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EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR PESTICIDE
PETITIONS PUBLISHED IN THE FEDERAL REGISTER  

EPA Registration Division contact: Laura Nollen, (703) 305-7390

Interregional Research Project Number 4 (IR-4)

Petition Numbers 2E6426 and 9E7625

	EPA has received pesticide petitions (PP# 2E6426 and 9E7625) from
Interregional Research Project Number 4 (IR-4), 500 College Road East,
Suite 201 W., Princeton, NJ  08540, proposing, pursuant to section
408(d) of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C.
346a (d), to amend 40 CFR part 180.184 by establishing a tolerance for
residues of linuron, (3-(3,4-dichlorophenyl)-1-methoxy-1-methylurea) and
its metabolites convertible to 3,4-dichloroaniline, calculated as
linuron, in or on the raw agricultural commodities pea, dry at 0.07
parts per million (ppm); parsley, leaves at 2.5 ppm; and parsley, dried
leaves at 7.0 ppm for PP# 9E7625; and horseradish at 0.050 ppm for PP#
2E6426. Additionally, IR-4 is requesting to amend 40 CFR part 180.184(c)
by deleting the regional tolerance in or on parsley, leaves at 0.25 ppm
for PP# 9E7625. 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.

A. Residue Chemistry

1. Plant and animal metabolism.  The qualitative nature of the residue
in plants is adequately understood. Metabolism studies with corn,
soybeans, and potatoes indicate that linuron is absorbed from the soil
and translocated. The metabolic pathway involves demethylation to 3-
(3,4-dichlorophenyl)-1-methoxyurea which is further metabolized to
3,4-dichloroaniline; metabolism may also occur through demethoxylation
of linuron. The terminal residues of concern are the parent and its
metabolites which are convertible to 3,4-dichloroaniline.

2. Analytical method. Adequate enforcement methods are available for the
determination of linuron in plant and animal commodities. The Pesticide
Analytical Manual (PAM) Vol. II lists a colorimetric method (Method I,
Bleidner et. al.) and a paper chromatographic method (Method II).
Residues of diuron may interfere in Method I. A modified version of
Method I (H. L. Pease, Journal of Agric. and Food Chem., 1962, Vol. 10,
p. 279), which includes a cellulose column step to separate linuron from
diuron, is currently the preferred method for the enforcement of
tolerances. Both these methods determine linuron and all metabolites
hydrolyzable to 3,4-dichloroaniline and have limits of detection of 0.05
ppm. 

3. Magnitude of residues. 

a. Plant residues.  

i. PEA (DRY): Tolerance for residues of linuron are being proposed for
the raw agricultural commodities pea (dry) at a level of 0.07 ppm.  Six
field trials were conducted in the major dry pea producing regions of
the US. The pesticide was applied under conditions simulating commercial
application techniques. The pea (dry) seeds were harvested and sampled
using techniques simulating local commercial practices. The samples were
analyzed for 3,4-DCA (expressed as linuron) and the results indicate
residues ranging between < 0.01 ppm and 0.052 ppm in the pea (dry)
samples. Concurrent recoveries were all within the acceptable range of
70% to 120%. Storage stability recoveries also indicate that the
residues were stable under the conditions in which the samples were held
between harvest and analysis. Therefore, the results reported in this
study are considered reliable.

ii. PARSLEY: This petition also proposes to replace the current regional
tolerance for parsley leaves with a national tolerance for fresh parsley
(leaves & stems) at 2.5 ppm and dried parsley (leaves & stems) at 7.0
ppm.  Two field trials were conducted, one each in CA and OR. The
pesticide was applied under conditions simulating commercial application
techniques. The parsley leaves and stems samples were harvested
simulating commercial practices. Additionally, at the CA trial, one
untreated and one treated dried parsley (leaves and stem) samples were
generated to calculate a concentration factor. The samples were analyzed
for 3,4-DCA (expressed as linuron) and the results indicate a maximum
residue of 1.3 ppm in the fresh parsley samples and 2.8 ppm in the dried
parsley sample. The concentration factor in the dried parsley sample was
calculated as 2.75. Concurrent recoveries were mostly within the
acceptable range of 70% to 120%. Storage stability recoveries also
indicate that the residues were stable under the conditions in which the
samples were held between harvest and analysis. 

