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arsenic acid Chemical Fact Sheet 9/86

                         CHEMICAL FACT SHEET FOR:
                               ARSENIC ACID

FACT SHEET NUMBER: 91
DATE ISSUED: SEPTEMBER, 1986


                     1.  DESCRIPTION OF CHEMICAL

- Chemical Names:  Arsenic acid, Orthoarsenic acid
- Common Name:  Arsenic Acid
- Trade Names:  Desiccant L-10 to the minus R, Hi Yield to the minus R,
  H-10, Poly Brand Desiccant, Hi Yield to the minus R, Synergized H-1O
  to the minus R
- EPA Shaughnessy Code:  006801
- Chemical Abstracts Service (CAS) Number:  7778-39-4
- Pesticide Types:  Dessicant, wood preservative
- Chemical Family:  Inorganic arsenicals
- U.S. and Foreign Producers:  Penwalt Corporation
                               Voluntary Purchasing Corporation


                  2.  USE PATTERNS AND FORMULATIONS

- Application Sites:  Terrestrial crop use on machine and stripper
  harvested cotton as a desiccant; Non-food use on seed crop okra
  (Arizona only) as a desiccant.
- Types of Formulations:  75% soluble concentrate formulation
  intermediate, also used as end-use product.
- Types and Methods of Application:  Foliar spray (single application at
  least 4 and 10 days prior to harvest of cotton and okra,
  respectively).
- Application Rates:  Cotton -- 2.94 to 4.42 pounds active per acre
                         Okra -- 4.42 pounds active per acre
  (Note:  1 quart of 75% liquid = about 2.94 pounds active ingredient).
- Usual Carriers:  Water


                        3.  SCIENCE FINDINGS

Chemical Characteristics

- Physical state:  Aqueous solution
- Oxidation state:  Pentavalent Arsenic
- Color:  Pale yellow to pale green
- Odor:  None
- Boiling point:  Not available
- Specific gravity: 1.884 at 20 degrees C
- Solubility:  Readily soluble in water, forming various As salts
- Stability:  Most stable under conditions favoring oxidation and at
  high pH; under reduction conditions or low pH,  
  pentavalent form may convert to trivalent arsenic.
  - Unusual handing characteristics:  Reacts with fabric, galvanized
    metals, black iron and certain other metals resulting in 
    deterioration, corrosion, or liberation of toxic gases
    (e.g., hydrogen, arsine).

Forms of inorganic arsenic referended in the Registration Standard
 
- Arsenic acid:  H3AsO4, containing arsenic in a +5 oxidation form
- Sodium arsenate (Na3AsO4):  The sodium salt of arsenic acid, also +5
- Arsenic trioxide (As203):  An oxide of arsenic, containing arsenic
  in a +3 oxidation form
- Sodium arsenite (NaAsO2):  A sodium compound related to arsenic
  trioxide, also +3


