[Federal Register Volume 63, Number 165 (Wednesday, August 26, 1998)]
[Notices]
[Pages 45487-45497]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 98-22430]


-----------------------------------------------------------------------

ENVIRONMENTAL PROTECTION AGENCY

[PF-826; FRL-6023-5]


Notice of Filing of Pesticide Petitions

AGENCY: Environmental Protection Agency (EPA).

ACTION: Notice.

-----------------------------------------------------------------------

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 the docket control number PF-826, must 
be received on or before September 25, 1998.
ADDRESSES: By mail submit written comments to: Public Information and 
Records Integrity Branch, Information Resources and Services Division 
(7502C), Office of Pesticides Programs, Environmental Protection 
Agency, 401 M St., SW., Washington, DC 20460. In person bring comments 
to: Rm. 119, CM #2, 1921 Jefferson Davis Highway, Arlington, VA.
    Comments and data may also be submitted electronically to: opp-
[email protected]. Follow 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

[[Page 45488]]

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: The product manager listed in the 
table below:

------------------------------------------------------------------------
                                   Office location/                     
        Product Manager            telephone number          Address    
------------------------------------------------------------------------
Beth Edwards (PM 3)...........  Rm. 206, CM #2, 703-    1921 Jefferson  
                                 305-5400, e-            Davis Hwy,     
                                 mail:edwards.beth@epa   Arlington, VA  
                                 mail.epa.gov.                          
Sidney Jackson (PM 22)........  Rm. 233, CM #2, 703-    Do.             
                                 305-7610, e-mail:                      
                                 jackson.sidney@epamai
l.epa.gov.                             
------------------------------------------------------------------------

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 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 supports granting of 
the petition. Additional data may be needed before EPA rules on the 
petition.
    The official record for this notice of filing, as well as the 
public version, has been established for this notice of filing under 
docket control number [PF-826] (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. Comments 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 number (insert docket number) and appropriate 
petition number. Electronic comments on notice may be filed online at 
many Federal Depository Libraries.

List of Subjects

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

Dated: August 13, 1998.

    James Jones,

Director, Registration Division, Office of Pesticide Programs.

Summaries of Petitions

    Petitioner summaries 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 petitioners and represent the views of 
the petitioners. EPA is publishing the petition summaries verbatim 
without editing them in any way. The petition summary announces the 
availability of a description of the analytical methods available to 
EPA for the detection and measurement of the pesticide chemical 
residues or an explanation of why no such method is needed.

1. AgrEvo USA Company (acting as registered US agent for Hoechst 
Schering AgrEvo, S.A.)

PP 7F4909

    EPA has received a pesticide petition (PP 7F4909) from AgrEvo USA 
Company (acting as registered U.S. agent for Hoechst Schering AgrEvo, 
S.A.), 2711 Centerville Road, Wilmington, DE 19808 proposing pursuant 
to section 408(d) of the Federal Food, Drug, and Cosmetic Act, 21 
U.S.C. 346a(d), to amend 40 CFR part 180 by establishing a tolerance 
for residues of deltamethrin in or on various food and feed 
commodities. Tolerances are currently established at 40 CFR 180.435 in 
or on the following commodities for residues of deltamethrin [(1R, 3R)-
3(2,2-dibromovinyl)-2,2-dimethylcyclopropanecarboxylic acid (S)-alpha-
cyano-3-phenoxybenzyl ester] and relevant metabolites: cottonseed at 
0.04 parts per million (ppm), cottonseed oil at 0.2 ppm, tomatoes at 
0.2 ppm, and tomato products (concentrated) at 1.0 ppm.
    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.
    Based on the fact that tralomethrin, another synthetic pyrethroid 
insecticide, is rapidly metabolized in plants and animals to 
deltamethrin, and the toxicological profile of the two compounds is 
similar, it is appropriate to consider a combined exposure assessment 
for tralomethrin and deltamethrin.

A. Residue Chemistry

    1. Plant metabolism. Deltamethrin metabolism studies in tomatoes, 
corn, apples, and cotton demonstrate the same metabolic pathway. 
Furthermore, plant metabolism studies have been conducted following 
application of tralomethrin in cotton, corn, cabbage, and tomatoes. 
These studies have demonstrated that the metabolism of tralomethrin 
involves debromination to deltamethrin and its isomers. Thus, a similar 
metabolic pathway has been shown to occur in a variety of crops 
following either direct application of deltamethrin (cotton, corn, 
apples, and tomatoes) or in-plant formation of deltamethrin via 
debromination of applied tralomethrin (tomatoes, cotton, corn, and 
cabbage). As a result of this substantial information base, it is 
concluded that the residues of toxicological concern in/on growing 
crops following application of tralomethrin or deltamethrin are 
tralomethrin, cis-deltamethrin, and its isomers, trans-deltamethrin and 
alpha-R-deltamethrin.
    2. Analytical method. Analytical methods for determining residues 
of tralomethrin and deltamethrin in various commodities for which 
registrations have been approved, or are being sought, have been 
submitted to the Agency. These methods, based on

[[Page 45489]]

gas chromatography (GLC) equipped with an electron capture detector 
(ECD) and a DB-1 (or equivalent) capillary column, are used for the 
determination of tralomethrin, cis-deltamethrin, trans-deltamethrin, 
and alpha-R-deltamethrin in various raw agricultural, animal derived, 
and processed commodities. These methods were independently validated 
and are appropriate for the determination of residues of tralomethrin 
and deltamethrin in various food and feed commodities after application 
of these ingredients to target growing crops, and after use in food/
feed handling establishments.
    3. Magnitude of residues. Residues of tralomethrin, deltamethrin, 
and its metabolites are not expected to exceed the proposed tolerance 
levels as a result of the use of these active ingredients on target 
crops, or at target sites.

