[Federal Register Volume 62, Number 83 (Wednesday, April 30, 1997)]
[Notices]
[Pages 23455-23460]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 97-10893]


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ENVIRONMENTAL PROTECTION AGENCY

[PF-728; FRL-5600-8]


Notice of Filing of Pesticide Petitions

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 agricultural commodities.

DATES: Comments, identified by the docket control number PF-728, must 
be received on or before May 30, 1997.

ADDRESSES: By mail submit written comments to: Public Response and 
Program Resources Branch, Field Operations Divison (7505C), Office of 
Pesticides Programs, Environmental Protection Agency, 401 M St., SW., 
Washington, DC 20460. In person bring comments to: Rm. 1132, CM #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. 1132 at the 
address given above, from 8:30 a.m. to 4 p.m., Monday through Friday, 
excluding legal holidays.

FOR FURTHER INFORMATION CONTACT: By mail, George LaRocca, Product 
Manager, (PM 13), Registration Division (7506C), Office of Pesticide 
Programs, Environmental Protection Agency, 401 M St., S.W., Washington, 
DC 20460. Office location, telephone number and e-mail address: Crystal 
Mall #2, 1921 Jefferson Davis Highway, Arlington, VA, 703-305-6100; e-
mail: [email protected].

SUPPLEMENTARY INFORMATION: 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 raw 
agricultural 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 
supports grantinig of the petition. Additional data may be needed 
before EPA rules on the petition.
    The official record for this notice, as well as the public version, 
has been established for this notice of filing under docket control 
number PF-728 (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:
    [email protected]


    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 file format or ASCII 
file format. All comments and data in electronic form must be 
identified by the docket control number (PF-728) and appropriate 
petition number. Electronic comments on this notice may be filed online 
at many Federal Depository Libraries.

    Authority: 21 U.S.C. 346a.

List of Subjects

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

    Dated: April 10, 1997.

Stephen L. Johnson,
Director, Registration Division, Office of Pesticide Programs.

Summaries of Petitions

    Below summaries of the pesticide petitions are printed. The 
summaries of the petitions were prepared by the petitioners. 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.

1. Gowan Company

PP 6F4738

    EPA has received a pesticide petition (PP 6F4738) from Gowan 
Company, P. O. Box 5569, Yuma, AZ 85366-5569. The petition proposes, 
pursuant to section 408 of the Federal Food, Drug and Cosmetic Act 
(FFDCA), 21 U.S.C. 346a(d), to amend 40 CFR part 180 to establish 
tolerances for the acaricide hexythiazox (The chemical name of 
hexythiazox is trans-5-(4-chlorophenyl)-N-cyclohexyl-4-methyl-2-
oxothiazolidine-3-carboxamide.) and its metabolites (Metabolites 
containing the (4-chlorophenyl)-4-methyl-2-oxo-3-thiazolidine moiety 
are included in the tolerance expression.) in or on the raw 
agricultural commodities stone fruits (except plums) at 1 part per 
million (ppm), almonds at 0.2 ppm and almond hulls at 10 ppm, and also 
in milk, cattle meat and cattle fat at 0.05 ppm and cattle meat 
byproducts at 0.1 ppm. The proposed analytical method is high 
performance liquid chromatography with an ultraviolet detector (HPLC 
with UV detection).

A. Residue Chemistry

    1. Plant metabolism. The metabolism of hexythiazox in apples, 
pears, grapes and citrus has been studied. The major portion of the 
residue is parent compound. The metabolites are hydroxycyclohexyl and 
ketocyclohexyl analogs of hexythiazox and the amide formed by loss of 
the cyclohexyl ring.
    2. Animal metabolism. The metabolism of hexythiazox in goats, hens 
and rats has been studied. Metabolic pathways in animals are similar to 
those in plants.
    3. Analytical method. An adequate analytical method (HPLC with UV 
detection) is available for enforcement purposes. Parent compound and 
all of its metabolites are converted to a common moiety before 
analysis.

[[Page 23456]]

    4. Magnitude of residues. Twenty-four stone fruit residue trials 
were conducted over three years. The geographic distribution of the 
trials agrees with the recommendation given in the ``EPA Residue 
Chemistry Guidance'' (1994). In these trials, the maximum combined 
residues of hexythiazox and its metabolites were 0.52 ppm. Seven almond 
residue trials were conducted over three years. In these trials, the 
maximum combined residues of hexythiazox and its metabolites were 0.17 
ppm in almond nutmeat and 7.5 ppm in the raw agricultural commodity 
almond hulls.

