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linuron (Lorox) Herbicide Profile 6/84

                        CHEMICAL FACT SHEET FOR:
                                LINURON
FACT SHEET NUMBER: 28
DATE ISSUED: JUNE , 1984
                       1.  DESCRIPTION OF CHEMICAL
- Generic Name:  3-(3,4-Dichlorophenyl)-1-methoxy-1-methylurea 
  (C9H10C12N202)
- Common Name:  linuron
- Trade Name:  Alfanox, Linurex, Londax, Lorox
- EPA Shaughnessy Code:  035506
- Chemical Abstracts Service (CAS) Registry Number:  330-55-2
- Year of Initial Registration:  1966
- Pesticide Type:  Herbicide
- Chemical Family:  Substituted urea
- U.S. and Foreign Producers:  E. I. duPont de Nemours and Company,
  Drexel Chemical Company, Griffin Corporation, Vertac Chemical Corp.,
  Bayer AG, Makhteshim-Agan, Pennwalt Holland B. V., Rhone-Poulenc,
  Staveley Chemicals Ltd., and Universal Crop Protection Ltd.
                     2.  USE PATTERNS AND FORMULATIONS
- Application sites:  Linuron is a substituted urea compound registered
  for use as a herbicide to control a wide variety of annual and
  perennial broadleaf and grassy weeds on both crop and noncrop sites.
  Linuron is registered for use on numerous crop sites such as forage
  crops, field crops, fruits, vegetables, and ornamental crops.  In
  noncrop applications, linuron is used on alleys, fencerows, fairways,
  highway rights-of-way, sodfields, streets, and vacant lots.
- Types of formulations:  Linuron is available as a wettable powder,
  granular flowable, and liquid suspension.
- Types and methods of application:  Linuron is applied as follows:
  broadcast or band upon the soil surface, using ground or aerial
  equipment.
- Application rates:  0.5 lbs. a.i./A to 3.0 lbs. a.i./A on crop sites;
  and 1.0 lbs. a.i./A to 3.0 lbs. a.i./A on noncrop sites.
- Usual carriers:  Water, oil, and clay.
                             3.  SCIENCE FINDINGS
- Chemical Characteristics
  Technical linuron is an odorless, white, crystalline solid.  It is
  stable towards oxidation and moisture under conventional conditions
  and decomposes at 180-190 C.  The chemical does not exhibit any
  unusual handling hazards.
- Toxicological Characteristics
- Acute toxicology studies on linuron are as follows:                                           
-
  - Oral LD50 in rats:  1,500 mg/kg body weight, Toxicity Category III
  - Dermal LD50 in rats:  > 2,000 mg/kg body weight, Toxicity Category
    III
  - Inhalation LC50 in rats:  218 mg/l/hr, Toxicity Category IV
  - Skin irritation in rabbits:  slight irritant, Toxicity Category
    III
  - Eye irritation in rabbits:  slight irritant, Toxicity Category III
- Chronic toxicology studies on linuron are as follows:
  - A 2-year chronic feeding study on rats has shown that
    interstitial testicular (ISC) adenomas occurred in all dosage
    groups (control, 50.0, 125.0, and 625.0 ppm), both during the two
    years and then at term.
  - A chronic feeding study was conducted on male and female mice at
    diet levels of 0.0, 50.0, 150.0, and 1,500 ppm of linuron.  The
    study showed a statistically significant increase of
    hepatocellular adenomas in the female mice from the highest dose
    group (1,500 ppm).  A significant increase of hepatocellular
    adenomas was also observed among the males in the lowest dose
    group (50 ppm).  The levels of methemoglobin were increased in
    treated mice of both sexes; this increase was related to the
    linuron administration.
  - A 2-year dog study did not demonstrate carcinogenesis, but showed
    hemosiderin deposition at 125 and 625 ppm.
  - In several mutagenicity tests, linuron did not affect DNA repair
    but may have inhibited mouse testicular DNA synthesis.  Linuron
    has not been shown to be active in the Ames test.  Linuron did not
    affect S. typhimurium in vivo in the mouse peritoneal cavity.
 - Major routes of human exposure:
   - The non-dietary exposure to linuron by a farmer as an applicator
     or mixer/loader is very high.
   - The dietary exposure to linuron residues by the U.S. population is
     probable because of its consumption of treated crops.
- Physiological and Biochemical Behavioral Characteristics
  - Absorption characteristics:  Linuron is most readily absorbed
    through the root system; less through foliage and stems.
  - Translocation:  Linuron is translocated upward primarily in the
    xylem.
  - Mechanism of pesticidal action:  It is a strong inhibitor of
    photosynthesis (Hill reaction).
