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hydramethylnon (Amdro) Pesticide Tolerance Petition Filing 8/98

 

[Federal Register: August 14, 1998 (Volume 63, Number 157)]
[Notices]               
[Page 43702-43705]
>From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr14au98-79]

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ENVIRONMENTAL PROTECTION AGENCY

[PF-824; FRL-6023-2]

 
American Cyanamid Company; Pesticide Tolerance Petition Filing

AGENCY: Environmental Protection Agency (EPA).

ACTION: Notice.

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SUMMARY: This notice announces the initial filing of a pesticide 
petition proposing the establishment of regulations for residues of a 
certain pesticide chemical in or on various food commodities.
DATES: Comments, identified by the docket control number PF-824, must 
be received on or before September 14, 1998.
ADDRESSES: By mail submit written comments to: Information and Records 
Integrity Branch, Public Information and Services Divison (7502C), 
Office of Pesticides Programs, Environmental Protection Agency, 401 M 
St., SW., Washington, DC 20460. In person bring comments to: Rm. 119, 
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. 119 at the 
address given above, from 8:30 a.m. to 4 p.m., Monday through Friday, 
excluding legal holidays.

FOR FURTHER INFORMATION CONTACT: Marion J. Johnson, product Manager 2, 
Registration Division (7505W), Office of Pesticide Programs, 
Environmental Protection Agency, 401 M St., SW, Washington, DC 20460. 
Office location, telephone number, and e-mail address: Rm. 208, CM #2, 
1921 Jefferson Davis Highway, Arlington, VA 22202, (703) 305-6788; e-
mail: johnson.marion@epamail.epa.gov.
SUPPLEMENTARY INFORMATION: EPA has received a pesticide petition as 
follows proposing the establishment and/or amendment of regulations for 
residues of certain pesticide chemical in or on various food 
commodities under section 408 of the Federal Food, Drug, and Comestic 
Act (FFDCA), 21 U.S.C. 346a. EPA has determined that this petition 
contains data or information regarding the elements set forth in 
section 408(d)(2); however, EPA has not fully evaluated the sufficiency 
of the submitted data at this time or whether the data supports 
granting of the petition. Additional data may be needed before EPA 
rules on the petition.
    The official record for this notice of filing, as well as the 
public version, has been established for this notice of filing under 
docket control number [PF-824] (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

[[Page 43703]]

``ADDRESSES'' at the beginning of this document.
    Electronic comments can be sent directly to EPA at:
    opp-docket@epamail.epa.gov


    Electronic comments must be submitted as an ASCII file avoiding the 
use of special characters and any form of encryption. Comment and data 
will also be accepted on disks in Wordperfect 5.1/6.1 file format or 
ASCII file format. All comments and data in electronic form must be 
identified by the docket control number (PF-824) and appropriate 
petition number. Electronic comments on this notice may be filed online 
at many Federal Depository Libraries.

List of Subjects

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

    Dated:August 6, 1998.

Arnold E. Layne,

Acting Director, Registration Division, Office of Pesticide Programs.

Summary of Petition

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

 American Cyanamid Company

PP 2F2609

    EPA has received a pesticide petition (PP 2F2609) from American 
Cyanamid Company, P. O. Box 400, Princeton, NJ 08543-0400 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 [tetrahydro-5,5-dimethyl-2(1H)-pyrimidinone[3-4-
(trifluoromethyl)phenyl]-1-[2-[4-(trifluoromethyl)phenyl]ethenyl]-2-
propenylidene]hydrazone, hydramethylnon] in or on the raw agricultural 
commodity pineapples at 0.05 parts per million (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.