B. Toxicological Profile

    1. Acute toxicity. The acute oral and dermal LD50 of 
technical hexythiazox is greater than 5,000 mg/kg, and the 4-hour acute 
inhalation LC50 is greater than 2 mg/L. It is not a dermal 
irritant or sensitizer and is a mild eye irritant.
    2. Genotoxicity. The following genotoxicity tests were all 
negative: Ames gene mutation, Chinese hamster ovary (CHO) gene 
mutation, CHO chromosome aberration, mouse micronucleus and rat 
hepatocyte unscheduled DNA synthesis.
    3. Reproductive and developmental toxicity. Hexythiazox has not 
been observed to induce developmental or reproductive effects. The 
lowest reproductive or developmental NOEL (No Observed Effect Level) 
observed was 200 mg/kg/day, the highest dose tested, in a 2-generation 
rat reproduction study.
    4. Chronic toxicity. The Office of Pesticide Programs has 
established the Reference Dose (RfD) for hexythiazox at 0.025 mg/kg/
day. The RfD for hexythiazox is based on a 1-year dog feeding study 
with a NOEL of 2.5 mg/kg/day and an uncertainty factor of 100. The 
endpoint effect of concern was hypertrophy of the adrenal cortex in 
both sexes, decreased red blood cell counts, hemoglobin content and 
hematocrit in males.
    5. Carcinogenicity. The Agency has classified hexythiazox as a 
category C (possible human) carcinogen based on an increased incidence 
of hepatocellular carcinomas (p = 0.028) and combined adenomas/
carcinomas (p = 0.024) in female mice at the highest dose tested (1,500 
ppm) when compared to the controls as well as a significantly increased 
(p <0.001) incidence of pre-neoplastic hepatic nodules in both males 
and females at the highest dose tested. The decision supporting a 
category C classification was based primarily on the fact that only one 
species was affected and mutagenicity studies were negative. In 
classifying hexythiazox as a category C carcinogen, the Agency 
concluded that a quantitative estimate of the carcinogenic potential 
for humans should be calculated because of the increased incidence of 
liver tumors in the female mouse. A Q1* of 0.039 (mg/kg/day)-1 in human 
equivalents was calculated.

C. Aggregate Exposure

    Tolerances have been established (40 CFR 180.448) for combined 
residues of hexythiazox [trans-5-(4-chlorophenyl)-N-cyclohexyl-4-
methyl-2-oxothiazolidine-3-carboxamide] and its metabolites containing 
the (4-chlorophenyl)-4-methyl-2-oxo-3-thiazolidine moiety in or on 
apples at 0.02 ppm and pears at 0.3 ppm. The nature and metabolism of 
hexythiazox in plants and animals is adequately understood.
    Hexythiazox is also registered for use on outdoor ornamental plants 
by commercial applicators only. It is believed that non-occupational 
exposure from this use is very low. Hexythiazox is not registered for 
greenhouse, lawn, garden, or residential use. The environmental fate of 
hexythiazox has been evaluated, and the compound is not expected to 
contaminate groundwater or surface water to any measurable extent.
    1. Chronic Exposure. The Agency has estimated in the Federal 
Register of February 21, 1996, [61 FR 6552-6554] (FRL-5350-6), that 
current uses on apples and pears would result in an exposure of 
0.000051 mg/kg/day for the U.S. population, assuming that all residues 
are at tolerance levels and 100 percent of the crops are treated. Non-
nursing infants, the subgroup having the highest exposure, would have 
an exposure of 0.000600 mg/kg/day. Using the same conservative 
assumptions, it is calculated that the current and proposed uses 
together would result in an exposure of 0.001920 mg/kg for the U.S. 
population and 0.006598 mg/kg/day for non-nursing infants, which 
remains the most highly exposed subgroup.
    Actual exposure will be much lower, however. Only a small fraction 
of these crops will be treated with hexythiazox, and average residues 
are far below the tolerance levels. For example, residues in apples 
treated at 10 times the currently approved application rate remained 
below the limit of quantitation, 0.01 ppm. Also, residues in apple 
juice are expected to be less than 50 percent of the residue level in 
the whole fruit. Average residues in stone fruits except cherries are 
expected to be 7 percent of the proposed tolerance level, average 
residues in cherries are expected to be 11 percent of the tolerance 
level and average residues in almond nutmeat are expected to be below 
20 percent of the proposed tolerance level. Furthermore, only a very 
small percentage of crops (less than 1 percent up to 5 percent, 
depending on the crop) are expected to be treated with hexythiazox. 
When actual residues rather than tolerance levels and the percentage of 
treated crop are taken into account, then the actual exposure is 
estimated to be 0.0000013 mg/kg/day for the U.S. population.
    Gowan has not conducted a detailed analysis of potential exposure 
to hexythiazox via drinking water or outdoor ornamental plants. 
However, it is believed that chronic exposure from these sources is 
very small.
    2. Acute exposure. No developmental, reproductive or mutagenic 
effects have been observed with hexythiazox. Therefore, an analysis of 
acute exposure has not been conducted.
    3. Cumulative effects note. At this time Gowan has not reviewed 
available information concerning the potentially cumulative effects of 
hexythiazox and other substances that may have a common mechanism of 
toxicity. For purposes of this petition only, Gowan is considering only 
the potential risks of hexythiazox in its aggregate exposure.

