[Federal Register Volume 65, Number 245 (Wednesday, December 20, 2000)]
[Notices]
[Pages 79834-79839]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 00-32152]


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ENVIRONMENTAL PROTECTION AGENCY

[PF-981; FRL-6751-9]


Notice of Filing Pesticide Petitions to Establish Tolerances for 
Certain Pesticide Chemicals in or on Food

AGENCY:  Environmental Protection Agency (EPA).

ACTION:  Notice.

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SUMMARY:  This notice announces the initial filing of pesticide 
petitions proposing the establishment of regulations for residues of 
certain pesticide chemicals in or on various food commodities.

DATES:  Comments, identified by docket control number PF-981, must be 
received on or before January 19, 2001.

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-981 in the subject line on the first page of your 
response.

FOR FURTHER INFORMATION CONTACT:  By mail: Bipin C. Gandhi, 
Registration Division (7505C), Office of Pesticide Programs, 
Environmental Protection Agency, 1200 Pennsylvania Ave., NW., 
Washington, DC 20460; telephone number: (703) 308-8380; 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 codes         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,'' ``Regulations and Proposed Rules,'' 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-981. 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

[[Page 79835]]

available for inspection in the Public Information and Records 
Integrity Branch (PIRIB), Rm. 119, Crystal Mall #2, 1921 Jefferson 
Davis Hwy., 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-981 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 Hwy., 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-981. 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 pesticide petitions as follows proposing the 
establishment and/or amendment of regulations for residues of certain 
pesticide chemicals 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 these petitions contain 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 these petitions. Additional 
data may be needed before EPA rules on the petitions.

List of Subjects

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


    Dated: December 8, 2000.
James Jones,

Director, Registration Division, Office of Pesticide Programs.

Summaries of Petitions

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

Firmenich Incorporated

1. PP 6E4757

    EPA has received a pesticide petition (PP 6E4757) from Firmenich 
Incorporated, P.O. 5880, Princeton, NJ 08543 proposing, pursuant to 
section 408(d) of the FFDCA, 21 U.S.C. 346a(d), to amend 40 CFR part 
180, to establish an exemption from the requirement of a tolerance for 
octanal when used as an inert ingredient in the pesticide formulations 
applied to growing crops or to raw agricultural commodities (RACs) 
after harvest under 40 CFR 180.1001(c) and applied to animals under 40 
CFR 180.1001(e). 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 support granting of the 
petition. Additional data may be needed before EPA rules on the 
petition.

A. Residue Chemistry

    Since this petition is for an exemption from the requirement of a 
tolerance, an analytical method is not required.

B. Toxicological Profile

    As part of the EPA policy statement on inert ingredients published 
in the Federal Register of April 22, 1987 (52 FR 13305) (FRL -3190-1), 
the Agency set forth a list of studies which generally are used to 
evaluate the risks posed by the presence of an inert ingredient in a 
pesticide formulation. However, where it can be determined without that 
data that the inert ingredient will present minimal or no risk, the 
Agency generally does not require some or all of the listed studies to 
rule on the proposed tolerance or exemption from

[[Page 79836]]

the requirement of a tolerance for an inert ingredient.
    The data that Firmenich believes supports establishing an exemption 
from tolerance is summarized below. More detailed information has been 
provided to the Agency.
    Octanal has been used in foodstuffs as a flavoring agent since the 
1900's and is approved by the Food and Drug Administration (FDA) as 
generally recognized as safe (GRAS) (21 CFR 172.515) and by the Council 
of Europe as in the list of substances granted ``A status''-- may be 
used in foodstuffs (COE No. 97). It is recognized by the flavor and 
extract manufacturer's association as GRAS (GRAS 3 (2797)).
    1. Acute toxicity. The LD50 of octanal has been 
determined to be 5.63 grams/kilogram (g/kg) for the rat. In an acute 
inhalation toxicity study with rats, no mortality was found after 8 
hours of exposure to a concentrated vapor of octanal. The dermal 
LD50 in rabbits was found to be 6.35 milligram/Liter/
kilogram (mg/L/kg) using a 24 hour occluded patch.
    The LC50 of octanal was found to be 7.9 mg/L in fish 
(Poecilia reticulata) and >111 mg/kg in the bird (redwing blackbird). 
These values are in agreement with the ECOSAR calculated values of 6.1 
mg/L for fish, 2.3 mg/L for Daphnia, and 13.0 mg/L for green algae.
    2. Genotoxicty. An Ames test with and without S-9 using strains TA 
98, TA 100, TA 1535, and TA 1537 at 3 mol/plate produced no 
adverse effects.
    3. Reproductive and developmental toxicity. Toxicity and 
teratogenicity of octanal was evaluated in chickens by injecting 50 
chick embryos suprablastodermally at 72 hours of incubation with 0.05M 
octanal in olive oil. The teratogenicity reproductive effect for 
octanal was 4.16% versus 7.9% for the solvent alone.
    4. Subchronic toxicity. In a 12-week subchronic study with 12 rats 
per sex per dose using a mixture of aldehydes from C-8 to C-12, there 
were no adverse effects at 12.4 mg/kg.
    5. Endocrine disruption. Octanal is not structurally similar to any 
substances known to be an endocrine disrupter.

