[Federal Register Volume 67, Number 167 (Wednesday, August 28, 2002)]
[Notices]
[Pages 55243-55249]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 02-21585]


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ENVIRONMENTAL PROTECTION AGENCY

[OPP-2002-0185 FRL-7194-6]


Notice of Filing a Pesticide Petition to Establish 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 for residues of a 
certain pesticide chemical in or on various food commodities.

DATES: Comments, identified by docket ID number OPP-2002-0185, must be 
received on or before September 27, 2002.

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

[[Page 55244]]

that you identify docket ID number OPP-2002-0185 in the subject line on 
the first page of your response.

FOR FURTHER INFORMATION CONTACT: By mail: Bipin 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 ID number OPP-2002-0185. 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 ID number OPP-2002-0185 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 ID number OPP-2002-0185. 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 
ID 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 for residues of a certain 
pesticide chemical in or on various food commodities under section 408 
of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a. 
EPA has determined that

[[Page 55245]]

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: August 16, 2002.
Debra Edwards,
Acting Director, Registration 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 Lyondell Chemical Company and represents the 
view of Lyondell Chemical Company. 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.

 Lyondell Chemical Company

 PP 2E6484

     EPA has received a pesticide petition (2E6484) from Lyondell 
Chemical Company, 1221 McKinney Street, Suite 1600, Houston, TX 77253-
2583 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 for 2-
methyl-1, 3-propanediol in or on all raw agricultural commodities. 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.

A. Residue Chemistry

    1. Plant metabolism. The nature of the residues of 2-methyl-1,3-
propanediol in plants has not been studied. However, biodegradability 
studies suggest that the primary residue is the parent, as 2-methyl-1, 
3-propanediol is slowly degraded by microorganisms. However, once 
metabolism by microorganisms is initiated, complete degradation to 
carbon dioxide and water results.
    2. Analytical method. An exemption from tolerance is requested for 
2-methyl-1,3-propanediol. Therefore, an analytical method for 
measurement of residues is unnecessary.
    3. Magnitude of residues. Calculated maximum residues, based on the 
maximum concentration of pesticides in food crops, are approximately 19 
milligrams/kilogram (mg/kg) commodity.