D. Determination of Safety for U.S. Population

    1. Chronic Risk. The Agency has calculated in the Federal Register 
of February 21, 1996, [61 FR 6552-6554], (FRL-5350-6), assuming that 
residues are at tolerance levels and 100 percent of crops are treated, 
that the current use on apples and pears utilizes 0.2 percent of the 
RfD for the U.S. population and 2.4 percent of the RfD for non-nursing 
infants. Using these same assumptions, it is calculated that all 
current and proposed uses would result in TMRCs equivalent to 7.7 
percent of the RfD for the U.S. population and 26.4 percent of the RfD 
for non-nursing infants. However, when actual residues rather than 
tolerance levels and the percent of crop treated are taken into 
account, actual chronic risk for the U.S. population is expected to be 
only 0.005 percent of the RfD.
    The actual dietary carcinogenic risk to the U.S. population is 
calculated to be 5  x  10-8, which is well below the Agency's criterion 
of 1  x  10-6.
    2. Acute Risk. An estimate of acute risk with this compound has not 
been conducted since no acute reproductive or developmental effects 
have been observed.

[[Page 23457]]

E. Determination of Safety for Infants and Children

    In assessing the potential for additional sensitivity of infants 
and children to residues of hexythiazox, EPA considered data from 
developmental toxicity studies in the rat and rabbit and a 2-generation 
study in the rat. The developmental toxicity studies are designed to 
evaluate adverse effects on the developing organism resulting from 
pesticide exposure during prenatal development to one or both parents. 
Reproduction studies provide information relating to effects from 
exposure to the pesticide on the reproductive capability of mating 
animals and data on systemic toxicity.
    No developmental or reproductive effects have been observed in any 
study with hexythiazox. The lowest acute NOEL was 2,400 ppm in the diet 
(200 mg/kg/day), the highest dose tested, in the 2-generation rat 
reproduction study. In the rat developmental study, the maternal and 
fetotoxic NOEL was 240 mg/kg/day and the developmental NOEL was 2,160 
mg/kg/day, the highest dose tested. In the rabbit developmental study, 
the maternal and developmental NOEL was 1,080 mg/kg/day, the highest 
dose tested.
    Taking into account current toxicological data requirements, the 
database for hexythiazox relative to prenatal and postnatal effects is 
complete. In the rat developmental study, the NOELs for maternal 
toxicity and fetotoxicity were the same, which suggests that there is 
no special prenatal sensitivity in the absence of maternal toxicity. 
Furthermore, the lowest developmental or reproductive NOEL is two 
orders of magnitude higher than the chronic NOEL on which the RfD is 
based. It is concluded that there is a reasonable certainty of no harm 
to infants and children from aggregate exposure to hexythiazox 
residues.

F. International Tolerances

    Codex maximum residue levels (MRLs) of 1 mg/kg (1 ppm) have been 
established for residues of hexythiazox in cherries and peaches. The 
U.S. tolerance proposal for stone fruits is in harmony with these MRLs. 
There are no Codex MRLs for the other commodities in this petition.

2. AgroEvo Environmental Health

PP 7F4820

    EPA has received a pesticide petition from AgroEvo Environmental 
Health, 95 Chestnut Ridge Road, Montvale, NJ 07645. The petition 
proposes, pursuant to section 408 of the Federal Food, Drug and 
Cosmetic Act (FFDCA), 21 U.S.C. 346a(d), to amend 40 CFR part 180 to 
establish tolerances for deltamethrin in or on food and feed items as a 
result of use in food and feed handling establishments at 0.05 part per 
million (ppm). This petition was assigned Pesticide Petition Number 
7F4820 (formerly 4H5710) and was initially announced in the Federal 
Register of February 8, 1995 [60 FR 7539-7541], (FRL-4926-4). A 
tolerance of 0.02 ppm was proposed for residues of deltamethrin in or 
on food and feed items, and published for comment in the Federal 
Register dated November 30, 1995 [60 FR 61504-61506], (FRL-4983-5). In 
an effort to harmonize with a similar tolerance established in Germany, 
the proposed tolerance was increased to 0.05 ppm per comments received 
from the German Ministry of Health. The proposed analytical method is 
high performance liquid chromatography with an ultraviolet detector.

