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4,5-Dichloro-2-n-octyl-3(2H)-isothiazolone - Pesticide Petition Filing 9/98

[Federal Register: September 23, 1998 (Volume 63, Number 184)]
[Notices]
[Page 50907-50911]
>From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr23se98-70]

[[Page 50907]]

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ENVIRONMENTAL PROTECTION AGENCY

[PF-827; FRL-6023-6]

Rohm and Haas Company; Pesticide Tolerance Petition Filing

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 for residues of a

certain pesticide chemical in or on food contact paper and paperboard.
DATES: Comments, identified by the docket control number PF-734, must
be received on or before October 23, 1998.
ADDRESSES: By mail submit written comments to: Information and Records
Integrity Branch, Public Information and Services Divison (7502C),
Office of Pesticides Programs, Environmental Protection Agency, 401 M
St., SW., Washington, DC 20460. In person bring comments to: Rm. 119,
Crystal Mall #2, 1921 Jefferson Davis Highway, Arlington, VA.
    Comments and data may also be submitted electronically by following
the instructions under ``SUPPLEMENTARY INFORMATION.'' No confidential
business information should be submitted through e-mail.
    Information submitted as a comment concerning this document may be
claimed confidential by marking any part or all of that information as
``Confidential Business Information'' (CBI). CBI should not be
submitted through e-mail. Information marked as CBI will not be
disclosed except in accordance with procedures set forth in 40 CFR part
2. A copy of the comment that does not contain CBI must be submitted
for inclusion in the public record. Information not marked confidential
may be disclosed publicly by EPA without prior notice. All written
comments will be available for public inspection in Rm. 119 at the
address given above, from 8:30 a.m. to 4 p.m., Monday through Friday,
excluding legal holidays.

FOR FURTHER INFORMATION CONTACT: Marshall Swindell, PM 33,
Antimicrobial Division (7510W), Office of Pesticide Programs,
Environmental Protection Agency, 401 M St., SW, Washington, DC 20460.
Office location, telephone number, and e-mail address: Rm. 6B, Crystal
Station #1, 2800 Jefferson Davis Highway, Arlington, VA 22202, (703)
308-6341; e-mail: swindell.marshall@epamail.epa.gov.
SUPPLEMENTARY INFORMATION: EPA has received a pesticide petition as
follows proposing the establishment and/or amendment of regulations for
residues of certain pesticide chemical in or on food contact paper and
paperboard 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 supports
granting of the petition. Additional data may be needed before EPA
rules on the petition.
    The official record for this notice of filing, as well as the
public version, has been established for this notice of filing under
docket control number [PF-827] (including comments and data submitted
electronically as described below). A public version of this record,
including printed, paper versions of electronic comments, which does
not include any information claimed as CBI, is available for inspection
from 8:30 a.m. to 4 p.m., Monday through Friday, excluding legal
holidays. The official record is located at the address in
``ADDRESSES'' at the beginning of this document.
    Electronic comments can be sent directly to EPA at:
    opp-docket@epamail.epa.gov

    Electronic comments must be submitted as an ASCII file avoiding the
use of special characters and any form of encryption. Comment and data
will also be accepted on disks in Wordperfect 5.1/6.1 file format or
ASCII file format. All comments and data in electronic form must be
identified by the docket control number (PF-827) and appropriate
petition number. Electronic comments on this notice may be filed online
at many Federal Depository Libraries.

List of Subjects

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

    Dated: September 1, 1998.

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 views of the
petitioner. EPA is publishing the petition summaries verbatim without
editing them 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.

