CHEMICAL HAZARD  INFORMATION PROFILE*

                        DRAFT  REPORT


                            Ziram

                          137-30-4
                     September 30,  1983
                         DISCLAIMER

,oment is a preliminary draft, and has not been peer and
 ratively reviewed within EPA.  It should not be construed to
 t Agency policy.   Mention of tradenames or commercial pro not
 te endorsement or recommendation for use.

 cal Hazard Information Profile (CHIP) is part of the first stage in
 ssment of risk by the Office of Toxic Subjstances _(OTS) of cnemicals
 977 TSCA Chemical Substance Inventory, and enables OTS to decide on
 ition for the subject chemical regarding level of concern and the
  further assessment.   The CHIP contains a summary and preliminary
•nt of readily available health, environmental effects, and exposure
 n general, no in depth critical evaluation or validation of the
 performed.  Several  levels of management and' technical review have
 formed on this CHIP  within the Assessment Division of OTS.

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                             DRAFT REPORT


                  CHEMICAL HAZARD INFORMATION PROFILE


Subject   Ziram                            Prepared by    'lary  Lou Daughertv

Chemical Name  Zinc, bis(dimethylcarbamo-  Chemical Effects  Information Center

dithioato-S.S)-(T-4)-. (9 CD	  Oak Ridge National  Laboratory	
CAS No. 137-30-4	

Date of Report-   September 30, 1983	

Rationale for Selection    Carcinogenicity - NTP Bioassay  (NTP 1983) .    	
Summary

     Ziram has a relatively high, production volume  (1,880,000 pounds  in
the U.S. 1981) and is used primarily as a rubber accelerator and  as a
fungicide on fruits and vegetables.

     NIOSE projected that 27,889 workers, mainly in  the rubber  industry,
are exposed to ziram.  The survey on which this figure was based  did not
include workers in the pesticide or agriculture industries, however.
Although industrial monitoring data were not found,  Russian and Italian
data document significant levels of the compound in  the work environment
of ziran manufacturing facilities, suggesting  that worker exposure could
occur in U.S. industry as well.

     Ziram is released into the environment when applied to crops as a
fungicide, or to aquatic systems as a molluscicide.  No data on release
from industrial sites was located.  Experimental data suggest that, once
released, the compound is fairly stable and may retain its biological
activity for a month or more before chemical and perhaps biological
degradation are complete.

     Consumers could be exposed to ziram by using the compound  as a
garden fungicide or by ingesting contaminated  fruits and vegetables.
However, it is possible that routine household washing of produce would
minimize exposure via ingestion.

     Various types of toxicities have been demonstrated in experimental
animals, humans, and a broad spectrum of environmental species  exposed to
ziram.  The two most significant findings are  carcinogenicity in  the male
rat thyroid following oral administration of the compound, and
chromosomal abnormalities in humans exposed to the compound in  the
workplace.  Other effects of the compound include teratogemcity  and
reproductive tczicity in rats, rabbits, mice,  and chickens,
hematological changes in animals and humans,   irritation of the skin,
eyes, and respiratory tract in exposed workers,  and possible

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cnoliaesterase umioition in aumans.  The nmtagenicity of zir    in
experimental systems is equivocal.  Ziram is lethal to aq.uat   species at
fairly low concentrations and it inhibits the growth and me   ^olic
processes of bacteria in soil and water.

     The combination of factors described above for zira  (high
production volume, possible release into the workplace, probable release
into the environment, and toxic effects) constitute a -otential  for risk
to human health and the environment.  Monitoring data for the workplace
and environment would be useful in more effectively correlating  the
exposure potential and toxic effects of the chemical for a complete
assessment of the health and environmental hazards of the compound.
                                      11

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                             TABLE OF CONTENTS

                    Chemical Hazard Information. Profile

                                   Ziram
  I.   SUMMARY OF AVAILABLE DATA 	   1

  A.   Chemical Identity 	   1
  B.   Physical and Chemical Properties 	   1
  C.   Exposure	   2

      1.   Worker Exposure Considerations	   2
      2.   Consumer Exposure	   8
      3.   Environmental Exposure 	   9


  D.   Human Health Effects 	  11
      1.   Metabolism	  11
      2.   Lethality	  12
      3.   Carcinogenicity 	  15
      4.   Mutagenicity	  18
      5.   Teratogenicity/Reproductive Effects	  20
      6.   Other Effects 	  21


  E.   Environmental Effects	  25


  F.   Existing Standards 	  29


  G.   Other Relevant Information 	  30


 II.   Preliminary Risk Assessment	  30

  A.   Exposure Assessment	  30
  B.   Human Health Risk Assessment 	  36
  C.   Environmental Risk Assessment	  38


III.   References		  40

  A.   Literature Cited	 .	  40
  B.   Secondary Sources Searched 		  53

      1.   Books	  53
      2.   Data Bases 	  57

  C.   Search Strategy  	  59
                                    111

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I.  Summary of Available Data

A.  Chemical Identity

    1.  CAS Registry Number   137-30-4
    2.  Chemical Name:  Zinc, bis(dimetliylcarbamoditii .oato-S, S'}-,  (T-4)-
                        (9CI)
    3.  Synonyms'  Zinc, bis (dimethyldithiocarbamato)-  (SCI);  Aaprotect,
                   Aavolex; Accelerator L, Aceto ZDED,  Aceto  ZDMD,
                   Alcobam AM, Antene, Bis (dimethyldithiocarbamato)zinc,
                   Carbamodithioic acid, dimethyl-,  zinc  salt,  Carbazinc,
                   Corono corozate, Corozate,  Crittam,  Cuiaan,  Cuinan L,
                   Cymate, Dimethylcarbamdithioic  acid, zinc  complex,
                   Dimethylcarbamodithioic acid, zinc salt,
                   D}.methyldithiocarbmic acid,  zinc  at  Duprina  90,
                   Eptac 1, Fuel as in Ultra, Fuel as in, Fungostop,  Karbam
                   White, Methasan, Methazate,  Methyl cimate,  Methyl
                   zimate. Methyl ziram; Mezene, Milbam.  Mxlban,  Molurame,
                   Mycronil, Orchard brand ziram,  Pomarzol Z-forte,  Prodaram,
                   Rodisan, Soxinol PZ, Tricarbamix  Z,  Triscabol, Vancide,
                   Vulcacure ZM; Vulkacit L, Vulkacite  L, Z 75, Z-C Spray,
                   Zarlate; Zerlate, Zimate; Zinc  dimethyldithiocarbamate,
                   Ziram, Zirberk, Zirthane,
        Note:  Sax (1975) lists "ziram" as a  synonym for zinc
               diethyldithiocarbamate.  For this report,  it was assumed  that
               "ziram", when encountered in the literature reviewed, was a
               synonym  for zinc dime thy Idithiocarbamate,  unless otherwise
               stated.
        Structural Formula.
                               *3C\  /\/\
                                  1— C    Zn   C— M
                               a/  VV
        Molecular Formula   CgHi2N2S4Zn
B.  Physical and Chemical Properties

