[Federal Register Volume 62, Number 100 (Friday, May 23, 1997)]
[Rules and Regulations]
[Pages 28350-28355]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 97-13645]



[[Page 28350]]

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

ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 180

[OPP-300496; FRL-5719-8]
RIN 2070-AB78


Cyclanilide; Pesticide Tolerances

AGENCY: Environmental Protection Agency (EPA).

ACTION: Final rule.

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

SUMMARY: This regulation establishes tolerances for residues of the 
plant growth regulator, cyclanilide, in or on the food commodities 
cottonseed, cotton gin byproducts, milk, fat, meat, meat by-products, 
and kidney of cattle, goats, horses, hogs and sheep. Rhone-Poulenc Ag 
Company submitted a petition to EPA under the Federal Food, Drug, and 
Cosmetic Act (FFDCA) as amended by the Food Quality Protection Act of 
1996 (Pub. L. 104-170) requesting the tolerances.
DATES: This regulation becomes effective May 23, 1997. Written 
objections and requests for hearings must be received on or before July 
22, 1997.

ADDRESSES: Written objections and hearing requests, identified by the 
docket control number, [OPP-300496], may be submitted to: Hearing Clerk 
(1900), Environmental Protection Agency, Rm. M3708, 401 M St., SW., 
Washington, DC 20460. Fees accompanying objections and hearing requests 
shall be labeled ``Tolerance Petition Fees'' and forwarded to: EPA 
Headquarters Accounting Operations Branch, OPP (Tolerance Fees), P.O. 
Box 360277M, Pittsburgh, PA 15251. A copy of any objections and hearing 
requests filed with the Hearing Clerk should be identified by the 
docket control number and submitted to: Public Information and Records 
Integrity Branch, Information Resources and Services (7506C), Office of 
Pesticide Programs, Environmental Protection Agency, 401 M St., SW., 
Washington, DC 20460. In person, bring copy of objections and hearing 
requests to: Rm. 1132, CM #2, 1921 Jefferson Davis Hwy., Arlington, VA.
    A copy of objections and hearing requests filed with the Hearing 
Clerk may also be submitted electronically by sending electronic mail 
(e-mail) to: [email protected]. Copies of objections and 
hearing requests must be submitted as an ASCII file avoiding the use of 
special characters and any form of encryption. Copies of objections and 
hearing requests will also be accepted on disks in WordPerfect in 5.1 
file format or ASCII file format. All copies of objections and hearing 
requests in electronic form must be identified by the docket number 
[OPP-300496]. No Confidential Business Information (CBI) should be 
submitted through e-mail. Electronic copies of objections and hearing 
requests on this rule may be filed online at many Federal Depository 
Libraries.
FOR FURTHER INFORMATION CONTACT: By mail: Cynthia Giles-Parker, Team 
Leader (22), Registration Division, Environmental Protection Agency, 
401 M St., SW., Washington, DC 20460. Office location and telephone 
number and e-mail address: Room 227, CM#2, 1921 Jefferson Davis 
Highway, Arlington, VA (703-305-7740). e-mail: giles-
[email protected].
SUPPLEMENTARY INFORMATION: In the Federal Register of December 23, 1996 
(61 FR 67544)(FRL-5577-1), EPA issued a notice pursuant to section 
408(d)of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 
346a(d), announcing the filing of a pesticide tolerance petition (PP 
6F4643) by Rhone-Poulenc AG Company, P.O. Box 12014, Research Triangle 
Park, NC 27709 to EPA requesting that the Administrator amend 40 CFR 
part 180 by establishing tolerances for residues of the plant growth 
regulator, cyclanilide [1-(2,4-dichlorophenylaminocarbonyl)-
cyclopropane carboxylic acid] determined as 2,4-dichloroaniline 
(calculated as cyclanilide) in or on the food commodities cottonseed at 
0.60 parts per million (ppm); cotton gin byproducts at 25.0 ppm; milk 
at 0.04 ppm; fat of cattle, goats, horses, hogs and sheep at 0.10 ppm; 
meat of cattle, goats, horses, hogs and sheep at 0.02 ppm; meat by-
products (except kidney) of cattle, goats, horses, hogs and sheep at 
0.20 ppm; and kidney of cattle, goats, horses, hogs and sheep at 2.0 
ppm. There were no comments received in response to the notice of 
filing.