B. Toxicological Profile

    1. Acute toxicity. The acute oral LD50 values for 
deltamethrin in the rat are 66.7 milligram/kilograms (mg/kg) for males, 
86 mg/kg for females, and for tralomethrin 99 mg/kg for males, 157 mg/
kg for females when administered in sesame oil. The oral 
LD50 for deltamethrin when administered in aqueous methyl 
cellulose was greater than 5,000 mg/kg for both sexes. The dermal 
LD50 in rabbits was greater than 2,000 mg/kg for both 
materials. Inhalation 4-hour LC50 values in the rat are 2.2 
mg/L for deltamethrin and greater than 0.286 mg/L for tralomethrin.
    2. Genotoxicty. No indication of genotoxicity was noted in a 
battery of in vivo and in vitro studies conducted with either 
deltamethrin or tralomethrin.
    3. Reproductive and developmental toxicity--i. Deltamethrin. A rat 
developmental toxicity study conducted with deltamethrin indicated a 
maternal no observed effect level (NOEL) of 3.3 mg/kg/day based on 
clinical observations, decreased weight gain and mortality. The 
developmental NOEL was 11 mg/kg/day higest dose tested (HDT).
    In a rabbit developmental toxicity study with deltamethrin, 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 HDT.
    A 3-generation rat reproduction study and a more recent, 2-
generation rat reproduction study with deltamethrin indicated the NOEL 
for both parents and offspring was 80 ppm (4-12 mg/kg/day for adults 
and 18-44 mg/kg/day for offspring) based on clinical signs of toxicity, 
reduced weight gain and mortality at 320 ppm HDT.
    ii. Tralomethrin. In a rat developmental toxicity study with 
tralomethrin the NOEL for maternal and developmental toxicity was 
judged to be greater than or equal to 18 mg/kg/day HDT.
    No evidence of developmental toxicity was observed in either of two 
rabbit developmental toxicity studies conducted with tralomethrin. In 
one study, the maternal NOEL was 12.5 mg/kg/day based on mortality 
while the developmental NOEL was judged to be greater than or equal to 
25 mg/kg/day HDT. In the second study, the maternal NOEL was 8 mg/kg/
day based on body weight effects while the developmental NOEL was 32 
mg/kg/day HDT.
    In a 2-generation reproduction study with tralomethrin in rats, the 
parental NOEL was 0.75 mg/kg/day based on body weight deficits while 
the NOEL for offspring was 3.0 mg/kg/day, also based on body weight 
deficits.
    4. Subchronic toxicity-- i. Deltamethrin. A 90-day rat oral 
toxicity study was conducted with deltamethrin which was administered 
by gavage. The NOEL was judged to be 1.0 mg/kg/day based on reduced 
body weight gain and slight hypersensitivity. In a more recent 90-day 
rat dietary study with deltamethrin, the NOEL was judged to be 300 ppm 
(23.9 mg/kg/day for males, 30.5 mg/kg/day for females) based on 
uncoordinated movement, unsteady gait, tremors, increased sensitivity 
to sound, shakes and spasmodic convulsions. The difference in the 
NOEL's between the two studies is attributed to the different routes of 
exposure (gavage in oil vs. administered in diet).
    A 12-week study was conducted with deltamethrin in mice. The NOEL 
was 300 ppm (61.5 mg/kg/day in males and 77.0 mg/kg/day in females) 
based on chronic contractions, convulsions, poor condition, decreased 
weight gain and mortality.
    Two 13-week dog studies were conducted with deltamethrin. In the 
first study, beagle dogs were administered deltamethrin by capsule 
using PEG 200 as a vehicle. The NOEL for this study was 1 mg/kg/day 
based on tremors, unsteadiness, jerking movements, salivation, 
vomiting, liquid feces and/or dilatation of the pupils. In the second 
study, deltamethrin was administered by capsule without a vehicle to 
beagle dogs. The NOEL for this study was 10 mg/kg/day based on unsteady 
gait, tremors, head shaking, vomiting and salivation. The difference in 
toxicity between the two studies is attributed to the enhanced 
absorption resulting from the use of PEG 200 as a vehicle in the first 
study.
    A 21-day dermal toxicity study was conducted with deltamethrin in 
rats. The NOEL for systemic toxicity was determined to be 1,000 mg/kg/
day.
    In a subchronic inhalation study, rats were exposed to aerosolized 
deltamethrin for 6 hours per day, 5-days per week, for a total of 14-
days over 3 weeks. Based on slightly decreased body weights and 
neurological effects at higher dose levels, it was concluded that 3 
g/l was the NOEL for systemic effects in this study.
    ii. Tralomethrin. Tralomethrin was administrated by gavage in corn 
oil to rats for 13 weeks. Based on mortality, decreased activity and 
motor control, soft stools, labored breathing and significantly lower 
absolute and relative mean liver weights, the NOEL was considered to be 
1 mg/kg/day.
    Tralomethrin was administered by capsule to beagle dogs for 13 
weeks. The NOEL for this study was 1.0 mg/kg/day based on refusal of 
milk supplement, tremors, exaggerated patellar response, unsteadiness 
and uncoordinated movement.
    A 21-day dermal toxicity study was conducted with tralomethrin on 
rats. No systemic effects were observed, therefore the systemic NOEL 
for this study was 1,000 mg/kg/day.
    5. Chronic toxicity and oncogenicity-- i. Deltamethrin. 
Deltamethrin was administered in the diet to beagle dogs for 2 years. 
No treatment-related effects were observed and the NOEL was judged to 
be 40 ppm (1.1 mg/kg/day). In a more recent study, deltamethrin was 
administered by capsule (without a vehicle) to beagle dogs for 1 year. 
The NOEL in this study was considered to be 1 mg/kg/day based on 
clinical signs, decreased food consumption and changes in several 
hematology and blood chemistry parameters.
    Two rat chronic toxicity/oncogenicity studies were conducted with 
deltamethrin. In the first study, the test substance was administered 
via the diet to rats for 2 years. The NOEL for this study was 20 ppm (1 
mg/kg/day) based on slightly decreased weight gain. In a more recent 
study, deltamethrin was administered to rats in the diet for 2 years. 
The NOEL for this study was considered to be 25 ppm (1.1 and 1.5 mg/kg/
day for males and females, respectively), based on neurological signs, 
weight gain effects and increased incidence and severity of 
eosinophilic hepatocytes and/or balloon cells. No evidence of 
carcinogenicity was noted in either study.