    5.  Molecular Weight.  305.82  (Sandiaeyer 1981)
    6.  Physical State.  White odorless powder  (Martin  and Worthing  1974)
    7.  Melting Point  (°C)   240  (Martin  and Worthing 197 *)
    8.  Boiling Point  (°C)   Not  found
    9.  Solubilities
(a)
             Water - 65 ppm at 25°C  (Martin  and Worthing  1974),
                     almost insoluble  (Hawley 1977)
             Von-aqueous solvents -
                            Solubility in 1,00 ml solvent at
                            25"C - < 0.2 g,  alcohol, < 0.5 g,
                            acetone, < 0.5 g, benzene, < 0.2 g,
                            carbon tetrachloride, < 0.2 g, ether,
                            0.5 g, naphtha (Windholz et al. 1976)

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          (c)   Other sol-vents - Soluble in dilute alkali, c
               (Martin and Worthing 1974), and concentrated
               (Hawley 1977)
                                                         ^n disulphide
                                                         drochloric acid
          Dissociation Constant
          Partition Coefficient
10.
11.
     12.
     13.
     14.   Reactivity
                        Not found
                        Not found.  [Bioconce .ration Factor - 59
                        (Kenaga 1980) (Calculated from a water
                        solubility of 65 pp_i)].
Density (specific gravity).  1.71 (Hawley 1977)
Volatility   Vapor pressure negligible at room temperature (Hayes
             1982).
            The dithiocarbamates, in general, are very reactive
            compounds that possess strong metal-binding
            characteristics, interact with sulfhydryl compounds,
            and undergo many reactions involving oxidation and loss
            of sulfur.  The degradation of dithaocarbamates is   '
            mainly influenced by oxygen and humidity (Engst and
            Schnaak 1974, as reported in Fishbein 1976).  Under
            mild conditions, dithiocarbamate salts are oxidized  to
            yield thiuram disulfides.  This reaction can occur on
            exposure to air, as can the formation of monosulfides
            with the liberation of sulfur.  Ziram is stable under
            normal conditions (Hayes 1982, Worthing 1979), having
            good stability to moisture and dilute acids (Sittig  1980),
            but can be oxidized to the tetramethyl compound,  TMTD or
            thiram (tetramethylthiuram disulfide) (Lowen 1961, as
            reported in Fishbein 1976) which is also a fungicide.
            Acid hydrolysis of ziram yields dimetylainine and carbon
            disulfide as principal degradation products (Engst and
            Schnaak 1974, Lowen 1961, Weed 1953, all reported in
            Fishbein 1976) .  Ziram can form a flammable dust
            (Windholz 1976) .
     15. Other.
         (a) Odorless when pure (Hawley 1977)
         (b) W/V Conversion (mg/m-3 approx. equal to 1 ppm)  - 12.48
             (Sandmeyer 1981)
         (c) Soil Sorption Coefficient - 440 (Kenaga 1980)  (Calculated from a
             water solubility of 65 ppm).
  C.   Exposure

      1.  Worker Exposure Considerations

      a.  Production Volume/Manufacturers

      U.S production of ziram (under the name zinc dimethyldithiocarbamate)
for the years 1977-1981 is summarized in Table 1 (USTTC 1978, 1979, 1980,
1981, 1982. all reported in USEPA 1983a)

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                     Table 1. U.S. Production of Ziram
                           (Thousands of Pounds)


                1977     1978     1979     1980     1981

                1.710    2,231    3,765    2,461    l.J'O
      The nonconfidential file of the TSCA Chemical Substance  Inventory
indicates that 5 companies reported 1977 production of  ziram  totalling 230-
2,300 thousand pounds.  Three other companies reported  1977 production but
did not report production volumes (USEPA 1983b, as reported in DSEPA
1983a).

      The following U.S. companies currently produce ziram (SRI Interna-
tional 1983a, as reported in USEPA 1983a)

Company                                         Plant Location

Fike Chemicals, Inc.                            Nitro,  WV

FMC Corporation
    Agricultural Chemical Group                 Middleport, NI

The Goodyear Tire i Rubber Co.
    Chemical Division                           Akron,  OH

Uniroyal, Inc.
     Uniroyal Chemical Division                 Naugatuck, CT

R. T. Vanderbilt Company, Inc.
     Vanderbilt Chemical Corporation, subs id.   Murray, KY


      In addition to those listed above, with the exception of FMC  Corpora-
tion, the following U.S. Companies were reported to produce ziram in 1977
(USEPA 1983b, as reported in USEPA 1983a)

Com-pa ny                                         Plant Location

Alco Chemical Corporation                       Chattanooga, TN

Brin-Mont Chemicals, Inc.                       Greensboro, NC
Pennwalt Corporation                            Wyandotte, MI

Rockmart Chemical Corporation   _               Aramcnee, GA
      b. Imports/Importers

      Separate data on  imports of ziraia  are  not  available  (USEPA 1983a) .
           o
      The  nonconfidential file of the TSCA Chemical  Substance  Inventory
indicates  that one company  imported  ziram in 1977  in the range  of 10,000-

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100,000 pounds (USEPA 19S3b, as reported  in USEPA 1983a).   I    adition,  two
companies imported ziram in 1977 but did  not disclose  the  a   .its,  and
three companies reported that they were importers of zirap    :  did  not
import any in 1977.  laporters were not identified  in  USE"   (1983a)


      c.  Technical Product and Process Type

      Ziram is available in the U.S. as dusts containing 3.5-76%  of  the
chemical, as wettable powders containing  30-96% of  the chemical,  as  aqueous
suspensions containing 30-40% of the chemical and as a 0.1% paste (USEPA
1973, as reported in IARC 1976).

      In Japan, ziram is available as  a technical grade product containing
98% of the chemical and less than 0.5% water, 0.4-0.5% sodium  chloride and
1.0-1.1% other impurities (mostly zinc methyldithiocarbamate)  (Japanese
Ministry of Agriculture ? Forestry 1975,  as reported in IARC 1976).

      The two methods for the synthesis of ziram are described below.  It
is not known which of the methods is more important commercially.

      Ziram may be produced by the precipitation of sodium  dimethyldithio-
carbamate with zinc stil fate, zinc chloride, or zinc oxide.  The sodium
dimethyldithiocarbamate is made by the reaction of  carbon  disulfide  and
dimethylamme in aqueous sodium hydroxide at 20-30°C (IARC  1976,  Sittig
1980, SRI International 1980, SRI International 1983b,  all  reported  in
USEPA 1983a).

      A more direct method involves the reaction of dimethylamme,  carbon
disulfide, and water-insoluble zinc oxide or zinc hydroxide.  The direct
reaction method has been claimed to have  the following advantages   a
shorter reaction time, more economical use of raw materials, fewer  steps,
improved utilization of the heat of reaction, and much larger yield  of fin-
ished product per unit of reactor volume  (Sittig 1980,  as  reported  in USEPA
1983a).                                   *

      In the direct process, zinc oxide or hydroxide is added  to  a jacketed
mixer and an approximately equivalent  quantity of dimethylamme is  added as
quickly as possible,  After several minutes of very intensive mixing, an
approximately equivalent amount of carbon disulfide is added,  followed by
intensive mixing.  The reaction temperature is maintained  at 0-150°C and
the pressure is generally maintained in the range of subatmospheric  to 100
psi.  After completion of the reaction, the water of reaction  ana any
excess carbon disulfide or dimetaylamine  are removed by vacuum  distillation
(Sittig 1980, as reported in USEPA 1983a)


      d.  Industrial and Occupational  Uses

      No evidence was found for the commercial use  of  ziram as  a  chemical
intermediate.  The compound i-s used mainly as a ruboer accelerator  and as a
fungicide (USEPA 1983a) .  It has been  used as a rubber accelerator  since
1943,  ziram's fungicidal activity was first obvserved in  1944  (IARC 1976).