iii. HORSERADISH: This petition also proposes to reactivate petition #
2E6426 proposing a tolerance for horseradish at 0.050 ppm.  To support
this petition, horseradish was treated with one application of linuron
at a rate of approximately 1.5 lb ai/A.  One broadcast application to
the soil surface, after transplanting but prior to crop emergence, was
made.  Horseradish roots were collected 76 to 77 days following the
application.  No quantifiable residues in any of the treated samples
were found. No residues above the lowest level of method validation
(0.050 ppm) were observed in the control samples, and method sitablitiy
testing indicates that these results are reliable.  

b. Animal residues: EPA determined, in earlier tolerances reassessments
for linuron, that there is no reasonable expectation of secondary
residues will occur in milk, and eggs, or meat, fat and meat byproducts
of livestock.  Therefore, there remains a reasonable expectation that no
residues of linuron will occur in meat, milk, poultry, or eggs from the
current, and proposed, linuron tolerances.

B. Toxicological Profile

1. Acute toxicity.  In an acute oral toxicity study conducted in rats,
the oral LD50 value for technical linuron was determined to be 2600
mg/kg (Toxicity Category III). The dermal LD50 in rats was established
at >2000 mg/kg (Toxicity Category III).  A inhalation four hour LC50
exposure of rats to linuron resulted in a LC50 of >2.05 mg/L  (Toxicity
Category IV).  Application of linuron to the rabbit eye resulted in
slight conjunctival redness at 24 hours, which was clear by 72 hours
(Toxicity Category III). No corneal opacity or irritation of the iris
was noted. A primary dermal irritation study in rabbits demonstrated
that application of linuron produced no irritation (Toxicity Category
IV). No dermal sensitization occurred with linuron in guinea pigs.

2. Genotoxicity. Technical linuron did not produce gene mutation in an
Ames assay, in which Salmonella typhimurium bacteria were tested without
activation up to 5.0 µg/plate and with activation up to 100 µg/plate.
In an in vitro assay using CHO cells, linuron did not produce gene
mutations when tested up to 0.50 mM in a nonactivated system and up to
1.0 mM in an S9-activated system. Similarly, linuron did not induce bone
marrow chromosome aberrations in vivo, and in other tests for
genotoxicity, linuron did not induce unscheduled DNA synthesis in
isolated rat hepatocytes.

3. Reproductive and developmental toxicity. In a developmental toxicity
study conducted with technical linuron in Sprague-Dawley rats, dietary
doses of 50, 125, or 625 ppm (5.0, 12.1, or 49.8 mg/kg/day,
respectively) were administered on days 6-15 of gestation. The NOAELs
for maternal systemic toxicity and developmental toxicity were 12.1
mg/kg/day. The LOAEL of 625 ppm (49.8 mg/kg/day) for maternal systemic
toxic effects was based upon decreased body weight and food consumption
values. The developmental toxicity LOAEL of 49.8 mg/kg/day was based on
increased postimplantation loss and increases in the litter and fetal
incidences of resorptions.  When linuron was administered by gavage to
New Zealand White rabbits at doses of 5, 25, or 100 mg/kg/day on days 7
through 19 of gestation, a maternal systemic toxicity LOAEL was observed
at 25 mg/kg/day. Based upon reduced maternal body weight, the NOAEL was
5 mg/kg/day. At the high-dose level (100 mg/kg/day), maternal body
weight, food consumption, absolute liver weight, and liver-to-body
weight ratios were decreased. The developmental toxicity NOAEL was 25
mg/kg/day, based upon increased abortions, decreased mean number of
fetuses per litter, decreased fetal body weight, and increased incidence
of fetuses with skeletal variations at100 mg/kg/day (the developmental
toxicity LOAEL).

 In a two-generation reproductive toxicity study in Sprague- Dawley
rats, dietary levels of 12.5, 100, or 625 ppm linuron (males: 0.8, 6.8,
or 40.3 mg/kg/day; females: 1.0, 8.3, or 54.1 mg/kg/day) were
administered.  Since no evidence of adverse effects on fertility or
reproductive performance was noted, the reproductive toxicity LOAEL was
undetermined, and the reproductive toxicity NOAEL was estimated to be
greater than 625 ppm (40.3 and 54.1 mg/kg/day for males and females,
respectively). The parental systemic toxicity NOAEL was 12.5 ppm, and
the systemic LOAEL was 100 ppm, based upon decrements in parental body
weight gain. In addition, at the 625 ppm level, testicular and
epididymal abnormalities (testicular atrophy and intratubular fibrosis;
epididymal inflammatory response or oligospermia) and ocular
abnormalities (mineralization of the cornea; lens degeneration) were
observed at histopathological evaluation of the F1 adults. Further
evaluation of reproductive organ weight and hormone data from the F1
adults of this 2-generation study combined with an in vitro analysis of
the ability of linuron and its metabolites to compete for binding to the
androgen receptor resulted in the conclusion that linuron is a weak
androgen receptor antagonist. These results support the hypothesis that
rats exposed to linuron could develop interstitial cell hyperplasia and
subsequent adenomas (Leydig cell tumors) of the testicular tissue via a
mechanism of sustained hypersecretion of luteinizing hormone induced by
the antiandrogenic potential of linuron.