C. Aggregate Exposure

    Consistent with section 408(c)(2)(B) of FFDCA, Firmenich believes 
that, based on this submission, the Agency has sufficient information 
to assess the hazards of octanal and make a determination on aggregate 
exposure, consistent with section 408(b)(2) for tolerance exemption for 
the residues of octanal on growing crops, RACS after harvest, and 
animals.
    Dietary exposure. For the purpose of assessing the potential 
dietary exposure under these exemptions, Firmenich Incorporated 
considers that octanal could be present in all raw and processed 
agricultural commodities.
     1. Food. Octanal is a GRAS substance 21 CFR 172.515 and is 
included by the Council of Europe in the list of substances granted ``A 
status''--may be used in foodstuffs (COE No. 97). The flavors and 
extract manufacturer's association states: Generally recognized as safe 
as a flavor ingredient--GRAS 3, (2797). The Joint Expert Committee on 
food additives has established an allowable daily intake (ADI) of 0.1 
mg/kg (with nonanal) (1984). Therefore, no concerns for risk associated 
with any potential exposure scenarios are reasonably foreseeable.
    2. Drinking water. Due to the low water solubility (estimated 91 
mg/L by ECOSAR), only very low drinking water exposure is expected and 
would not contribute significantly to the ADI. Therefore, no concerns 
for risk associated with any potential exposure scenarios are 
reasonably foreseeable.

D. Cumulative Effects

    Section 408(b)(2)(D)(v) of FFDCA requires that, when considering 
whether to establish, modify, or revoke a tolerance or tolerance 
exemption, the Agency consider ``available information'' concerning the 
cumulative effects of particular chemical's residues and ``other 
substances that have a common mechanism of toxicity''. Octanal has been 
in public use since the 1900's and the lack of observed toxicity after 
acute and chronic exposure would suggest that a cumulative risk 
assessment is therefore not necessary.

E. Safety Determination

    1. U.S. population. Octanal has been granted self-affirmed GRAS 
status in the United States, is approved for food use in Europe, and by 
the World Health Organization (WHO) Joint Expert Committee on food 
additives, with an ADI of 0.1 mg/kg (based on nonanal). Based on this 
material's low-risk profile, there is reasonable certainty that no harm 
to the U.S. population will result from aggregate exposure to octanal.
    2. Infants and children. FFDCA section 408 provides that EPA shall 
apply a 10-fold margin of safety for infants and children in the case 
of threshold effects to account for prenatal and postnatal toxicity and 
the completeness of the data base unless EPA concludes that a different 
margin of safety will be safe for infants and children. Margins of 
safety are incorporated into EPA risk assessment either directly 
through the margin of exposure (MOE) analysis or through using 
uncertainty (safety) factors in calculating a dose level that poses no 
appreciable risk to humans.
    Due to the extensive available toxicological data base including 
sub-chronic toxicity studies and the expected low toxicity of this 
compound, Firmenich Incorporated does not believe a safety factor 
analysis is necessary in assessing the risk of these compounds. For the 
same reasons, Firmenich believes the additional safety factor is 
unnecessary.

F. International Tolerances

    There are no known international tolerances for octanol.