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Of tie total 2,231,000 pounds produced  in  the U.S.  in  1978,  -   estimated
400,000 pounds (ISTa) were used as a fungicide on  agricultur-   :rops  (SRI
International 1980, as reported in USEPA 1983a)

      Ziram is used in the rubber-processing  industry  as     accelerator or
promoter which functions by interacting with  sulfur  to ..  -rease  the  rate  of
vulcanization (IAK.C 1976).  Because of  its high cure rr.e,  ziram is  some-
tines called an ultra-accelerator (Taylor  and Son 1982,  as  reported  in
USEPA 1983a) .  Ziram is a primary accelerator for cures  at  120°C and a
secondary accelerator with thiazoles  (Heinisch 1974, as  reported in  USEPA
1983a).

      Ziram is used as an accelerator for  the following  types  of rubber
isobutylene-isoprene, isoprene (natural and synthetic),  nitrile-butadiene,
and sytrene-butadiene.  It is also used as a  curing  agent for
poly(fluoroalkoxyphosphazenes),  these phosphazenes  are  not  believed to be
important commercially, however (SRI  International 1983b, as reported in
USEPA 1983a).

      Ziram is a protective fungicide which prevents disease—causing fungi
from entering plants, but does not kill established  infestations (SRI
International 1980, as reported in USEPA 1983a) at concentrations  of 0.2-
0.T"a active ingredient (Gunther and Gunther 1971).   Protective  fungicides
are generally applied to uninfested crops, and require frequent  applica-
tions thereafter.  Of the 400,000 pounds of ziram used in the U.S. for
fungicidal purposes in 1978, 300,000 pounds were  used  on deciduous fruits
(excluding apples and citrus fruits), and  100,000 pounds were  used on
vegetables (SRI International 1980, as reported in USEPA 1983a).

      Ziram is used extensively on almonds and peaches to control  shot hole
(Septoria spp.), brown rot (Alternaria  spp.), and peachleaf  curl.  It is
also used on vegetables, and as a repellent to rabbits (Personal communica-
tion to J. Leitzke from the Registration Division of the Office  of Pesti-
cides).  In the U.S., ziram is registered  for use on 24  fruit  and vegetable
crops and on several commercial and household ornamental flowers (USEPA
1973, as reported in USEPA 1983a).

      Ziram is approved for use in animal  glue and  adhesives which are used
in food—contact articles, non—food contact paper  coatings,  industrial cool-
ing water, latex-coated articles, neoprene, paper and  paperboard,  textiles,
and plastics  (polyethylene and polystyrene) (USEPA 1980, as  reported in
USEPA 1983a).  In 1976, one source reported that  small amounts  of  ziram
were used for these purposes (IARC 1976).

      Ziram is usea as a slimicide in paper Bills,  and,  in  a mixture with
zinc 2-aercaptobenzothiazole, as a preservative in  the textile  industry and
elsewhere (Trotz and Pitts 1981, as reported  in USEPA  1983a) .   Ziram is an
effective molluscicide against most aquatic snails at  3-5 ppm  in water
(Hadler 1982).

      The classification of the commercial and possible  uses of  ziram in
accordance with the Chemical Use Standard  Encoding System (ChemDSES) (Goen
et al. 1980, as reported in USEPA 1983a)  is as follows

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   321   (Accelerators)/2S.09.03 15-5  (Synthetic elastomers,   s.c.)
   321   (Accelerators)723.09.03 05-5  (Natural rubber)
   321   (Accelerators)/28.09.03.10-0  [Polyisoprene elastc   3 (excludes
                                      natural rubber)]
   321   (Accelerators)/28.09.03.01-1  (Acrylonitrile-but- -ene elastomers)
   321   (Accelerators)/28.09.03.08-8  [Styrene-butadien~ alastomers (S-type)]
   326   (Fungicides)/01.01.07-9  (Fruits)
   362   (Fungicides)/01.01,05-7  [Vegetables (except raises, roots, and
                                 tubers)]
   362   (Fungicides)701.01.04-6  (Roots and tubers)
   362   (Fungicides)701.01.08-0  (Nuts)
   166   (Animal repellants)
   362   (Fungicides)01.01.12.01-5  (Ornamental nursery products)
   362   (Fungicides)728.14.05-7  (Water and waste-water treatment chemicals)
   362   (Fungicides)/28.13.02-3  (Organic adhesives)
   362   (Fungicides)726.06.03.03-8  (Food packaging products)
   362   (Fungicides)730.01.l6-7  (Rubber goods, n.e.c.)
   321   (Accelerators)/28.09.03.03-3  [Chloroprene elastomers (neoprene)]
   362   (Fungicides)726.02-8  (Paper)
   362   (Fungicides)726.03-9  (Paperboard)
   362   (Fungicides)722.02-4  (Textile goods, n.e.c.)
   362   (Fungicides)730.02-2  (Plastics products)
   116   (Slime preventatives)728.10.02.03-3  (Fungicides)
   108   (Biocides)/28.10.12-2  (Pesticides and biocides n.e.c.)
      e.  Processors

      The following companies are major U.S. producers of synthetic rubber,
and may process ziram during synthetic rubber manufacture (Dun's Marketing
Services 1982, as reported in USEPA 1983a).


Ashland Oil, Inc.                                 Ashland, KY

CHR Industries                                    New Haven, CT

Copolymer Rubber Chemical Corporation             Baton Rouge, LA
Dexter Corporation                                Windsor Locks, CT
Eastman Kodak Company                             Rochester, NY

Firestone Tire ? Rubber                           Akron, OH

General Latex ff Chemical Corporation              Cambridge, MA

Goodyear Tire ^ Ruboer Company                    Akron, OH
Goodyear Rubber Plantations Company               Akron,OH

UCT Incorporated                                  Louisville, KY

      The following companies are major U.S. paper producers and may pro-
cess ziram danag paper manufacture (Dun's Marketing Services 1982, as
reported in USEPA 1983a).

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American Can Company                              Greenwich,

Consolidated Cover Company                        Whittier,

Crown Zellerbach Corporation                      San Fra-   oco,  CA

Hudson Pulp and Paper Corporation                 Danen   CT

Lydall Incorporated                               Manchester,  CT

Potlatch Corporation                              San Francisco,  CA

Sonat Incorporated                                Birmingham,  AL

Southwest Forest Industries                       Phoenix, AZ

St. Francisville Paper Company, Incorporated      San Francisco,  CA

Times Mirror Company                              Los Angeles,  CA


      £.  Detection Methods

      Methods for the detection of ziram based on polarography (Budnikov  et
al. 1974, Zlisenko and Vekshtein 1973, Supin et al. 1973,  all  reported  in
USEPA 1983a) and colorimetry (Rangswamy et al. 1970, as reported  in USEPA
1983a) have been described.