I. Statutory Background

    Section 408 of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 
U.S.C. 301 et seq., as amended by the Food Quality Protection Act of 
1996, Pub. L. 104-170) authorizes the establishment of tolerances 
(maximum residue levels), exemptions from the requirement of a 
tolerance, modifications in tolerances, and revocation of tolerances 
for residues of pesticide chemicals in or on food commodities and 
processed foods. Without a tolerance or exemption, food containing 
pesticide residues is considered to be unsafe and therefore 
``adulterated'' under section 402(a) of the FFDCA, and hence may not 
legally be moved in interstate commerce. For a pesticide to be sold and 
distributed, the pesticide must not only have appropriate tolerances 
under the FFDCA, but also must be registered under section 3 of the 
Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA, 7 U.S.C. 
136 et seq.).
    Section 408 was substantially amended by the Food Quality 
Protection Act of 1996 (FQPA). Among other things, the FQPA amends the 
FFDCA to bring all EPA pesticide tolerance-setting activities under a 
new section 408 with a new safety standard and new procedures. New 
section 408(b)(2)(A)(i) allows EPA to establish a tolerance (the legal 
limit for a pesticide chemical residue in or on a food) only if EPA 
determines that the tolerance is ``safe.'' Section 408(b)(2)(A)(ii) 
defines ``safe'' to mean that ``there is a reasonable certainty that no 
harm will result from aggregate exposure to the pesticide chemical 
residue, including all anticipated dietary exposures and all other 
exposures for which there is reliable information.'' This includes 
exposure through food, drinking water, and from pesticide use in 
gardens, lawns, or buildings (residential and other indoor uses) but 
does not include occupational exposure. Section 408(b)(2)(C) requires 
EPA to give special consideration to exposure of infants and children 
to the pesticide chemical residue in establishing a tolerance and to 
``ensure that there is a reasonable certainty that no harm will result 
to infants and children from aggregate exposure to the pesticide 
chemical residue....''

II. Risk Assessment and Statutory Findings

    EPA performs a number of analyses to determine the risks from 
aggregate exposure to pesticide residues. First, EPA determines the 
toxicity of pesticides based primarily on toxicological studies using 
laboratory animals. These studies address many adverse health effects, 
including (but not limited to) reproductive effects, developmental 
toxicity, toxicity to the nervous system, and carcinogenicity. Second, 
EPA examines exposure to the pesticide through the diet (e.g., food and 
drinking water) and through exposures that occur as a result of 
pesticide use in residential settings.

A. Toxicity

    1. Threshold and non-threshold effects. For many animal studies, a 
dose response relationship can be determined, which provides a dose 
that causes adverse effects (threshold effects) and doses causing no 
observed effects

[[Page 28351]]

(the ``no-observed effect level'' or ``NOEL'').
    Once a study has been evaluated and the observed effects have been 
determined to be threshold effects, EPA generally divides the NOEL from 
the study with the lowest NOEL by an uncertainty factor (usually 100 or 
more) to determine the Reference Dose (RfD). The RfD is a level at or 
below which daily aggregate exposure over a lifetime will not pose 
appreciable risks to human health. An uncertainty factor (sometimes 
called a ``safety factor'') of 100 is commonly used since it is assumed 
that people may be up to 10 times more sensitive to pesticides than the 
test animals, and that one person or subgroup of the population (such 
as infants and children) could be up to 10 times more sensitive to a 
pesticide than another. In addition, EPA assesses the potential risks 
to infants and children based on the weight of the evidence of the 
toxicology studies and determines whether an additional uncertainty 
factor is warranted. Thus, an aggregate daily exposure to a pesticide 
residue at or below the RfD (expressed as 100% or less of the RfD) is 
generally considered acceptable by EPA. EPA generally uses the RfD to 
evaluate the chronic risks posed by pesticide exposure. For shorter 
term risks, EPA calculates a margin of exposure (MOE) by dividing the 
estimated human exposure into the NOEL from the appropriate animal 
study. Commonly, EPA finds MOEs lower than 100 to be unacceptable. This 
hundredfold margin of exposure is based on the same rationale as the 
hundredfold uncertainty factor.
    Lifetime feeding studies in two species of laboratory animals are 
conducted to screen pesticides for cancer effects. When evidence of 
increased cancer is noted in these studies, the Agency conducts a 
weight of the evidence review of all relevant toxicological data 
including short-term and mutagenicity studies and structure activity 
relationship. Once a pesticide has been classified as a potential human 
carcinogen, different types of risk assessments (e.g., linear low dose 
extrapolations or margin of exposure (MOE) calculation based on the 
appropriate NOEL) will be carried out based on the nature of the 
carcinogenic response and the Agency's knowledge of its mode of action.
    2. Differences in toxic effect due to exposure duration. The 
toxicological effects of a pesticide can vary with different exposure 
durations. EPA considers the entire toxicity data base, and based on 
the effects seen for different durations and routes of exposure, 
determines which risk assessments should be done to assure that the 
public is adequately protected from any pesticide exposure scenario. 
Both short and long durations of exposure are always considered. 
Typically, risk assessments include ``acute'', ``short-term'', 
``intermediate term'', and ``chronic''. These assessments are defined 
by the Agency as follows.
    i. Acute risk. Acute risk, by the Agency's definition, results from 
1-day consumption of food and water, and reflects toxicity which could 
be expressed following a single oral exposure to the pesticide 
residues. High end exposure to food and water residues are typically 
assumed.
    ii. Short-term risk. Short-term risk results from exposure to the 
pesticide for a period of 1 to 7 days, and therefore overlaps with the 
acute risk assessment. Historically, this risk assessment was intended 
to address primarily dermal and inhalation exposure which could result, 
for example, from residential pesticide applications. However, since 
enaction of FQPA, this assessment has been expanded to include both 
dietary and non-dietary sources of exposure, and will typically 
consider exposure from food, water, and residential uses when reliable 
data are available. In this assessment, risks from average food and 
water exposure, and high-end residential exposure, are aggregated. 
High-end exposures from all three sources are not typically added 
because of the very low probability of this occurring in most cases, 
and because the other conservative assumptions built into the 
assessment assure adequate protection of public health. However, for 
cases in which high-end exposure can reasonably be expected from 
multiple sources (e.g. frequent and widespread homeowner use in a 
specific geographical area), multiple high-end risks will be aggregated 
and presented as part of the comprehensive risk assessment/
characterization. Since the toxicological endpoint considered in this 
assessment reflects exposure over a period of at least 7 days, an 
additional degree of conservatism is built into the assessment; i.e., 
the risk assessment nominally covers 1 to 7 days exposure, and the 
toxicological endpoint/NOEL is selected to be adequate for at least 7 
days of exposure. (Toxicity results at lower levels when the dosing 
duration is increased.)
    iii. Intermediate-term risk. Intermediate-term risk results from 
exposure for 7 days to several months. This assessment is handled in a 
manner similar to the short-term risk assessment.
    iv. Chronic risk assessment. Chronic risk assessment describes risk 
which could result from several months to a lifetime of exposure. For 
this assessment, risks are aggregated considering average exposure from 
all sources for representative population subgroups including infants 
and children.