2. PP 6E4758

    EPA has received a pesticide petition (PP 6E4758) to establish an 
exemption from the requirement of a tolerance for ethyl maltol when 
used as an inert ingredient in the pesticide formulations applied to 
growing crops or to RAC after harvest under 40 CFR 180.1001(c) and 
applied to animals under 40 CFR 180.1001 (e). 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 support granting of the petition. Additional data may be 
needed before EPA rules on the petition.

A. Residue Chemistry

    Since this petition is for an exemption from the requirement of a 
tolerance an analytical method is not required.

B. Toxicological Profile

    As a part of the EPA policy statement on inert ingredients 
published in the Federal Register of April 22, 1987 (52 FR 13305) (FRL 
-3190-1), the Agency set forth a list of studies which generally are 
used to evaluate the risks posed by the presence of an inert ingredient 
in a pesticide formulation. However, where it can be determined without 
that data that the inert ingredient will present minimal or no risk, 
the Agency generally does not require some or all of the listed studies 
to rule on the proposed tolerance or exemption from the requirement of 
a tolerance for an inert ingredient.
    The data that Firmenich believes supports establishing an exemption 
from tolerance is summarized below. More detailed information has been 
provided to the Agency.
    Ethyl maltol has been used in foodstuffs as a flavoring agent since 
the

[[Page 79837]]

1950's and is approved by the FDA as GRAS (21 CFR 172.515) and by the 
Council of Europe as in the list of substances granted ``A status''--
may be used in foodstuffs (COE No. 692). It is recognized by the flavor 
and extract manufacturer's association as GRAS (GRAS 10 (3487)).
    1. Acute toxicity. The LD50 of ethyl maltol has been 
determined to be 1.15 g/kg for the rat, 0.78 g/kg in the mouse, and 
1.27 g/kg in the chicken. While there is no known aquatic testing, the 
ECOSAR program predicts that ethyl maltol would be practically non 
toxic to fish (LC50= 2.3 g/L), Daphnia (LC50= 1.1 
to 3 g/L) and green algae (EC50= 0.6 to 1.4 g/L).
    2. Genotoxicty. An Ames test with and without S-9 using strains TA 
1535, TA 1537, TA 1538, TA 1539 and TA 100 at up to 3.6 mg/plate in 
DMSO or water produced no adverse effects.
    In a micronucleus test with male and female NMRI mice, no adverse 
effects were observed at 24, 48, or 72 hours at 980 mg/kg.
    In a study with Drosophila melangaster the number of sex-linked 
lethal (SRL) chromosomes was counted. The no effect level was 14 
millimolar ethyl maltol.
    3. Reproductive and developmental toxicity. Toxicity and 
teratogenicity of ethyl maltol was evaluated in chickens by injecting 
50 chick embryos suprablastodermally at 72 hours of incubation with 
0.05M ethyl maltol in olive oil. The teratogenicity reproductive effect 
for ethyl maltol was 4.16% versus 7.9% for the solvent alone.
    4. Subchronic toxicity. In a 90-day study with male and female 
Beagle dogs, no effects were observed when the animals were fed 500 mg/
kg ethyl maltol orally. In a study with weanling Albino rats feed 
concentrations of ethyl maltol for 90 days, effects were noted in the 
kidney at 1,000 mg/kg. No mortality occurred.
    5. Chronic toxicity. A 2-year rat reproduction study with ethyl 
maltol involving two separate litters of offspring was conducted at 
levels up to 200 mg/kg. No adverse effects on the parents or offspring 
were observed. Similarly in a 2-year study with Beagle dogs, no adverse 
effects were seen in the parents or offspring at up to 200 mg/kg.
    6. Animal metabolism. The excretion rate of ethyl maltol was 
measured in the dog by both oral and intravenous routes of 
administration. Beagle dogs were fed 200 mg/kg of ethyl maltol daily 
for 99 days and the urine and feces collected for 24 hours after day 
98, and 99. Urinary excretion of the test substance averaged 0.13% of 
the daily dose, while excretion of the sulfate and glucuronide 
conjugates averaged 64.0%. Similarly, 64.5% of a single intravenous 10 
mg/kg dose of ethyl maltol was excreted as the conjugates in 24 hours 
and 66.3% in 72 hours.
    7. Endocrine disruption. Ethyl maltol is not structurally similar 
to any substances known to be an endocrine disrupter.