      Gas chromatography has been used to determine ziram  residues in food
samples (McLeod and McCully 1969, as reported in USEPA 1983a).  Thin layer
chromatographic methods have been described in which the presence of ziram
was shown by spraying with a sodium azide—iodine reagent (Klisenko and
Vekshtein 1973, as reported in USEPA 1983a) or with cupric chloride
hydroxylamine (Fishbein 1975, as reported in USEPA 1983a) .  In another
method, ziram was hydrolyzed and the products reacted to yield strongly
fluorescent derivatives (van Hoof and Heyndrickx 1973, as  reported in USEPA
1983a) which were separated by thin-layer chronatography and visualized
under ultra-violet light.  This procedure was capable of demonstrating  the
presence of 20 ng ziram.  According to USEPA (1983a), other methods for the
chromatographic analysis of carbamates, including ziram, have  been reviewed
by Fishbein and Zielinski (1967).


      g.  Monitoring Data/Worker Exposure

      U.S. occupational monitoring data for ziram were not found.  Russian
stadies, however, have demonstrated that occupational exposure can occur.
Enikeev (1968, as reported in Hayes 1982) pointed out that aerosols of
ziram in the workplace appear to constitute its principal  danger. Enikeev
(1967, as reported in Chem Abstr 72.35486o) reported that  Russian workers
in several ziram-producing plants were exposed to dust levels  of  0.5-130
ing/in1', depending on location.  Pilinskaya (1970) measured  average dust  lev-
els of 1.95 and 3.7 mg/m^ m the store and packing areas of a  ziram plant,
with levels reaching 71.3 mg/m^ during some temporary disturbances of the
technological processes.  Martson an3 Pilinskaya (1971, as reported in
USEPA 1983a) collected ziram on filters from air in a manufacturing plant.
Concentrations were determined colorimetrically to be 0.8  to 3.7  mg/m*.

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      Wolf and Durhan (1966, as reported  in Deichman and Ge-   .  1969)
estimated tne relative acute tosicity hazard of pesticides     spraymen  and
ranked z iram as one of the least dangerous.

      Based on. the National Occupational  Hazard Survey,  JOSH  (1980, as
reported in USEPA 1983a) projected that 27,889 workers  , .ire occnpationally
exposed to ziram.  This projection is based upon  the fallowing exposures
found during the survey (it should be noted that  worL.rs engaged in  the
production of ziram, or its use as a pesticide, were not included in this
survey)
SIC Code           Name                                  Number  of  Exposures

2513               Upholstered Household Furniture               2
2822               Synthetic Rubber                            15
3069               Fabricated Rubber Products, n.e.c.         259
3357               Nonferrous Wire Drawing and Insulating      12
5099               Wholesalers, n.e.c.                           4
      2.  Consumer Exposure

      Documentation of consumer exposure  to ziram was not  found.  However,
the possibility of such exposure must be  considered  since  the  compound  is
commonly used as a fungicide on fruits and vegetables. Consumer  contact may
occur through actual use of ziram as a pesticide or  through  the  ingestion
of ziram-contaminated produce.

      Limited data were found for the levels of pesticide  residues  detected
in fruits.  It was demonstrated in one study that immediately  after treat-
ment of peach trees with ziram, when the  fruits were small and green, resi-
dues of the pesticide on the fruit exceeded 7 ppm, however,  when the  fruit
had matured, residues were no longer detectable, either on the skin or  in
the pulp (Primo Yufera et al. 1967, as reported in Chem Abstr  67  42620r).
In another study, apples were treated with 1% ziram, according to a typical
procedure and the residues of the compound were measured  in  washed  and
unwashed samples (Ryazanova 1967l>, as reported in Chem Abstr 71  2469z) .  In
the unwashed apples, the ziram residue did not exceed 1 mg/kg,   washing
reduced the residue by approximately 10—fold.  Treatment with  1% ziram
resulted in bitter-tasting apples.  Tolerances for residues  of ziram  in or
on raw agriculturel commodities in the U.S. nave been set  at 7 ppm  for
fruits and vegetables, and 0.1 ppm for almonds and pecans  (USEPA 1980a, as
reported in DSEPA 1983a)   Details are given in Section F.,  Standards and
Regulations.

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      3.  Env.ronmentai

      a.  Environmental Release

      Environmental monitoring data were not  found  for  zi~    other  than the
levels detected on fruits treated with the  compound  for  f  .^icidal  purposes
as described in section I.C.2  (Consumer Exposure).   Reside  levels  ranged
from approximately 1 to > 7 ppm on treated  fruits in tt;  two  studies  con-
ducted in Russia and Spain (Ryazanova 19671),  as reported  in  Chem  Abstr
71 2469z, Primo Yufera et al.  1967, as reported in  Cham Abstr 67  42620r).

      The use of ziram as an agricultural fungicide  and  as a  molluscicide
would be expected to result in contamination  of the  soil  and  aquatic
environments, respectively.  Rain would tend  to wash residues of  the  pesti-
cide from fruits and vegetables into the soil.
      b.  Environmental Fate

          i.  Persistence

      Because of its use as an agricultural  fungicide, the persistence  of
ziram on or in plants treated with the compound has been of  interest  from
an agricultural, as well as from an environmental, viewpoint.  Various  stu-
dies have been performed to determine persistence of  the compound under
different conditions.   Ziram residues disappeared in about  a month from
lettuce, carrots, and celery, grown and sprayed in a  greenhouse  and stored
at 4°C  (Villa et al. 1976, as reported in Chem Abstr  88 16949u).  Washing
of the vegetables immediately after spraying removed  92% of  the  pesticide.
Field persistence of the pesticide (applied  at the concentration of 1820
ppm) on leaves of 12 woody plant species averaged 2.7 days and varied from
1 to 10 weeks, as determined by a cellophane bioassay technique  (Neely
1970).  These results were dependent upon plant species, but in  10 of the
12 woody plants species persistence was <_ 3  weeks.  Generally, ziram  is not
considered to be stable under environmental  conditions (Nitsche  et al.
1974).

      Gretillat (1961, as reported in Strufe 1968) determined the per-
sistence of ziram in an aquatic environment  by testing its molluscicidal
activity under laboratory conditions and in  field trials.  In the labora-
tory, the activity of the compound (5 and 10 ppm) decreased  considerably
between the 30th and the 45th days, while in the field, a concentration of
10 ppm  continued to show marked molluscicidal activity after 35  days, and
was still slightly effective after ^2 days.

      The presence of inorganic salts decreases the staoility of ziram  in
water (Gonnert and Strufe 1962, as reported  in Strufe 1968).  No explana-
tion of these results was given.

             Biodegradation - Microbial degradation of ziram has been
observed.  Raghu 11976, as reported in Chem Abstr 89-37937z) demonstrated
that a  Pseudomonas sp., isolated from soil,  was capable of degrading  ziram

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                                     10
    that dimethyl dithiocarbamate— aminobutyric acid was  the r  ^ or  polar
metabolite,  Etges et al. (1965)  isolated a  small, gram  neg-  ,  e coccoba—
cillus from molluscicide test chambers which had  contained    -  snail,
Australorbis glabratus,, and observed that ziram could  ser-   _s  sole  source
of nitrogen for the bacterium, provided glucose was presc   as  a source  of
carbon and energy.  It should be  noted that  ziram has  be  a  shown to  inhibit
growth and metabolic processes in bacteria  (Section I.F  4)  and  may there-
fore inhibit biodegradation under certain circumstanced.

             Photodegradation - In  the laboratory, using  aquaria exposed to
STinlight for several hours each day, Deschiens and Floch  (1965, as reported
in Strufe 1968) found that active ingredient remains residually active for
45 days at a starting concentration of 5 ppm.