- Environmental Characteristics
  - Adsorption and leaching in basic soil types:  Adsorption increases
    as clay content and/or organic matter content of soil increases;
    clays of high exchange capacity absorb more linuron than those of
    low exchange capacity.
  - Microbial breakdown:  Microbes are the primary factor in the
    breakdown of linuron in soils.
  - The available environmental fate data are insufficient to fully
    assess the degradation, metabolism, mobility, dissipation, and
    accumulation activities of linuron.  When additional studies are
    submitted, a complete environmental assessment can be made.
Ecological Characteristics
- Avian LC50:  >3,000 mg/kg
- Fish LC50:  (96-hour), 16 ppm for bluegill and rainbow trout
- LC50:  (72-hour) >40 ppm for crawfish
- LC50:  (48-hour) >40 ppm for tadpole
NOTE:  When additional ecological effects data are submitted, a
complete hazard assessment can be made.
- Tolerance Assessments
  - Since linuron and diuron have certain metabolites in common, c1-(3,
    4-dichlorophenyl)-3-methylurea (DCPMU), and 3,4-dichlorophenylurea
    (DCPU)], the Agency will consider diuron's residue contribution in
    the tolerance reassessment of linuron for the following commodities:
    corn, sorghum, grains, wheat, asparagus, meat (red), and cottonseed.
  - If the complete tolerance reassessments for the above commodities
    are favorable, tolerances for residues of linuron and metabolites
    (which will hydrolyze to form 3,4-dichloroaniline) will have to be
    proposed for residues in milk and eggs at 0.05 ppm.
  - The tolerances listed below have not been revised:
Commodities                                       Parts per million
Asparagus                                                3.0
Carrots                                                  1.0
Cattle, fat                                              1 0
Cattle, meat byproducts                                  1.0
Cattle, meat                                             1.0
Celery                                                   1.0
Corn, field, fodder                                      1.0
Corn, field, forage                                      1.0
Corn, fresh, (sweet)                                     0.25
Corn, grain (including pop)                              0.25
Corn, pop, fodder                                        1.0
Corn, pop, forage                                        1.0
Corn, sweet, fodder                                      1.0
Corn, sweet, forage                                      0.25
Goats, fat                                               1.0
Goats, meat by-products                                  1.0
Goats, meat                                              1.0
Hogs, fat                                                1.0
Hogs, meat by-products                                   1.0
Hogs, meat                                               1.0
Horses, fat                                              1.0
Horses, meat by-products                                 1.0
Horses, meat                                             1.0
Parsnips (with or without tops)                          0.5
Parsnips, tops                                           0.5
Potatoes                                                 1.0
Sheep, fat                                               1.0
Sheep, meat by-products                                  1.0
Sheep, meat                                              1.0
Sorghum, fodder                                          1.0
Sorghum, forage                                          1.0
Sorghum, grain (milo)                                    0.25
Soybeans (dry or succulent)                              1.0
Soybeans, forage                                         1.0
Soybeans, hay                                            1.0
Wheat, forage                                            0.5
Wheat, grain                                             0.25
Wheat, hay                                               0.5
Wheat, straw                                             0.5
- Problems Known to Have Occurred With Use of the Chemical
  Exposure of humans to linuron through runoff contamination of surface
  water after heavy spring precipitation has occurred in Northwestern
  Ohio.
- Summary Science Statement
  - Linuron has low acute mammalian toxicity, and its uses are not
    expected to adversely affect avian and mammalian wildlife.  The
    metabolism of linuron in plants and animals is adequately
    understood.
  - Dietary exposures to linuron have induced dose-related tumors in the
    rat testes and mouse liver.  The available toxicology data are
    insufficient to fully assess the long-term reproductive and
    teratogenic potential of linuron.
         4.  SUMMARY OF REGULATORY POSITION AND RATIONALE
  - Use classification:  restricted use classification
  - Unique label warning statements:
    - The use of this product may be hazardous to your health.  This
      product contains linuron, which has been determined to cause 
      tumors in laboratory animals.
    - Do not reenter treated areas for 24 hours following application
      unless protective clothing is worn.
  - Summary of risk/benefit review:
    - The Agency has determined that linuron has exceeded the 
      oncogenicity risk criteria and requires special review.  Dietary 
      exposure to linuron indicated clear evidence of oncogenicity for 
      male rats using the NTP criteria.  Using these data, the Agency 
      calculated nondietary risk.  The most realistic scenario is a 
      farmer with no protection, who mixes/loads and applies this 
      herbicide.  This calculation resulted in a risk of 3.6 x 10-4 to 
      2.2 x 10-3.  It is possible that the actual risk may even be 
      higher, because the commercial applicator exposure was not 
      included.  The Agency also calculated dietary risk.  The most 
      realistic scenario for dietary risk is the combination of maximum 
      residue expected (MRE) and percent crop, which resulted in a risk 
      of 1.5 x 10-5.