C. Aggregate Exposure

    Consistent with section 408(c)(2)(B) of FFDCA, Firmenich 
Incorporated believes that, based on this submission, the Agency has 
sufficient information to assess the hazards of ethyl maltol and make a 
determination on aggregate exposure, consistent with section 408(b)(2) 
for tolerance exemption for the residues of ethyl maltol on growing 
crops, RACs after harvest, and animals.
    Dietary exposure. For the purpose of assessing the potential 
dietary exposure under these exemptions, Firmenich Incorporated 
considers that ethyl maltol could be present in all raw and processed 
agricultural commodities.
    1. Food. Ethyl maltol is a GRAS substance 21 CFR 172.515 and is 
included by the Council of Europe in the list of substances granted ``A 
status''--may be used in foodstuffs (COE No. 692). The flavors and 
extract manufacturer's association states: Generally recognized as safe 
as a flavor ingredient--GRAS 3, (3487). The Joint Expert Committee on 
food additives has established an ADI of 0.2 mg/kg) (1974). Therefore, 
no concerns for risk associated with any potential exposure scenarios 
are reasonably foreseeable.
    2. Drinking water. While ethyl maltol is soluble in water, it has 
been used since the 1950's in beverages, candies, and other food items. 
The lack of observed toxicity after acute and chronic exposure would 
indicate that the presence of trace amounts of ethyl maltol in drinking 
water would pose no appreciable risk to humans.

D. Cumulative Effects

    Section 408(b)(2)(D)(v) of FFDCA requires that, when considering 
whether to establish, modify, or revoke a tolerance or tolerance 
exemption, the Agency consider ``available information'' concerning the 
cumulative effects of particular chemical's residues and ``other 
substances that have a common mechanism of toxicity''. Ethyl maltol has 
been in public use since the 1950's and the lack of observed toxicity 
after acute and chronic exposure would suggest that a cumulative risk 
assessment is therefore not necessary.

E. Safety Determination

    1. U.S. population. Ethyl maltol has been granted self-affirmed 
GRAS status in the United States, is approved for food use in Europe, 
and by the WHO Joint Expert Committee on food additives, with an ADI of 
0.2 mg/kg. Based on this material's low-risk profile, there is 
reasonable certainty that no harm to the U. S. population will result 
from aggregate exposure to ethyl maltol.
    2. Infants and children. FFDCA section 408 provides that EPA shall 
apply a 10-fold margin of safety for infants and children in the case 
of threshold effects to account for prenatal and postnatal toxicity and 
the completeness of the data base unless EPA concludes that a different 
margin of safety will be safe for infants and children. Margins of 
safety are incorporated into EPA's risk assessment either directly 
through the MOE analysis or through using uncertainty (safety) factors 
in calculating a dose level that pose no appreciable risk to humans.
    Due to the extensive available toxicological data base including 
sub-chronic toxicity studies and the expected low toxicity of this 
compound, Firmenich Incorporated does not believe a safety factor 
analysis is necessary in assessing the risk of these compounds.

F. International Tolerances

    There are no known international tolerances for ethyl maltol.

3. PP 6E4759

    EPA has received a pesticide petition (6E4759), to amend 40 CFR 
part 180, to establish an exemption from the requirement of a tolerance 
for ethyl methylphenylglycidate when used as an inert ingredient in the 
pesticide formulations applied to growing crops or to raw agricultural 
commodities after harvest under 40 CFR 180.1001(c) and applied to 
animals under 40 CFR 180.1001 (e). 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 
support granting of the petition. Additional data may be needed before 
EPA rules on the petition.

A. Residue Chemistry

    Since the petition is for an exemption from the requirement of a 
tolerance, an analytical method is not required.