A three-generation reproductive toxicity study in Sprague-Dawley rats
was conducted with linuron at dietary levels of 25, 125, or 625 ppm
(approximately 2, 10.0, and 55.0 mg/kg/day for males and females).
Parental systemic effects observed included reduced premating body
weight in females of all three generations at 125 and 625 ppm, reduced
body weights at weaning for 125 ppm dams, and alopecia in both sexes for
the F0 and F1b adults at 625 ppm. Based upon the findings at the
mid-dose level, the systemic LOAEL was determined to be 125 ppm (10.0
mg/kg/day), and the systemic NOAEL was 25 ppm (2.0 mg/kg/day). The
reproductive toxicity NOAEL was 25 ppm (2.0 mg/kg/day) and the
reproductive toxicity LOAEL was determined to be 125 ppm (6.25
mg/kg/day), based on the following findings. Fertility was reduced in
generations at 625 ppm F2a through F3a. Pup survival was consistently
decreased at 625 ppm, with most deaths occurring in the first 24 hours
postpartum, and a trend for decreased viability from days 1-4. Weanling
body weights were decreased for F1b and F2b male and female pups at 125
ppm and 625 ppm. Absolute liver and kidney weights of weanlings (both
sexes) were decreased, and histopathology of the 625 ppm F2b weanlings
identified an increased incidence of liver atrophy (decreased
cytoplasmic clear spaces of hepatocytes). This study was flawed by the
lack of histopathological data on the adult animals; however, the
systemic study results are considered to be supportive of those obtained
from the two-generation study with linuron.

4. Subchronic toxicity. A 3-month subchronic study was conducted with
linuron in rats at dietary levels of 80, 400, and 3000 ppm (4, 20, and
150 mg/kg/day).  Observations of decreased red blood cell count and
increased white blood cell count were noted at 400 ppm. At the high-dose
(3000 ppm) growth was retarded. Based upon hematological findings, 400
ppm (20 mg/kg/day) was established as the LOAEL; the NOAEL was 80 ppm (4
mg/kg/day). The requirement for a 90-day feeding study in dogs was
satisfied by the completion of two acceptable chronic studies conducted
with linuron in beagles.

5. Chronic toxicity.  In a 1-year dog study linuron was fed to groups of
4

beagles/sex/dose at dietary levels of 10, 25, 125, or 625 ppm (male:
0.29, 0.79, 4.17, or 18.6 mg/kg/day; females: 0.3, 0.77, 3.49, or 16.1
mg/kg/day, respectively). In a previous 2-year dog study, linuron was
administered in the diet to beagle dogs at 25, 125, or 625 ppm (0.625,
3.13, or 15.63 mg/kg/day); increased incidences of abnormal pigment was
observed in the blood of animals at all dose levels.  Decreased red
blood cell count, hematocrit, and hemoglobin levels were also noted in
males at 625 ppm. Since the abnormal pigment was postulated to be met-
and sulfhemoglobin, assays for these substances were conducted in the
1-year study. The presence of one or both substances in the blood was
confirmed for both sexes in the 125 and 625 ppm dose groups at all
intervals tested (3, 6, 9, and 12 months). At 625 ppm, evidence of red
blood cell destruction was noted as increased hemosiderin deposition in
the Kupffer cells of the liver (male and female), slight decreases in
erythrocyte count, hemoglobin, and hematocrit levels, and a small
increase in the bone marrow erythropoiesis. Secondary hematological
changes at 625 ppm included increased platelet count, leukocyte count,
and serum cholesterol levels. In addition, absolute liver weight was
increased in males at 625 ppm; relative liver weight was increased in
males at 125 and 625 ppm. Based upon hematology changes, the LOAEL for
systemic toxicity was 125 ppm (4.17 mg/kg/day for males; 3.49 mg/kg/day
for females). The NOAEL was 25 ppm (0.79 mg/kg/day for males; 0.77
mg/kg/day for females). 