[[Page 45490]]

    Two mouse oncogenicity studies were conducted with deltamethrin. In 
the first study, deltamethrin was administered in the diet for 2 years. 
No adverse effects were observed and the NOEL was judged to be 100 ppm 
(12 and 15 mg/kg/day, respectively, for males and females). In a more 
recent study, deltamethrin was administered in the diet to mice for 97 
weeks. The NOEL was considered to be 1,000 ppm (15.7 and 19.6 mg/kg/
day) based on a higher incidence of poor physical condition and a 
slight transient weight reduction. There was no evidence of 
oncogenicity in either study.
    ii. Tralomethrin. Tralomethrin was administered to beagle dogs by 
capsule for 1 year at initial dosages of 0, 0.75, 3.0 and 10.0 mg/kg/
day. Due to trembling, ataxia, prostration and convulsions, the high 
dosage was lowered to 8 mg/kg/day at study week 4 and lowered again to 
6 mg/kg/day on study week 14. On the 14 week of study, the 0.75 mg/kg/
day dosage was raised to 1.0 mg/kg/day. Based on body weight changes, 
convulsions, tremors, ataxia and salivation, the NOEL for this study 
was considered to be 1 mg/kg/day.
    Tralomethrin was administered by gavage to rats for 24 months. The 
NOEL for this study was 0.75 mg/kg/day based on salivation, 
uncoordinated movement, inability to support weight on limbs and 
decreased body weight parameters. No evidence of carcinogenicity was 
observed.
    A 2 year mouse oncogenicity study was conducted with tralomethrin 
administered by gavage. The NOEL was judged to be 0.75 mg/kg/day based 
on higher incidences of dermatitis and mortality, salivation, 
uncoordinated involuntary movements and aggressiveness. No evidence of 
oncogenicity was observed.
    6. Neurotoxicity. Acute delayed neurotoxicity studies in hens were 
conducted for both deltamethrin and tralomethrin. In both cases, the 
study results were negative indicating that neither material causes 
delayed neurotoxicity.
    In an acute neurotoxicity study with deltamethrin in rats, effects 
were noted after a single oral administration of a dose of 50 mg/kg. In 
addition, potential effects (limited to a single male and female) were 
observed at a dose level of 15 mg/kg. Therefore, the no observed 
adversed effect level (NOAEL) for neurotoxicity in this study was 5 mg/
kg.
    In a subchronic neurotoxicity study with deltamethrin in rats, 
effects were noted after daily dietary administration for 13 
consecutive weeks at 800 ppm. The NOAEL for systemic toxicity and 
neurotoxicity in this study was found to be 200 ppm (14 and 16 mg/kg/
day for males and females, respectively).
    7. Animal metabolism-- i. Deltamethrin. 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.
    ii. Tralomethrin. Tralomethrin is rapidly metabolized to 
deltamethrin after debromination. The metabolic pattern of the 
debrominated tralomethrin is exactly the same as that of the metabolic 
pattern of deltamethrin.
    8. Endocrine effects. No special studies have been conducted to 
investigate the potential of deltamethrin or tralomethrin 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 or tralomethrin to 
produce any significant endocrine effects is considered to be minimal.

C. Aggregate Exposure

    Based on the fact that tralomethrin is rapidly metabolized in 
plants and animals to deltamethrin, and the toxicological profile of 
the two compounds is similar, it is appropriate to consider combined 
exposure assessments for tralomethrin and deltamethrin.
    Deltamethrin and tralomethrin are broad spectrum insecticides used 
to control pests of crops, ornamental plants and turf, and domestic 
indoor and outdoor (including dog collars and direct application to 
livestock), commercial, and industrial food use areas. Thus, aggregate 
non-occupational exposure would include exposures resulting from non-
food use 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.
    1. Dietary exposure--Food. Food tolerances have been established 
for residues of tralomethrin and/or deltamethrin and its metabolites in 
or on a variety of raw agricultural commodities. These tolerances, in 
support of registrations, currently exist for residues of tralomethrin 
on broccoli, cottonseed, head lettuce, leaf lettuce, soybeans, 
sunflower seed, and cottonseed oil. Also, tolerances in support of 
registrations currently exist for deltamethrin on cottonseed and 
cottonseed oil. Additionally, tolerances have been established for 
tralomethrin to support its use in food/feed handling establishments, 
and for deltamethrin on tomatoes and concentrated tomato products to 
support the importation of tomato commodities treated with 
deltamethrin. Further, a food/feed handling establishment use, and 
associated tolerances, is pending for deltamethrin. Additional 
tolerances are being proposed for deltamethrin in the subject pesticide 
tolerance petition. Potential acute exposures from these relevant food 
commodities were estimated using a Tier 3 acute dietary risk assessment 
(Monte Carlo Analysis) following EPA guidance. Potential chronic 
exposures from food commodities under the established food and feed 
additive tolerances for deltamethrin and tralomethrin, plus the pending 
tolerances for deltamethrin associated with use in food/feed handling 
areas, and the tolerances proposed in this petition for deltamethrin, 
were estimated using NOVIGEN's dietary exposure evaluation mode (DEEM). 
This chronic risk assessment was conduced using anticipated residues 
based on field trial or monitoring data, percent crop treated, and 
percent food handling establishments treated.
    2. Drinking water . Tralomethrin and deltamethrin are immobile in 
soil and, therefore, will not leach into groundwater. Additionally, due 
to the insolubility and lipophilic nature of deltamethrin and 
tralomethrin, any residues in surface water will rapidly and tightly 
bind to soil particles and remain with sediment, therefore not 
contributing to potential dietary exposure from drinking water.
    A screening evaluation of leaching potential of a typical 
pyrethroid was conducted using EPA's pesticide root zone model (PRZM3). 
Based on this screening assessment, the potential concentrations of a 
pyrethroid in ground water at depths of 1 and 2 meters are essentially 
zero <0.001 parts per billion (PPB). Surface water concentrations for 
pyrethroids were estimated using PRZM3 and Exposure Analysis Modeling 
System (EXAMS) using Standard EPA cotton runoff and Mississippi pond 
scenarios. The maximum concentration predicted in the simulated pond 
was 0.052 ppb. Concentrations in actual drinking water would be much 
lower than the levels predicted in the hypothetical, small, stagnant 
farm pond model since

[[Page 45491]]

drinking water derived from surface water would normally be treated 
before consumption. Based on these analyses, the contribution of water 
to the dietary risk estimate is negligible.
    3. Non-dietary exposure. As noted above, deltamethrin and 
tralomethrin are broad spectrum insecticides registered for use on a 
variety of food and feed commodities. Additionally, registrations are 
held for non-agricultural applications including turf and lawn care 
treatments, broadcast carpet treatments (professional use only), indoor 
fogger, spot, crack and crevice treatments, insect baits, lawn and 
garden sprays and indoor and outdoor residential, industrial and 
institutional sites including those for Food/Feed Handling 
Establishments.
    To evaluate non-dietary exposure, the ``flea infestation 
control''senario was chosen to represent a plausible but worst case 
non-dietary (indoor and outdoor) non-occupational exposure. This 
scenario provides a situation where deltamethrin and/or tralomethrin is 
commonly used and they can be used concurrently for a multitude of 
uses, e.g., spot and/or broadcast treatment of infested indoor surfaces 
such as carpets and rugs, treatment of pets and treatment of the lawn. 
This hypothetical situation provides a very conservative, upper bound 
estimate of potential non-dietary exposures. Consequently, if health 
risks are acceptable under these conditions, the potential risks 
associated with other more likely scenarios would also be acceptable.
    Because tralomethrin is rapidly metabolized to deltamethrin, and 
the toxicology profiles of deltamethrin and tralomethrin are virtually 
identical, a non-dietary and aggregate (non-dietary + chronic dietary) 
exposure/risk assessment has been conducted for the combination of both 
active ingredients. The total exposure to both materials was expressed 
as ``deltamethrin equivalents'' and these were compared to the 
toxicology endpoints identified for deltamethrin.