B. Toxicological Profile

    1. Acute toxicity--i. Acute oral toxicity in rats. Five healthy 
male and five healthy female albino rats were dosed orally with 2-
methyl-1, 3-propanediol at 5.0 g/kg of body weight. The rats were 
observed at 1-, 2- and 4-hours post dose and twice daily for 14 days 
for mortality and toxicity. Body weights were recorded pretest, weekly 
and at termination. All animals were examined for gross pathology. All 
animals survived the 5.0 g/kg oral dose in generally good health. 
Physical signs of diarrhea, chromorhinorrhea and soiling of the 
anogenital area were noted during the observation period. Body weight 
increases were normal. Necropsy results were normal in 8-10 animals. 
Soiling of the anogenital area and pink fluid in the urinary bladder 
were noted in two animals. The LD50 is greater than 5.0 g/kg 
of body weight.
    ii. Acute dermal toxicity in rabbits. Five healthy male and five 
healthy nulliparous and non-pregnant female New Zealand albino rabbits 
were dosed dermally with 2-methyl-1, 3-propanediol at 2.0 g/kg of body 
weight. The test article was kept in contact with the intact skin for 
24 hours. The rabbits were observed 1, 2 and 4 hours post dose and 
twice daily for 14 days for mortality and toxicity. Body weights were 
recorded pretest, weekly and at termination. Skin reactions were scored 
on days 1, 7 and 14. All rabbits were examined for gross pathology. 
Abnormal tissues were preserved in 10% buffered formalin for possible 
future microscopic examination. Nine of ten animals survived the 2.0 g/
kg dermal application. One female died on day 12 with no abnormal 
predeath physical signs. Necropsy of the dead animal revealed 
abnormalities of the lungs, pleural cavity, liver and gastrointestinal 
tract, as well as soiling of the anogenital area and red staining 
around the mouth. Physical signs noted in survivors included diarrhea, 
yellow nasal discharge, few feces, bloated abdomen and soiling of the 
anogenital area. Body weight changes were normal in 7 of 9 survivors. 
Two animals lost weight during the study. Dermal reactions, absent to 
slight on day 1, were absent on days 7 and 14. Necropsy results of 
survivors were normal in 4 of 9 animals. Abnormalities of the kidneys 
and gastrointestinal tract, as well as soiling of the anogenital area 
were noted in the remaining animals. In addition, one animal exhibited 
a tissue mass and hemorrhagic areas on the dorsal abdominal cavity. The 
LD50 is greater than 2.0 g/kg of body weight. The one death 
did not appear to be related to the effect of the test article, as the 
animal appeared normal for 11 days.
    iii. Primary dermal irritation in rabbits. Six healthy New Zealand 
Albino rabbits were dosed dermally with 2-methyl-1, 3-propanediol. 0.5 
milliliter (mL) of the test article was applied to two intact and two 
abraded sites/rabbit for a total dose of 2.0 mL/rabbit. The test 
article was kept in contact with the skin for 4 hours at which time the 
wrappings were removed and dermal reactions were scored at 4, 24, 48 
and 72 hours after test article application. The skin was also 
evaluated for ulceration and necrosis or any evidence of tissue 
destruction at these time periods. There was no erythema or edema noted 
during the observation period.
    iv. Eye irritation in rabbits. Nine healthy New Zealand albino 
rabbits, free from evidence of ocular irritation or corneal damage, as 
determined by pretest fluorescein dye procedures, were dosed with 2-
methyl-1, 3-propanediol. 0.1 mL of the test article was placed into the 
conjunctival sac of one eye of each rabbit. Six eyes remained unwashed. 
Three eyes were washed 20-30 seconds after dosing for 1 minute with 
lukewarm water. The eyes were examined and scored by the Draize 
technique on days 1, 2 and 3. The primary eye irritation score for each 
rabbit, each day, was calculated. The daily average and range were also 
calculated. UNWASHED: All six eyes appeared normal during the study. 
WASHED: There was no corneal opacity or iritis. Slight conjunctival 
irritation, noted in 1 of 3 eyes, cleared by day 2. Two eyes appeared 
normal during the study.
    v. Acute 4-hour inhalation toxicity in rats. The acute inhalation 
toxicity of 2-methyl-1, 3-propanediol was studied by nose-only exposure 
of one group of five male and five female rats to a test atmosphere 
containing the limit concentration of 5.1 and 0.2 g/2-methyl-1, 3-
propanediol per m3 for a 4-hour period. The mass median 
aerodynamic diameter (MMAD) of the particles in the

[[Page 55246]]