In a 2-year feeding/carcinogenicity study, linuron was administered to
Crl:CD(SD)BR Sprague-Dawley rats at dietary levels of 50, 125, or 625
ppm (2.5, 6.25, or 31.25 mg/kg/day). Testicular interstitial cell
adenoma incidences were increased in mid- and high-dose males (125 and
625 ppm, respectively). In addition, various indications of red blood
cell destruction and turnover (increased mean corpuscular volume,
decreased red blood cell count, and possible reticulocytosis) were
observed in both sexes at 125 and 625 ppm. Hemoglobin content was not
affected in males at any dose and was reduced at 6- and 12-months in >
125 ppm females. Therefore, based on reduced hemoglobin levels, the
LOAEL for systemic toxicity for females was 125 ppm (6.25 mg/kg/day).
The systemic NOAEL for females was 50 ppm (2.5 mg/kg/day), and the
systemic NOAEL for males was 625 ppm (31.25 mg/kg/day).  In another
two-year rat feeding study, in which groups of albino rats were treated
with dietary linuron at levels of 25, 125, or 625 ppm (1.25, 6.25, or
31.25 mg/kg/day), the systemic NOAEL was determined to be 125 ppm. At
the LOAEL of 625 ppm (31.25 mg/kg/day), growth retardation was observed.
In addition, at that dietary level, hemosiderin content of the spleen
was increased for both sexes, marrow fat was reduced for females, the
ratio of myeloid-to-erythroid precursors was reduced for males, and the
incidence of endometrial hypoplasia was increased for females. These
findings were considered to be indicative of hemolysis. An 18-month
feeding study was conducted in Crl:CD(SD)BR rats to study the effects of
linuron (94.5%) on methemoglobin and  sulfhemoglobin blood
concentrations. The dietary levels tested were 25, 125, or 625 ppm
(1.25, 6.25, or 31.25 mg/kg/day). Based upon significant changes noted
in blood pigments in mid- and high-dose female rats and in high-dose
male rats, the LOAEL was determined to be 625 ppm (31.25 mg/kg/day) and
125 ppm (6.25 mg/kg/day) for male and female rats, respectively. The
corresponding NOAELs for male and female rats were 125 and 25 ppm (6.25
and 1.25 mg/kg/day).  In a two-year feeding/oncogenicity study in CD-1
mice, linuron was administered in the diet at levels of 50, 150, or 1500
ppm (12, 35, or 455 mg/kg/day).  A statistically significant increase in
the incidence of hepatocellular adenomas was observed at 1500 ppm for
female mice. At 1500 ppm, body weight and body weight gain were
decreased for both males and females throughout the study. Methemoglobin
values were increased at all dietary levels for both sexes. Mean
absolute and relative liver weights were increased for females at 1500
ppm. For both males and females at that level, histopathological
evaluation identified increased incidences of hemosiderosis of the
spleen and hepatocytomegaly, hepatocellular cytoplasmic alteration,
hepatocellular vacuolization, hemorrhage, and necrosis of the liver. A
NOAEL was not established; the systemic toxicity LOAEL, based on
increased methemoglobin values, was < 50 ppm (12 mg/kg/day).

6. Animal metabolism. The qualitative nature of the residue in ruminants
and poultry is adequately understood. An acceptable metabolism study
with goats indicates that linuron is rapidly metabolized by
demethylation, demethoxylation, and hydroxylation and is primarily
eliminated by excretion. The metabolism of linuron in poultry has been
found to be consistent with the goat study. The terminal residues of
concern are the parent and its metabolites which are convertible to
3,4-dichloroaniline.

7. Metabolite toxicology. The metabolism and tissue distribution of
[phenyl- 14C](U) 

linuron was studied in male and female Sprague-Dawley rats. 
Radiolabeled linuron was administered as a single gavage dose to 2
rats/sex/dose at 24 mg/kg and 400 mg/kg and also as a single 400 mg/kg
gavage dose following dietary pretreatment at 100 ppm (approximately 10
mg/kg) to 2 rats/sex/dose. To further elucidate the metabolic pathway of
linuron, a second study was conducted in which a single oral dose of 400
mg/kg of 14C-linuron was administered by gavage to five Sprague-Dawley
rats  per sex. The results from these studies indicate that linuron was
extensively metabolized by male and female rats at both the low- (24
mg/kg) and high-dose (400 mg/kg) levels when administered by gavage. The
majority of the administered 14C-linuron was eliminated in the urine
and, to a lesser extent, in the feces, within 96-120 hours. In general,
tissue and organ residues were very low (<1%) at both dose levels, and
there was no indication of accumulation or retention of linuron or its
metabolites. The major metabolites identified in the urine and feces
were hydroxy-norlinuron and norlinuron. Approximately 4-5% and 6-8% of
the urinary and fecal metabolites, respectively, remained unidentified.
Exposure to linuron appears to induce mixed function oxidative enzymes.

