of 0, 2, 5, 10, 25, and 50 ppm to groups of 10 male and 10 
female albino rats for 2 years. There were no adverse effects on 
survival of the males. Decreased survival of the females in the 25 and 
50 ppm dose groups and accelerated growth rate in females in lower dose 
groups were observed. Males in the 50 ppm group also were observed to 
have accelerated growth. No treatment-related biochemical or 
histopathological effects were noted. NOAEL = 10 ppm, or 0.5 mg/kg/day.
    For sodium pyrithione, EPA has established in the RED a RfD of 
0.005 mg/kg/day based upon a chronic rat study NOAEL of 0.5 mg/kg/day 
and an uncertainty factor of 100.
    6. Animal metabolism. Three older animal metabolism studies are 
available for zinc pyrithione. In two studies radio labeled material is 
administered by intravenous injection and in one study oral dosing is 
used. In an intravenous study in Yorkshire pigs, \14\C-labeled sodium 
and zinc pyrithione are compared. For both compounds, urine appears to 
be the major route of excretion for the administered radio label. 
Significantly less radio label was recovered in the urine for the zinc 
salt than the sodium salt, as expected because the zinc salt has a very 
low

[[Page 56899]]

solubility in water. Presumably insoluble salt in the blood was 
captured and eliminated through the bile duct into the feces. In a 
study in which \14\C-zinc pyrithione or \65\Zn-zinc pyrithione were 
administered intravenously to rabbits, the animals were sacrificed at 6 
hours after dosing and levels of radio label determined in urine, 
tissue and blood. The \14\C-labeled pyrithione was substantially 
excreted (75%) in the urine, but the \65\Zn remained relatively 
constant in the blood and tissue. The retention of zinc is expected 
because it readily forms coordination complexes with biochemical 
molecules and it is also an essential trace element in the diet, being 
present naturally in significant amounts in food, tissue and blood.
    When \14\C-labeled zinc pyrithione was administered by the oral 
route to Sprague-Dawley rats, most of the radio labeled material (up to 
84%) was excreted through the urine and the feces (up to 21%). Male 
rats appeared to metabolize and excrete zinc pyrithione more rapidly 
than female rats.
    7. Endocrine disruption. There is no evidence to suggest that the 
active ingredient has an effect on any endocrine system. Developmental 
toxicity tests using both zinc and sodium pyrithione showed no evidence 
of maternal or fetal toxicity except at the limit dose. In a 2-
generation reproduction study in Crl:CD(SD)BR rats in which sodium 
pyrithione was administered by gavage, a parental NOAEL of 0.5 mg/kg/
day and a reproductive NOAEL of 1.5 mg/kg/day were established. At 
maternally toxic doses, a slightly decreased number of pups were born 
per litter in both generations, possibly as a consequence of reduced 
mating success due to hind limb atrophy.

C. Aggregate Exposure

    The risk analysis for the use of 3M sponges includes estimates of 
total exposure to zinc and sodium pyrithione in all their uses 
registered by EPA or approved by FDA, not just sponges. The use of zinc 
pyrithione as a popular active ingredient in dandruff shampoos is of 
particular importance because it involves direct application to human 
skin. The analysis also includes four different sets of exposure 
assumptions:

    A realistic adverse case exposure scenario.
    A worst case exposure scenario.
    A highly exaggerated worst case set of assumptions.
    EPA's exposure assumptions.

    Even the realistic adverse case assessment hugely overestimates 
exposure and can therefore, be considered to provide an absolute upper 
bound exposure estimate. The worst case and exaggerated worst case 
scenarios include a number of obviously even more unreasonable 
assumptions designed simply to test the sensitivity of the realistic 
adverse case numbers to changing assumptions.
    Various routes of exposure that could result from use of the sponge 
are considered in the analyses, as follows:

    Ingestion
    Incidental residues in food from the use of the sponge in home 
kitchens.
    Contaminated drinking water.
    Use of sponges for teething for a lifetime (EPA's analysis 
only).