D. Cumulative Effects

     When considering a tolerance, the Agency must consider ``available 
information'' concerning the cumulative effects of a particular 
pesticide's residues and ``other substances that have a common 
mechanism of toxicity''. AgrEvo USA Company, acting as registered U.S. 
agent for Hoechst Schering AgrEvo SA, believes that ``available 
information'' in this context includes not only toxicity, chemistry, 
and exposure data, but also scientific policies and methodologies for 
understanding common mechanisms of toxicity and conducting cumulative 
risk assessments.
    Further, AgrEvo does not have, at this time, available data to 
determine whether tralomethrin and/or deltamethrin have a common 
mechanism of toxicity with other substances. For the purposes of this 
tolerance action, therefore, no assumption has been made that 
tralomethrin and/or deltamethrin have a common mechanism of toxicity 
with other substances.

E. Safety Determination

    1. U.S. population. The toxicity and residue data base for 
deltamethrin and tralomethrin are considered to be valid, reliable and 
essentially complete according to existing regulatory requirements. No 
evidence of oncogenicity has been observed for either compound. In 
accordance with EPA's ``Toxicology Endpoint Selection Process'' 
Guidance Document for acute exposures, the toxicology endpoint from the 
deltamethrin rat acute neurotoxicity study, 5.0 mg/kg/day, is used. For 
chronic exposures to deltamethrin and tralomethrin, the Reference Dose 
(RfD) of 0.01 mg/kg bodyweight/day established for deltamethrin based 
on the NOEL from the 2-year rat feeding study and a 100-fold safety 
factor to account for interspecies extrapolation and intraspecies 
variation is used.
    For the overall U.S. population, acute dietary exposure at the 
99.9th percentile results in a margin of exposure (MOE) of 1,406; the 
MOE for the 99th percentile is 3,500; and at the 95th percentile the 
MOE is 8,613. For the overall U.S. population, chronic dietary exposure 
results in a utilization of 1.4% of the reference dose. Using an upper 
bound estimate of potential non-dietary exposures for a worst case 
scenario (flea treatment) results in an MOE of 160,000 for adults. 
Utilizing the scenario of chronic dietary exposure plus an upper bound 
estimate of potential non-dietary exposure from a worst case scenario 
(flea treatment), it is shown that for aggregate exposure to 
deltamethrin and tralomethrin there is an MOE of 31,100 for adults. 
There is generally no concern for MOE's greater than 100. For chronic 
exposure, there is generally no concern for exposure 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.
    In conclusion, there is reasonable certainty that no harm will 
result to the U.S. population, in general, from dietary or aggregate 
exposure to deltamethrin and/or tralomethrin.
    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 pre-natal and post-natal exposure to the 
pesticide. None of these studies conducted with deltamethrin or 
tralomethrin indicated developmental or reproductive effects as a 
result of exposure to these materials.
    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 chronic aggregate risk to 
infants and children and an additional uncertainty factor is not 
warranted. Also, the NOEL of 5.0 mg/kg/day from the rat acute 
neurotoxicity study is appropriate to use in acute dietary, short term 
non-dietary, and aggregate exposure assessments.
    For the population subgroup described as non-nursing infants, less 
than 1 year old, the MOE for acute dietary exposure at the 99.9th 
percentile is 666; at the 99th percentile the MOE is 1,491; and at the 
95th percentile the MOE is 8,755. For the population subgroup described 
as children 1-6 years old, the MOE for acute dietary exposure is 871 
for the 99.9th percentile; at the 99th percentile the MOE is 1,527; and 
at the 95th percentile the MOE is 3,167. For non-nursing infants, 
chronic dietary exposure results in a utilization of 1.9% of the RfD, 
and

[[Page 45492]]

for children 1-6 years old 3.7% of the reference dose is utilized. 
Using an upper bound estimate of potential non-dietary exposures for a 
worst case scenario (flea treatment) results in an MOE of 6,100 for 
infants less than 1 year old, and an MOE of 6,600 for children 1-6 
years old. Utilizing the scenario of chronic dietary exposure plus an 
upper bound estimate of potential non-dietary exposure from a worst 
case scenario (flea treatment) it is shown that for aggregate exposure 
to deltamethrin and tralomethrin, there is an MOE of 6,775 for infants 
less than 1 year old, and an MOE of 5,700 for children 1-6 years old. 
There is generally no concern for MOE's greater than 100. For chronic 
exposure, there is generally no concern for exposure 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.
    In summary, there is reasonable certainty that no harm will result 
to infants and children from aggregate exposure to either deltamethrin 
or tralomethrin.

F. International Tolerances

     Deltamethrin is a broad spectrum insecticide used throughout the 
world to control pests of livestock, crops, ornamentals 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/current CODEX MRL's and proposed/established tolerances for 
deltamethrin is presented below:

----------------------------------------------------------------------------------------------------------------
                Commodity                  Proposed Tolerance (USEPA) (PPM)   Proposed/Current MRL (CODEX) (PPM)
----------------------------------------------------------------------------------------------------------------
Barley, grain...........................                                0.50                                 1.0
Broccoli................................                                0.50                                 0.2
Cattle, fat.............................                                0.15                                 ---
Cattle, mbyp............................                                0.05                                 ---
Cattle, meat............................                                0.05                                 ---
Cereal grain dust.......................                                65.0                                 ---
Corn, field, grain......................                                 1.0                                 1.0
Corn, pop, grain........................                                 0.5                                 1.0
Corn, sweet, grain......................                                 0.5                                 1.0
Corn, forage (field)....................                                 0.7                                 ---
Corn, fodder (field)....................                                 7.0                                 0.5
Cucurbits vegetables....................                                0.05                                 0.2
Eggs....................................                                0.02                                 ---
Goats, fat..............................                                0.15                                 ---
Goats, mbyp.............................                                0.05                                 ---
Goats, meat.............................                                0.05                                 ---
Hogs, fat...............................                                0.15                                 ---
Hogs, mbyp..............................                                0.05                                 ---
Hogs, meat..............................                                0.05                                 ---
Horses, fat.............................                                0.15                                 ---
Horses, mbyp............................                                0.05                                 ---
Horses, meat............................                                0.05                                 ---
Lettuce, head...........................                                 1.0                                 0.2
Lettuce, leaf...........................                                 3.0                                 0.5
Milk, Fat (reflecting 0.07 ppm in whole                                                                         
 milk)..................................                                 0.6                         0.01 (milk)
Oats, grain.............................                                 0.5                                 1.0
Poultry, fat............................                                 0.3                                 ---
Poultry, mbyp...........................                                0.02                                 ---
Poultry, meat...........................                                0.02                                 ---
Rice, grain.............................                                 0.5                                 1.0
Rye, grain..............................                                 0.5                                 1.0
Sheep, fat..............................                                0.15                                 ---
Sheep, mbyp.............................                                0.05                                 ---
Sheep, meat.............................                                0.05                                 ---
Sorghum, grain..........................                                 1.0                                 1.0
Sorghum, forage.........................                                 0.5                                 ---
Sorghum, fodder.........................                                 2.0                                 0.5
Soybeans................................                                0.05                                 0.1
Sunflower seed..........................                                0.05                                 0.1
Tomatoes................................                                 0.3                                 0.2
Triticale, grain........................                                 0.5                                 1.0
Wheat, forage...........................                                 8.0                                 ---
Wheat, grain............................                                 1.0                                 1.0
Wheat, hay..............................                                 8.0                                 0.5
Wheat, straw............................                                 8.0                                 0.5
Corn, refined oil.......................                                10.0                                 ---
Corn, flour.............................                                 3.0                                 ---
Corn, meal..............................                                 2.0                                 ---
Tomato products (concentrated)..........                                 1.5                                 ---
Wheat bran..............................                                 4.0                                 5.0
Wheat germ..............................                                 8.0                                 ---
Soybean hulls...........................                                0.25                                 0.5
Cereal bran.............................                                 2.0                                 ---
Rice hulls..............................                                 6.0                                 ---

[[Page 45493]]

                                                                                                                
Corn, milled byproducts.................                                 3.0                                 ---
----------------------------------------------------------------------------------------------------------------

    As far as can be determined, no CODEX MRL's are established or 
proposed for tralomethrin.

G. Proposed Tolerances

    This pesticide petition proposes to amend 40 CFR 180.435 for the 
insecticide deltamethrin as it relates to the following raw 
agricultural, food, or feed commodities:

------------------------------------------------------------------------
              Commodity                        Parts per million        
------------------------------------------------------------------------
Barley, grain.......................                                 0.5
 Broccoli...........................                                 0.5
 Cattle, fat........................                                0.15
 Cattle, mbyp.......................                                0.05
 Cattle, meat.......................                                0.05
 Cereal bran........................                                 2.0
 Cereal grain dust..................                                65.0
 Corn, field, grain.................                                 1.0
 Corn, pop, grain...................                                 0.5
 Corn, sweet, grain.................                                 0.5
 Corn, forage (field)...............                                 0.7
 Corn, fodder (field)...............                                 7.0
 Corn, refined oil..................                                10.0
 Corn, flour........................                                 3.0
 Corn, meal.........................                                 2.0
 Corn, milled byproducts............                                 3.0
 Cottonseed.........................                                0.04
 Cottonseed oil.....................                                 0.2
 Cucurbits vegetables...............                                0.05
 Eggs...............................                                0.02
 Goats, fat.........................                                0.15
 Goats, mbyp........................                                0.05
 Goats, meat........................                                0.05
 Hogs, fat..........................                                0.15
 Hogs, mbyp.........................                                0.05
 Hogs, meat.........................                                0.05
 Horses, fat........................                                0.15
 Horses, mbyp.......................                                0.05
 Horses, meat.......................                                0.05
 Lettuce, head......................                                 1.0
 Lettuce, leaf......................                                 3.0
 Milk, Fat (reflecting 0.07 ppm in                                      
 whole milk)........................                                 0.6
Oats, grain.........................                                 0.5
 Poultry, fat.......................                                 0.3
Poultry, mbyp.......................                                0.02
 Poultry, meat......................                                0.02
 Rice, grain........................                                 0.5
 Rice, hulls........................                                 6.0
 Rye, grain.........................                                 0.5
 Sheep, fat.........................                                0.15
 Sheep, mbyp........................                                0.05
 Sheep, meat........................                                0.05
 Sorghum, grain.....................                                 1.0
 Sorghum, forage....................                                 0.5
 Sorghum, fodder....................                                 2.0
 Soybeans...........................                                0.05
 Soybean hulls......................                                0.25
 Sunflower seed.....................                                0.05
 Tomatoes...........................                                 0.3
Tomato products (concentrated)......                                 1.5
 Triticale, grain...................                                 0.5
 Wheat, bran........................                                 4.0
 Wheat, forage......................                                 8.0
 Wheat, germ........................                                 8.0
 Wheat, grain.......................                                 1.0
 Wheat, hay.........................                                 8.0
 Wheat, straw.......................                                 8.0
------------------------------------------------------------------------


[[Page 45494]]

H. Conclusions

    The proposed establishment of food and food/feed additive 
tolerances for deltamethrin resulting from application to growing 
crops, stored grain, and direct application to livestock would not pose 
a significant risk to human health, including that of children, and is 
in compliance with the requirements of the Food Quality Protection Act 
of 1996. Thus, the tolerances proposed for residues of deltamethrin can 
be established.

2. Gowan Company

PP 8F4985

    EPA has received a pesticide petition (PP 8F4985) from Gowan 
Company, P.O. Box 5569, Yuma, AZ 85366-5569 proposing pursuant to 
section 408(d) of the Federal Food, Drug, and Cosmetic Act, 21 U.S.C. 
346a(d), to amend 40 CFR part 180 by establishing a tolerance for 
residues of the acaricide hexythiazox in or on strawberries, apples, 
wet apple pomace, cottonseed and cotton gin byproducts. The chemical 
name of hexythiazox is trans-5-(4-chlorophenyl)-N-cyclohexyl-4-methyl-
2-oxothiazolidine-3-carboxamide. Metabolites containing the (4-
chlorophenyl)-4-methyl-2-oxo-3-thiazolidine moiety are included in the 
tolerance expression. Time-limited tolerances for strawberries, cotton 
seed and cotton gin byproducts are currently in effect. Gowan Company 
has proposed that the tolerances for cotton seed and cotton gin 
byproducts be geographically limited to California only. A permanent 
tolerance exists for apples, but Gowan Company proposes to increase the 
tolerance level in connection with a proposed change in the use 
pattern. A tolerance for residues in wet apple pomace has not been 
proposed previously.
    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. The 
proposed analytical method is high performance liquid chromatography 
with an ultraviolet detector. As required by section 408(d) of the 
FFDCA, as recently amended by the Food Quality Protection Act (FQPA) 
Pub. L. 104-170, Gowan Company included in the petition a summary of 
the petition and authorization for the summary to be published in the 
Federal Register in a notice of receipt of the petition. The summary 
represents the views of Gowan Company; EPA, as mentioned above, is in 
the process of evaluating the petition. As required by section 
408(d)(3) of the FFDCA, EPA is including the summary as a part of this 
notice of filing.