B. Aggregate Exposure

    In examining aggregate exposure, FFDCA section 408 requires that 
EPA take into account available and reliable information concerning 
exposure from the pesticide residue in the food in question, residues 
in other foods for which there are tolerances, residues in groundwater 
or surface water that is consumed as drinking water, and other non-
occupational exposures through pesticide use in gardens, lawns, or 
buildings (residential and other indoor uses). Dietary exposure to 
residues of a pesticide in a food commodity are estimated by 
multiplying the average daily consumption of the food forms of that 
commodity by the tolerance level or the anticipated pesticide residue 
level. The Theoretical Maximum Residue Contribution (TMRC) is an 
estimate of the level of residues consumed daily if each food item 
contained pesticide residues equal to the tolerance. In evaluating food 
exposures, EPA takes into account varying consumption patterns of major 
identifiable subgroups of consumers, including infants and children. 
The TMRC is a ``worst case'' estimate since it is based on the 
assumptions that food contains pesticide residues at the tolerance 
level and that 100% of the crop is treated by pesticides that have 
established tolerances. If the TMRC exceeds the RfD or poses a lifetime 
cancer risk that is greater than approximately one in a million, EPA 
attempts to derive a more accurate exposure estimate for the pesticide 
by evaluating additional types of information (anticipated residue data 
and/or percent of crop treated data) which show, generally, that 
pesticide residues in most foods when they are eaten are well below 
established tolerances.
    Percent of crop treated estimates are derived from Federal and 
private market survey data. Typically, a range of estimates are 
supplied and the upper end of this range is assumed for the exposure 
assessment. By using this upper end estimate of percent of crop 
treated, the Agency is reasonably certain that exposure is not 
understated for any significant subpopulation group. Further, regional 
consumption information is taken into account through EPA's computer-
based model

[[Page 28352]]

for evaluating the exposure of significant subpopulations including 
several regional groups, to pesticide residues. For this pesticide, the 
most highly exposed population subgroup (non-nursing infants < 1 year 
old) was not regionally based.