A. Residue Chemistry

    1. Plant metabolism. Metabolism studies were conducted on grass and 
pineapples utilizing two distinct <SUP>14</SUP>C-radiolabeled forms of 
hydramethylnon. Based on these studies, the qualitative nature of the 
residues of hydramethylnon in plants is understood and the parent 
molecule is considered to be the only residue of concern.
    2. Analytical method. Adequate enforcement methodology is available 
in PAM II (Method I) to enforce the tolerance expression. A 
confirmatory method has recently been submitted to the FDA for 
inclusion in PAM II.
    3. Magnitude of residues. Based on the results of seven pineapple 
field trials, including two studies conducted at 5x the maximum 
application rate, residues of hydramethylnon are not expected to exceed 
0.05 ppm in/on pineapples. Processing studies have demonstrated that 
residues are not expected to concentrate in pineapple processed 
commodities. The Agency has previously established a time-limited 
tolerance at this level to cover residues that may occur as a result of 
use under section 18 emergency authorizations issued to the State of 
Hawaii. Secondary residues of hydramethylnon are not expected in animal 
commodities and no tolerances for secondary residues of hydramethylnon 
in livestock commodities are currently established.

B. Toxicological Profile

    1. Acute toxicity. Based on the results of the acute toxicity data, 
hydramethylnon does not exhibit significant acute toxicity. For the 
acute oral study in rats, the LD<INF>50</INF> in males was 817 mg/kg 
and the LD<INF>50</INF> in females was 1,502 mg/kg. The LD<INF>50</INF> 
for the acute dermal study in rabbits was greater than 2,000 mg/kg and 
the 4-hour LC<INF>50</INF> for acute inhalation in rats was 2.9 mg/l 
(males and females combined). Hydramethylnon is not a dermal irritant 
or a skin sensitizer and is a mild eye irritant.
    2. Genotoxicty. The following genotoxicity tests were all negative: 
Salmonella typhimurium/Escherichia coli reverse gene mutation assay, 
Schizosaccharomyces pombe P1 forward gene mutation assay, in vitro 
Chinese Hamster Ovary (CHO) chromosome aberration, Saccharomyces 
cerevisiae D4 mitotic gene conversion assay. The data suggest that 
hydramethylnon is not genotoxic in microbial test systems or 
clastogenic in cultured mammalian cells and does not induce dominant 
lethality in male rat germinal cells. The evidence of male infertility 
and testicular atrophy at 90 mg/kg/day in the dominant lethal assay is 
consistent with similar findings observed in the chronic rat study, the 
18-month mouse feeding study, the 2-generation reproduction study, and 
the 91-day oral gavage study in dogs.
    3. Reproductive and developmental toxicity. There is no evidence in 
the prenatal developmental toxicity studies in either rats or rabbits 
of alterations to CNS development, nor is there any indication of 
neurotoxicity in the other short or long-term oral studies in rats, 
mice or dogs. No evidence of the increased sensitivity of the 
developing offspring was noted as the no-observed effected levels 
(NOELs) for developmental toxicity in the rat (10 milligrams/kilogram/
body weight/day (mg/kg/bwt/day) and the rabbit 5 mg/kg/bwt/day were 
greater than the NOELs for maternal toxicity 3 mg/kg/bwt/day for the 
rat and < 5 mg/kg/bwt/day for the rabbit). Hydramethylnon is not 
teratogenic in either the rat or rabbit. Hydramethylnon is a male 
reproductive toxicant which appears to specifically target the germinal 
cells and/or tissues in the testes. In a 2-generation rat reproduction 
study, there was no evidence of systemic toxicity, nor was there any 
evidence of direct toxicity in the offspring. The reproductive NOEL was 
25 ppm (1.66 mg/kg/day for males) and the lowest observed effect level 
(LOEL) was 50 ppm (3.32 mg/kg/day for males), based upon 
histopathological findings in the testes and the epididymides. Also, at 
75 ppm (5.05 mg/kg/day in males), reproductive performance of the males 
was decreased with longer precoital intervals, lower pregnancy rates, 
reduced gestation weight gain for females and smaller litters.
    4. Subchronic toxicity. The following are the results of the 
subchronic toxicity tests that have been conducted with hydramethylnon: 
91-day feeding study in rats (NOEL 2.5 mg/kg/bwt/day); 91-day gavage 
study in dogs (NOEL < 3 mg/kg/bwt/day); 21-day dermal study in rabbits 
(NOEL 250 mg/kg bwt/day). For both the short- and intermediate-term 
margin of exposure (MOE) calculations, the Agency's Hazard 
Identification Committee recommended use of the systemic NOEL 
(freestanding) of 250 (mg/kg/day) from the 21-day dermal toxicity study 
in New Zealand white rabbits. Non-adverse signs at the NOEL