aerosol was 2.4 frequent modulation (Fm) with a mean geometric standard 
deviation of 1.4. After exposure, the rats were kept for a 14-day 
observation period. Except for a slightly decreased breathing rate in 
the fourth hour of exposure in one female animal, no exposure-related 
abnormalities were seen during or shortly after exposure or during the 
14-day observation period and no mortality occurred. For rats of this 
strain and age, mean body weight gain was considered to be within the 
normal range. Findings at necropsy were limited to the lungs. Thickened 
hyalin spots or small areas were seen on all lobes of the lungs in all 
female and in three male animals. In a fourth male animal small white 
areas were seen on all lobes of the lungs. It was concluded that the 4-
hour LC50 value of 2-methyl-1, 3-propanediol is higher than 
5.1 g/m3 for both sexes.
    vi. Dermal sensitization guinea pig maximization test. 2-Methyl-1, 
3-propanediol was evaluated for delayed contact hypersensitivity (skin 
sensitization) in guinea pigs that received intradermal and epidermal 
exposures. The study was carried out in accordance with the 
Organization for Economic Cooperation and Development (OECD) Guideline 
No. 406, ``Skin Sensitization'', EEC Directive 84/449/EEC, Part B.6, 
``Skin Sensitization'' and in accordance with the method described by 
Magnusson and Kligman, ``Allergic Contact Dermatitis in the guinea pig 
- Identification of Contact Allergens''. In order to identify the 
slightly irritating and the non-irritating test substance 
concentrations, a preliminary study was carried out. In the main study, 
the experimental animals were intradermally injected with a 10% 
concentration and epidermally exposed to the undiluted test substance, 
while the control animals were similarly treated, but with the vehicle 
only and with a dry patch. Immediately after the epidermal exposure, 
the skin irritation was scored. Two weeks after the epidermal 
application all animals were challenged with test substance 
concentrations of 100%, 50% and 25%, and the vehicle distilled water. 
The challenge reactions were assessed 24-48 hours after bandage 
removal. The epidermal exposure of 2-methyl-1, 3-propanediol in the 
induction phase resulted in no skin irritation. The epidermal exposure 
of 2-methyl-1, 3-propanediol in the challenge phase resulted in three 
positive sensitization reactions in response to the 50% test substance 
concentration. Under the conditions used in this study, 2-methyl-1, 3-
propanediol resulted in a sensitization rate of 15%. Applying the 
rating of allergenicity described by Kligman A.M. (1966) on the results 
obtained in this test, 2-methyl-1, 3-propanediol is considered to have 
mild sensitizing properties.
    2. Genotoxicty--i. Mutagenic Activity of 2-methyl-1,3-propanediol 
in an in vitro mammalian cell gene mutation test with V79 (Chinese 
hamster cells). 2-Methyl-1,3-propanediol was tested in an in vitro 
mammalian cell gene mutation test with V79 chinese hamster cells in the 
presence and absence of a metabolic activation system (S9-mix). 2-
Methyl-1,3-propanediol was tested up to and including a concentration 
of 5,000 milligram/milliliter (mg/mL) in the absence and presence of 
S9-mix. 2-Methyl-1, 3-propanediol did not induce a significant, dose-
related increase in the mutant frequency at the hypoxanthine 
phophoribosyl transferase (HPRT-locus), either with or without 
metabolic activation, in two independently repeated experiments. Under 
the same conditions the positive control chemicals 
ethylmethanesulphonate (6 mm) and dimethylnitrosamine (8mm) produced 
14-23-fold and 8-10 fold increases respectively in the mutant 
frequency, demonstrating the sensitivity of the assay and the 