Rohm and Haas Company

PP 8F4977

    EPA has received a pesticide petition 8F4977 from Rohm and Haas
Company, 100 Independence Mall West, Philadelphia, PA 19106-2399,
proposing pursuant to section 408(d) of the Federal Food, Drug, and
Cosmetic Act, 21 U.S.C. 346a(d), to amend 40 CFR part 180 to establish
an exemption from the requirement of a tolerance for 4,5-Dichloro-2-n-
octyl-3(2H)-isothiazolone (CASRN 64359-81-5), in or on food contact
paper and paperboard. EPA has determined that the petition contains
data or information regarding the elements set forth in section
408(d)(2) of the FFDCA; however, EPA has not fully evaluated the
sufficiency of the submitted data at this time or whether the data
supports granting of the petition. Additional data may be needed before
EPA rules on the petition.
    Alternatively, this petition is proposing, pursuant to section 409
of the FFDCA, 21 U.S.C. 348, to amend 21 CFR 176.170 and 176.300, to
establish a regulation for the use of 4,5-Dichloro-2-n-octyl-3(2H)-
isothiazolone in or on food contact paper and paperboard. Regulatory
authority for the rule proposed by this petition currently resides with
EPA. EPA intends to transfer this regulatory authority to FDA, by
rulemaking, pursuant to section 201(q)(3) of the FFDCA, 21 U.S.C.
321(q)(3). Any final regulation based on this petition will be
determined by the status of the rulemaking at the time of the
petition's final disposition.
    Rohm and Haas Company's 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 Rohm and Haas Company and
represents the views of Rohm and Haas Company. 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.

A. Residue Chemistry

    This petition is not for residues in or on raw agricultural
commodities. It is for residues in or on food contact paper

[[Page 50908]]

and paperboard. Accordingly, the residue chemistry data submitted are
solely for the residues remaining in food contact paper and paperboard
and coatings on food contact paper and paperboard when the subject
slimicide (4,5-dichloro-2-n-octyl-3(2H)-isothiazolone, CASRN 64359-81-
5, hereafter referred to as RH-287) is used in the following
applications: for addition to pulp and paper mill process water to
control slime-forming microorganisms, for addition to coatings that
will be used on paper and paperboard to preserve the paper, for
application to wet lap at pulp mills prior to manufacture of paper, and
for addition to dispersed pigments that will be used in the manufacture
of paper and paperboard. Each of these applications is discussed
separately below.
    1. Residues in paper and paperboard from treatment of process
water. Gas chromatography with mass spectral detection was used to
analyze paper from a field trial where the maximum use concentration (4
part per million (ppm) in the slurry water, 0.033 lb. RH-287 per ton of
paper) was added to the process water. Paper from this trial had a
concentration of RH-287 that ranged from 6.9 to 35.4 ppm based on the
weight of the paper. Samples of paper that had 25 ppm RH-287 were
extracted with food simulants using standard FDA protocols for
determining food additive extractables from food contact materials.
Samples were extracted for 24 hours with the appropriate aqueous and
fatty food simulants for uncoated paper. The concentration of RH-287 in
the food simulants was 0.68 <greek-m>g RH-287/inch<SUP>2</SUP> of paper
in the aqueous simulant and <0.22 <greek-m>g RH-287/inch<SUP>2</SUP> of
paper in the fatty food simulant.
    2. Residues from coated paper and paperboard. Samples of paper were
coated with either a latex-based coating or a starch-based coating. The
concentration of RH-287 in the latex-coated paper was 100 ppm of RH-287
based on the weight of paper, whereas the concentration in the starch-
coated paper was 145 ppm based on the weight of paper. These papers
were then extracted with food simulating solvents using standard FDA
methods for 24 hours. The concentration of RH-287 found in the aqueous
food simulant was 1.23 <greek-m>g/inch<SUP>2</SUP> in the latex-coated
paper and 2.64 <greek-m>g/inch<SUP>2</SUP> in the starch-coated paper.
The concentration of RH-287 found in the fatty food simulant was 4.78
<greek-m>g/inch<SUP>2</SUP> in the latex-coated paper and 5.02
<greek-m>g/inch<SUP>2</SUP> in the starch-coated paper.
    3. Residues in paper from wet lap treated with RH-287. The maximum
use level for treatment of wet lap is 100 ppm of RH-287 based on the
dry weight of the fiber. Laboratory-made paper containing 108 ppm of
RH-287 was repulped in a manner consistent with the actual repulping of
wet lap. From this experiment it was found that the final paper
contained 15 ppm of RH-287. Using standard FDA assumptions, this
concentration is equivalent to 0.70 <greek-m>g RH-287/inch<SUP>2</SUP>
of paper.
    4. Residues from dispersed pigments in paper and paperboard. The
allowable concentration of RH-287 in dispersed pigments is between 10
and 50 ppm. Since dispersed pigments will be a component of latex or
starch-type coatings, the coated paper migration study encompassed
these uses. As a result, no separate migration studies were conducted
with paper prepared from dispersed pigments that were treated with RH-
287. The dietary contribution of RH-287 from dispersed pigments is
expected to be at most 21% of the dietary contribution for the coated
paper.
    5. Analytical method. This is a tolerance exemption petition and,
accordingly, no enforcement analytical method is proposed.