III. Toxicological Profile

    EPA has evaluated the available toxicity data and considered its 
validity, completeness, and reliability as well as the relationship of 
the results of the studies to human risk. EPA has also considered 
available information concerning the variability of the sensitivities 
of major identifiable subgroups of consumers, including infants and 
children. The nature of the toxic effects caused by cyclanilide is 
discussed below.
    1. Acute toxicity. The acute oral toxicity study resulted in a 
LD50 of 315 milligrams/kilogram (mg/kg) for males and 208 
mg/kg for females. The acute dermal toxicity in rabbits resulted in an 
LD50 in either sex of greater than 2,000 mg/kg. The acute 
inhalation study in rats resulted in a LC50 greater than 
2.64 mg/liter. In an acute oral neurotoxicity study in rats fed 0, 15, 
50 and 150 mg/kg, the NOEL was 50 mg/kg and the LOEL was 150 mg/kg 
based on gait abnormalities, increased abdominal muscle tone, and 
slightly decreased motor activity test.
    2. Mutagenicity. Cyclanilide was negative for mutagenic activity in 
the bacterial reverse mutation tests (duplicate tests), forward gene 
mutation (CHO/HGPRT) test and mouse micronucleus test (duplicate 
tests). Positive findings (clastogenicity) were seen in the in vitro 
chromosomal aberrations study with Chinese hamster ovary cells at high 
doses near the limit of cytotoxicity. Since cyclanilide caused liver 
toxicity in several studies, a confirmatory rat unscheduled DNA 
synthesis (UDS) test needs to be conducted with cyclanilide.
    3. Rat metabolism. In the rat metabolism study radioactive 
cyclanilide was rapidly absorbed after oral administration. The 
principal route of elimination was by renal excretion of the parent 
compound and amino acid conjugates. Methylation was a minor metabolic 
pathway.
    4. Sub-chronic toxicity. i. In a rat 90-day feeding study the No 
Observed Effect Level (NOEL) was 54.6 mg/kg/day for males and 62.4 mg/
kg/day for females. The Lowest Observed Effect Level (LOEL) for males 
was 113.2 mg/kg/day and for females it was 121.4 mg/kg/day based on 
reductions in body weight, body weight gain, and food consumption, 
clinical signs, and increased liver weight in males and females.
    ii. In a 90-day mouse feeding study the NOEL for males was 38 mg/
kg/day and 43 mg/kg/day for females. The LOEL was 364 mg/kg/day for 
males and 416 mg/kg/day for females based on mortality, elevated 
alkaline phosphatase, increased absolute, relative liver weights, focal 
hepatocellular necrosis, and handling induced rigidity.
    iii. In a 21-day rabbit dermal toxicity study the NOEL was equal or 
greater than 1,000 mg/kg/day. The LOEL was greater than 1,000 mg/kg/
day.
    iv. In a 90-day mammalian neurotoxicity study the NOEL for males 
was equal or greater than 78.6 mg/kg/day and for females was 4.0 mg/kg/
day. The LOEL was greater than 78.6 mg/kg/day for males and was 35.8 
mg/kg/day for females based on increased motor activity and decreased 
body weight.
    5. Chronic feeding toxicity and carcinogenicity. i. In a 1-year 
feeding study in dogs fed diets containing 0, 40, 160, or 640 ppm 
(equivalent to 0, 1.5, 5.3, and 21.2 mg/kg/day for males and 0, 1.3, 
5.2, and 21.5 mg/kg/day for females) the NOEL was 5.3 mg/kg/day for 
males and 5.2 mg/kg/day for females. The LOEL was 21.2 mg/kg/day for 
males and 21.5 mg/kg/day for females based on decreased body weight 
gain, elevated enzymes and gross and histopathological liver lesions.
    ii. In a chronic feeding and carcinogenicity study in rats fed 
diets containing 0, 50, 150, 450, or 1,000 ppm (equivalent to 0, 2.0, 
6.2, 18.9 and 43.1 mg/kg/day for males and 0, 2.6, 8.1, 25.5, and 58.6 
mg/kg/day for females) the chronic NOEL was equal or greater than 43.1 
mg/kg/day for males and was 8.1 mg/kg/day for females. The chronic LOEL 
was greater than 43.1 mg/kg/day for males and was 25.5 mg/kg/day for 
females based on decreased body weight gains and histopathological 
changes in liver. The study was negative for carcinogenicity.
    iii. In a carcinogenicity study in mice fed diets containing 0, 50, 
250, or 1,000 ppm (equivalent to 0, 8.4, 41.8, and 168 mg/kg/day for 
males and 0, 10.6, 52.4, and 206 mg/kg/day for females) the chronic 
NOEL was 41.8 mg/kg/day for males and was 52.4 mg/kg/day for females. 
The chronic LOEL was 168 mg/kg/day for males based on decreased weight 
gain and was 206 mg/kg/day for females based on decreased weight gain. 
The study was negative for carcinogenicity.
    According to the new proposed guidelines for Carcinogen Risk 
Assessment (April, 1996), the appropriate descriptor for human 
carcinogenic potential of cyclanilide is ``Not Likely''. The 
appropriate subdescriptor is ``has been evaluated in at least two well 
conducted studies in two appropriate species without demonstrating 
carcinogenic effects''.
    6. Developmental toxicity. i. In a developmental toxicity study in 
rats fed 0, 3, 10, and 30 mg/kg/day the maternal NOEL was 10 mg/kg/day 
and the maternal LOEL was 30 mg/kg/day based on decreased body weight 
gain and food consumption. The developmental NOEL was 30 mg/kg/day 
(Highest Dose Tested).
    ii. In a developmental toxicity study in rabbits fed 0, 3, 10, and 
30 mg/kg/day the maternal NOEL was 10 mg/kg/day and the maternal LOEL 
was 30 mg/kg/day based on wobbly gait, partial hindlimb paralysis and 
emaciation. The developmental NOEL was 30 mg/kg/day (Highest Dose 
Tested).
    iii. In a 2 generation reproduction study in rats fed 0, 30, 300 or 
1,000 ppm (equivalent to 0, 1.9, 19.0 or 64.1 mg/kg/day for P 
(Parental) Males; 0, 2.0. 20.2, or 70.4 mg/kg/day for F1 males; 0, 2.3, 
21.8, or 84.5 mg/kg/day for P females; and 0, 2.4, 25.9, or 85.7 mg/kg/
day for F1 females), the systemic NOEL was less than 2.0 mg/kg/day for 
males and less than 2.4 mg/kg/day for females. The systemic LOEL was 
2.0 mg/kg/day for males based on reduced early post-weaning weight 
gains. The systemic NOEL for females was 2.4 mg/kg/day based on reduce 
early post-weaning body weight gains and increased renal 
mineralization. The reproduction NOEL is 2.3 mg/kg/day and the 
reproduction LOEL is 21.8 mg/kg/day based on decreased mean pup weight.