    Per cutaneous absorption
    Dermal contact with sponges and dishwater.
    Exposure to sodium and zinc pyrithione that do not result from the 
use of the sponge but are included in the analyses are as follows:
    Per cutaneous absorption

    Dandruff shampoo.
    Additive for plastics, adhesives, grouts, caulking, paints, 
yarns and fabrics.

    All components of 3M's aggregate exposure analysis are summarized 
below and the methods and assumptions used in calculating the numbers 
are discussed in detail. In summary, huge margins of safety were found, 
as expected, when exposures were compared to the established NOELs and 
NOAELs.
    In EPA's own analysis, dietary exposures were compared to the acute 
and chronic RfDs for zinc pyrithione. An acute RfD for zinc pyrithione 
was set at 0.005 mg/kg/day using an uncertainty factor (UF) of 100 and 
the lowest observed NOAEL of 0.5 mg/kg/day from a subchronic dietary 
exposure study described above. A chronic RfD of 0.0005 mg/kg/day was 
calculated using the NOAEL of 0.5 mg/kg/day from the developmental 
toxicity study in the rat described above and an UF of 1,000. The 
additional UF of 10 was included by EPA for protection of infants and 
children. The subchronic study was used, rather than available chronic 
dietary toxicity study in rats, because the chronic study was 
determined by EPA not to meet current guidelines. The Agency intends to 
ask for a new study. Although an acceptable chronic study is available 
for sodium pyrithione and a RfD of 0.005 mg/kg/day has been established 
for this sodium salt based on those data, EPA determined that sodium 
pyrithione cannot be used as a surrogate for assessing the risks posed 
by sponges containing the zinc salt.
    1. Dietary exposure. Use of the 3M sponge by institutions is 
considered by EPA to be a food use of a pesticide, requiring a 
tolerance or exemption from a tolerance. In assessing aggregate risk, 
two incidental ways in which low level residues in food might originate 
have been considered. First, the worst case and exaggerated worst case 
assessments assume that all dishes used for service of food and 
beverages are hand washed (i.e., no dishwashers) in water with dish 
detergent using a 3M sponge. Furthermore, the dishes are never rinsed, 
thereby leaving a slight residue of zinc pyrithione on the surface of 
each dish that may become a component of food. The realistic adverse 
case assumes that the normal practice of rinsing dishes after washing 
is followed, thereby eliminating dishes as a source of residues in 
food.
    The second way in which residues in food might originate is from 
contact with counters that have been cleaned with dishwater containing 
trace levels of zinc pyrithione. A discussion of the assumptions used 
in assessing exposure from counters can be found below. Dietary 
exposure is assumed to occur also, for the purpose of aggregate 
exposure and risk assessment, through drinking water containing minute 
levels of zinc pyrithione originating from home dishwater effluent 
discharged to publicly owned water treatment systems. Again, the 
assumptions behind the assessment are discussed below.
    EPA added a scenario in which children may become exposed to zinc 
pyrithione through chewing sponges while teething. Incidental ingestion 
exposures were calculated for infants using a formula for foreign 
object/matter non-dietary ingestion as set forth in EPA's Occupational 
and Residential Exposure Test Guidelines, Series 875, Part D--Exposure 
and Risk Assessment Calculations, Test Guideline No. 875.2900. Assuming 
children will teeth on sponges for a lifetime, EPA calculated that the 
margin of exposure (MOE) was acceptable.
    For other dietary exposures, EPA assumed 3M's exaggerated worst 
case scenario.
    i. Food-incidental residues from dishes. 3M's analysis begins by 
assuming that all dishes are washed by hand using a sponge and that the 
same amount of zinc pyrithione is extracted from the sponge by 
dishwater every time. The amounts assumed from the extraction study are 
12.4 ppm (adverse and worst case) and 29.6 ppm (exaggerated worst 
case). The extraction study was designed to estimate the total amount 
of zinc pyrithione that might be extracted from a sponge during a 
single use. A 50 mL volume of extract was used for convenience. A mean 
extract