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.
    4. Magnitude of residues--i. Strawberries. Seventy samples of 
treated strawberries were analyzed. The maximum residue observed (MRO) 
at a preharvest interval of 3-days was 2.06 ppm and the average residue 
was 0.67 ppm. A tolerance of 3 ppm was proposed.
    ii. Cotton. Twenty residue studies were conducted in the U.S., 
Brazil, and Spain. Four additional studies, including a processing 
study, were conducted in California. The MRO in cotton seed was 0.097 
ppm and the average residue was 0.065 ppm. A tolerance of 0.2 ppm was 
proposed. The maximum residue observed in cotton gin byproducts was 
2.29 ppm and the average residue was 1.07 ppm. A tolerance of 3 ppm was 
proposed. The proposed tolerances are geographically limited to 
California only. A field crop rotation study indicated that residues 
would not be present in crops planted 4-months after application of 
hexythiazox.
    iii. Apples--a total of 20 trials were conducted. The maximum 
residue in apples having a preharvest interval of 1-month was 0.38 ppm 
and the average residue was 0.14 ppm. A tolerance of 0.4 ppm was 
proposed. Processing studies indicated that hexythiazox residues 
concentrate by a factor of 1.7 in wet apple pomace, and a tolerance of 
0.7 ppm was proposed.

B. Toxicological Profile

    1. Acute toxicity. The acute oral and dermal LD50 of 
technical hexythiazox is > 5,000 mg/kg, and the 4-hour acute inhalation 
LC50 is > 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, 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 no-observed effected level (NOEL) 
was 200 milligram/kilogram/day (mg/kg/day), the highest dose tested 
(HDT), 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 HDT (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 HDT. 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. Use on several other crops had 
been previously proposed [PP 6F4738], and an aggregate exposure 
analysis has taken into consideration all current and proposed uses. 
The nature and metabolism of

[[Page 45495]]

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. A chronic dietary exposure analysis was 
conducted for the general U.S. population and 26 population subgroups. 
In this analysis it was assumed that 100% of crops were treated. A 
chronic exposure of 0.000172 mg/kg/day was calculated for the average 
U.S. population. Non-nursing infants, the most heavily exposed 
subgroup, had a calculated exposure of 0.000972 mg/kg/day. Actual 
exposure would be much lower, however, because far less than 100% of 
crops would be treated.
    The Agency 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.

D. Cumulative Effects

    At this time the Agency 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, the Agency is considering only the potential 
risks of hexythiazox in its aggregate exposure.

E. Safety Determination

    1. U.S. population--i. Chronic risk. Chronic risk was calculated 
using anticipated residue concentrations from all current and proposed 
uses of hexythiazox and assuming that 100% of each crop is treated. 
Dietary exposure of the general U.S. population was equivalent to 0.7% 
of the RfD. Exposure of the most heavily exposed subgroup, non-nursing 
infants, was equivalent to 3.9% of the RfD.
    ii. Oncogenic risk. Oncogenic risk was evaluated using anticipated 
residue concentrations and taking into account the percent of crop 
known or expected to be treated. Lifetime oncogenic risk for the U.S. 
population was calculated to be 4.5 x 10-7.
    iii. Acute risk. An estimate of acute risk with this compound has 
not been conducted since no acute reproductive or developmental effects 
have been observed.
    2. 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 HDT, 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 HDT. In 
the rabbit developmental study, the maternal and developmental NOEL was 
1,080 mg/kg/day, the HDT.
    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 MRLs of 0.5 mg/kg for residues of hexythiazox in strawberries 
and apples have been established. The U.S. tolerance proposals are 
somewhat at variance with the Codex MRLs because they are based upon 
different preharvest intervals. Also, it is believed that the U.S. 
proposed tolerance levels allow for a greater margin of safety than the 
Codex MRLs. There are no Codex MRLs for the other commodities in this 
petition. There are no Canadian or Mexican MRLs for hexythiazox. (Beth 
Edwards).

3. Interregional Research Project

 PP 7E4833

    EPA has received a pesticide petition (PP 7E4833) from the 
Interregional Research Project Number 4 (IR-4), proposing pursuant to 
section 408(d) of the Federal Food, Drug, and Cosmetic Act, 21 U.S.C. 
346a(d), to amend 40 CFR part 180 by establishing tolerances for 
residues of the herbicide glyphosate [N-phosphonomethyl)glycine] in or 
on the raw agricultural commodities (RACs) durian at 0.2 ppm, 
mangosteen at 0.2 ppm, and rambutan at 0.2 ppm. Durian, mangosteen, and 
rambutan are tree fruits which are grown commercially in Hawaii and 
Puerto Rico.
    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. This 
notice includes a summary of the petition prepared by Monsanto 
Agricultural Group (MAG), the registrant.

A. Residue Chemistry

    1. Plant metabolism. The nature of the residue in plants and 
animals is adequately understood. The residue to be regulated is the 
parent glyphosate.
    2. Analytical method. There is a practical analytical method for 
detecting and measuring levels of glyphosate in or on food with a 
limits of detection (0.05 ppm) that allows monitoring of food with 
residues at or above the levels set in these tolerances. EPA has 
provided information on this method to FDA.
    3. Magnitude of residues. The proposed use for glyphosate is for 
orchard floor treatment. The registrant referenced extensive experience 
and data with glyphosate in/on tree fruit and nuts crops which show 
that when orchard floor applications are made, no detectable residues 
of the herbicide are recovered in the harvested fruit. Based on these 
data Monsanto expects no detectable residues of glyphosate in durian, 
mangosteen or rambutan when glyphosate is applied in a similar manner.
    Tolerances for the combined residues of glyphosate and its 
metabolite, aminomethylphosphonic acid (AMPA), have been established at 
0.2 ppm on a number of tree fruit and nuts, as well as a variety of 
tropical fruit: acerola, atemoya, avocado, banana, breadfruit, 
canistel, carambola, cherimoya cocoa beans, coconuts, dates, figs, 
genip, jaboticaba, jackfruit, longan, lychee,

[[Page 45496]]

mango, mayhaw, passion fruit, persimmon, pomegranate, sapodilla, 
sapote, soursop, sugar apple and tamarind. Any secondary residues 
occurring in milk, eggs, meat, fat, liver and kidney of cattle, goats, 
horses, hogs, poultry and sheep are covered by existing tolerances.
    The Agency's Health Effects Division - Metabolism Committee has 
determined that AMPA should be dropped from the tolerance expression. 
Tolerances that are the subject of this notice are based solely on 
residues of glyphosate.