IV. Aggregate Exposures

    1. From food and feed uses. The primary source for human exposure 
to cyclanilide will be from ingestion of both raw and processed 
agricultural commodities from cotton, milk, and meat. A DRES chronic 
exposure analysis was conducted using tolerance level residues and 100% 
crop treated information to estimate the Theoretical Maximum Residue 
Contribution (TMRC) for the general population and 22 subgroups.
    2. From potable water. As a worst case screen, upper bound 
estimates (acute/chronic) of the concentration of cyclanilide that 
might be found in surface water have been calculated with the generic 
expected environmental concentrations (GENEEC) screening model program. 
For cotton, based on the assumption of one application aerially at the 
maximum application rate 0.25 lb active ingredient/acre), GENEEC 
calculates the peak (acute)

[[Page 28353]]

concentration in runoff water adjacent to the application area to be 
8.4 ppb and the chronic concentration to be 7.7 ppb.
    3. From non-dietary uses. There are no non-food uses of cyclanilide 
registered under the Federal Insecticide, Fungicide and Rodenticide 
Act, as amended. No non-dietary exposures are expected for the general 
population.
    4. Cumulative exposure to substances with common mechanism of 
toxicity. Section 408(b)(2)(D)(v) requires that, when considering 
whether to establish, modify, or revoke a tolerance, the Agency 
consider ``available information'' concerning the cumulative effects of 
a particular pesticide's residues and ``other substances that have a 
common mechanism of toxicity.'' The Agency believes that ``available 
information'' in this context might include not only toxicity, 
chemistry, and exposure data, but also scientific policies and 
methodologies for understanding common mechanisms of toxicity and 
conducting cumulative risk assessments. For most pesticides, although 
the Agency has some information in its files that may turn out to be 
helpful in eventually determining whether a pesticide shares a common 
mechanism of toxicity with any other substances, EPA does not at this 
time have the methodologies to resolve the complex scientific issues 
concerning common mechanism of toxicity in a meaningful way. EPA has 
begun a pilot process to study this issue further through the 
examination of particular classes of pesticides. The Agency hopes that 
the results of this pilot process will increase the Agency's scientific 
understanding of this question such that EPA will be able to develop 
and apply scientific principles for better determining which chemicals 
have a common mechanism of toxicity and evaluating the cumulative 
effects of such chemicals. The Agency anticipates, however, that even 
as its understanding of the science of common mechanisms increases, 
decisions on specific classes of chemicals will be heavily dependent on 
chemical specific data, much of which may not be presently available.
    Although at present the Agency does not know how to apply the 
information in its files concerning common mechanism issues to most 
risk assessments, there are pesticides as to which the common mechanism 
issues can be resolved. These pesticides include pesticides that are 
toxicologically dissimilar to existing chemical substances (in which 
case the Agency can conclude that it is unlikely that a pesticide 
shares a common mechanism of activity with other substances) and 
pesticides that produce a common toxic metabolite (in which case common 
mechanism of activity will be assumed).
    EPA does not have, at this time, available data to determine 
whether cyclanilide has a common mechanism of toxicity with other 
substances or how to include this pesticide in a cumulative risk 
assessment. Unlike other pesticides for which EPA has followed a 
cumulative risk approach based on a common mechanism of toxicity, 
cyclanilide does not appear to produce a toxic metabolite produced by 
other substances. The Agency has determined that there are no 
metabolites of toxicological concern associated with cyclanilide. 
Cyclanilide appears to be the only know pesticide member of its class 
of chemistry and there are no reliable data to indicate that this 
chemical is structurally or toxicologically similar to existing 
chemical substances at this time. Therefore it appear unlikely that 
cyclanilide bears a common mechanism of activity with other substances. 
For the purposes of this tolerance action, therefore, EPA has not 
assumed that cyclanilide has a common mechanism of toxicity with other 
substances.