[[Page 56900]]

concentration of 12.4 ppm in 50 mL, used for the realistic adverse case 
and worst case analyses, results from vigorous extraction of the sponge 
with 50 ml of 0.1% dish detergent in water at 65  deg.C, much hotter 
than normal dishwater, thereby releasing 0.62 mg of zinc pyrithione. A 
95% upper bound estimate for extraction with 1.0% dish detergent in 
water at 65  deg.C is used for the exaggerated worst case calculations, 
wherein 1.48 mg are released. Informal measurements of the amount of 
detergent necessary to make a quite sudsy dishwater demonstrate that 
less than 0.1% by weight is needed. The analysis also assumes that the 
average volume of water used each time a load of dishes are washed is 
10 liters. Hence, a dilution factor of 200 is applied to the 
concentration of the original extract. If it were assumed that the 
entire volume of dish water has the same concentration of zinc 
pyrithione as the experimental extract, the amount in solution would 
substantially exceed the original active ingredient in the sponge.
    For the worst case and exaggerated worst case analyses, it is 
assumed, based on gravimetric measurements, that 0.25 mL of dishwater, 
on the average, remains uniformly distributed over the surface of a 
drained but not rinsed plate or cup. It is also assumed that food or 
drink acquires the entire amount of residue from one side (50% of the 
surface area) of each plate or cup and that on an average each person 
uses a total of 12 plates and cups a day. For the realistic adverse 
case it is assumed that the plates and cups are rinsed free of 
dishwater, a normal practice, and therefore, have no residual zinc 
pyrithione to transfer to food.
    a. Incidental residues from counters and other surfaces. It is 
assumed that the same dishwater is also used to wash counters and other 
surfaces that may come in contact with solid foods. A wet residue level 
of 1 mg/cm\2\ is applied in the analysis, in keeping with the value 
used by FDA for the amount of non-rinsed sanitizing solutions remaining 
on cleaned dishes, cups and counters in, for example, a bar. Also 
borrowing from FDA, it is assumed that 1.55 g/cm\2\ of food contacts 
the counter and that an individual consumes 3,000 g of food total per 
day, 50% of which is solids. These figures are used by FDA for 
assessments involving packaged food and drink products. An uncut apple 
or tomato placed on a counter, for example, might be expected to have a 
much higher weight to area value.
    In the realistic adverse case, it is assumed that 50% of all solid 
food consumed by an individual comes into contact with a counter 
cleaned with dishwater as described above and that the food absorbs all 
the available zinc pyrithione residue. In the worst case and 
exaggerated worst case analyses, it is assumed that 100% of the solid 
food consumed by an individual has contact with a counter or other 
surface containing zinc pyrithione residues and absorbs all those 
residues.
    b. EPA analysis. In terms of exposure, EPA assumed 3M's exaggerated 
worst case scenario and added to it the assumption that infants would 
use sponges for teething for a lifetime. Both acute and chronic dietary 
risks were calculated using somewhat different assumptions for body 
weights, consumption amounts, and lifetime exposure durations. The risk 
calculations were also broken down for the U.S. population, females 13 
and older, and infants and children. The smallest margin of exposure 
(MOE), calculated by EPA was for chronic (lifetime) exposure to infants 
and children at 2,673, with the overall chronic MOE for the U.S. 
population calculated to be 138,121.
    ii. Drinking water. A number of obvious worst case assumptions were 
made in estimating potential exposure to zinc pyrithione in drinking 
water from use of the 3M sponge. A figure of 157 gallons was used for 
the average water usage per person per day, and the average publicly 
owned treatment works (POTW) was assumed to treat 1.45 x 10\6\ gallons 
per day and serve a population of 9,200 persons. It was assumed that 
every household hand washes all dishes (no dishwashers) and that every 
time dishes are washed a sponge is used. It is also assumed that each 
household does one load of dishes per person per day. The extraction 
levels used above for zinc pyrithione are applied in this analysis as 
well.
    Other than in the amount of extract, the three cases analyzed 
differ in assumptions regarding which sponge is used and the amount of 
dilution of POTW effluent by receiving waters. In the realistic adverse 
case, it is assumed that 20% of the sponges used each day are new. This 
assumption means that sponges are replaced on the average every 5 days, 
rather than the 6 to 8 weeks normally found by consumer research. The 
replacement figure increases to 50% and 100% for the worst case and 
exaggerated worst case respectively. Used sponges are assumed to 
release minimal zinc pyrithione to dishwater. It is also assumed that 
60%, 80% and 100% of all households use the 3M sponge in going from the 
realistic adverse case to the exaggerated worst case. The amount by 
weight of zinc pyrithione extracted from the sponge during each washing 
is calculated and assumed to be discharged to the POTW with each 
persons daily allotment of water. The POTW is assumed to remove none of 
the zinc pyrithione before the water effluent is discharged. The 
effluent is assumed to be diluted to a minimal degree by receiving 
waters and these same waters are assumed to be returned to the 
community as drinking water, with the level of zinc pyrithione 
conserved throughout the cycle. Furthermore, every individual is 
assumed to consume only tap water as a beverage (i.e., no packaged 
drinks such as soda, milk, bottled water, prepackaged infant formula).
    Using a different approach wherein a drinking water level of 
comparison (DWLOC) is calculated, EPA concluded without explanation 
that the concern for drinking water exposures should be higher than 
calculated by 3M. The DWLOC is the concentration of a pesticide in 
drinking water that would produce an unacceptable aggregate risk, 
considering all other food and non-occupational exposures. EPA 
calculated acute DWLOCs for the U.S. population, for females 13 and 
older, and for infants and children of 174 parts per billion (ppb), 174 
ppb, and 50 ppb, respectively. Chronic DWLOCs were calculated to be 84 
ppb, 84 ppb, and 20 ppb, respectively, for the same subpopulations. 3M 
calculated, as described above and summarized in Table 5, below zinc 
pyrithione levels of 0.03 to 1.25 ppb using extremely conservative 
assumptions. 3M's uppermost value comes from a scenario that uses the 
upper 95% probability bound leachate value for sponges extracted in 
high temperature water containing extreme levels of detergent. The 
scenario also assumes that 100% of the U.S. population uses a new 
sponge every time dishes are washed and that the wash water is recycled 
as drinking water with only a 2x dilution factor. If water usage is 157 
gallons per individual per day, and dishwater were recycled directly, 
each sink of dishwater would need to be diluted by a factor of 100 or 
more to supply the requisite amount of water.
    2. Non-dietary exposure--i. Dermal absorption from dishwashing. To 
estimate the potential dermal dose of zinc pyrithione associated with 
use of the sponge during dishwashing, it was assumed that an adult will 
immerse both hands and one-half of their forearms in dishwater for a 
total of 1-hour per day. Again the concentration of zinc pyrithione in 
the dishwater was varied from case-to-case, as described earlier. 
Dermal permeability and