B. Toxicological Profile

    1. Acute toxicity. Results from an acute oral study in rats show a 
combined lethal dose (LD)50 for glyphosate of >5,000 
milligram/kilogram (mg/kg).
    An acute dermal study in rabbit resulted in a LD50 of > 
5,000 mg/kg.
    The results of a primary eye irritation study in the rabbit showed 
severe irritation for glyphosate acid. However, glyphosate is normally 
formulated as one of several salts and eye irritation studies on the 
salts showed essentially no irritation.
    A primary dermal irritation study showed essentially no irritation.
    A primary dermal sensitization study showed no sensitization. Based 
on these data, Monsanto concludes that the acute toxicity and 
irritation potential of glyphosate is low.
    2. Genotoxicity. A number of mutagenicity studies were conducted 
and were all negative. These studies included: chromosomal aberration 
in vitro (no aberrations in Chinese hamster ovary cells were caused 
with or without S9 activation); deoxyribonucleic acid(DNA) repair in 
rat hepatocyte; in vivo bone marrow cytogenic test in rats; rec-assay 
with B. subtilis; reverse mutation test with S. typhimurium; Ames test 
with S. typhimurium; and dominant-lethal mutagenicity test in mice.
    Negative results were obtained when glyphosate was tested in a 
dominant-lethal mutation assay. While this assay was designed as a 
genetic toxicity test, agents that can affect male reproduction 
function will also cause effects in this assay. More importantly, the 
multi-generation reproduction study in rodents is a complex study 
design which measures a broad range of endpoints in the reproductive 
system and in developing offspring that are sensitive to alterations by 
chemical agents. Glyphosate has been tested in two separate multi-
generation studies and each time the results demonstrated that 
glyphosate is not a reproductive toxin.
    3. Reproductive and developmental toxicity. An oral developmental 
toxicity study with rats given doses of 0, 300, 1,000 and 3,500 
milligram/kilogram/day (mg/kg/day) with a maternal no-observed-effect 
level (NOEL) of 1,000 mg/kg/day based on clinical signs of toxicity, 
body weight effects and mortality, and a fetal NOEL of 1,000 mg/kg/day 
based on reduced body weights and delayed sternebrae maturation at the 
highest dose tested (HDT) of 3,500 mg/kg/day.
    An oral developmental toxicity study with rabbits given doses of 
0,75, 175 and 350 mg/kg/day with a maternal of NOEL of 175 mg/kg/day 
based on clinical signs of toxicity and mortality, and a fetal NOEL of 
350 mg/kg/day based on no developmental toxicity at any dose tested.
    A 3-generation reproduction study with rats fed dosage levels of 0, 
3, 10 and 30 mg/kg/day with a NOEL for systemic and reproductive/
developmental parameters of 30 mg/kg/day based on no adverse effects 
noted at any dose level.
    A 2-generation reproduction study with rats fed dosage levels of 0, 
100, 500 and 1,500 mg/kg/day with a NOEL for systemic and developmental 
parameters of 500 mg/kg/day based on body weight effects, clinical 
signs of toxicity in adult animals and decreased pup body weights, and 
a reproductive NOEL of 1,500 mg/kg/day.
    4. Subchronic toxicity. A 90-day feeding study in mice fed dosage 
levels of 0, 5,000, 10,000 and 50,000 with a NOEL of 10,000 ppm based 
on body weight effects at the high dose.
    A 90-day feeding study in rats fed dosage levels of 0, 1,000, 5,000 
and 20,000 ppm with a NOEL of 20,000 ppm based on no effects even at 
the HDT.
    A 90-day feeding study in dogs given glyphosate, via capsule, at 
doses of 0, 200, 600 and 2,000 mg/kg/day with a NOEL of 2,000 mg/kg/day 
based on no effects even at the HDT.
    5. Chronic toxicity. The reference dose (RfD) for glyphosate based 
on maternal effects in a developmental study with rabbits (NOEL of 175 
milligram/killogram/body weight day (mg/kg/bwt/day)) and using a 
hundred-fold safety factor is calculated to be 2.0 mg/kg/bwt/day.
    The EPA Carcinogenicity Peer Review Committee has classified 
glyphosate in Group E (evidence of non-carcinogenicity for humans), 
based upon lack of convincing carcinogenicity evidence in adequate 
studies in two animal species. There was no evidence of carcinogenicity 
in an 18-month feeding study in mice and a 2 year feeding study in rats 
at the dosage levels tested (DLT). The doses tested were adequate for 
identifying a cancer risk.
    A mouse carcinogenicity study with mice fed dosage levels of 0, 
150,750 and 4,500 mg/kg/day with a NOEL of 750 mg/kg/day based on body 
weight effects and microscopic liver changes at the high dose. There 
was no carcinogenic effect at the HDT of 4,500 mg/kg/day.
    A 12-month oral study in dogs given glyphosate, via capsule, at 
doses of 0, 20, 100 and 500 mg/kg/day with a NOEL of 500 mg/kg/day 
based on no adverse effects at any dose level.
    A 24-month chronic/feeding carcinogenicity study with rats fed 
dosage levels of 0, 89, 362 and 940 mg/kg/day (males) and 0, 113, 457 
and 1,183 mg/kg/day (females) with a systemic NOEL of 362 mg/kg/day 
based on body weight effects in the female and eye effects in males. 
There was no carcinogenic response at any dose level.
    A 26-month chronic/feeding carcinogenicity study with rats fed 
dosage levels of 0, 3, 10 and 31 mg/kg/day (males) and 0, 3, 11 and 34 
mg/kg/day (females) with a systemic NOEL of 31 mg/kg/day (males) and 34 
mg/kg/day (females) based on no carcinogenic or other adverse effects 
at any dose level.
    Monsanto believes that these data support their conclusion that 
glyphosate does not produce adverse reproductive effects and is not a 
developmental toxin, mutagen, carcinogen or a neurotoxin.
    6. Animal metabolism. Animal metabolism data were not submitted 
with this petition. However, Monsanto believes that the treated 
commodities are not fed to animals, therefore, there will be no 
residues transferred to meat, milk, poultry, or eggs.