             Hydrolysis - No data were found for  ziram.   However,  The half
life of diethyldithiocarbamate in acid solution ranges from 2 mm  at pH  4.0
to 860 mm at pH 6.6 (Hylin and Chin 1968).  At pH 5.7,  the approximate  pH
of moist leaf surfaces, the half  life was 107 mm.  Hyl in and  Chin (1968)
suggest that the dimethyl derivative would probably behave  in  a similar
manner.

      Klisenko and Vekshtem  (1973, as reported in Chem Abstr  82:39300r)
listed the following as degradation products of dimethyldithiocarbamate
fungicides, inclusive of ziram, in  water  tetramethylthiourea,  dimethylam-
monium dimethyldithiocarbamate, and sulfur.

             Oxidation - The oxidation of ziram to thiram has been
demonstrated in solution, but has not yet been demonstrated  in  the soil
(Munnecke 1967, as reported in Goring and Hamaker 1972).  Thiram,  in turn,
appears to be both microbially and  nonbiologically degraded  in  soil
(Munnecke and Mickail 1967, as reported in Goring and  Hamaker  1972).

             Bioaccumulation - Ziram does not appear to be  stored  in the
tissues of rats and dogs (Vettorazzi 1979, Hodge  1956, as reported in Hayes
1982).

      In a long term study rats were administered 2500 ppm  ziram in  the
diet for two years.  At the end of  the study the  animals  had about 4 ppm of
the compound in the liver.  However, the concentration of zinc  stored in
the bone increased almost linearly, corresponding to the  logarithm of the
concentration of ziram in the diet, the mean zinc concentration ranged from
180 to 300 ppm of zinc in bone ash  in animals maintained  for 2  years on
diets containing 0 and 2500 ppm of  ziram, respectively.   Thus,  it  appears
that ziram itself is nor stored in  the tissue, out the zinc metabolized
from  it is stored to a slight degree (Hodge  et al. 1956,  as reported in
Hayes 1982)

      Tewari and Singh (1979, as  reported in Chem Abstr  91  33611g)
described  a technique for the extraction of  ziram from autopsy  tissues,  but
it  is not  clear if the material was actually found in  the tissues  or added
experimentally.

      The bioconcentration factor for ziram  was calculated  from its water

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                                     11
solubility (65 ppm) by Kenaga  (1980)   The  calculated  factor     59  for
ziran is not considered high (the  author  suggests  that chea    _s with a
value of over 1000 are those which need further  hazard eva"   .ion).

          11.  Transport

               Air - No data were  found.

               Water - Paul mi  (1963, as  reported  in Strufe 1968)  investi-
gated the adsorption of ziram by mud  in the  laboratory,  and found that 11-
30% of the active ingredient that  was added  to overlying water was  adsorbed
within the first few minutes,  and  that 16-33% was  adsorbed within 24 hours.
Gonnert and Strufe (1962, as reported in  Strufe  1968)  performed a similar
study in aqueous solution after addition  of  different  concentrations of
pond mud (0.55%, 1.35%, 2.4%).  The amount  of ziram adosrbed  increased with
the concentration of pond mud  and  with time  (19% was adsorbed by 1  hour
with 0.55% mud; 96% was adsorbed by 3 hours  in 2.4% mud).

               Soil - The available data  for the mobility of  ziram  through
the soil are conflicting.  Munneke (1961, as reported  in Singhal and Bansal
1978) and Helling et al. (1974, as reported  in Singhal and Bansal 1978)
measured the mobility of ziram  in  soil columns and soil  thin—layer  chroma—
tography (TLC) plates, respectively,  and  found the chemical to be  immobile.
Singhal and Bansal (1978), on  the  other hand, me-asured the mobility of
ziram using soil TLC and observed  high mobility.   Singhal and Bansal
applied high concentrations of  ziram  to tneir plates which may account for
the high mobility of their samples, thus  suggesting that the  concentrations
of chemicals may affect their  mobility.   It  is not clear if the TLC tech-
niques employed by Helling et  al.  were the  same  as those used by Singhal
and Bansal, if not, this is another factor which could result in the con-
flicting observations of the two groups.                ~~

      Singhal and Bansal (1978) also  determined  that the rate of movement
of ziran through the soil was  also a  function of pfl and soil  particle size,
but not of soil organic content.   The mobility of  the  chemical increased  as
the acidity or alkalinity of the soil increased  and decreased with  a
decrease in soil particle size.
  D.  Human Health Effects

      1.  Metabolism

      \ thorough  study  of  the metabolism  of  ziram  in  rats  was  conducted  by
Veknstein and Klinsenko  (1971)   The  compound was  administered in a  single
oral dose of 500  mg/kg  and  the  animals were  killed 30 minutes,  16 and  24
hours, and 2, 3,  and  6  days  after  administration of the  compound.  The
organs, blood, and urine were analyzed for  the  presence  of ziram  and  its
transformation products, tetramethylthiuram  disulfide (TJfTD),
tetramethylthiourca,  the dimethylamine salt  of  diiaethyldithiocarbamic  acid
(DMA salt of DMDTCA)    The  levels  of  the  parent compound and  its

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                                     12
metabolites, as detected by thin layer  chromatography  at  the   .nous  tine
points, are summarized in Taole 2.  The zirain was  rapidly d    ributed and
was completely or almost completely metabolized by day 3.       metabolites,
on the other nand, persisted at significant  levels in  most   rgans  for up  to
6 days.  Additional analysis by a colonmetric method  der  ^trated that  the
organs also contained large amounts of  free  carbon disui-u.de  on the first
and second days of the experiment (56 and  115 ug/g,  respectively).  Carbon
disulfide accumulated in the lungs  (owing  to ziram in  ^he other organs and
tissues) and was eliminated in expired  air.  In addition  to  carbon disul-
fide, the expired air also contained small amounts of  dime thylamine.

      In other studies, unspecified doses  of ^^S-ziram were  administered
orally to rats (Izmirova and Marinov 1972, Izmirova  1972,  both reported  in
Hayes 1982).  The animals eliminated a  portion  (the  amount  could not  be
determined from the literature) of  the  administered  dose  in  the feces,  57%
of that portion was unchanged ziram, and the remainder consisted of 5
chloroform-soluble metabolites.  The majority of  the administered  dose,
however, was metabolized to 5 water soluble metabolites which were excreted
in the urine The five chloroform—soluble metabolites were also detected  in
the gastric contents (among other locations), demonstrating  that a part  of
the breakdown of ziram occurs before absorption (Hayes 1982) .   The differ-
ences in the oral and intraperitoneal LD5Q values for  the  compound also
suggest this (Table 3).