[[Page 43704]]

included decreased food consumption in males and females, and 
thrombocytopenia in females.
    5. Chronic toxicity. The EPA has established the Reference Dose 
(Rfd) for hydramethylnon at 0.01 mg/kg/day. This RfD is based on a 6-
month feeding study in dogs with a NOEL of 1.0 mg/kg/day based on an 
increased incidence of soft stools, mucoid stools, and diarrhea at the 
LOEL of 3.0 mg/kg/day. An uncertainty factor of 100 was used during 
calculation of the RfD. Based on a statistically significant increase 
in lung adenomas and combined lung adenomas/carcinomas in female mice, 
hydramethylnon has been classified as a Group C chemical (possible 
human carcinogen) by the Agency's Cancer Peer Review Committee. The 
Committee recommended using the RfD approach for risk assessment.
    6. Animal metabolism. Adequate rat and goat metabolism studies are 
available for hydramethylnon. Results of ruminant metabolism and 
feeding studies clearly demonstrate that there is no reasonable 
expectation that residues of hydramethylnon in pineapple processed 
commodities will be transferred to milk or edible tissues. Hence, no 
tolerances on any food items derived from ruminants are required for 
hydramethylnon.
    7. Metabolite toxicology. The parent molecule is the only moiety of 
toxicological significance which needs regulation in plant commodities.
    8. Endocrine disruption. EPA is required to develop a screening 
program to determine whether certain substances (including all 
pesticides and inerts) ``may have an effect in humans that is similar 
to an effect produced by a naturally occurring estrogen, or such other 
endocrine effect''. The Agency is currently working with interested 
stakeholders, including other government agencies, public interest 
groups, industry and research scientists in developing a screening and 
testing program and a priority setting scheme to implement this 
program. Congress has allowed 3 years from the passage of FQPA (August 
3, 1999) to implement this program. At the present time, no reliable 
information is available to indicate that hydramethylnon has a 
potential to have an effect in humans that is similar to effects 
produced by naturally occurring estrogen or other endocrine substances.

C. Aggregate Exposure

    1. Dietary exposure. A 0.05 ppm tolerance for the residues of 
hydramethylnon has only been established for grasses and as there is no 
reasonable expectation that residues in grass will be transferred to 
the milk and edible tissues of ruminants, no tolerances for 
hydramethylnon have been established on any food items. Thus, there is 
no contribution to the aggregate exposure of hydramethylnon residues 
from dietary sources. Therefore, the following risk assessment to 
assess dietary exposures and risks from hydramethylnon will be based on 
dietary exposures resulting from only the pending tolerance in/on 
pineapples.
    2. Food--i. Acute exposure and risk. Acute dietary risk assessments 
are performed for a food-use pesticide if a toxicological study has 
indicated the possibility of an effect of concern occurring as a result 
of a 1-day or single exposure. The acute dietary (food only) risk 
assessment is not required as the Agency's Hazard Identification 
Committee did not identify any acute dietary risk endpoints.
    ii. Chronic exposure and risk. In response to EPA's granting of an 
emergency exemption under FIFRA section 18 authorizing the use of 
hydramethylnon in pineapples in Hawaii, a time-limited tolerance of 
0.05 ppm was established in/on pineapple fruits. The Agency has 
conducted a chronic dietary risk assessment based on very conservative 
assumptions -- 100% of pineapple commodities will contain 
hydramethylnon residues and those residues will be at the level of the 
required tolerance -- which results in an overestimate of human dietary 
exposure. Thus, in making a safety determination for this time-limited 
tolerance, HED has taken into account this conservative exposure 
assessment. Based on similar considerations, the pending hydramethylnon 
tolerance in/on pineapples results in a TMRC that is equivalent to the 
following percentages of the RfD of 0.01 mg/kg/day:

                                                                        
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                 Population Subgroup                          %RfD      
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U.S. Population......................................              <0.1%
Nursing Infants......................................              <0.1%
Non-Nursing Infants (<1 year old)....................               0.2%
Children (1-6 years old).............................               0.1%
Children (7-12 years old)............................              <0.1%
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    The subgroups listed above are: (i) the U.S. population (48 
States); (ii) those for infants and children; and, (iii) the other 
subgroups for which the percentage of the RfD occupied is greater than 
that occupied by the subgroup U.S. population (48 States).
    3. Drinking water. Based on its physical and chemical properties, 
(extremely low water solubility of 7-9 ppb at 25  deg.C and rapid 
aqueous photolysis with a \1/2\ of less than 1 hour), there is no 
concern for exposure to residues of hydramethylnon in potable water. 
Hydramethylnon is also immobile in soil and does not leach because it 
is strongly adsorbed to all common soil types; thus hydramethylnon and 
its degradates are not expected to leach to groundwater. There are no 
established Maximum Contaminant Levels (MCLs) for residues of 
hydramethylnon in drinking water and no health advisory levels for this 
active ingredient in drinking water have been issued. Because the 
Agency lacks sufficient water-related exposure data to complete a 
comprehensive drinking water risk assessment for many pesticides, EPA 
has commenced and nearly completed a process to identify a reasonable 
yet conservative bounding figure for the potential contribution of 
water-related exposure to the aggregate risk posed by a pesticide. In 
developing the bounding figure, EPA estimated residue levels in water 
for a number of specific pesticides using various data sources. The 
Agency then applied the estimated residue levels, in conjunction with 
appropriate toxicological endpoints (RfD's or acute dietary NOEL's) and 
assumptions about body weight and consumption, to calculate, for each 
pesticide, the increment of aggregate risk contributed by consumption 
of contaminated water. While EPA has not yet pinpointed the appropriate 
bounding figure for exposure from contaminated water, the ranges the 
Agency is continuing to examine are all below the level that would 
cause hydramethylnon to exceed the RfD if the tolerance being 
considered in this document were granted. The potential exposures 
associated with hydramethylnon in water, even at the higher levels the 
Agency is considering as a conservative upper bound, would be 
negligible and there is a reasonable certainty of no harm if the 
pending tolerance is granted.
    4. Non-dietary exposure. Hydramethylnon is currently registered for 
use on the following residential non-food sites: recreational areas, 
ornamental plants, lawns, turf, and household or domestic dwellings. 
However as the vapor pressure of hydramethylnon is less than 2 x 
10<SUP>-8</SUP> mm of Hg at 35 and 45  deg.C, the potential for non-
occupational exposure by inhalation is insignificant. Moreover, based 
on the current and proposed use patterns, chronic exposure is not 
likely. Although there may be short- and intermediate-term non-
occupational dermal exposure scenarios, dermal absorption studies 
conducted with the

[[Page 43705]]

2% gel formulation indicate that less than 1% of the dose is dermally 
absorbed after 10-hours. In addition, the Agency has reviewed risk 
assessments and accepted the existence of more than adequate margins of 
exposure ((MOE) of 658 for both commercial and homeowner applicators 
and MOEs of >540 for post-application homeowner exposures) for other 
hydramethylnon-based products, containing up to 2% active ingredient. 
Thus, this new use pattern does not present any incremental risk of 
exposure to hydramethylnon residues.

D. Cumulative Effects

    To the best of our knowledge, hydramethylnon is the only registered 
pesticide which belongs to a unique chemical class, the pyrimidinones 
(amidinohydrazones). Unlike other pesticides for which EPA has followed 
a cumulative risk approach based on a common mechanism of toxicity, 
hydramethylnon does not appear to produce a toxic metabolite produced 
by other substances. Therefore, the potential for cumulative effects of 
hydramethylnon and other chemicals having a common mechanism of 
toxicity should not be of concern and for the purposes of this 
tolerance action, it is assumed that hydramethylnon does not have a 
common mechanism of toxicity with other substances.