metabolizing activity of the S9-mix. It was concluded that 2-methyl-
1,3-propanediol is not mutagenic in the V79/HPRT gene mutation test 
system under the experimental conditions described in this report.
    ii. Chromosomal aberrations in cultured peripheral human 
lymphocytes. 2-Methyl-1,3-propanediol was examined for the induction of 
chromosome aberrations in cultured peripheral human lymphocytes in the 
presence and absence of a metabolic activation system (Aroclor-1,254 
induced rat liver S9-mix). 2-Methyl-1,3-propanediol was tested up to 
and including 500 mg/mL in the absence and presence of S9-mix for a 24 
hour and a 48 hour fixation period in the first experiment, and for a 
24 hour fixation period in the second experiment. None of the tested 
concentrations induced a statistically and biologically significant 
increase in the number of cells with chromosome aberrations, either in 
the absence or in the presence of S9-mix. Positive control chemicals, 
mitomycin concentration (C) and cyclophosphamide, both produced a 
statistically significant increase in the incidence of cells with 
chromosome aberrations, indicating that the test conditions were 
optimal and that the metabolic activation system (S9-mix) functioned 
properly. It is concluded that 2-methyl-1, 3-propanediol is not 
clastogenic in human lymphocytes under the experimental conditions 
described in this report.
    iii. Ames Salmonella/Microsome Test. 2-Methyl-1, 3-propanediol was 
tested in the Ames Salmonella/microsome plate test up to and including 
a concentration of 5,000 mg/plate in the absence and presence of S9-
mix. The test substance did not induce a dose-related increase in the 
number of reverent (His+) colonies in each of the four tester strains 
(TA1535; TA1537; TA98 and TA100). These results were confirmed in an 
independently repeated experiment. The test substance was not 
considered mutagenic in this test system.
    3. Reproductive and developmental toxicity--i. Embryotoxicity and 
Teratogenicity Study. Timed pregnant female wistar rats were 
administered 2-methyl-1, 3-propanediol at dosage levels of 300, 600 or 
1,000 mg/kg body weight by oral gavage daily on gestation days 0 to 20. 
Control group females received daily oral administration of water 
(Milli-U). Female body weights were determined daily and food 
consumption of females was determined at periodic intervals during 
pregnancy. On day 21 of gestation, all females were euthanized and 
subjected to examination post-mortem and external, thoracic and 
abdominal macroscopic findings were recorded. The ovaries, and uterine 
horns were dissected and examined for the number of corpora lutea, the 
weight of the gravid uterus, the number and distribution of live 
fetuses and embryo-fetal deaths, the weight and sex of each live fetus 
and externally visible foetal macroscopic abnormalities. Alternate live 
fetuses of each litter were preserved in 96% ethanol or Bouin's fluid, 
and subjected to skeletal or visceral examinations respectively.
    Oral dosing of pregnant female wistar rats with 2-methyl-1, 3-
propanediol, at dose levels of 300, 600 or 1,000 mg/kg body weight/day 
during days 0 to 20 of gestation inclusive, revealed no maternal 
toxicity.
    Treatment at 600 and 1,000 mg/kg body weight/day was associated 
with a slight increase in embryonic resorptions and a corresponding 
slight decrease in live litter size, compared with the concurrent 
controls. However, as all values remained within the laboratory 
background control ranges, the findings were considered to be of 
doubtful toxicological significance.
    There was no indication of an adverse effect of 2-methyl-1, 3-
propanediol on morphological development or skeletal ossification in 
utero.