      Ziram and similar dithiocarbamates are probably  metabolized  princi-
pally by the liver microsomal mixed function oxidase  (NTP 1983).  Neal  et
al. (1977, as reported in NTP 1983) have suggested that the  known  impair-
ment of microsomal drug metabolism by sulfur—containing compounds,  and
especially carbon disulfide, is due to  the binding of  an  active form  of
sulfur to the microsomal and cytochrome P450 systems.
      2.  Lethality

      Lethality data  (Table 3)  indicate  that  ziram  is  of moderate  to  high
acute oral toxicity,  according  to  the  scale of  Gosselin et  al .  (1977)    The
higher toxicity of the compound via  intraperitoneal  injection  compared  to
oral administration suggests  that  absorption  of oral doses  is  relatively
slc'y and/or incomplete (Hayes 1982).   In another study, 8 of 10 rats  died
after being fed 6000  ppm  ziram  for 14  days, while only 1 of 20  died after
being fed 5000 ppm for 13 weeks (NTP 1983).   Mice survived  feeding of 5000
ppm for 14 days, but  10 of 10 fed  10,000 ppm  died on days 5, 6,  or 7  of
treatment (NT? 1983)   Sixteen  of  20 mice  diea  during  weeks 3,4,5 and  3
of 13 ffeess treatment with 5000 ppm  (NTP 1983)
      Subchronic exposure of  8  raboits  to  dust  containing  14  71 ^ 1.65
      ziram 4 h/ day  for 1 month resulted  in  4 deaths  (Enikeev 1967,  as
reported in Chem Abstr 72 35486o) .  When  the concentration was reduced  to  5
mg/m3 only 2 of 10 rabbits died following  4  months  exposure,  4 h/day.
Ingestion of 0 5 liter of ziram was fatal  to a  man  within  a few hours.
Clinical findings included focal  necrosis  of the mucosa  of the small
intestine, congestion ana microscopic  edema  of  many organs, diapedetic

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                          Table 2   Distribution  of 71rara. TMTD   and  DMA Salt  of  DMDTCA*  In the  Organs

                               of  Albino Rats foil on Ing a Single Administration of 500 fig/kg 71mm
Time elapsed
after adminis-
tration of
tho prcfnration

10 ii i i tcs
16 houv
21 hours
2 dnys
3 days
6 days

30 minutes
16 hours
24 hours
2 d n y s
3 dnys
6 days

30 minutes
16 hours
24 hju-s -
2 dnyci
3 days
6 dnys
Intestine

9 6
35 6
48 3
2 6
2 86
0 77

0 6
3 57
7 9
7 96
5 57
4 93


4 77
3 45




+ 0 45
+ 0 67
i 1 04
± 0 27
1 0 27
±014

i 0 06
i 0 32
i 0 23
+ 0 27
+ 0 37
i 0 22

0
± 0 55
±013
0
0
0
Blood

10 » 0 96
24+0 24
3 44 + 0 41
2 8 ± 0 21
~ 0
0

0
0
0 43 ± 0 04
0 67 ± 0 02
0 5 ± 0 03
0 3 ± 0

0
4 0 ± 0 24
1 7 i 0 12
1 67 ± 0 09
1 67 ± 0 08
1 0 + 0 05
Liver
Zlram
26 2 + 072
5 35 ± 0 5«
35+03
6 8/ + 0 36
2 25 ± 0 16
1 25 ± 0 09
TKTO
0
0
5 13 ± 0 21
10 1 ± 0 35
3 84 + 0 23
3 5 ± 0 36
DMA salt of
0
1 87 ± 0 09
0
2 94 + 0 29
1 63 ±0 09
09 + 0
Spleen
. !'«/«.


6 8 ±
7 3 ±
5 8 i

. I'g/g.


60 +
10 9 +
98 +
8 86 ±
DMDTCA

0 85 +
13 +
38 9 T
8 +
5 71 7
Tetramcthylthlouren
30 minutes
16 hour*
24 hours
2 doy^
3 days
6 days


1 73
3 7


0
0
±04
± 0 55
0
0
No data
No date
No data
No data
No data
No data
0
0 8 ± 0 08
0 93 7 0 06
1 0? + 0 17
1 79 + 0 15
1 41 + 0 37

0 57 +
28 +
45 +
2 0 ^
8 57 ±
|ig/nU>
0
0
0 38
0 97
0 46
0
|ig/mL
0
0
0 39
0 97
0 44
0 25
I'g/g.l
0
0 04
0 12
1 5
0 29
0 23
Adrenals

0
0
2 38 + 0 19
35 5 + I 08
0
0
•
0
0
0
0
17 8 + 1 19
11 2 ± 0 86
ig/mlb
0
5 0 + 0 43
57+016
20 + 2 82
6 25 + 0 53
5 71 + 1 27
Kidneys

1 18 + 0 08
3 0 + 0 36
No data
0
0
03 +0

0
0
No data
6 67 + 0 74
7 15 + 0 37
2 4 ± 0 09

0
5 + 075
No dnta
0
0
1 6 ± 0 26
lungs

0
0
0
0
0
0

0
0
0
0
0
0

0
5 45 J. 1 07
47 5 ± I 41
60 8 ± 1 97
67 4 ± 7 15
™ + 2 75
Urine

No
No
No




No
No
No
22 6
34 0
1 02



Mo
5 7
3 8
0 47

data
data
data
0
0
0

data
data
data
+ 1 02
± 0 90
± 0 09

0
0
dn t a
+ 1 47
+ 07
± 0 02
content, |ig/g
0
0 0«
0 4
0 51
0 26
0 76
No dnta
No data
No data
No data
No data
No data
No data
No dirt a
No dtta
No d« t a
No d; t»
No dnta
No dita
No data
No dnta
No d n t a
Mo dn t n
No dnta
No
No
No
Ho
Ho
No
datr
dull
dati
dati
da In
da t K
     TMTP " tetramethylthlnram dlsnlflde, DMA  talt of DMU1CA = dimethylamlnc  salt  of  dlmethyIdlthlocarbnmlc  acid

     bUn!t designations have been changed from  those  stated  In the  tianslated  article  (|ig/g. m,/'"g  for  rlrnm   pg/I,  |ig/ml
for DMA salt of DMDTCA) In tho belief that the  translation was in error   The  translated  unit designations  for T'flD  and
tetramcthyllhloorea appear to ba consistent with  the  dnta presented

Source   Vekshtein and Khltsento 1971

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                                        1-1
hemorrhages ,
alveolar and
Species
Rat
Rat
Rat, male
Rat, female
Rat
Rat
Mouse
Mouse
Mouse
Mouse, male
Mous e
Mouse
Rabbit
Raboit
Rabbit
focal atelectases, acute emphysema, and desquanr -a of
oroncaial epithelium (Bulkan 1974, as reported 3ayes 1982).
Table 3. Lethality of Ziram
Route
Oral
Oral
I. P. a
I. P.
Inj ection
Inhal.b
Oral
I.V.c
I. P.
I. P.
Inj ection
Inhal.b/2 kr
Oral
I. P.
Inj ection
LDfO (mg/kg)
500
1400
23
33
1340
1230
480
18
17
73
220
1056d
400
5-50
270
R.^ Terence
FAO/Y7HO (1965, as
reported in Fishbein
1976).
Hodge et al. (1952, as
reported in Fishbein
1976) .
Hodge et al . (1952. as
reported in Hayes 1982) ,
Hodge et al. (1952, as
reported in Hayes 1982) .
Ryazanova (1967b, as
reported in Chem Abstr
71 2469z) .
Lewis and Tatkin (1980).
Lewis and Tatkin (1980) .
Lewis and Tatkin (1980).
Kligman and Rosenweig
(1948, as reported in
Hayes 1982) .
Hodge et al . (1952, as
reported in Hayes 1982) .
Ryazanova 1967b, as
reported in Chem Abstr
71 2469z) .
Enikeev (1967, as reported
in Chem Abstr 72 35486b).
Brieger and Hodes (1949,
as reported in Hayes
1982)
Hodge et al. (1952, as
reported in Hayes 1982)
Ryazanova (1967b, as
reportea in Chem Abstr
71 2469z) .
a Intraperitoneal
b T—I. -1 * *. -._
  A *Hi t* A <* «. Jk w A*
c Intravenous