V. Determination of Safety

A. Chronic Risk

    The Reference Dose (RfD) for cyclanilide is 0.007 mg/kg/day. This 
value is based on the systemic LOEL of 30 ppm (2.0 mg/kg/day in males 
and 2.4 mg/kg/day in females) from the rat reproductive study. The NOEL 
was not achieved (less than 30 ppm the Lowest Dose Tested). Reduced 
body weights in young post-weaning F1 males and females and increased 
renal mineralization in adult F1 females were observed at this level. 
An Uncertainty Factor (UF) of 300 was applied to the LOEL based on an 
Uncertainty Factor of 100 to account for interspecies extrapolation and 
intraspecies variability and an additional Uncertainty Factor of 3 to 
account for the lack of a NOEL in the reproductive toxicity study.
    The chronic analysis showed that exposure from the proposed new 
tolerances in or on cottonseed, cotton gin trash, milk, and meat for 
non-nursing infants (the subgroup with the highest exposure) would be 
77% of the Reference Dose (RfD). The exposure for the general U.S. 
population would be 15% of the RfD. Based on the estimated exposures to 
cyclanilide from drinking water, the percentage of the RfD utilized for 
non-nursing infants (the subgroup with the highest exposure) would be 
10% of the Reference Dose (RfD). The exposure for the general U.S. 
population would be 6% of the RfD. There is no established Maximum 
Concentration Level or Health Advisory Level for cyclanilide under the 
Safe Drinking Water Act. For the aggregate dietary exposures from food 
and drinking water, the percentage of the RfD utilized for non-nursing 
infants (the subgroup with the highest exposure) would be 91% of the 
Reference Dose (RfD). The exposure for the general U.S. population 
would be 21% of the RfD.
    The analysis for cyclanilide is a worst case estimate of dietary 
exposure with all residues at tolerance levels and 100% of the 
commodities assumed to be treated with cyclanilide.

B. Acute Risk

    An acute dietary analysis was conducted to determine the Margin of 
Exposure from how close the high end exposure comes to the lowest 
observed effect level of 150 mg/kg/day in the rat acute oral 
neurotoxicity study. Generally acute dietary margins of exposure 
greater than 100 tend to cause no dietary concern. The high end MOE for 
cyclanilide for all population subgroups was greater than 5,000 and is 
above the acceptable level and demonstrates no acute dietary concerns.
    The Acute MOE for drinking water is estimated to be greater than 
47,000 for all population subgroups. The acute dietary MOE greater than 
100 indicates that there is not acute dietary risk concern from acute 
drinking water cyclanilide exposure.
    The aggregate acute MOE for non-nursing infants (the subgroup with 
the highest exposure) would be greater than 8,000. The acute MOE for 
the general U.S. population would be greater than 11,000.

C. Conclusion

    Based on these risk estimates EPA concludes that there is a 
reasonable certainty of no harm from aggregate exposure to cyclanilide 
for consumers, including major identifiable subgroups and infants and 
children.

VI. Additional Safety Factor for Infants and Children

    FFDCA section 408 provides that EPA shall apply an additional 
tenfold margin of safety for infants and children in the case of 
threshold effects to account for pre-and post-natal toxicity and the 
completeness of the database unless EPA determines that a different 
margin of safety will be safe for infants and children. Margins of 
safety are incorporated into EPA risk assessments either directly 
through use of a margin of exposure analysis or through using

[[Page 28354]]

uncertainty (safety) factors in calculating a dose level that poses no 
appreciable risk to humans. In either case, EPA generally defines the 
level of appreciable risk as exposure that is greater than 1/100 of the 
no observed effect level in the animal study appropriate to the 
particular risk assessment. This hundredfold uncertainty (safety) 
factor/margin of exposure (safety) is designed to account for combined 
inter- and intra-species variability. EPA believes that reliable data 
support using the standard hundredfold margin/factor not the additional 
tenfold margin/factor when EPA has a complete data base under existing 
guidelines and when the severity of the effect in infants or children 
or the potency or unusual toxic properties of a compound do not raise 
concerns regarding the adequacy of the standard margin/factor.
    An additional Uncertainty Factor of 10 was not used for cyclanilide 
because (1) the experimental data provided no indication of increased 
sensitivity of fetal animals to in utero exposure to cyclanilide or of 
neonates to pre-weaning exposure to cyclanilide; (2) the endpoint upon 
which the RfD was set, decreased body weight gain in young post-weaning 
rats, was observed in young, growing animals and therefore already 
considered the increased sensitivity of young animals in the 
determination for the LOEL; and (3) treatment related effects seen in 
other animals did not indicate potential pre or post-natal effects of 
concern to infants or small children. An additional safety factor of 3 
was incorporated to account for the fact that a NOEL was not determined 
in the study used to establish the RfD.