                         5.  SUMMARY OF MAJOR DATA GAPS
- The following toxicology data are required:
  - Two teratology studies, one in rat and one in another species
    (rabbit).  A 2-generation reproduction study in rats is required;
    this study must be designed to incorporate concerns regarding the
    significance of interstitial cell adenomas.  Note that in the former
    studies (rat and dog), reticulocytes and erythroid precursors were
    not measured.  This is a data gap, since at the high dose level (625
    ppm), hemosiderin was observed in rats, and also at 125 and 625 ppm
    in the dog.  (This data may be filled by appropriate design
    inclusion into the required reproduction study above.  The
    registrant must consult with the Agency on the appropriate
    protocol.)
  - Mutagenicity and related data are required, which (1) satisfy the 3
    mutagenicity testing category requirements, (2) adequately identify
    the risks, and, where possible, identify the mechanisms associated
    with positive findings in rodent chronic studies.  The Agency is
    requiring data relating levels of sulf- and methemoglobin following
    dietary exposure for certain substituted phenyl urea compounds such
    as linuron.  This testing may be combined with other testing
    involving dietary exposure, such as the reproduction study.  Dose
    levels must be such that a NOEL may be established.
  - The following four mutagenicity studies have been received and are
    in Agency review:
    - 1. Mutagenicity Evaluation In (Salmonella typhimurium), HLR
         1006-83, 5/5/83
    - 2. Unscheduled ONA Synthesis/Rat Hepatocytes In Vitro, HLR 190-
         83, 6/3/83
    - 3. CHO/HGPRT Assay for Gene Mutation, HLR 540-83, 12/16/83
    - 4. In Vivo Bone Marrow Chromosome Study in Rats, HLO 378-83,
         9/1/83
  - The available toxicology data are insufficient to fully assess the
    long-term reproductive and teratogenic potential of linuron.  Long-
    term studies must be submitted from one to two years after receipt
    of the guidance package.  Please refer to the toxicology data tables
    under 158.135 for the specific dates for which long-term data must
    be submitted.  Short-term studies must be submitted within six
    months after receipt of this guidance package.
- The following environmental fate data are required:
  - Hydrolysis test
  - Photodegradation test in water
  - Photodegradation test in soil
  - Photodegradation test in air
  - Metabolism test in aerobic soil
  - Metabolism test in anaerobic soil
  - Leaching and adsorption/desorption
  - Mobility (volatility) test in the lab
  - Mobility (volatility) test in the field
  - Dissipation study in soil
  - Dissipation study in soil (long-term)
  - Accumulation study in fish
  - Special testing on applicator exposure
 - Reentry data requirements
NOTE:  Long-term studies must be submitted from one to four years
after receipt of the guidance package.  Please refer to the
environmental fate data tables under 158.130 for the specific dates
for which long-term data must be submitted.  Short-term studies must
be submitted within six months after receipt of the guidance package.
- The following ecological effects data are required:
  - Acute avian toxicity
  - Acute toxicity, freshwater fish
  - Acute toxicity, freshwater invertebrates
  NOTE: Acute studies must be submitted within six months after receipt
  of this guidance package.
- The physical/chemical requirements listed in the 158.120, Product
  Chemistry data tables must be submitted, particularly:
  - Solubility
  - Vapor pressure
  - Octanol/water partition coefficient
  NOTE:  These studies must be submitted within six months after receipt
  of this guidance package.
- The following residue data are required:
  - Residue data for asparagus, carrots, celery, corn, cottonseed,
    parsnips, potatoes, sorghum, soybeans, and wheat are required to
    reflect uses of the 50%, dry flowable (DF), and 4 lb/gal, flowable
    concentrate (FIC) formulations.  Data reflecting uses of the 50% DF
    are required for the following commodities:  carrots (aerial
    applications), potatoes (aerial applications), soybeans
    (preemergence), sorghum (forage), wheat (forage and hay), asparagus
    (preemergence), and cottonseed (two applications per season).  Data
    pertaining to residues in dehydrated potato products are required.
  NOTE:  Long-term studies must be submitted within one year after
  receipt of this guidance package.
                          6.  CONTACT PERSON AT EPA
Robert U. Taylor
Product Manager (25)
Environmental Protection Agency (T5-767C)
401 M Street, S.W.
Washington, DC  20460
(703) 557-1800
DISCLAIMER:
THE INFORMATION PRESENTED IN THIS CHEMICAL INFORMATION FACT SHEET
IS FOR INFORMATIONAL PURPOSES ONLY AND NOT TO BE USED TO FULFILL
DATA REQUIREMENTS FOR PESTICIDE REGISTRATION AND REREGISTRATION.