B. Toxicological Profile

    As a part of the EPA policy statement on inert ingredients 
published in the

[[Page 79838]]

Federal Register of April 22, 1987 (52 FR 13305) (FRL -3190-1), the 
Agency set forth a list of studies which can generally be used to 
evaluate the risks posed by the presence of an inert ingredient in a 
pesticide formulation. However, where it can be determined without that 
data that the inert ingredient will present minimal or no risk, the 
Agency generally does not require some or all of the listed studies to 
rule on the proposed tolerance or exemption from the requirement of a 
tolerance for an inert ingredient.
    The date that Firmenich believes supports establishing an exemption 
from tolerance is summarized below. More detailed information has been 
provided to the Agency.
    Ethyl methylphenylglycidate has been used in foodstuffs as a 
flavoring agent since the 1930's and is approved by the FDA as GRAS (21 
CFR 182.60) and by the Council of Europe as in the list of substances 
granted ``A status''-- may be used in foodstuffs (COE No. 6002). It is 
recognized by the flavor and extract manufacturer's association as GRAS 
(GRAS 3 (2444)).
    1. Acute toxicity. The LD50 of ethyl 
methylphenylglycidate has been determined to be 5.47 g/kg for the rat, 
5.6 mL/kg for the mouse, and 4.05 g/kg for the guinea pig.
    Due to the very low water solubility of ethyl methylphenylglycidate 
and the octanol/water coefficient (estimated Kow 3.0), acute aquatic 
toxicity testing is thereby precluded.
    2. Genotoxicty. An Ames tests with S-9 fractions from Aroclor-
pretreated rats at doses up to 3.6 mg/plate with and without S-9 gave 
no adverse effect. Similarly, an Ames test, with strains TA98, TA 100, 
TA1535, TA1537 and TA97, also gave no adverse effects. A Drosophila 
melagaster and micronucleus test on mouse bone marrow appeared weakly 
mutagenic in the Drosophila only.
    A chinese hamster ovary (CHO) cell study with ethyl 
methylphenylglycidate treated 8-12 hours without rat S-9 and 2 hours 
with S-9, gave positive sister chromatid exchange effects without S-9 
over the full range of doses tested, 16 - 160 g/mL, and no 
effect with S-9 over the whole range. Similarly, there were significant 
increases in chromosome aberrations over the range 50-500 g/mL 
with and without S-9.
    3. Reproductive and developmental toxicity. Toxicity and 
teratogenicity of ethyl methylphenylglycidate was evaluated in chickens 
with mortality and structural & functional defects being evaluated. The 
teratogenicity NOEC was 25 mg/egg and the LD50 was 8.16 mg/
egg.
    A mouse carcinogenicity and mutagenesis study was conducted in 15/
sex/dose male and female mice by intraperitoneal injection 3X per weeks 
for 8 weeks at the maximum tolerance dose (MTD) and 0.20X MTD of ethyl 
methylphenylglycidate. There were 10 deaths at 0.45 g/kg and 4 deaths 
at 2.15 g/kg. Similarly, an intraperitonile ethyl methylphenylglycidate 
study with male and female mice showed no effects at the highest dose 
treated, 1,856 mg/kg.
    4. Subchronic toxicity. In a 16-week rat study with male and female 
Osborne-Mendel rats at 10,000 parts per million (ppm) ethyl 
methylphenylglycidate weight changes, reproductive effects, growth 
retardation in males, and marked testicular atrophy was observed. In a 
1-year study with male and female Osborne-Mendel rats, no effects were 
observed at 2,500 ppm of ethyl methylphenylglycidate on growth, 
haematology or macroscopic/microscopic tissue examination. In a second 
study, ethyl methylphenylglycidate, was fed to male and female rats for 
15 weeks at 0.0, 0.02, 0.1, and 0.5% in the diet. No effect was 
observed on the growth rate, food consumption, or water consumption of 
the animals. The only effect attributable to the test substance were 
increased organ weight changes in the animals fed at the 0.5% level. 
The no observed adverse effect level was 0.1% ethyl 
methylphenylglycidate, corresponding to 150 and 60 mg/kg/day 
respectively at the beginning and end of the study.
    5. Chronic toxicity. In a rat study, male and female rats were fed 
for 1.5 to 2 years at 0.1% and 0.5% ethyl methylphenylglycidate in 
their diet. No effects were observed at the 0.1% level. At 0.5% in the 
diet, neurotoxic effects, body weight (bwt) changes, pareses of the 
rear extremities with histological degeneration of the ischia nerve, 
and growth inhibition were observed. In a second study with 48 Wistar 
rats/sex at 0, 0.02, 0.1, and 0.5 EMPG in the diet for 2 years, no 
effects were observed at 0.1% (EMPG intake of approximately 35 mg/kg/
day ethyl methylphenylglycidate for the males and 60 mg/kg/day ethyl 
methylphenylglycidate for the females). At 0.5%, weight changes, liver, 
micropathology in other organs, significant decrease in body weight in 
females, increased incidents of histopathology changes in lymph nodes, 
pancreas, adrenal glands, and liver were noted. No differences in 
mortality, hematology, serum chemistry, renal function, organ weights, 
or motor coordination were observed at any dose.
    6. Endocrine disruption. Ethyl methylphenylglycidate is not 
structurally similar to any substances know to be an endocrine 
disrupter.