A. Residue chemistry

    1. Analytical Method. A practical analytical method using gas - 
liquid chromatography is available for detecting and measuring levels 
of deltamethrin in food and feed items. This method is used for the 
determination of cis-deltamethrin, trans-deltamethrin, and alpha-R-
deltamethrin. The limit of quantitation (LOQ) is 0.02 mg/kg (ppm). The 
enforcement methodology has been submitted to the Food and Drug 
Administration for publication in the Pesticide Analytical Manual 
Volume II (PAM II).
    2. Nature and Magnitude of the Residue in Food and Feed Items. The 
nature of the residues of deltamethrin in plants and animals relevant 
to the establishment of food and feed additive tolerances is adequately 
understood. The residue of concern is deltamethrin. In studies 
conducted to support this use, residue levels of deltamethrin in food 
and/or feed items after applications to food- and feed-handling 
establishments were below the LOQ, i.e., below 0.02 ppm. There is no 
reasonable expectation of secondary residues in eggs, meat, milk, or 
poultry from the proposed use as delineated in 40 CFR 180.6(a)(3).

B. Toxicological Profile

    1. Acute Toxicity. The acute rat oral LD50 of 
deltamethrin technical was 66.7 mg/kg (males) and 86 mg/kg (females) 
when administered in sesame oil and greater than 5,000 mg/kg in both 
sexes when administered in 1 percent aqueous methylcellulose. The acute 
dermal LD50 was greater than 2,000 mg/kg when administered 
to rabbits in either polyethylene glycol or 1 percent aqueous 
methylcellulose, and greater than 2,940 mg/kg when administered to rats 
in 1 percent aqueous methylcellulose. The 4-hour rat inhalation 
LC50 was 2.2 mg/l. Deltamethrin was slightly irritating to 
rabbit eyes, non-irritating to rabbit skin, and did not induce skin 
sensitization in guinea pigs.
    2. Subchronic Toxicity. In a 90-day study, deltamethrin was mixed 
with polyethylene glycol 200 (PEG 200) and administered by gavage to 
rats at dose levels of 0, 0.1, 1, 2.5 and 10 mg/kg/day. The only 
treatment-related effects observed were reduced body weight gain in 
rats at 2.5 and 10 mg/kg/day and slight hypersensitivity in rats at 10 
mg/kg/day at week 6, but not at week 13. The NOEL in this study was 1.0 
mg/kg/day. In a more recent 90-day study (not yet submitted to the 
Agency), deltamethrin was administered via the diet to rats at dietary 
concentrations of 30, 300, 1,000, 3,000 and 6,000 ppm. All animals in 
the 3,000 and 6,000 ppm groups and several animals from the 1,000 ppm 
group died or were killed in extremis during the first few weeks of the 
study. Decreased food and water consumption, decreased weight gain and 
a variety of neurological signs of toxicity (including uncoordinated 
movement, unsteady gait, tremors, increased sensitivity to sound, ``wet 
dog shakes'' and spasmodic convulsions) were noted in these three dose 
groups. A slight but statistically significant decrease in weight gain 
was noted in females at 30 and 300 ppm but was considered to be of 
equivocal significance because of the lack of a clear, consistent dose-
response relationship. There were no changes in clinical pathology 
parameters, organ weights or gross or microscopic pathology at any dose 
level. Thus, the NOEL for this study was considered to be 300 ppm (23.9 
mg/kg/day in males and 30.5 mg/kg/day in females).
     A 12-week feeding study of deltamethrin was conducted in mice at 
dietary concentrations of 0, 30, 300, 3,000 and 6,000 ppm. Effects 
noted at 3,000 and 6,000 ppm consisted of clinical signs of toxicity 
(clonic contractions, convulsions and poor condition), decreased weight 
gain and mortality. A very slight decrease in weight gain was noted in 
males at 30 and 300 ppm but was considered to be of equivocal 
significance. There were no effects on hematology, blood chemistry, or 
organ weights.
    The only histopathological lesions noted were thymic involution and 
lipid depletion in the adrenal glands of animals at 3,000 and 6,000 
ppm, which

[[Page 23458]]