B. Toxocological Profile

    1. Acute toxicity. RH-287 Technical (96.9% active ingredient) is
slightly to moderately toxic by the oral route, with an acute oral
LD<INF>50</INF> in rats of 1636 milligram/kilogram (mg/kg) (MRID
42977701) and in mice of 567 mg/kg (MRID 43471601). RH-287 is
considered corrosive to the skin and eyes. A formulation of RH-287 in
xylene produced skin sensitization in guinea pigs (MRID 126793). RH-287
is irritating to the respiratory tract via inhalation exposure; the 4
hr inhalation LC<INF>50</INF> in rats was 0.26 mg/liter (MRID
43471602).
    Acute toxicity studies conducted on an end-use product containing
4.25% RH-287 with surfactants in water indicated that the product was
practically non-toxic by either the oral or dermal routes; the oral and
dermal LD<INF>50</INF> in rats was > 5,000 and > 2,000 mg/kg product,
respectively (MRID 44259302 and 44259303, respectively). The 4.25%
product was slightly irritating to the skin (MRID 44259306) but was
corrosive to the eyes (MRID 44259305). The 4 hr inhalation
LC<INF>50</INF> for the use product in rats was 1.3 mg/liter product
(MRID 44259304).
    2. Genotoxicity. RH-287 Technical was negative (non-mutagenic) in
the Ames Salmonella gene mutation assay (MRID 43471605), negative in a
gene mutation assay in Chinese hamster ovary (CHO) cells (MRID
43471606), negative in in vitro chromosomal aberration assay in CHO
cells (MRID 43471607), and negative in a mouse in vivo micronucleus
assay (MRIDs 43471601, 43471608, and 43901901). RH-287 is judged to be
non-genotoxic.
    3.  Subchronic toxicity. RH-287 Technical (98.8% active ingredient)
was administered in the diet to groups (10/sex/group) of
Crl:CD<Register> BR rats for three months at dietary concentrations of
0, 100, 500, 1,000, and 4,000 ppm (MRID 43471603). No treatment-related
mortality was observed. Significant reductions in body weight and body
weight gain were observed at 1,000 ppm in females and at 4,000 ppm in
both sexes. Food consumption was transiently reduced at 1,000 ppm in
females. Food and water consumption were reduced throughout the
treatment period at 4,000 ppm in both sexes. Serum triglyceride levels
were decreased at 1,000 ppm in females; several other clinical
chemistry parameters were affected in both sexes at 4,000 ppm.
Histological findings indicative of gastric irritation were limited to
the forestomach and were observed at 1,000 and 4,000 ppm in both sexes.
The no-observed effect level (NOEL) for RH-287 when administered in the
diet to rats for three months was 500 ppm (equivalent to 32.5 and 36.7
mg/kg/day in males and females, respectively).
    4. Chronic toxicity/oncogenicity. Chronic toxicity and oncogenicity
studies have not been conducted with RH-287 since these studies were
not required for the FIFRA registration of RH-287 Technical. Chronic
toxicity and oncogenicity studies are judged not to be warranted for
RH-287 based on the primary toxicity of gastric irritation observed in
the RH-287 three-month dietary toxicity study described above, its non-
mutagenic potential, and its negligible dietary exposure (see below).
    5. Developmental toxicity. RH-287 Technical was administered to
pregnant rats by daily oral gavage on days 6-15 of gestation at 0, 10,
30, 100, and 300 mg/kg/day, and dams were killed on day 20 for cesarean
sectioning (MRID 43471604). Significant mortality was observed at 300
mg/kg/day, and this group was terminated prior to day 20. Maternal body
weight change was reduced at 100 mg/kg/day. Feed consumption was
reduced throughout the treatment period at 100 mg/kg/day but was
increased in this group following the treatment period. An increased
number of litters from rats dosed with 100 mg/kg/day had fetuses with
wavy ribs, a skeletal variation. There were no treatment-related
effects on the numbers of early or late resorptions, live fetuses per
litter, fetal body weight or sex ratio, external, soft-