C. Aggregate Exposure

    Consistent with section 408(c)(2)(B) of FFDCA, Firmenich 
Incorporated believes that, based on this submission, the Agency has 
sufficient information to assess the hazards of ethyl 
methylphenylglycidate and make a determination on aggregate exposure, 
consistent with section 408(b)(2) for tolerance exemption for the 
residues of ethyl methylphenylglycidate on growing crops, RACs after 
harvest, and animals.
    Dietary exposure. For the purpose of assessing the potential 
dietary exposure under these exemptions, Firmenich Incorporated 
considers that ethyl methylphenylglycidate could be present in all raw 
and processed agricultural commodities.
    1. Food. Ethyl methylphenylglycidate is a GRAS substance 21 CFR 
182.60 and is included by the Council of Europe in the list of 
substances granted``A status''--may be used in foodstuffs (COE No. 
6002). The flavors and extract manufacturer's association states: 
Generally recognized as safe as a flavor ingredient--GRAS 3, (2444). 
The Joint Expert Committee on food additives has established an ADI of 
0.5 mg/kg (1984). Therefore, no concerns for risk associated with any 
potential exposure scenarios are reasonably foreseeable.
    2. Drinking water. Due to the low water solubility (estimated 87 
mg/L by ECOSAR), only very low drinking water exposure is expected and 
would not contribute significantly to the ADI. Therefore, no concerns 
for risk associated with any potential exposure scenarios are 
reasonably foreseeable.

D. Cumulative Effects

    Section 408(b)(2)(D)(v) of FFDCA requires that, when considering 
whether to establish, modify, or revoke a tolerance or tolerance 
exemption, the Agency consider ``available information'' concerning the 
cumulative effects of particular chemical's residues and ``other 
substances that have a common mechanism of toxicity''. Ethyl 
methylphenylglycidate has been in public use since the 1930's and the 
lack of observed toxicity after acute and chronic exposure would 
suggest that a cumulative risk assessment is therefore not necessary.

E. Safety Determination

    1. U.S. population. Ethyl methylphenylglycidate has been granted 
self-affirmed GRAS status in the United States, is approved for food 
use in Europe, and by the WHO Joint Expert Committee on food additives, 
with an

[[Page 79839]]

ADI of 0.5 mg/kg. Based on this material's low-risk profile, there is 
reasonable certainty that no harm to the U. S. population will result 
from aggregate exposure to ethyl methylphenylglycidate.
    2. Infants and children. FFDCA section 408 provides that EPA shall 
apply a ten-fold MOE for infants and children in the case of threshold 
effects to account for prenatal and postnatal toxicity and the 
completeness of the data base unless EPA concludes that a different 
margin of safety will be safe for infants and children. Margins of 
safety are incorporated into EPA's risk assessment either directly 
through the MOE analysis or through using uncertainty (safety) factors 
in calculating a dose level that pose no appreciable risk to humans.
    Due to the extensive available toxicological data base including 
chronic toxicity studies and the expected low toxicity of this 
compound, Firmenich Incorporated does not believe a safety factor 
analysis is necessary in assessing the risk of these compounds. For the 
same reasons, Firmenich believes the additional safety factor is 
unnecessary.

F. International Tolerances

    There are no known international tolerances for ethyl methyl-
phenylglycidate
[FR Doc. 00-32152 Filed 12-19-00; 8:45 am]
BILLING CODE 6560-50-S