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                               15
3.  Carcinogenicity

a.  Type of Test   Carcinogenicity

    Species   F344/N rats, 5 weeks old, 50 males  an    0  females/group
    Dose/Route   0, 300, or 600 ppm 2iram  in  food  -jr  103 weeks.
                 The average daily consumption of  ziram  by  low-  and
                 nigh—dose rats throughout the c_jor part of  the  study
                 was about 11 and 22 mg/kg for males and 13 and  26
                 mg/kg for females.
    Results   The rats were observed twice daily  for signs  for morbidity
              or mortality,  clinical  signs,  body  weights,  and feed
              consumption were recorded monthly.   The  animals were
              killed on days 729-745,  and  all were necropsied and
              examined histopathologically.   Survival, feed comsump—
              tion, and mean body weights  of  rats  of each sex were not
              adversely affected by the treatment.  The  rats could have
              possibly tolerated higher doses.

              The only statistically significant  tumor incidence  in this
              study was the increased  incidence of C-cell carcinomas in
              the thyroid of the high  dose male rats.  Fourteen percent
              (7/49) of the animals of this group  had  the carcinomas,
              compared to 4% (2/49) in the low dose group and 0%  in the
              control group (P < 0.05).  There was also  a significant
              cose—related trend for male  rats with with C-cell  carcinomas
              (P < 0.01) and for males having either C-cell carcinomas
              or C-cell adenomas (P <  0.05).  Neither  C-cell adenomas nor
              C-cell carcinomas were were  significantly  increased in female
              rats.  The high-dose females exhibited a significant decrease
              in fibroadenomas of the mammary glands (P  < 0.05).  Also
              observed in the thyroid  of both males and  females, but
              either not dose—related  or not  statistically  significant,
              were C-cell hyperplasia, thyroglossal duct cysts,  and
              follicular-cell adenomas or  carcinomas.  The  investigators
              concluded that under the conditions  of this study, ziram
              was carcinogenic for male F344/N rats (OTP 1983a).
b.  Type of Test   Carcinogenicity

    Ssecies   Random-bred rats, 60

    Dose/Routg   70 ag ziram/kg in >vater twice weekly by  stomach  tube
                 for 22 months (ziram, 90.5°o pure).

    Controls   Untreated, <*6 rats
    Results   Ten of 60 rats survived for 22 months and 4 developed
              tumors (2 malignant hepatomas and 2  fibrosarcoiaas)
              (p < 0.01), one of the 46 surviving  controls developed a
              fibrosarcoina  (Andrianova and Alekseev 1970, as reported
              in IARC 1976) .

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                               16
c   Type of Test   Carcinogenicity

    Species   Rats, 48 random bred

    Dose/Route   15 mg z irani (90.5% pure) administer   _n a
                 subcutaneously implanted 250 mg pa_  fin pellet.

    Controls   Not implanted with paraffin pellets

    Results   Ten rats survived 22 months and 3 developed tumors
              (1 hepatoma, 1 fibrosarcoma, and 1 lymphosarcoma of
              the intestine) (p < 0.02).  No tumors were observed
              at the site of implantation.  One of 46 controls that
              were still alive at 22 months developed a fibrosarooma
              (Andnanova and Alekseev 1970, as reported in IARC 1976).


d.  Type of Test   Carcinogenicity

    Species   Rochester rats, 25 males, and 25 females

    Dose/Route   0, 25, 250, or 2500 mg ziram/kg of
                 diet for 2 years (purity of ziram not specified).
    Results   Eleven tumors were found in the treated rats which
              included 3 malignant tumors of the pituitary and
              2 thyroid adenomas in the high dose group.  One
              animal in. the low dose group had a hyperplastic
              thyroid.  Seven tumors developed in the control rats,
              bnt their locations were not specified (Hodge et al.
              al. 1956).  The tumor incidence was not dose-related
              and morphologically similar tumors had been found in
              the two-year old animals, therefore, the investigators
              concluded that ziram is not carcinogenic.


e.  Type of Test•  Carcinogenicity

    Species   B6C3F1 mice, 6 weeks old, 50 males and 50 females/group

    Dose/Route.  0, 600, or 1200 ppm ziram in feed for 103 weeks.
                 After the first half-year of the study the average
                 daily consumption of ziram was 196 mg/kg for male and
                 248 mg/kg for female mice of the high dose groups.
                 The corresponding averages for males and females
                 of the low dose groups were 122 and 131 mg/kg,
                 respectively.

    Results   The  animals were observed twice daily for signs of
              moroidity or mortality and clinical signs, body weights,
              and  feed consumption *ere recorded monthly.  The mice
              were killed on days 729-742.  All animals were necropsied
              and  examined histopathologically   Although survival of
              the mice was not affected by ziram treatment, the mean
              body weight gain was depressed by approximately 15—20%
              in treated males throughout the study, and in high-dosed
              females, after week 80.  In contrast to the rats in this
              study (Section l.C.S.a), the mice probably could not have
              tolerated higher doses.  The incidence of alveolar/

-------
                              17
              bronchiolar adenonas was significantly (P   0 05)
              increased in high dose female mice (cont  ,, 2/50, 4°?>,
              low-dose,  5/49,  10%, high-dose, 10/50, "  )  #-ith an
              equally significant dose-response trer    The combined
              incidence of alveolarbronchiolar ader~  > or carcinomas
              in female mice of the high—dose gron^  ,as significantly
              higher than that of the controls (P   0.05)  (control,
              4/50,  8%.  low-dose, 6/49, 12%. hig -dose, 11/50, 22%),
              and showed a significant positive trend (P < 0.05).
              The increased incidence of lung tumors in male mice was not
              statistically significant.  Pulmonary adenomatous hyper-
              plasia was observed in both control and treated male and
              female mice.  This hyperplasia, however, was consistent
              with that caused by chronic Sendai infection which had been
              diagnosed in untreated animals from the same animal shipment
              and present in the same room as the experimental animals.
              Six of the high-dose females with adenomatous hyperplasia
              had pulmonary tumors, whereas  4 of the 24 high-dose females
              without pulmonary adenomatous hyperplasia also had pulmonary
              tumors.  Also observed in females, but not in males, at
              increased incidences were malignant lymphomas (not statis-
              tically significant at P = 0.5), malignant lymphocytic
              lymphomas (P < 0.05 increasing trend), and lymphoid
              hyperplasia (controls, 0/50, high-dose, 7/50, 14%).  The
              investigators concluded that ziram was not carcinogenic in
              male mice, and that the interpretation of the increase in
              lung tumors in female mice is complicated by the intercurrent
              Sendai virus infection (NTP 1983).

f.   Type of Test   Carcinogenicity

    Species.  (C57BL/6xC3H/Anf)Fi and (C57BL/6xAKR)Fl mice, 18 males
              and 18 females per strain
    Dose/Route   4.6 mg/kg, commercial ziram in gelatin, was
                 administered by gavage when animals were 7 days
                 of age, and the same dose, not adjusted for
                 increasing body weight, was administered daily for
                 up to 4 weeks of age.  During the time that the
                 animals were between 4 and approximately 78 weeks
                 old the compound was administered orally at the
                 rate of 15 mg/kg of diet.