Toxicological Characteristics

- Acute toxicity:  Although arsenic is known to be highly toxic by
  ingestion, few animal studies are available on the active ingredient,
  or on the formulated products of arsenic acid. Moreover, the toxicity
  of arsenic compounds may vary widely depending in the type of
  formulation and the form of inorganic arsenic in the product.
  - Oral (rat) - 40-100 mg/kg.  Rats are not a good test species,
  however, since, alone among animal test species, they retain
  arsenic in their bodies without significant excretion.  Humans are
  known to be more sensitive to acute arsenic effects than rats.
  - Dermal - Undetermined.
  - Inhalation - Undetermined.
  - Eye and Skin Irritation - Undetermined.
  - Dermal Sensitization - Undetermined.
- Chronic toxicity
  - Oncogenicity:
    - Arsenic compounds, including arsenic acid, have been classified
      as Class A oncogens.  Epidermiological studies on workers in
      copper smelting and pesticide manufacturing, and on populations
      exposed to excess levels of arsenic in well water in Taiwan are
      the basis for this classification.  Inhalation exposure leads to
      lung cancers, and ingestion exposure has shown a correlation
      with development of skin cancers.
    - The lifetime inhalation oncogenic risks to workers from the
      cotton use have been estimated at negligible for applicators,
      and 10 to the minus (-4) to 10 to the minus (-5) for mixer/
      loaders.
    - Dermal and oral oncogenic risks have not been calculated
      because the risk models are still undergoing Agency review.
      Completion of this review is expected in late 1986 or early
      1987.
  - Mutagenicity:
    - The sodium salt of arsenic acid (sodium arsenate) and the sodium
      salt of arsenous acid (a related form of arsenic) have been
      found to be mutagenic, that is, to interact with DNA to cause
      heritable effects.  Numerous assays have been conducted on cells
      in vitro.  Other observed effects include interference with DNA
      repair mechanisms, direct toxicity to mammalian gonads, and
      positive effects in microbial systems.  Other evidence suggests
      that similar effects may occur in vivo.  Sodium arsenite is a
      more potent mutagen than sodium arsenate.
  - Teratogenicity/fetotoxicity:
    - Sodium arsenate has been shown to produce teratogenic or
      fetotoxic effects in hamsters (15-25 mg/kg intravenously); mice
      (40-45 mg/kg intraperitoneally); and rats (20-50 mg/kg
      interperitoneally).  Similar results have been obtained with
      sodium arsenite at lower dosages.  These results have not been
      demonstrated using an oral route of exposure, or have been found
      only at dosages that also cause significant maternal mortality.
      Because the effects have been shown only using routes of
      exposure that are not likely to occur with pesticide use, and
      because the studies were not adequate to establish no-observed
      effect levels (NOELs) the Agency will require an oral
      teratogenicity study in two species other than the rat.
  - Reproductive effects:
    - No data that meet Agency standards are available.  A
      reproduction study on a species other than the rat will be
      required.
  - Neurotoxicity:
    - Subchronic and chronic exposure to arsenic compounds causes
      peripheral and central nervous system neuropathy, the effects of
      which vary from slight to severe depending on the level and
      duration of exposure.
    - Other subchronic and chronic effects:
      - Inorganic arsenic compounds have been observed to cause
        cardiovascular, skin, blood, and liver and kidney effects in
        humans.  The same effects have been observed in experimental
        animals.  The NOEL for blood effects in dogs is 50 ppm (1.25
        mg/kg).  The NOEL for liver effects in rats of arsenites is 62.5
        ppm and of arsenates is 125 ppm.
    - Metabolism:
      - The metabolism of inorganic arsenic compounds in animals is well
        known.  The pentavalent form, such as arsenic acid, is
        metabolized by reduction into the trivalent form, followed by
        transformation into organic forms which are excreted within
        several days via the urine.  All mammals exhibit this metabolism
        except rats, which retain arsenic in their bodies for up to 90
        days.


Physiological and Biochemical Behavioral Characteristics

- Mechanism of Pesticide Action - Protein denaturation and enzyme
  inactivation, resulting in desiccation of plant foliage and stems.


Environmental Characteristics

- Few data are available on the environmental fate of arsenic acid.
  Arsenic is a naturally occurring compound that is ubiquitous and
  exists in different forms (species) depending on environmental
  conditions.  Arsenic acid rapidly dissolves in water.  The arsenic
  moiety of the residue cannot be distinguished from natural arsenic
  in the soil.  Special environmental fate data are required to be
  submitted.  Studies on environmental fate of arsenic acid must be
  designed to differentiate between natural and pesticide sources of
  arsenic.
- Groundwater concerns:  Arsenic has been detected in groundwater
  underlying areas of arsenic acid use.  However, the source of this
  contamination cannot be determined.  Limited information currently
  available suggests that arsenic acid will not leach significantly.
  Additional data are required to further evaluate leaching potential.


Ecological Characteristics

- Avian acute toxicity:  No data available
- Avian dietary toxicity:  Mallard duck - 1606 ppm
                           Bobwhite quail - 168 ppm
- Freshwater fish toxicity:  Bluegill sunfish - 66.8 ppm
                             Rainbow trout - 53.1 ppm
- Aquatic invertebrates:  Daphnia magna - 6.5 ppm
- Based on limited data, the Agency characterizes arsenic acid as
  moderately toxic to birds by ingestion in the diet.  Arsenic acid is
  slightly toxic to fish and moderately toxic to aquatic invertebrates.
- Endangered Species:  Cotton desiccant use may pose a potential
  hazard to the Attwater's Greater Prairie Chicken in three Texas
  counties (Victoria, Refugio, and Fort Bend).  The Agency has
  referred arsenic acid to the Office of Endangered Species, U.S.
  Department of Interior, for review as part of a group of cotton
  pesticides, and will require labeling to protect this endangered
  species.


Tolerance Assessment

- A tolerance of 4.0 ppm in cottonseed oil has been established for
  arsenic acid, expressed as arsenic trioxide (As203) (40 CFR 180.180).
  The use on okra seed crop is a non-food use for which no tolerance is
  required.
- Because the metabolism and chronic effects of inorganic arsenic in
  humans are well-known, the Agency is not requiring the submission of
  chronic feeding studies on arsenic acid per se.  For regulatory
  purposes, and until teratogenicity and reproduction studies are
  submitted, the Agency has calculated a provisional acceptable daily
  intake (PADI) based upon studies using sodium arsenate.
- Based upon a dog study having a NOEL of 50 ppm (1.25 mg/kg of actual
  arsenic) and a safety factor of 100, the PADI is 0.0165 mg/kg/day of
  As203, and the maximum permissible intake for a 60 kg person is 0.99
  mg/day.
- Available residue data indicate that the maximum residue that will
  theoretically occur in cottonseed from use of arsenic acid is 0.009
  mg/day.  The maximum residue therefore uses 0.009/0.99 of the
  maximum permissible intake, or 0.9%.