[[Page 56901]]

absorbed amount were calculated using methods recommended by EPA.
    ii. Per cutaneous absorption from dandruff shampoo. Information on 
the absorption of zinc pyrithione from the use of dandruff shampoos was 
obtained from FDA's docket supporting formal rulemaking leading to a 
monograph establishing conditions under which over-the-counter drug 
products for the control of dandruff, seborrheic dermatitis, and 
psoriasis are ``generally recognized as safe and effective.'' In a 
study involving 30 human subjects, a shampoo containing radio labeled 
zinc pyrithione (\14\C in the 2- and 6-positions) was applied in both a 
sink shampoo procedure (head exposure only) and a shower shampoo (total 
body exposure). All wash water and towels, etc. were retained and 
biological samples of skin, hair, blood and urine collected for a 
period of ten days following application. Recovery of radio label was 
essentially 100%.
    An average upper level systemic load of zinc pyrithione was 
calculated from the urinary output data to be 1 g/kg/day. 
Absorption was greatest for subjects with seborrheic dermatitis, and 
the absorbed material was derived from solid zinc pyrithione deposited 
on the head, rather than from the soluble zinc pyrithione complexed 
with detergent in the commercial shampoo.
    For this aggregate exposure analysis, in the realistic adverse case 
it was assumed that all persons have chronic dandruff and use a 
dandruff shampoo every day, absorbing the maximum dose of the active 
ingredient. In the worst case and exaggerated worst case, it is assumed 
that all persons have seborrheic dermatitis and use the dandruff 
shampoo every day for life (i.e., the treatment has no curative effect 
on the seborrheic dermatitis). It was also assumed that infants and 
small children do not use dandruff shampoo on a regular basis. Using 
these assumptions, exposure from use of zinc pyrithione in dandruff 
shampoo was found to be three orders of magnitude higher than exposure 
from all other uses of zinc pyrithione.
    EPA assumed 3% dermal absorption of zinc pyrithione for non-dietary 
exposures. In contrast, for assessments involving dermal exposure to 
sodium pyrithione, the Agency has used an absorption value of 0.1% in 
risk assessments. In its assessment of aggregate risk for the sponge, 
EPA did not consider exposures through the use of dandruff shampoos 
containing zinc pyrithione.