8. Endocrine disruption.  EPA is required under the FFDCA, as amended by
FQPA, to develop a screening program to determine whether certain
substances (including all pesticide active and other ingredients) “may
have an effect in humans that is similar to an effect produced by a
naturally occurring estrogen, or other such endocrine effects as the
Administrator may designate.”  Following recommendations of its
Endocrine Disruptor and Testing Advisory Committee (EDSTAC), EPA
determined that there was a scientific basis for including, as part of
the program, the androgen and thyroid hormone systems, in addition to
the estrogen hormone system.  EPA also adopted EDSTAC’s recommendation
that the Program include evaluations of potential effects in wildlife. 
For pesticide chemicals, EPA will use FIFRA and, to the extent that
effects in wildlife may help determine whether a substance may have an
effect in humans, FFDCA authority to require the wildlife evaluations. 
As the science develops and resources allow, screening of additional
hormone systems may be added to the Endocrine Disruptor Screening
Program (EDSP). 

There is some evidence of an impact of linuron on the endocrine system
from special in vitro receptor binding studies and studies in laboratory
animals provided by DuPont and by publications from other organizations.
 In in vitro binding studies, linuron exhibited weak androgen receptor
antagonist activity.  When administered at doses that significantly
exceed human exposure, linuron increased Leydig cell tumors in a 2-year
rat study.   Published studies that utilized similar doses reported
impacts on male rats in reproductive and developmental toxicology
studies.  

When the EPA EDSP is fully implemented, Tier-1 and Tier-2 testing will
provide additional data to confirm the mode-of-action associated with
adverse effects in laboratory animals and to assess the potential human
risks.

C. Aggregate Exposure

1. Dietary exposure -- Residue of concern. Tolerances for residues of
linuron in/on plant and animal commodities are expressed in terms of
linuron (3-(3,4-dichlorophenyl)-1- methoxy-1-methyl-urea) [40 CFR
§180.184(a) and (b)].  The EPA has concluded that the residues of
concern are linuron and its metabolites convertible to
3,4-dichloroaniline, expressed as linuron; residues of
3,4-dichloroaniline need not be regulated separately.  Adequate
enforcement methods are available for the determination of linuron
residues of concern in/on plant and animal tissues. The current
enforcement methods determine linuron and all metabolites hydrolyzable
to 3,4-dichloroaniline.

2. Food. The EPA established the relevant toxicity endpoint for linuron
at an acute reference dose of 0.12 mg/kg/day (females 13-49 only). The
acute dietary exposure is two percent of the acute population adjusted
dose for the highest estimated population subgroup (females 13-49 years
old). Since the estimated risk is not greater than 100% of the aPAD,
acute risk does note exceed HED’s level of concern.

Chronic dietary exposure, resulting from the registered and proposed
uses of linuron on proposed new crops is well within the acceptable
limits for all sectors of the population, as predicted by the Chronic
Module of the Dietary Exposure Evaluation Model (DEEM-FCID™ software,
Exponent, Inc., Version 2.14).  The percentage or proportion of a crop
that is treated can have a significant effect on the exposure profile. 
In this case, it was assumed for all crops that 100% were treated with
linuron.  

Chronic dietary (food) risk estimates associated with the use of linuron
does not exceed the Agency’s level of concern (> 100% cPAD) for any
population subgroup including the most highly exposed population
subgroup, children ages 1-2 years. The chronic dietary risk for children
ages 1-2 years is 66% of the chronic PAD, and 23% for the general U.S.
population.  The chronic reference dose is 0.0077 mg/kg/day.  Because
the predicted exposures, expressed as percentages of the cRfD, are well
below 100%, there is reasonable certainty that no chronic effects would
result from dietary exposure to linuron. 

3. Drinking water. Chronic drinking water exposure analyses were
calculated for linuron using EPA screening concentration models for
ground water SCI-GROW and surface water FIRST.  Results indicate that a
reasonable certainty exists that linuron residues in drinking water will
not contribute significantly to the aggregate human risk.