[[Page 50909]]

tissue, or head abnormalities, or skeletal malformations. The NOELs for
maternal and fetal toxicity in this study were 10 and 30 mg/kg/day,
respectively. RH-287 was not teratogenic in rats.
    6. Pharmacokinetics. The absorption, distribution, and excretion of
oral administration of 20 and 250 mg/kg <SUP>14</SUP>C-RH-287 were
investigated in male and female Crl:CD<Register> BR rats (MRID 43471609
and 43901901). <SUP>14</SUP>C-RH-287 was moderately rapidly absorbed;
peak plasma concentrations were achieved between 6 and 24 hr.
<SUP>14</SUP>C-RH-287 was rapidly excreted mostly within two days after
dosing and primarily in the feces. Tissues and residual carcasses
contained negligible amounts of <SUP>14</SUP>C-label four days after
dosing indicating that <SUP>14</SUP>C-RH-287 does not bioaccumulate.
    7. Reference dose (RfD). EPA has not previously set an RfD for RH-
287 since at the time of registration review for RH-287 microbicide
(EPA Reg. No. 707-224) Rohm and Haas did not request use in food
contact materials. Based on the subchronic NOEL of 32.5 mg/kg/day and
an uncertainty factor of 100, Rohm and Haas Company proposes an RfD for
RH-287 of 0.325 mg/kg/day (based on minimal gastric irritation and
decreased body weight and food consumption). An RfD of 0.325 mg/kg/day
leads to the following allowable daily intakes (ADI) for adult males
and females and for children and infants:
    Adult male (70 kg), ADI = 22.8 mg/day;
    Adult female (60 kg), ADI = 19.5 mg/day;
    Child (20 kg), ADI = 6.5 mg/day; and
    Infant (8 kg), ADI = 2.6 mg/day.
    Since the RfD for RH-287 is based primarily on the physico-chemical
effect of gastric irritation, a wide difference in the susceptibility
between children/infants and adults would not be anticipated. The
gastric irritation effects are likely a function of the concentration
of RH-287 in the stomach, which is a function of the amount of RH-287
per unit of body weight. Thus, exposure to a given mg/kg/day dose of
RH-287 is expected to yield similar gastric concentrations of RH-287
among infants, children, and adults. An RfD of 0.325 mg/kg/day is
judged to be an appropriate safe maximum ingestion dose for RH-287.