C. Aggregate Exposure

    1. Dietary exposure--Food. For purposes of assessing the potential 
dietary exposure, Monsanto has estimated aggregate exposure based on 
the tolerances for glyphosate on jackfruit, sugar apple and lychee, all 
with established 0.2 ppm tolerances. As the consumption of durian, 
mangosteen and rambutan is so limited, the theoretical maximum residue 
contribution (TMRC) calculations were based on similar or related 
tropical fruit: durian and jackfruit are similar in size, with thick 
rinds and similar growth habit; mangosteen and sugar apple fruit are 
also similar in size and growth habit: and rambutan and lychee are from 
the same botanical family, the Sapindaceae. The fruit are not fed to 
animals, therefore, there will be no exposure of humans to residues 
transferred to meat, milk, poultry, or eggs. Other potential sources of 
exposure of the general population to residues of pesticides are

[[Page 45497]]

residues in drinking water and exposure from non-occupational sources.
    Based on the available acute toxicity data, Monsanto believes that 
glyphosate does not pose any acute dietary risks.
    2. Drinking water. A Maximum Concentration Level (MCL) has been 
established for residues of glyphosate in drinking water at 0.7 mg/l 
since glyphosate is approved for direct application to water. The MCL 
represents the level at which no known or anticipated adverse health 
effects occur, allowing for an adequate margin of safety (MOE), and is 
based on the RfD.
    Monsanto reports that glyphosate adsorbs strongly to soil and is 
not expected to move vertically below the 6-inch soil layer; residues 
are expected to be immobile in soil. Glyphosate is readily degraded by 
soil microbes to AMPA, which is degraded to carbon dioxide. Monsanto 
believes that glyphosate and AMPA are not likely to move to ground 
water due to their strong adsorptive characteristics. However, due to 
its aquatic use patterns and through erosion, glyphosate does have the 
potential to enter surface waters, where, according to Monsanto, it 
will adsorb to sediment and undergo microbial degradation.
    3. Non-dietary exposure. Exposure (non-occupational) of the general 
population to glyphosate is expected based on the currently-registered 
uses; however, due to the low acute toxicity and lack of other 
toxicological concerns, Monsanto believes that the risk posed by non-
occupational exposure (NOE) to glyphosate is minimal.

D. Cumulative Effects

    Because the existing data base is insufficient to fully assess 
cumulative toxic effects that may be caused by glyphosate along with 
other chemical compound(s) that may share a common mechanism of 
toxicity, Monsanto believes that any consideration of such an analysis 
of toxicity is inappropriate at this time.

E. Safety Determination

    1. U.S. population. The TMRC for existing, published tolerances for 
glyphosate is 0.021460 mg/kg/bwt/day or 1.0% of the RfD for the overall 
U.S. population. Even using conservative exposure assumptions and 
substituting the more widely consumed jackfruit, sugar apple and 
lychee, there is not enough exposure to calculate a significant 
contribution to the TMRC. As the exposure from durian, mangosteen and 
rambutan would be even less, the aggregate exposure of these three 
fruits will not add to the RfD for the overall U.S. population. EPA 
generally has no concern for exposures below 100% of the RfD. 
Therefore, based on the completeness and reliability of the toxicity 
data and the conservative exposure assessment, Monsanto concludes that 
there is a reasonable certainty that no harm will result from aggregate 
exposure to residues of glyphosate, including all anticipated dietary 
exposure and all other non-occupational exposures.
    2. Infants and children. In assessing the potential for additional 
sensitivity of infants and children to residues of glyphosate, data 
were considered from developmental toxicity studies in the rat and 
rabbit and multi-generation reproduction studies in rats.
    No birth defects were observed in the offspring of rats given 
glyphosate by gavage at dose levels of 0, 300, 1,000, and 3,500 mg/kg/
day on days 6 through 19 of gestation. The NOEL for this study was 
1,000 mg/kg/day based on maternal and developmental toxicity observed 
at the HDT, 3,500 mg/kg/day. The high-dose in this study was 3.5 times 
higher than the limit dose that is currently required by the 
guidelines.
    No birth defects were observed in the offspring of rabbits given 
glyphosate by gavage at dose levels of 0, 75, 175, and 350 mg/kg/day on 
days 6 through 27 of gestation. The NOEL for this study is considered 
to be 175 mg/kg/day based on maternal toxicity at the high-dose of 350 
mg/kg/day. Because no developmental toxicity was observed at any dose 
level, the developmental NOEL is considered to be 350 mg/kg/day.
    Male and female rats were fed glyphosate at dose levels of 0, 3, 
10, and 30 mg/kg/day every day throughout the production of three 
successive generations. No adverse treatment-related effects on 
reproduction were observed. Because no toxicity was noted even at the 
HDT, a second reproduction study at higher dose levels (HDLs) was 
performed and is described below.
    Male and female rats were fed glyphosate at dose levels of 0, 100, 
500, and 1,500 mg/kg/day every day throughout the production of two 
successive generations. Reduced body weights and soft stools occurred 
at 1,500 mg/kg/day (3% of the diet); therefore, the systemic NOEL is 
considered to be 500 mg/kg/day. Glyphosate did not affect the ability 
of rats to mate, conceive, carry or deliver normal offspring at any 
dose level.
    3. Reference dose. The TMRC for existing, published and pending 
tolerances (including durian, mangosteen, and rambutan) for glyphosate 
range from 0.015 for nursing infants to 0.049 for non-nursing infants 
(0.8 to 2.5% of the RfD). EPA generally has no concern for exposures 
below 100% of the RfD. Therefore, based on the completeness and 
reliability of the toxicity data and the conservative exposure 
assessment, Monsanto concludes that there is a reasonable certainty 
that no harm will result from aggregate exposure to residues of 
glyphosate, including all anticipated dietary exposure and all other 
non-occupational exposures.
    4. Endocrine effects. No known factors were identified in sub-
chronic, chronic or developmental toxicity studies to indicate any 
endocrine-modulating activity by glyphosate.

F. International Tolerances

    Codex maximum residue levels (MRLs) have not been established for 
residues of glyphosate on durian, mangosteen and rambutan. (Sidney 
Jackson).
[FR Doc. 98-22430 Filed 8-25-98; 8:45 am]
BILLING CODE 6560-50-F