[[Page 55247]]

    In this embryotoxicity and teratogenicity study, the no observed 
effect Level (NOEL) was 300 mg/kg body weight/day.
    At the request of Lyondell Chemical Company, an independent review 
of the embryotoxicity and teratogenicity study was conducted by a 
reproductive and developmental toxicity expert, L. Irvine (TAS-
Environ). The purpose of the review was to clarify the slight changes 
on embryonic resorptions and litter size that were observed in the 
original study. The reviewer examined the detailed animal data from the 
first study and control animal developmental/reproductive performance 
incidence data from another laboratory with recent experience with the 
same rat strain and supplier and historical data obtained from the 
animal supplier. The latter information was included in the review due 
to the laboratory's limited control data on this rat strain that was 
available for interpretation of the 2-methyl-1, 3-propanediol study.
    The reviewer found the following: (1) In comparison with the 
available data, it was obvious that the incidence of embryonic deaths 
in the control group of the 2-methyl-1, 3-propanediol study was 
unusually low and that the values in the treated groups were more 
typical for the strain; (2) statistically significant inter-group 
differences in embryonic resorptions would not have been expected in 
comparison with a more representative control group; and (3) since 
there were no other indications of potential embryotoxicity and since 
there was clearly no dose-related difference in mean live litter size, 
one could strengthen the study conclusion to state the findings are 
highly unlikely to be of toxicological significance.
    The findings of the TAS-Environ review support and strengthen the 
original conclusions that discount the toxicological significance of 
changes in embryonic resorptions and litter size observed for 2-methyl-
1, 3-propanediol in the embryotoxicity and teratogenicity study.
    ii. Prenatal developmental toxicity in rats. The potential maternal 
toxicity and prenatal developmental toxicity of the test article, 2-
methyl-1, 3-propanediol were evaluated. The test article in the 
vehicle, deionized water, was administered to three groups of 25 bred 
Crl:CD (SD)IGS BR rats once daily from gestation days 0 through 19. 
Dosage levels were 100, 300 and 1,000 mg/kg/day administered at a dose 
volume of 5 mL/kg. A concurrent control group composed of 25 bred 
females received the vehicle, deionized water, on a comparable regimen 
at 5 mL/kg. The route of administration was oral by gastric intubation. 
Clinical observations, body weights and food consumption were recorded. 
On gestation day 20, a laparohysterectomy was performed on all animals. 
The uteri and ovaries were examined and the numbers of fetuses, early 
and late resorptions, total implantations and corpora lutea were 
recorded. Mean gravid uterine weights and net body weight changes were 
calculated for each group. The fetuses were weighed, sexed and examined 
for external, soft tissue and skeletal malformations and variations.
    All maternal animals survived to the scheduled necropsy on 
gestation day 20. No treatment-related clinical findings were observed 
at any dose level. Body weights, body weight gains, gravid uterine 
weights, net body weights, net body weight gains and food consumption 
were unaffected by treatment at any dose level. No test article-related 
internal findings were observed in the dams at any dose level.
    Intrauterine growth and survival were unaffected by test article 
administration at any dose level. The fetal malformations and 
developmental variations observed in the treated groups were considered 
to be spontaneous in origin.
    Based on the results of this study, the no observed adverse effect 
level (NOAEL) for maternal toxicity and prenatal developmental toxicity 
is 1,000 mg/kg/day, the highest dose level tested.
    iii. Two-generation reproductive toxicity study in rats. This study 
was conducted to evaluate the potential adverse effects of 2-methyl-1, 
3-propanediol administration on the reproductive capabilities of the 
F0 and F1 generations and on F1 and 
F2 neonatal survival, growth, and development. The test 
article was administered orally by gavage once daily for at least 70 
consecutive days prior to mating to three groups of F0 and 
F1 parental Crl:CD (SD)IGS BR rats (30/sex/group). A control 
group of identical design received deionized water on a comparable 
regimen. Test article administration continued throughout mating, 
gestation and lactation, until euthanasia for F0 and 
F1 parental animals. All parental animals were observed 
twice daily for appearance and behavior. Clinical observations, body 
weights, and food consumption were recorded at appropriate intervals 
prior to mating and during gestation and lactation. All F0 
and F1 females were allowed to deliver and rear their pups 
until weaning on lactation day 21. On lactation day 21, 35 pups/sex/
group from the pairing of the F0 animals, including five 
potential replacement animals/sex/group were selected for use in the 
F1 generation. These animals were dosed from postnatal day 
(PND) 22-27, inclusively. On PND 28, 30 offspring/sex/group were 
selected to constitute the F1 generation. The remaining 5 
offspring/sex/group were submitted for necropsy. Developmental 
landmarks anogenital distance, balanopreputial separation and vaginal 
patency were evaluated for the selected F1 rats. Unselected 
F0 and F1 pups were necropsied on postnatal day 
(PND) 21-28; selected organs were weighed on PND 21. All surviving 
F0 and F1 parental animals received a complete 
detailed gross necropsy following the completion of weaning of the 
F0 and F1 pups, respectively; selected organs 
were weighed. Spermatogenic endpoints (sperm motility, morphology and 
numbers) were recorded for all F0 and F1 males, 
and ovarian primordial follicle and corpora lutea counts and the 
presence or absence of growing and antral follicles were recorded for 
10 F0 and 10 F1 females in each of the control 
and high-dose groups. Designated tissues from 10 F0 and 
F1 parental animals/sex/group in the control and 1,000 mg/
kg/day groups and from all parental animals that were found dead or 
euthanized in extremis were examined microscopically. In addition, any 
tissues that appeared abnormal were also examined microscopically.
    No test article-related mortalities or clinical findings were 
observed in the F0 or F1 generation. One 
F0 male in the 300 mg/kg/day group was euthanized in 
extremis during week 2 due to shallow, slow respiration and excreta-
related findings on the day prior to and on the day of euthanasia. At 
necropsy, this animal had a dilated left renal pelvis (hydronephrosis) 
and white content and white areas on the right renal pelvis. The 
pathology for this animal was determined microscopically to be 
pyelonephritis. All other F0 animals survived to the 
scheduled necropsy. In the F1 generation, one control group female was 
found dead during study week 27 (prior to pairing) due to accidental 
mechanical trauma to the neck. All F1 animals that were 
paired survived to the scheduled necropsy.
    Reproductive parameters were not adversely affected by test article 
administration at dose levels of 100, 300 and 1,000 mg/kg/day during 
the F0 or F10 generations. No adverse test 
article-related effects on weekly, gestation or lactation body weight, 
body weight gain, food consumption or food efficiency were observed in 
the F0 or F1 generations.
    No test article-related macroscopic or microscopic internal 
findings were observed in the F0 or F1 generation