Reported Pesticide Incidents

- In the period from 1966-1981, 8 incidents were reported to the
  Agency concerning arsenic acid related to its cotton use.  Among
  these, one involved one human fatality and two persons hospitalized,
  three involved cattle, and four involved crop damage from spray
  drift of arsenic acid from nearby farms.


Summary Science Statement

- Arsenic acid is a form of inorganic arsenic.  Such compounds are
  acutely toxic to humans by ingestion.  Inorganic arsenical compounds
  have been classified as Class A oncogens, demonstrating positive
  oncogenic effects based on sufficient human epidermiological
  evidence.  The weight of evidence indicates that inorganical
  arsenical compounds are also mutagens.  Although there is
  teratogenic and fetotoxic potential based on intravenous and
  intraperitoneal routes of exposure, there is insufficient evidence
  by the oral route to confirm arsenic acid's teratogenic or fetotoxic
  effects.  Neurotoxic effects have been demonstrated after acute,
  subchronic and chronic exposures.  The metabolism of arsenical
  compounds in humans is well-documented, but animal studies are not
  adequate to determine no observed effect levels (NOELs) and
  acceptable daily intakes (ADIs).
  - The environmental fate of arsenic acid is not well documented.
  Studies to demonstrate its fate must take into account the fact that
  inorganic arsenicals are natural constituents of the soil, and that
  the forms of inorganic arsenic may change depending on environmental
  conditions.  Based on very limited data, arsenic acid is not
  predicted to leach significantly.  Although elevated levels of
  arsenic have been found in groundwater in Texas, the source of the
  arsenic cannot be determined; non-pesticide sources may have been
  the cause.
- Arsenic acid is moderately toxic to birds, slightly toxic to fish
  and moderately toxic to aquatic invertebrate species.


           4.  SUMMARY OF REGULATORY POSITION AND RATIONALE

- Arsenic acid is currently undergoing Agency Special Review, based upon
  its oncogenic and teratogenic effects.  Products will remain
  registered until the conclusion of this review.  New uses, however,
  will not be accepted.
- Arsenic acid products will be restricted to use by certified
  applicators, because of its acute toxicity and oncogenicity.
- Use restrictions based upon groundwater concerns are not warranted at
  the present time.
- Reentry intervals are not required because use as a desiccant does not
  lead to significant exposure to field workers.
- Protective clothing is specified for mixer/loaders and applicators,
  because of the acidic properties of arsenic acid, and its potential
  oncogenic risks to mixer/loaders and applicators.
- Endangered species labeling statements are required because of
  potential hazard to the Attwater's Greater Prairie Chicken in Texas.
  An avian residue monitoring study is required to determine actual
  levels of arsenic acid in avian feed items.
- Tolerances will be reassessed based upon residue and metabolism
  studies to be submitted.  A rotational crop restriction may be needed
  if follow up crops take up arsenic acid residues from the soil.


                5.  SUMMARY OF MAJOR DATA GAPS

- Product chemistry data - arsenic acid               Feb. 1987
- Residue chemistry data - arsenic acid               Feb. 1988
  - Plant and animal metabolism
  - Analytical methodology for residues
  - Magnitude of residues in cotton
- Environmental fate studies
  - Metabolism in soil                                Dec. 1988
  - Leaching                                          Aug. 1987
  - Laboratory volatility                             Aug. 1987
  - Soil dissipation                                  Dec. 1988
  - Rotational crop studies                           Dec. 1989
- Toxicology studies
  - Acute toxicity                                    Feb. 1987
  - Teratology (rabbit and mouse or hamster)          Dec. 1987
  - Reproduction (rodent other than rat)              Dec. 1989
  - Dermal penetration                                Aug. 1987
  - Glove permeability                                Feb. 1987
- Ecological effects studies
  - Avian acute toxicity                              May 1987
  - Residue monitoring study on avian food items      Dec. 1987
  - Aquatic invertebrate early life stage             Dec. 1987


                   6.  CONTACT PERSON AT EPA

Richard F. Mountfort
Product Manager No. 23
U.S. Environmental Protection Agency
TS-767C
401 M St., SW
Washington, D.C 20460
703-557-1830


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.