VII. Other Considerations

    1. Endocrine effects. No evidence of endocrine effects on the 
systems of mammals was reported in the toxicology studies described 
above. There was no observed pathology of the endocrine organs in these 
studies. There is no evidence at this time that cyclanilide causes 
endocrine effects.
    2. Metabolism in plants and animals. The metabolism of cyclanilide 
in plants and animals is adequately understood for purposes of these 
tolerances. There are no Codex Alimentarius Commission (Codex) Maximum 
Residue Levels (MRLs) for cyclanilide. An adequate analytical method, 
gas chromatography with electron-capture detection, is available for 
enforcement purposes. Because of the long lead time from establishing 
these tolerances to publication of the enforcement methodology in the 
Pesticide Analytical Manual, Vol. II, the analytical methodology is 
being made available in the interim to anyone interested in pesticide 
enforcement when requested from: Calvin Furlow, Public Information 
Branch, Field Operations Division (7506C), Office of Pesticide 
Programs, Environmental Protection Agency, 401 M St., SW., Washington, 
DC 20460. Office location and telephone number: Room 1130A, CM#2, 1921 
Jefferson Davis Highway, Arlington, VA (703-305-5937).

VIII. Summary of Findings

    The analysis for cyclanilide for all population subgroups examined 
by EPA shows the proposed uses on cotton will not cause exposure at 
which the Agency believes there is an appreciable risk.
    Based on the information cited above, the Agency has determined 
that the establishment of the tolerances by amending 40 CFR part 180 
will be safe; therefore, the tolerances are established as set forth 
below.

IX. Objections and Hearing Requests

    The new FFDCA section 408(g) provides essentially the same process 
for persons to ``object'' to a tolerance regulation issued by EPA under 
new section 408(e) and (1)(6) as was provided in the old section 408 
and in section 409. However, the period for filing objections is 60 
days, rather than 30 days. EPA currently has procedural regulations 
which governs the submission of objections and hearing requests. These 
regulations will require some modification to reflect the new law. 
However, until those modifications can be made, EPA will continue to 
use those procedural regulations with appropriate adjustments to 
reflect the new law.
    Any person may, by July 22, 1997, file written objections to any 
aspect of this regulation and may also request a hearing on those 
objections. Objections and hearing requests must be filed with the 
Hearing Clerk, at the address given above (40 CFR 178.20). A copy of 
the objections and/or hearing requests filed with the Hearing Clerk 
should be submitted to the OPP docket for this rulemaking. The 
objections submitted must specify the provisions of the regulation 
deemed objectionable and the grounds for the objections (40 CFR 
178.25). Each objection must be accompanied by the fee prescribed by 40 
CFR 180.33(i). If a hearing is requested, the objections must include a 
statement of the factual issue(s) on which a hearing is requested, the 
requestor's contentions on such issues, and a summary of any evidence 
relied upon by the objector (40 CFR 178.27). A request for a hearing 
will be granted if the Administrator determines that the material 
submitted shows the following: There is a genuine and substantial issue 
of fact; there is a reasonable possibility that available evidence 
identified by the requestor would, if established, resolve one or more 
of such issues in favor of the requestor, taking into account 
uncontested claims or facts to the contrary; and resolution of the 
factual issue(s) in the manner sought by the requestor would be 
adequate to justify the action requested (40 CFR 178.32). Information 
submitted in connection with an objection or hearing request may be 
claimed confidential by marking any part or all of that information as 
CBI. Information so marked will not be disclosed except in accordance 
with procedures set forth in 40 CFR part 2. A copy of the information 
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.

X. Public Docket

    A record has been established for this rulemaking under the docket 
number [OPP-300496] (including any comments and data submitted 
electronically). 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 public 
record is located in Room 1132 Public Information and Records Integrity 
Branch, Information Resources and Services Division (7506C), Office of 
Pesticide Programs, Environmental Protection Agency, Crystal Mall #2, 
1921 Jefferson Davis Highway, Arlington, VA.
    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.
    The official record for this rulemaking, as well as the public 
version, as described above will be kept in paper form. Accordingly, 
EPA will transfer any copies of objections and hearing requests 
received electronically into printed, paper form as they are received 
and will place the paper copies in the official rule-making record 
which will also include all comments submitted directly in writing. The 
official rulemaking record is the paper record maintained at the 
address in ``ADDRESSES'' at the beginning of this document.