C. Aggregate Exposure

    1. Dietary exposure-- i. Food in contact with paper or paperboard
made in process water containing RH-287. Analysis of paper samples
manufactured in a papermill which used RH-287 amended slurry water by
gas chromatography with mass spectral detection revealed levels of RH-
287 in the paper ranging from 6.9 to 35.4 ppm. Samples of paper that
had 25 ppm were extracted with food simulating solvents using standard
FDA protocols for determining food additive extractables for 24 hours.
The levels of RH-287 recovered were 0.68 <greek-m>g/inch<SUP>2</SUP> of
paper in the aqueous food simulant and less than 0.22 <greek-m>g/
inch<SUP>2 </SUP> of paper in the fatty food simulant. The standard FDA
assumption is that 10 g of food is in contact with one inch<SUP>2</SUP>
of paper. Therefore, the corresponding food concentrations are 68 ppb
of RH-287 in aqueous food and 22 ppb of RH-287 in fatty foods. Using a
standard equation provided by the FDA for estimating dietary exposure
to an indirect food additive migrating from food packaging, the
hypothetical worst case potential for dietary exposure to RH-287 as a
result of RH-287 migration into foods in contact with paper and
paperboard made in process water containing RH-287 is:
    <M<INF>slimicide</INF>> =
f<INF>aqueous and acidic</INF>(M<INF>10 percent ethanol</INF>) +
f<INF>alcohol and fatty</INF>(M<INF>fatty</INF>)
    The food type distribution factors (f<INF>foodtype</INF>) are:
    f<INF>aqueous and acidic</INF> 0.57 + 0.01 = 0.58
    f<INF>alcohol and fatty</INF> 0.01 + 0.41 = 0.42
and <M> is the concentration of residues in food.
    <M<INF>slimicide</INF>> = 0.58(68 ppb) + 0.42(22 ppb)
    <M<INF>slimicide</INF>> = 48 ppb
    The above value of <M<INF>slimicide</INF>> was obtained from paper
that contained 25 ppm of RH-287. In the paper mill trial, the
concentration of RH-287 ranged from 6.9 to 35.4 ppm. To ensure that the
dietary concentration is conservatively estimated, the value for
<M<INF>slimicide</INF>> is adjusted upward by multiplying by 1.4 (35/
25) to give a concentration of 67 ppb. This value is then converted
into a dietary concentration by taking into consideration the
consumption factor for uncoated paper and paperboard, which is 10% for
this type of packaging material. As a result, the maximum dietary
concentration of RH-287 resulting from its use in slimicide
applications is 6.7 ppb (Diet<INF>slimicide</INF>).
    ii. Food in contact with paper or paperboard prepared with coatings
containing RH-287. Two different coatings were prepared. One was a
latex-based coating, and the other was a starch-based coating. The
latex coating was applied to paper at the maximum use level of 100 ppm
(based on the weight of paper). The concentration found in the aqueous
food simulant from the latex-based coating was 123 ppb and in the fatty
food simulant was 478 ppb. However, the starch-based coating was 145
ppm, approximately 50% higher. The starch values, 264 ppb for the
aqueous food simulant and 502 ppb in the fatty food simulant, can be
normalized to the maximum use level of 100 ppm of RH-287 by
multiplication by 0.69 (100/145) to give food concentrations of 182 ppb
for the aqueous food simulant and 346 ppb for the fatty food simulant.
Worst case calculations are based on using the concentration in the
aqueous food simulant from the starch coating and the concentration in
the fatty food simulant from the latex coating. This calculation takes
into account the rather rare possibility that starch coatings
containing RH-287 would be used exclusively with aqueous foods while
latex coatings would be used exclusively with fatty foods.
    <M<INF>coatings</INF>> =
f<INF>aqueous and acidic</INF>(M<INF>10 percent ethanol</INF>) +
f<INF>alcohol and fatty</INF>(M<INF>fatty</INF>)
    <M<INF>coatings</INF>> = 0.58(0.182) + 0.42(0.478)
    <M<INF>coatings</INF>> = 0.310 <greek-m>g RH-287/g of food = 310
ppb RH-287
    The <M<INF>coating</INF>> is converted into a dietary concentration
by utilizing a 10% consumption factor. The contribution to the diet
from paper prepared from latex and starch based coatings is 31 ppb
(Diet<INF>coating</INF>).
    iii. Food in contact with paper or paperboard made from wet lap
treated with RH-287. The maximum use level permitted for RH-287 on wet
lap is 100 ppm based on the dry weight of fiber. Wet lap consists of
approximately 50% fiber and 50% water and never contacts food directly.
It is a pulp product that requires further processing before paper can
be made from it. During the manufacture of paper from wet lap, the wet
lap is repulped in water. This slurry is approximately 0.5% to 1%
fiber. Laboratory experiments demonstrated that paper made from wet lap
contains only 14% of the RH-287 active material originally present in
the wet lap, indicating that most of the RH-287 is lost during the
repulping process.
    Paper manufactured from wet lap represents only 3% of all paper
made in North America. If we assume the worst case that all of the RH-
287 in the paper made from repulped wet lap migrates into food, then
the maximum RH-287 residues in food would be:
    <M<INF>wet lap</INF>> = (100 <greek-m>g/g of paper)(0.14)(0.05g of
paper/inch<SUP>2</SUP> of paper)(1 inch<SUP>2</SUP> of paper/10 g of
food) = 0.07 <greek-m>g/g = 70 ppb
    The above worst case value of RH-287 residues in food
(<M<INF>wet lap</INF>>) can then be converted to the dietary
contribution (Diet<INF>wet lap</INF>) by multiplication by the
consumption factor. The consumption factor for uncoated paper is 0.1,
and since wet lap represents only 3% of all paper made in North
America, the overall consumption factor for wet lap