D. Cumulative Effects

    It is 3M's position that zinc pyrithione should not be expected to 
have any effects cumulative with any other substances. It is EPA's 
position that the Agency ``does not at this time have the methodology 
to resolve scientific issues concerning common mechanisms of 
toxicity.'' Hence, for the time being EPA has not assumed that zinc 
pyrithione has a common mechanism of toxicity with other substances.

E. Safety Determination

    1. U.S. population. EPA has established an oral NOAEL for zinc 
pyrithione of 0.5 mg/kg/day based upon a chronic rat study. This value 
is confirmed in the NOAEL for a subchronic neurotoxicity study and a 2-
generation reproduction study. Using a substantial number of high 
exposure assumptions, the absolute upper limit exposure to zinc 
pyrithione was calculated for all uses in the realistic adverse case 
presented above. When exposure to zinc pyrithione through daily 
lifetime use of dandruff shampoo is included, a minimum adult MOE of 
128,000 was found, with total aggregate exposure at 7.81 x 10-\4\ mg/
kg/day. The exposure from the assumed daily use of dandruff shampoo is 
huge compared to the aggregate adult exposure from use of zinc 
pyrithione in sponges. Total adult exposure (oral + dermal) not 
counting shampoo is 1.20 x 10-\6\ mg/kg/day. The maximum possible daily 
intake of zinc pyrithione for all uses other than shampoo was 
calculated to yield an aggregate adult MOE of over 400,000, assuming an 
individual does not routinely (i.e., daily) use dandruff shampoo (see 
Table 2).
    2. Infants and children. Aggregate exposure to children was 
determined by adjusting the assumptions used for adults. The assessment 
was designed to examine exposure for non-nursing infants, the 
subpopulation that most often is calculated to have the highest 
exposure to pesticides in the diet in EPA's own assessments for most 
chemicals.
    In this assessment, it was assumed that the dietary consumption of 
food and water by infants was 2.5 times more per kg of body weight than 
for adults. Because a large portion of an infant's diet is liquids, the 
additional assumption was made that a smaller portion of the diet for 
infants than adults would be exposed to counters and other surfaces 
washed with dishwater. Therefore, absorption of zinc pyrithione from 
washed surfaces would be expected to be less. Non-nursing infants are 
also not expected to wash dishes or use dandruff shampoo on a regular 
basis, eliminating these routes of exposure. Maximum possible aggregate 
dietary exposure for non-nursing infants is calculated to be 1.92 x 
10-\6\ mg/kg/day, yielding an MOE of 260,000, far in excess of the 
1,000 fold safety factor applied by EPA in its assessment to calculate 
an RfD. The use of sponges for teething for a lifetime, which EPA 
included in its assessments, was not considered.

F. International Tolerances

    No international tolerances have been issued for the use of zinc 
pyrithione as a preservative in cellulose sponges.
[FR Doc. 00-24210 Filed 9-19-00; 8:45 am]
BILLING CODE 6560-50-F