[[Page 55248]]

males or females. Absolute and relative (to final body weight) organ 
weights were unaffected by test article administration for males and 
females in the F0 or F1 generations.
    Mean F0 or F1 pup body weights, sex ratios, 
live litter sizes, numbers of dead pups on lactation day 0 and 
viability indices were unaffected by test article administration. No 
test article-related effects on physical development or behavioral 
responses were observed for the F1 pups.
    No test article-related internal findings were noted in the 
F0 or F1 pups that died or were euthanized, or at 
the scheduled necropsies. Necropsy findings for the selected weanling 
pups did not suggest any effects of test article administration. No 
test article-related effects on estrous cycle or gestation length, 
parturtion, ovarian primordial, follicle and corpora lutea counts, the 
presence of growing and antral follicles, implantation site counts or 
spermatogenic endpoints sperm motility, morphology and numbers were 
observed in either the F0 or F1 generation.
    In conclusion, no parental, neonatal or reproductive toxicity was 
observed as a result of test article administration at dose levels of 
100, 300 and 1,000 mg/kg/day. Based on the results of this study, the 
no-observed-adverse-effect level (NOAEL) for parental, neonatal and 
reproductive toxicity is 1,000 mg/kg/day.
    4. Subchronic toxicity--i. Sub-acute 14-day oral toxicity in the 
rat. In this subacute 14-day toxicity study, 2-methyl-1, 3-propanediol 
was administered daily by gavage to SPF-bred wistar rats at 300, 600 or 
1,000 mg/kg/day, in order to provide a basis for selection of dose 
levels for a 90-day study. All animals were subjected to daily clinical 
observation. Body weight was measured on day 1, after 1 week and on the 
day before necropsy and food consumption weekly. During week 2 of 
treatment, both eyes of all animals were examined. On the day of 
termination blood was collected from each animal for clinical 
laboratory investigations. Subsequently, macroscopic observations and 
organ weights were recorded. A histopathological examination was 
performed on adrenals, heart, kidneys, liver, spleen, stomach and 
testes. There were no treatment-related changes for any of the 
treatment groups for the parameters evaluated. From the results 
presented in this report, a definitive no observed effect level (NOEL) 
of 1,000 mg/kg/day was established.
    ii. 90-day oral toxicity in the rat. In this sub-chronic 90-day 
oral toxicity study, 2-methyl-1, 3-propanediol was administered daily 
by gavage to SPF-bred Wistar rats. The study consisted of 4 groups, 
each comprising 10 males and 10 females, and dosed at 0, 300, 600 or 
1,000 mg/kg/day. Dose levels were selected based on the results of a 
14-day range finding study. (RCC NOTOX 09171).
    All animals were subjected to daily clinical observation. Body 
weight and food consumption were measured weekly and, for body weights, 
also on the day of necropsy. Ophthalmoscopic examinations were 
performed prior to commencement of treatment on all animals and at week 
13 on all animals of the control and high dose groups. During the last 
week of treatment (week 13) blood was collected from each animal for 
clinical laboratory investigations. At the end of week, all animals 
were necropsied and macroscopic observations and organ weights 
recorded. Samples of all tissues were taken and fixed. A selection of 
organs from animals of the control and high dose groups were 
histologically processed and subsequently subjected to pathological 
examination.
    There were no treatment-related changes for any of the treated 
groups for the parameters evaluated. From the results presented in this 
report, a definitive no observed effect level (NOEL) of 1,000 mg/kg/day 
was established.
    5. Chronic toxicity. Neither oncogenicity nor 2-year feeding 
studies in animals have been completed using 2-methyl-1, 3-propanediol 
as the test material.
    6. Endocrine disruption. Nothing in the available literature 
suggests that 2-methyl-1, 3-propanediol is an endocrine disruptor or 
that it possesses intrinsic hormonal activity.