The predicted chronic concentration for linuron maximum surface water
value was 38 ppb and mean was 18 ppb.  When the surface water
concentration was included in the chronic dietary risk assessment, the
chronic dietary risk for children ages 1-2 years is 73% of the chronic
PAD and 28% for the general U.S. population.   Because the predicted
exposures, expressed as percentages of the cRfD, are well below 100%,
there is reasonable certainty that no chronic effects would result from
exposure to linuron.

D. Cumulative Effects

EPA has not made a common mechanism of toxicity finding as to linuron.

Although linuron, diuron, and propanil all contain 3,4-DCA) in their
structures, HED has previously concluded that the three active
ingredients do not share a common mechanism of toxicity.  The analytical
method for quantifying residues of concern form applications of linuron
converts all residues to 3,4-DCA as a technical convenience.  However,
3,4-DCA is not a significant residue in diuron and animal plant
metabolism or hydrolysis studies.

For purpose of this tolerance action, therefore, linuron does not have a
common mechanism of toxicity with other substances.

E. Safety Determination

1. U.S. population. 

a. Acute risk. Based on the completeness and reliability of the acute
toxicology database EPA has established an acute RfD of 0.12 mg/kg/day
only for the population subgroup females 13 to 49 years of age. The
acute dietary exposure from food and water to linuron will occupy 3% of
the acute population adjusted dose (aPAD) for this subgroup.  This risk
assessment is based on upper-end    (95th percentile) exposure estimates
and assumed 100% crop treated.  

b. Chronic risk.  Based on the completeness and reliability of the
toxicology database and using the conservative assumptions presented
earlier, EPA has established a chronic RfD of 0.0077 mg/kg/day. It has
been concluded that the aggregate exposure for existing crops plus the
tolerances being proposed would utilize less than 28% of the cRfD for
the US population. Generally, exposures below 100% of the RfD are of no
concern because it represents the level at or below which daily
aggregate dietary exposure over a lifetime will not pose appreciable
risk to human health. Thus, there is reasonable certainty that no harm
will result from aggregate exposures to linuron residues.   

2. Infants and children. In assessing the potential for additional
sensitivity of infants and children to residues of linuron, data from
the previously discussed developmental and multigeneration reproductive
toxicity studies were considered.

    

Developmental studies are designed to evaluate adverse effects on the
developing organism resulting from pesticide exposure during pre-natal
development. Reproduction studies provide information relating to
reproductive and other effects on adults and offspring from pre-natal
and post-natal exposures to the pesticide. 

The toxicological database for linuron contains acceptable guidelines
developmental toxicity studies in rats and rabbits and multigeneration
reproduction toxicity studies in rats. A 2-generation reproduction study
in rats also examined histopathology of the reproductive organs of F0
and F1 generation males and females.  A 3-generation reproduction study
is also available.  In addition, several mechanistic studies were
conducted to explore biochemical and histopathological effects of
linuron on the young and adult male rats.  A cross-mating study was also
conducted with linuron.  These special mechanistic studies evaluated a
variety of endpoints including reproductive organ weights and
histopathology as well as hormone levels (leutenizing hormone,
testosterone, and estradiol).  The results from these studies provide
data for characterizing the potential endocrine disruption capabilities
of linuron.  The data show that linuron has a weak affinity for androgen
receptor as compared to procymidone and vinclozolin.   Linuron causes
dose-related alterations in androgen-dependent reproductive organ
development in male rats.  HED currently determines that the available
linuron data organ development in male rats.  HED currently determines
that the available linuron data base is adequate for assessing the
potentially increased susceptibility of the young to linuron exposure.
Based on this information HED concluded that the Food Quality Protection
Act Safety Factor of 10 x is not warranted, so it was reduced to 1x. 

FFDCA section 408 provides that EPA may apply an additional uncertainty
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 current toxicological data requirements, the database
for linuron relative to pre- and post-natal effects for children is
complete.  Conservative assumptions utilized to estimate aggregate
dietary exposures of infants and children to linuron demonstrated that
73% of the cRfD would be utilized for the highest exposed group,
Children 1-2 years old.  Therefore, it may be concluded that there is
reasonable certainty that no harm will result to infants and children
from aggregate exposures to linuron.  

F. International Tolerances

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’s) have been establish for linuron including the following:

Countries	Crop	Tolerance/MRL

Mexico	Potatoes	0.2 ppm

Canada	Potatoes	0.1 ppm

Canada	All other proposed crops	0.01 ppm (Default MRL)



There are no Codex or Mexican MRLs for linuron on the proposed crops.

Interregional Research Project No. 4 (IR-4); E. I. DuPont de Nemours &
Company      LINURON

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