[[Page 50910]]

paper is 0.003. The worst case overall amount of RH-287 in the diet
contributed from wet lap would be (70 ppb) (0.003) = 0.21 ppb.

    iv. Food in contact with paper or paperboard made with dispersed
pigments containing RH-287. As described above, the maximum level of
RH-287 in paper coatings contributed from dispersed pigments is 21% of
the value determined for the latex-coated paper. We can, therefore,
calculate the amount of RH-287 that dispersed pigments would contribute
to the diet by multiplying 31 ppb (Diet<INF>coating</INF>) by 0.21 =
6.5 ppb (Diet<INF>dispersed pigment</INF>).
    v. Summation of dietary exposure. The sum of the dietary
contributions of RH-287 from the different applications is shown below:
Diet<INF>slimicide</INF>             6.7 ppb
Diet<INF>coating</INF>             31.0 ppb
Diet<INF>wet lap</INF>             0.21 ppb
Diet<INF>dispersed pigment</INF>       6.5 ppb
Diet<INF>sum</INF>               44.4 ppb
    2.  Drinking water. The use of RH-287 as a slimicide for pulp and
paper mills does not provide for entry of RH-287 into drinking water
sources. Spent process water from such sites is treated as waste water,
typically on-site, prior to release into surface waters. There is no
provision for RH-287 to enter groundwater systems since RH-287 is not
registered for use directly on raw agricultural commodities.
    3. Non-dietary exposure. RH-287 is an industrial-use microbicide
whose only other registered water-treatment uses (i.e., other than use
in pulp and paper manufacturing) is as a slimicide control agent in
recirculating cooling water, air washer systems, recirculating closed
loop water cooling systems, decorative fountains, and can warmer and
brewery pasteurizers. All of the uses of RH-287 involve only
occupational exposures. There are no registrations and no intended uses
in residential scenarios.
    4. Estimated total daily intake. The daily diet for adults is 3 kg/
day. The worst case estimated daily intake (EDI) of RH-287 for adults
from possible residuals in food contact paper and paperboard is:
    EDI<INF>adult </INF>= 3.0 kg of food/day x 44.4 ppb = 133
<greek-m>g/day
    The daily diet differs in quantity for children of different ages.
At 6 months of age, the daily diet is 1.1 kg, and the mean body weight
for a 6 month old infant is 8 kg. In the age interval 4 to 6 years of
age, the daily diet is 2 kg/day, and the mean body weight of a child
this age is 20 kg. The EDI's for infants and children are based on
these total diet amounts and are:
    EDI<INF>infant</INF> = 1.1 kg of food/day x 44.4 ppb = 49
<greek-m>g/day
    EDI<INF>child</INF> = 2.0 kg of food/day x 44.4 ppb = 89
<greek-m>g/day
    Thus for a 6 month old infant (8 kg), a 4 to 6 year old child (20
kg), an adult woman (60 kg), and an adult man (70 kg), the daily
intakes of RH-287 associated with the above EDIs, expressed as
<greek-m>g/kg/day and as percent of RfD utilization (RfD = 0.325 mg/kg/
day = 325 <greek-m>g/kg/day) are:

----------------------------------------------------------------------------------------------------------------
                                                                    Dietary exposure       Percent RfD utilized
----------------------------------------------------------------------------------------------------------------
Infant........................................................    6.1 <greek-m>g/kg/day                      1.9
Child.........................................................    4.5 <greek-m>g/kg/day                      1.4
Woman.........................................................    2.2 <greek-m>g/kg/day                      0.7
Man...........................................................    1.9 <greek-m>g/kg/day                      0.6
----------------------------------------------------------------------------------------------------------------

    Rohm and Haas Company notes that in 40 CFR 180.1 (l) EPA has
defined that a ``negligible residue ordinarily will add to the diet an
amount which will be less than 1/2000th of the amount that has been
demonstrated to have no effect from feeding studies on the most
sensitive animal species tested.'' Thus, for a 100-fold uncertainty
factor based RfD, this means an RfD utilization of 5% or less. Rohm and
Haas considers, therefore, that under the hypothetical worst case
dietary exposure assessment, RH-287 residues are clearly negligible
residues.