were considered likely to be secondary effects of the stress induced by 
the poor physical condition of the animals. Consequently, 300 ppm (61.5 
mg/kg/day in males and 77.0 mg/kg/day in females) was considered to be 
the NOEL.
    In a 13-week study, deltamethrin was administered to beagle dogs by 
capsule at dose levels of 0, 0.1, 2, 2.5 and 10 mg/kg/day, using PEG 
200 as a vehicle. There was no mortality but animals at the top two 
dose levels exhibited various clinical signs of toxicity (e.g., 
tremors, unsteadiness, jerking movements, excessive salivation, 
vomiting, liquid feces, and/or dilatation of the pupils) and modified 
EEG patterns. No histopathological findings were observed. The NOEL for 
this study was considered to be 1.0 mg/kg/day.
    In a more recent study, deltamethrin was administered dry (without 
vehicle) via capsule to beagle dogs for 13 weeks at dose levels of 0, 
2, 10 and 50 mg/kg/day. No mortality occurred during the study but 
animals at 50 mg/kg/day exhibited decreased food consumption and weight 
gain and a variety of clinical signs including unsteady gait, tremors, 
shaking of the head, vomiting and salivation. There were no effects on 
clinical pathology, ophthalmoscopy, organ weights or pathology. The 
NOEL for this study was 10 mg/kg/day. The difference in toxicity 
between the two dog studies is attributed to the enhanced absorption 
resulting from the use of PEG 200 as a vehicle in the first study.
    In a 21-day dermal toxicity study, deltamethrin was admixed with 
polyethylene glycol and applied dermally to rats for 6 hours per day 
for 21 successive days at dose levels of 0, 100, 300 and 1,000 mg/kg/
day. Signs of local dermal irritation were noted at all dose levels. No 
conclusive evidence of systemic toxicity was noted at any dose level. 
However, because of slight, non-statistically significant decreases in 
weight gain and food consumption in males at 300 and 1,000 mg/kg/day, 
the EPA concluded that the NOEL for this study was 100 mg/kg/day.
    In a subchronic inhalation study, rats were exposed to aerosolized 
deltamethrin at concentrations of 0, 3, 9.6 and 56.3 g/l for 6 hours 
per day, 5 days per week, for a total of 14 days over 3 weeks. Signs of 
local irritation (agitated grooming and scratching) and excessive 
salivation were noted in all treated groups. Peripheral vasodilation 
was noted at 9.6 and 56.3 g/l. Ataxia and walking with arched back were 
noted at 56.3 g/l. Based on slightly decreased body weights and 
neurological effects at higher dose levels, AgroEvo Environmental 
Health concluded that 3 g/l was the NOEL for systemic effects in this 
study.
    3. Chronic Toxicity/Oncogenicity. In a 2-year feeding study, 
deltamethrin was administered to beagle dogs at dietary concentrations 
of 0, 1, 10 and 40 ppm. No treatment-related effects were noted in any 
animal. Thus, 40 ppm (1.1 mg/kg/day) was considered to be the NOEL. In 
a more recent study, deltamethrin was administered dry, via capsule, to 
beagle dogs for 1 year at dose levels of 0, 1, 10 and 50 mg/kg/day. 
Effects observed at 10 and 50 mg/kg/day included clinical signs of 
toxicity (e.g., unsteadiness, abnormal gait, tremors, chewing/
scratching of extremities and liquid feces), decreased food consumption 
(high dose only) and changes in several hematology and blood chemistry 
parameters. There were no treatment related gross or histopathological 
findings. The NOEL in this study was also considered to be 1 mg/kg/day.
    No evidence of oncogenicity was noted in either of two chronic rat 
feeding studies. In the first study, deltamethrin was administered to 
rats for 2 years at dietary concentrations of 0, 2, 20 and 50 ppm. The 
NOEL was considered to be 20 ppm (1 mg/kg/day) based on slightly 
decreased weight gain at 50 ppm. In a more recent study, deltamethrin 
was administered to rats for 2 years at dietary concentrations of 0, 
25, 125, 500 and 800 ppm. Neurological effects (uncoordinated movement 
of limbs, abnormal gait and unsteady gait) were noted at 500 and 800 
ppm during the first week of the study but subsided and were no longer 
apparent by Week 8. Minor effects on weight gain were also noted at 
these two dose levels. Microscopic evidence of slight hepatotoxicity 
(increased incidence and severity of eosinophilic hepatocytes and/or 
ballooned cells) was noted in males at 125 mg/kg/day and above. The 
NOEL for this study was considered to be 25 ppm (1.1 and 1.5 mg/kg/day 
for males and females, respectively).
    No evidence of oncogenicity was noted in two mouse oncogenicity 
studies. In the first study, deltamethrin was administered to mice for 
2 years at dietary concentrations of 0, 1, 5, 25 and 100 ppm. No 
adverse effects were noted at any dose level. Thus, the NOEL was 
considered to be 100 ppm (12 and 15 mg/kg/day in males and females, 
respectively). In a more recent study, deltamethrin was administered to 
mice for 97 weeks at dietary concentrations of 0, 10, 100, 1,000 and 
2,000 ppm. Effects noted at 2,000 ppm consisted of a slightly higher 
incidence of mice in poor physical condition and a slight, transient 
reduction in weight gain. Increased incidences of macroscopic and 
microscopic skin lesions, which were attributed to excessive 
scratching, were noted in animals at 1,000 and 2,000 ppm. The NOEL was 
considered to be 100 ppm (15.7 and 19.6 mg/kg/day for males and 
females, respectively).
    4. Genotoxicity. No evidence of genotoxicity was noted in a battery 
of in vitro and in vivo studies, including Salmonella and E. coli 
reverse bacterial mutation assays, an in vitro chromosomal aberration 
assay in Chinese hamster ovary (CHO) cells, an unscheduled DNA 
synthesis assay in rat hepatocytes, and a dominant lethal assay in 
mice.
    5. Reproductive and Developmental Toxicity. In a rat developmental 
toxicity study, deltamethrin was mixed with corn oil and administered 
by gavage during gestation days 6 through 15 at dose levels of 0, 1, 
3.3, 7 and 11 mg/kg/day. Maternal toxicity, as evidenced by clinical 
observations, decreased weight gain and mortality was noted at 7 and 11 
mg/kg/day. No evidence of developmental toxicity was noted at any dose 
level. Thus, the No Observable Effect Level (NOEL) was considered to be 
3.3 mg/kg/day for maternal toxicity and 11 mg/kg/day (highest dose 
tested) for developmental toxicity.
    In a rabbit developmental toxicity study, deltamethrin was 
administered by gavage in a vehicle of 0.5 percent aqueous 
carboxymethyl cellulose at dose levels of 0, 10, 25 and 100 mg/kg/day 
during gestation days 7 through 19. The maternal NOEL was considered to 
be 10 mg/kg/day based on decreased defecation at 25 and 100 mg/kg/day 
and mortality at 100 mg/kg/day. The developmental NOEL was considered 
to be 25 mg/kg/day based on retarded ossification of the pubic and tail 
bones at 100 mg/kg/day.
    In a 3-generation reproduction study, deltamethrin was suspended in 
corn oil and administered to rats at dietary concentrations of 0, 2, 20 
and 50 ppm. No treatment related effects were noted in either parents 
or offspring at any dose level. In a more recent 2-generation study 
(not yet submitted to the Agency), deltamethrin was administered to 
rats at dietary concentrations of 0, 5, 20, 80 and 320 ppm. The NOEL 
for both the parents and offspring was 80 ppm (equivalent to 
approximately 4 to 12 mg/kg/day in adults and 18 to 44 mg/kg/day in the 
offspring), based on clinical signs of toxicity, reduced weight gain, 
and mortality in both parents and offspring at 320 ppm. However, there 
were no effects on mating, fertility or developmental behavior at any 
dose level.