[[Page 28355]]

XI. Regulatory Assessment Requirements

    This final rule establishes a tolerance under section 408 of the 
FFDCA and is in response to a petition received by the Agency 
requesting the establishment of such a tolerance. The Office of 
Management and Budget (OMB) has exempted these types of actions from 
review under Executive Order 12866, entitled Regulatory Planning and 
Review (58 FR 51735, October 4, 1993). In addition, this final rule 
does not contain any information collections subject to OMB approval 
under the Paperwork Reduction Act (PRA), 44 U.S.C. 3501 et seq., or 
impose any enforceable duty or contain any unfunded mandate as 
described under Title II of the Unfunded Mandates Reform Act of 1995 
(UMRA) (Pub. L. 104-4). Nor does it require any prior consultation as 
specified by Executive Order 12875, entitled Enhancing the 
Intergovernmental Partnership (58 FR 58093, October 28, 1993), or 
special considerations as required by Executive Order 12898, entitled 
Federal Actions to Address Environmental Justice in Minority 
Populations and Low-Income Populations (59 FR 7629, February 16, 1994), 
or require OMB review in accordance with Executive Order 13045, 
entitled Protection of Children from Environmental Health Risks and 
Safety Risks (62 FR 19885, April 23, 1997).
    In addition, because tolerances that are established on the basis 
of a petition under section 408(d) of FFDCA, such as the tolerance in 
this final rule, do not require the issuance of a proposed rwule, the 
requirements of the Regulatory Flexibility Act (RFA) (5 U.S.C. 601 et 
seq.) do not apply. Prior to the recent amendments to the FFDCA, 
however, EPA had treated such actions as subject to the RFA. The 
amendments to the FFDCA clarify that no proposed rule is required for 
such regulatory actions, which makes the RFA inapplicable to these 
actions. Nevertheless, the Agency has previously assessed whether 
establishing tolerances, exemptions from tolerances, raising tolerance 
levels or expanding exemptions might adversely impact small entities 
and concluded, as a generic matter, that there is no adverse economic 
impact (46 FR 24950, May 4, 1981). In accordance with Small Business 
Administration (SBA) policy, this determination will be provided to the 
Chief Counsel for Advocacy of the SBA upon request.

XII. Submission to Congress and the General Accounting Office

    Under 5 U.S.C. 801(a)(1)(A), as added by the Small Business 
Regulatory Enforcement Fairness Act of 1996, the Agency has submitted a 
report containing this rule and other required information to the U.S. 
Senate, the U.S. House of Representatives, and the Comptroller General 
of the General Accounting Office prior to publication of this rule in 
today's Federal Register. This is not a ``major rule'' as defined by 5 
U.S.C. 804(2).

List of Subjects in 40 CFR Part 180

    Administrative practice and procedure, Agricultural commodities, 
Pesticides and pests, Recording and recordkeeping requirements.

    Dated: May 16, 1997.

Stephen L. Johnson,

Acting Director, Office of Pesticide Programs.
    Therefore, 40 CFR part 180 is amended as follows:

PART 180--[AMENDED]

    1. The authority citation for part 180 continues to read as 
follows:
    Authority: 21 U.S.C. 346a and 371.

    2. By adding Sec. 180.506 to read as follows:


Sec. 180.506   Cyclanilide; tolerances for residues.

    (a) General. Tolerances are established for residues of the plant 
growth regulator, cyclanilide, [1-(2,4-dichlorophenylaminocarbonyl)-
cyclopropane carboxylic acid] determined as 2,4-dichloroaniline 
(calculated as cyclanilide) in or on the following food commodities and 
processed feed:

------------------------------------------------------------------------
                                                              Parts Per 
                         Commodity                             Million  
------------------------------------------------------------------------
Cattle, fat................................................         0.10
Cattle, meat...............................................         0.20
Cattle, mbyp (except kidney)...............................          0.2
Cattle, kidney.............................................          2.0
Cottonseed.................................................         0.60
Cotton gin byproducts......................................         25.0
Goats, fat.................................................         0.10
Goats, meat................................................         0.20
Goats, mbyp (except kidney)................................         0.20
Goats, kidney..............................................          2.0
Horses, fat................................................         0.10
Horses, meat...............................................         0.20
Horses, mbyp (except kidney)...............................         0.20
Horses, kidney.............................................          2.0
Hogs, fat..................................................         0.10
Hogs, meat.................................................         0.20
Hogs, mbyp (except kidney).................................         0.20
Hogs, kidney...............................................          2.0
Milk.......................................................         0.04
Sheep, fat.................................................         0.10
Sheep, meat................................................         0.20
Sheep, mbyp (except kidney)................................         0.20
Sheep, kidney..............................................          2.0
------------------------------------------------------------------------

    (b) Section 18 emergency exemptions. [Reserved]
    (c) Tolerances with regional registrations.  [Reserved]
    (d)  Indirect or inadvertent residues. [Reserved]

[FR Doc. 97-13645 Filed 5-22-97; 8:45 am]
BILLING CODE 6560-50-F