E. Safety Determination

    1. U.S. population-- i. Acute risk . An acute endpoint has not been 
identified. The Agency's Hazard Identification Committee determined 
that this risk assessment is not required.
    ii. Chronic risk. Using the TMRC exposure assumptions described 
above, EPA has concluded that aggregate exposure to hydramethylnon from 
food will utilize <1% of the RfD of 0.01 mg/kg/day for the U.S. 
population. EPA generally has no concern for exposures below 100% of 
the RfD because the RfD represents the level at or below which daily 
aggregate dietary exposure over a lifetime will not pose appreciable 
risks to human health. In view of the negligible potential for exposure 
to hydramethylnon in drinking water and from non-dietary, non-
occupational exposure, the aggregate exposure is not expected to exceed 
100% of the RfD. EPA has concluded that there is a reasonable certainty 
that no harm will result from aggregate exposure to hydramethylnon 
residues. According to Agency policy, the residential uses of 
hydramethylnon do not fall under a chronic exposure scenario. Thus, it 
can be concluded that there is a reasonable certainty that no harm will 
result from chronic aggregate exposure to hydramethylnon residues.
    iii. Short- and intermediate-term risk. Short- and intermediate-
term aggregate exposure takes into account chronic dietary food and 
water (considered to be a background exposure level) plus indoor and 
outdoor residential exposure. Although hydramethylnon has residential 
uses, this new use pattern does not present any incremental risk of 
exposure to hydramethylnon residues. As discussed previously in section 
C. 4., the vapor pressure of hydramethylnon is less than 2 x 
10<SUP>-8</SUP> mm of Hg at 35 and 45  deg.C; thus, the potential for 
non-occupational exposure by inhalation is insignificant. Moreover, 
based on the physical and chemical properties of hydramethylnon, 
exposure from drinking water is not likely. Although there may be 
short- and intermediate-term occupational and non-occupational dermal 
exposures, the Agency has reviewed risk assessments and accepted the 
existence of more than adequate (MOEs of 658 for both commercial and 
homeowner applicators and MOEs of >540 for post-application homeowner 
exposures) for other hydramethylnon-based products, containing up to 2% 
active ingredient. Thus, as in the case for chronic exposure scenarios, 
it can be concluded that there is a reasonable certainty that no harm 
will result from short and intermediate-term exposures to 
hydramethylnon residues.
    2. Infants and children--i. Chronic risk. Using the TMRC exposure 
assumptions described above, EPA has concluded that aggregate exposure 
to hydramethylnon from food will utilize only 0.2% of the RfD of 0.01 
mg/kg/day for non-nursing infants <1 year old.
    ii. Safety factor for infants and children-- a. In general. In 
assessing the potential for additional sensitivity of infants and 
children to residues of hydramethylnon, EPA considered data from 
developmental toxicity studies in the rat and rabbit and a 2-generation 
reproduction study in the rat. EPA has concluded that the toxicological 
database for hydramethylnon is adequate and does not indicate an 
increased sensitivity of perinatal animals to pre- and/or post natal 
exposures. Therefore, no additional uncertainty factor for protection 
of infants and children are warranted for hydramethylnon.
    b. Developmental toxicity studies. In the rat developmental 
toxicity study, the developmental NOEL was 10 mg/kg/bwt/day with a NOEL 
for maternal toxicity of 3.0 mg/kg/bwt/day. In the rabbit developmental 
toxicity study the developmental NOEL was 5 mg/kg/bw/day with a NOEL 
for maternal toxicity of less than 5 mg/kg bwt/day.
    c. Reproductive toxicity study. A 2-generation reproduction study 
with hydramethylnon was conducted in rats. The data support a NOEL for 
reproductive toxicity of 50 ppm (4.2 mg/kg/bwt/day), while the NOEL for 
paternal toxicity was 25 ppm (2.1 mg/kg/bwt/day). No adverse effects 
were observed in the pups.
    These values are significantly higher than the NOEL used to 
calculate the RfD for the general U.S. population which is 0.01 mg/kg/
bwt/day. These results demonstrate that there is a reasonable certainty 
that no harm will result to infants rm: /diskb/cgi-bin-tmp/TMPBaaaavwra: No such file or directory
or children from aggregate exposure 
to hydramethylnon.

F. International Tolerances

    There are no Codex, Canadian or Mexican residue limits established 
for hydramethylnon in/on pineapple. Thus, harmonization is not an issue 
for this petition.
[FR Doc. 98-21902 Filed 8-13-98; 8:45 am]
BILLING CODE 6560-50-F