[[Page 23459]]

    6. Endocrine Effects. No special studies have been conducted to 
investigate the potential of deltamethrin to induce estrogenic or other 
endocrine effects. However, the standard battery of required toxicity 
studies has been completed. These studies include an evaluation of the 
potential effects on reproduction and development, and an evaluation of 
the pathology of the endocrine organs following repeated or long-term 
exposure. These studies are generally considered to be sufficient to 
detect any endocrine effects, yet no such effects were detected. Thus, 
the potential for deltamethrin to produce any significant endocrine 
effects is considered to be minimal.
    7. Metabolism. The absorption of deltamethrin appears to be highly 
dependent upon the route and vehicle of administration. Once absorbed, 
deltamethrin is rapidly and extensively metabolized and excreted, 
primarily within the first 48 hours.

C. Aggregate Exposure

    Deltamethrin is a broad spectrum insecticide used to control pests 
of crops, ornamental plants and turf, and domestic indoor and outdoor 
(including dog collars), commercial, and industrial food use areas. 
Thus, aggregate non-occupational exposure would include exposures 
resulting from non-food uses in addition to consumption of potential 
residues in food and water. Exposure via drinking water is expected to 
be negligible since deltamethrin binds tightly to soil and rapidly 
degrades in water. Because of the variety and nature of the non-food 
uses of deltamethrin, and the unavailability of reliable exposure data, 
we cannot fully evaluate potential exposure from these non-food uses. 
However, deltamethrin binds tightly to organic matter, is not easily 
dislodged from indoor surfaces, has very low vapor pressure, and is 
poorly absorbed through the skin. Furthermore, the formulations to 
which the general public would be exposed are relatively dilute and 
non-toxic. Thus, non-food exposures are not expected to pose a 
significant risk to the general public, or to infants and children.
    Potential dietary exposures from food commodities under the 
proposed tolerances for deltamethrin, plus the established tolerances 
for deltamethrin (40 CFR 180.435 and 185.1580) on cotton and tomato 
commodities, plus the pending temporary tolerances (under an 
Experimental Use Permit) on soybean commodities for deltamethrin were 
estimated using the Exposure 1 software system (TAS, Inc.) and the 
1977-78 USDA consumption data. Two scenarios were evaluated. In the 
first, worst case scenario, it was assumed that 100 percent of the 
crops for which a tolerance for deltamethrin is established or pending 
are treated with deltamethrin, all food and feed handling 
establishments are treated with deltamethrin, and that all residues 
resulting from these treatments are at tolerance level. In a second, 
slightly more realistic-case scenario, anticipated residues and percent 
crop treated adjustments were used, but again the unrealistic 
assumption was made that 100 percent of all food and feed handling 
establishments were treated with deltamethrin.