D. Cumulative Effects

    RH-287 has the intrinsic toxicological potential to produce
irritation at the site of contact at relatively high concentrations.
This chemico-physico (non-systemic) property is consistent with other
compounds which cause irritation effects at the site of application. We
have evaluated this effect in the context of the extremely low dietary
exposure to RH-287 in the subject indirect food additive application
and do not believe there is any evidence for a cumulative risk concern.

E. Safety Determination

    1. U.S. population. Since the use of RH-287 as a slimicide in pulp
and papermills is, under hypothetical worst case conditions, expected

to lead to at most only negligible indirect dietary exposures in adults
[i.e., not greater than 0.6 to 0.7% of the RfD for adults which is less
than the negligible criteria of 5% of RfD defined in 40 CFR 180.1(1)],
it is Rohm and Haas Company's judgment that there is a reasonable
certainty that no harm will come to adults from dietary exposure to RH-
287 residues which could occur in food contact paper and paperboard
produced in pulp and paper mills utilizing RH-287 for slime control,
and for paper coatings, wet lap, and dispersed pigment preservation in
accordance with its FIFRA labeling.
    2. Infants and children. Since the use of RH-287 as a slimicide in
pulp and papermills is, under hypothetical worst case conditions,
expected to lead to at most only negligible indirect dietary exposures
in infants and children [i.e., not greater than 1.4-1.9% of the RfD for
infants and children which is less than the negligible criteria of 5%
of RfD defined in 40 CFR 180.1(1)], it is Rohm and Haas Company's
judgment that there is a reasonable certainty that no harm will come to
infants and children from dietary exposure to RH-287 residues which
could occur in food contact paper and paperboard produced in pulp and
paper mills utilizing RH-287 for slime control, and for paper coatings,
wet lap, and dispersed pigment preservation in accordance with its
FIFRA labeling.
    3. Sensitive individuals. Since the RfD for RH-287 is based
primarily on the physico-chemical effect of gastric irritation, wide
differences in susceptibility to RH-287 based on metabolic differences
among individuals would not be anticipated. Because of this, and
because of the relatively large margins of safety for exposure to RH-
287 from food in contact with paper products (i.e., 5,300 to 17,000),
it is Rohm and Haas Company's judgment that there is a reasonable
certainty that no harm will come to individuals with pre-existing
gastro-intestinal tract conditions, such as ulcers, colitis, and
similar pathologies, from dietary exposure to RH-287 residues which
could occur in food contact paper and paperboard produced

[[Page 50911]]

in pulp and paper mills utilizing RH-287 for slime control, and for
paper coatings, wet lap, and dispersed pigment preservation in
accordance with its FIFRA labeling.

F. International Tolerances

    There are no Codex maximum residue levels (MRLs) established for
residues of RH-287.

G. Estrogenic Effects

    RH-287 is judged not to be an estrogenic material for the following
reasons:
    1. RH-287 is not structurally related to any known estrogenic
materials. Although RH-287 contains two chlorine atoms, these chlorine
atoms are readily released as chloride ions upon environmental
degradation;
    2. An extensive toxicology database on RH-287 and other
isothiazolones indicates that these materials do not cause direct
systemic toxicity. Relatively high concentrations of these materials
are only toxic to the site of application;
    3. Histopathologic examination in our RH-287 three-month dietary
study summarized above indicated no toxicity to reproductive organs;
and
    4. Our developmental toxicity study summarized above indicated no
reproductive toxicity.
    Thus, based on structure activity analysis and on toxicology
studies conducted with RH-287, there is no scientific evidence that
indicates, or even suggests, that RH-287 is estrogenic. (Karen Levy)

[FR Doc. 98-25448 Filed 9-22-98; 8:45 am]
BILLING CODE 6560-50-F