C. Aggregate Exposure

    1. Dietary exposure--i. Food. The inert, 2-methyl-1, 3-propanediol, 
will be added to water-soluble pesticide formulations as a solvent and/
or surfactant. These pesticide formulations will be applied to raw 
agricultural commodities as insecticides, herbicides or fungicides. The 
maximum amount of 2-methyl-1,3-propanediol in any particular 
formulation is expected to represent no more than 4% of the formulation 
or a maximum of 8 pounds of 2-methyl-1, 3-propanediol per acre of crop.
    The amount of 2-methyl-1,3-propanediol expected to be present in 
crops grown for human consumption is estimated based on the maximum 
potential residues of 2-methyl-1,3-propanediol on ready-to-eat raw 
agricultural commodities (i.e., scraped, peeled, washed, etc.) taken 
from the USDA Pesticide Data Program (1999).
    Potential residues of 2-methyl-1,3-propanediol were estimated from 
USDA pesticide residue studies from ready-to-eat fruits and vegetables. 
It has been projected that 2-methyl-1,3-propanediol will represent no 
more than 4% of any given pesticide formulation. However, as there are 
currently no data to describe the affinity that 2-methyl-1, 3-
propanediol may have for particular crops or for specific areas of a 
crop (i.e., skin, root, leaf), Lyondell Chemical Company assumed that 
100% of 2-methyl-1, 3-propanediol applied remains on the treated crop, 
a very conservative assumption. The highest pesticide residue, 19.0 mg/
kg food, was measured for fresh strawberries. Assuming that 3.0 kg food 
(solids and liquids) are consumed per day and that the maximum residue 
calculated for fruits and vegetables is present in the entire diet 19 
mg/kg food, the estimated daily intake (EDI) for an adult weighing 71.8 
kg is 0.8 mg 2-methyl-1, 3-propanediol/kg/day and the EDI for a child 
weighing 22.0 kg is estimated to be 2.58 mg 2-methyl-1, 3-propanediol/
kg/day.
    a. Acute exposure. Acute oral toxicity studies on 2-methyl-1,3-
propanediol conclude that adverse effects in rats and mice were seen 
throughout the 14 day observation period. Though a LOAEL was not 
established in either study, Lyondell Chemical Company determined a 
LOAEL of 5,000 mg/kg is reasonable based on the observations of initial 
adverse effects. Observable effects included diarrhea, chromorhinorrhea 
and soiling of the anogenital area. These effects were observable 
during the 14 days after dosing, and though no animals died, they can 
be considered observable adverse effects. The calculated acute 
reference dose (RfD) is 16.0 mg/kg/day based on the estimated acute 
toxicity LOAEL (5,000 mg/kg/day) and the appropriate uncertainty 
factors accounting for potential intraspecies variation, for potential 
interspecies variation, and the use of an estimated LOAEL in place of a 
NOAEL (10 x 10 x 3 or 300-fold uncertainty factor).
    b. Chronic Exposure. The calculated chronic RfD is based on a two-
generation reproductive toxicity study, in which the paternal, neonatal 
and reproductive NOAEL was determined to be 1,000 mg/kg/day. Using the 
appropriate uncertainty factors accounting for the potential 
intraspecies variation, for potential interspecies variation, and a 
worst case modifying factor (10 x 10 or 100-fold uncertainty

[[Page 55249]]

factor), the chronic RfD is estimated to be 10.0 mg/kg/day.
    ii. Drinking water. The theoretical residues calculated for dietary 
intake included intake from drinking water (one-half of the 3 kg food 
consumed per day is assumed to be liquids.) Since 2-methyl-1, 3-
propanediol is a surfactant, and is water soluble, it is expected that 
some exposure in drinking water will occur. However, it is unlikely 
that drinking water exposures exceeding those calculated above, 
assuming direct application of pesticides containing this inert would 
occur due to runoff or leaching into groundwater. Biodegradability 
studies indicate that 2-methyl-1, 3-propanediol is inherently 
biodegradable (modified Sturm test; 54% of the material degraded in the 
observed time.)
    2. Non-dietary exposure. 2-Methyl-1, 3-propanediol is currently 
used as a neutralizer, emollient, emulsifier, and humectant in numerous 
personal care products. The chemical is also used in the synthesis of 
polyester polyols for solvent and waterborne urethane and high solid 
and powder polyester coatings. The chemical also holds several FDA 
approvals and clearances for use in food contact applications, 
including its use in adhesives, resinous and polymeric coatings, paper 
and paperboard in contact with aqueous, fatty, and dry foods, 
slimicides, and polyurethanes in contact with bulk dry food.

D. Cumulative Effects

     There is insufficient information to determine whether other 
compounds have a common mechanism of toxicity to 2-methyl-1, 3-
propanediol.

E. Safety Determination

    1. U.S. population. Using the above estimated RfDs, the adult 
estimated daily intake (EDI) represents 5 percent of the acute RfD and 
8 percent of the chronic RfD. EPA generally has no concern for 
exposures below 100% of the RfD because the RfD represents the level at 
or below which daily aggregate dietary exposure over a lifetime will 
not pose appreciable risks to human health. It should be noted that the 
exposures estimates are conservative and exaggerated.
    2. Infants and children. The EDI for a child represents 16 percent 
of the acute RfD and 26 percent of the chronic RfD. Based on these 
data, it may be concluded that there is a reasonable certainty that no 
harm will result from aggregate exposure to 2-methyl-1, 3-propanediol 
residues to the U.S. population, including both adults and children.

F. International Tolerances

     There are no international tolerances listed for 2-methyl-1, 3-
propanediol.
[FR Doc. 02-21585 Filed 8-27-02; 8:45 am]
BILLING CODE 6560-50-S