D. Safety Determinations

    1. US Population in General. AgrEvo Environmental Health considers 
the toxicity and residue data base for deltamethrin to be valid, 
reliable and essentially complete according to existing regulatory 
requirements. No evidence of oncogenicity has been observed. A 
Reference Dose (RfD) of 0.01 mg/kg bodyweight/day has been established 
for deltamethrin based on the NOEL from the two-year rat feeding study 
and a 100-fold safety factor to account for interspecies extrapolation 
and intraspecies variation.
    Using the dietary exposure assumptions described above in section 
D, chronic dietary exposures utilize 17 percent of the deltamethrin 
Reference Dose in the worst-case scenario, and only 2.6 percent of the 
Reference Dose in the slightly more realistic-case scenario for the 
general population. Thus, even utilizing a number of unrealistic 
assumptions, the total of the RfD utilized for deltamethrin did not 
exceed 17 percent. There is generally no concern for exposures below 
100 percent of the RfD since it represents the level at or below which 
no appreciable risks to human health is posed. Therefore, there is 
reasonable certainty that no harm will result to the U.S. population in 
general from aggregate exposure to deltamethrin.
    2. Infants and Children. Data from developmental toxicity studies 
in rats and rabbits, and multigeneration reproduction studies in rats 
are generally used to assess the potential for increased sensitivity of 
infants and children. The developmental toxicity studies are designed 
to evaluate adverse effects on the developing organism resulting from 
pesticide exposure during prenatal development. Reproduction studies 
provide information relating to reproductive and other effects on 
adults and offspring from prenatal and postnatal exposure to the 
pesticide.
    No developmental effects were noted in a rat developmental toxicity 
study with deltamethrin, even at dose levels that produced clinical 
signs of toxicity, reduced body weight, and death in the dams. The 
maternal and developmental NOEL's in this study were 3.3 mg/kg/day and 
11 mg/kg/day (highest dose tested), respectively. The only 
developmental effect noted in the rabbit developmental toxicity study 
was possibly retarded ossification at 100 mg/kg/day, a dose level which 
also produced maternal mortality. The maternal and developmental NOEL's 
in this study were 10 mg/kg/day and 25 mg/kg/day, respectively. No 
effects were noted in either parents or offspring at the high dose 
level (50 ppm) in a 3-generation rat reproduction study. In a more 
recent 2-generation rat reproduction study (not yet submitted to the 
Agency), the NOEL for both the parents and offspring was 80 ppm 
(equivalent to approximately 4 to 12 mg/kg/day in adults and 18 to 44 
mg/kg/day in the offspring), based on a variety of toxic effects 
(clinical signs of toxicity, reduced weight gain, and mortality) in 
both parents and offspring at 320 ppm. However, there were no effects 
on mating, fertility, or developmental behavior at any dose level. 
Thus, these data do not provide any evidence of increased 
susceptibility to infants or children.
     FFDCA section 408 provides that EPA may apply an additional safety 
factor for infants and children in the case of threshold effects to 
account for pre- and post-natal toxicity and the completeness of the 
database. Based on the current toxicological data requirements, the 
database relative to pre- and post-natal effects in children is 
complete. Although no indication of increased susceptibility to younger 
animals was noted in any of the above studies, or in the majority of 
studies with other pyrethroids, several recent publications have 
reported that deltamethrin is more toxic to neonate and weanling 
animals than to adults. However, a joint industry group currently 
investigating this issue was unable to reproduce these findings. 
Furthermore, the RfD (0.01 mg/kg/day) that has been established for 
deltamethrin is already more than 1,000-fold lower than the lowest NOEL 
from the developmental and reproduction studies. Therefore, the RfD of 
0.01 mg/kg/day is appropriate for assessing aggregate risk to infants 
and children and an additional uncertainty factor is not warranted.
    Using the dietary exposure assumption described above in section D, 
chronic dietary exposures utilize 54 percent of the deltamethrin RfD in 
the

[[Page 23460]]

worst-case scenario, and only 10.2 percent of the RfD in the slightly 
more realistic-case scenario for the population subgroup described as 
non-nursing infants, less than 1 year old. Thus, even utilizing a 
number of unrealistic assumptions, the total of the RfD utilized for 
deltamethrin did not exceed 54 percent . There is generally no concern 
for exposures below 100 percent of the RfD since it represents the 
level at or below which no appreciable risks to human health is posed. 
Therefore, there is reasonable certainty that no harm will result to 
the most sensitive population subgroup described as non-nursing 
infants, less than one year old, from aggregate exposure to 
deltamethrin.

E. Cumulative Effects

    At the present time, there are insufficient data available to allow 
AgrEvo to properly evaluate the potential for cumulative effects from 
the various pyrethroids now being used, or from any other chemicals 
that may have similar mechanisms of toxicity. Furthermore, because of 
the need to utilize data from multiple registrants, such an analysis 
cannot be conducted by a single registrant. AgrEvo is currently 
participating in a joint industry effort to evaluate the potential 
aggregate risks from exposure to all pyrethroids but the results from 
this evaluation are not yet available. As an interim measure, AgrEvo 
has performed an initial evaluation of the potential combined 
effectsfrom exposure to two pyrethroids, deltamethrin and tralomethrin, 
that are currently registered by AgrEvo Environmental Health and AgrEvo 
USA Companies. A combined assessment of these two active ingredients is 
considered appropriate because tralomethrin is rapidly debrominated 
into deltamethrin and because the two molecules have essentially 
identical toxicology profiles.
    For the same reasons previously discussed for deltamethrin, non-
dietary exposures to tralomethrin are not expected to pose a 
significant risk to human health and, therefore, have not been 
evaluated. Potential dietary exposures to tralomethrin are, however, 
considered here. The RfD established for tralomethrin is 0.0075 mg/kg 
bodyweight/day based on a two-year rat feeding study and a 100 fold 
safety factor to account for interspecies extrapolation and 
intraspecies variation. Using the dietary exposure assumptions 
described above in section D, chronic dietary exposures utilize 16.9 
percent of the tralomethrin RfD in the worst-case scenario, and only 
3.9 percent of the tralomethrin RfD in the slightly more realistic-case 
scenario for the general population. For the population subgroup 
described as non-nursing infants, less than one year old, 32 percent of 
the RfD for tralomethrin is utilized in the worst-case scenario, and 
only 11 percent of the RfD for tralomethrin in the slightly more 
realistic-case scenario. (The crops/uses considered for tralomethrin 
are those for which tolerances have been established for experimental 
use permits and those listed in 40 CFR 180.422, 185.5450, and 
186.5450.)
    A simple cumulative risk assessment can be made by adding the 
percent RfD utilized for deltamethrin and tralomethrin. However, this 
is a gross overestimate because, based on efficacy, economics, and/or 
label restrictions, crops and food/feed handling establishments would 
not be concurrently treated with both products. This is especially 
important in considering food/feed handling uses because all foods are 
considered to contain residues of both deltamethrin and tralomethrin. 
Nonetheless, looking at this simple summation, it is shown that in the 
worst-case scenario described in section D, chronic dietary exposures 
utilize 33.9 percent of the RfDs for tralomethrin/deltamethrin, while 
in the slightly more realistic-case scenario only 6.5 percent of the 
RfDs for tralomethrin/deltamethrin are utilized. For the population 
subgroup described as non-nursing infants, less than one-year old, 86 
percent of the RfDs for tralomethrin/deltamethrin are utilized in the 
worst-case scenario, while only 21.2 percent of the RfDs for 
tralomethrin/deltamethrin are utilized in the slightly more realistic-
case scenario. Thus, even utilizing a number of unrealistic 
assumptions, and using a simple summation of percent RfD utilized for 
each active ingredient, the total of percent RfD utilized for 
deltamethrin/tralomethrin did not exceed 86 percent, and is actually 
less than 21.2 percent, for the population subgroup non-nursing 
infants, less than one year old. Therefore, there is reasonable 
certainty that no harm will result from cumulative aggregate exposures 
to deltamethrin and tralomethrin for the general population and/or 
infants and children.

G. International Tolerances

    Deltamethrin is a broad spectrum insecticide used throughout the 
world to control pests of livestock, crops, ornamental plants and turf, 
and household, commercial, and industrial food use areas. A 
reevaluation of the maximum residue limits (MRL s) was conducted in 
1994, in accordance with the EC Directive (91/414/EEC) Registration 
Requirements for Plant Protection Products. A comparison of the 
proposed CODEX MRLs and proposed tolerances for deltamethrin is 
presented below:


                                                                        
------------------------------------------------------------------------
                                   Proposed/Current        Proposed/    
                                          MRL             Established   
            Commodity            ---------------------------------------
                                        (CODEX)        Tolerance (USEPA)
------------------------------------------------------------------------
Food/Feed Handling Uses.........  0.05 ppm..........  0.05 ppm          
------------------------------------------------------------------------


[FR Doc. 97-10893 Filed 4-29-97; 8:45 am]
BILLING CODE 6560-50-F