    Controls   Untreated or received gelatin only, 79-90 mice of each
               sex and strain
    Results   tfhen compared to controls, tumor incidences *ere not
              significantly greater (p > 0.05) for any tumor type in
              any sex—strain subgroup or in the combined sexes of
              either strain (Innes et al. 1969, tfTIS 1969, as
              reported in IARC 1976) .


g.   Type of Test   Carcinogenicity

    Species   Strain A, 82 mice, and C57BL, 54 mice

-------
                                     IS
          Dose/Route   75 ng z iran/hg by stomach tube for 20    .^s
                       (purity of ziram unspecified).

          Results   The animals were killed 6 months after    3 beginning
                    of the experiment.  42/82 (51%)  (stra    0 and 5/54
                    (7%)  (C57B1) of the treated animals d  eloped lung
                    adenomas compared to 23/54 (43%) anr  j/28 of the
                    controls (p > 0.05) (Chernov and EL .tsenko 1969,
                    as reported in IARC 1976).


      h.   Type of Test   Carcinogenicity

          Species   (C57BL/6xC3H/Anf)F! and (C57BL/6xAKR)Fl mice,
                    18 males and 18 females per strain

          Dose/Route   46 4 mg commercial ziram/kg administered in a
                       single subcutaneous injection in gelatin on
                       the 28th day of life.

          Controls   141, 154, 161, and 157 untreated or vehicle-
                     inj ected mice.

          Results   Animals were observed until they were approximately
                    78 weeks old.  When compared to  controls, tumor
                    incidences were not significantly greater (p > 0.05)
                    for any tumor type in any sex-strain subgroup or in
                    the combined sexes of either strain (NTIS 1969, as
                    reported in IARC 1976) .  The IAJRC Working Group noted
                    that a negative result obtained  after a single s.c.
                    injection may not be an adequate basis for discounting
                    carcinogenicity.

      Hemminki et al.  (1980) tested ziram for alkylating ability and found
10 activity.  Both a synthetic (4-(p—nitrobenzyl)—pyridine) and a
Biological (deoxyguanosine) nucleophile were used in the alkylation
reactions, but there is no evidence that an. activation system was used.
      4.  Mntagenicity

      z.  Micrcbiai and Animal Studies

      The results of mutagenicity studies on ziram are conflicting.  For
example Hedenstedt et al.  (1979) demonstrated the mutagenicity of ziram  in
Salmonella typnimurium strains TA 1535, TA 98, and TA 100 with and without
metabolic activation, ffhile DeLorenzo et al. (1978) reported the compound
to be negative in the same strains  (Table 4).  The reason for tnese
differences in not clear.   Both groups of investigators reported negative
mutagenicity for strains TA 1537 and TA 1538.  Monya et al. (1978) also
reported, in an abstract,  that ziram was mutagenic in TA 100, but not  in TA
1537, TA 1538, and TA 98.   Kada (1980) reported that ziram is mutagenic  in
TA 1535 and TA 100, but not in TA 1537 and TA 98.  There are also
conflicting reports for the mntaggiiic activity of ziram in Drosophila
(Table 4).

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                                           Table  4   Mntasenlc1ty Testlag of Zlrsm
Species/
Call Systea
Salaonella tvphianrioa
TA 1535
TA 1535
TA 1537
TA 1538
TA 98
TA 98
TA 100
TA 100
TA153J TA1537
TA1538 TA98,
TA100
TA 100
TA1537 TA1535
TW8
rUOO TA1535
TA98 TA1537
TA 98
TA 98
TA 100
TA 1535
TA 1535
TA 1537
Eseherichia coll
IK hcr-
CAL as
Liquid holding
test
Strop, resist
5-JTT resist
Bacillus snbttlis
aec- assay
H17 Sao*
B45 8ec-
strain D4
Verticilllaa dial se

Honse bone

Barley seeds
Drosophila aeianocastar
Orosoohlla 2ela&ozaster

Drojooh-.il aelanoiaster

Rat tayoocytes
Zlrm
S-9 Concentration

10, 50 100 jig/plate
+ 10 50, 100 |ig/pl»te
10. 50. 100 ,ig/pl»te
10 50 100 i»g/plate
10 100 (ig/plate
+ 10, 100 fig/plate
5, 10 50 |ig/plata
+ 5. 10, 50 |ig/plata
- and * 10-1500 ilg/plate
Not itatad Not stated
Not stated Not stated
Not itatad Vot stated
Not itatad Not stated
+ 100 pg/plateb
0 3 10 100
333 tig/plate
+ ami - 33 ng/plata»
* 33 and 100 |ig/plateb
0. 3, 10. 33 100
333 |ig/plata
+ and - 0. 3 10 33
100, 333 jig/plateb
Not itatad Not stated
Vot stated Vot stated
Not stated Vot stated
Not stated Not stated

riot stated Not stated
* 06 (ig/disc
OS us/disc
500/1000 jpm (optimal or
Vot clear

ot .pp ica s ag g o 7 »j

Vot tpplieabla Vot stated
Vot applicable Vot stated
Vot applicable Vot stated

Vot applicable 0 OOJ"V

Vot applicable 1 0 and 10 pg/oL
Results

Fos (p < 0 05 s t 10 11$
p < 0 001 at 100 |ig)
Poi (p < 0 001 at 10 tig)
Nag (p > 0 05)
Veg (p > 0 05)
Pos (p < 0 05 at 100 |ig)
Pos (p < 0 001 at 10 |ig)
Pos (p < 0 001 at 5 |ig)
Pos (p < 0 001 at 5 |ig)
Nag
Poa
Nag.
Poa
Nag
Pos And Equivocal
Na,
Pos
Pos
Nag
Nag
Nag
Veg
Nag
Nag

Poi
Pos
Pos
Nag
?os
" 3t


Pos (3 5% chromosomal
aberratioua)
Poa for recessive
lethal I
lethals ^
Nag for recasaiva
lathals
62% and 99\ inhibition
respectively of Critiatad
•hynidlne uptake
Reference

Hedenstedt at al 1979
Hadenstadt at al 1979
Hedenstedt at al 1979
Hedenstedt at al. 1979
Hadanitedt «t al 19T9
Hedenstedt ot al 1979
Hedenstedt at al. 1979
Hedenstedt et al 1979
DeLorenia at al. 1978
Koriji at al 1978
Honya at al 1978
Eada at «1 1980
STada at tl 1980
NT? 1983b
HI? 1983b
NTP 1983b
NTP 1983b
tfTP 1983b
NTP 1983b
Iida at al 1930
Faarig 1974

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                                     20
      Kada (-1930) and Fahrig (1974) reported that ziram  is nc  -utagenic  in
E._ coli.  and Fahrig (1974) and Sieoert et al.  (1970) reporte   negative
results in a caitotic gene conversion test in S  cerevislae
      b.  Human Studies

      Abnormal chromosomes or chromatids were reported  in 5.9% of  cultured
lymphocytes of 9 workers (4 males working in a ziram  store and 5 females
employed as packers of the preparation) with 3 to 5 years of occupational
exposure, compared to 0.75% abnormalities in similar  cells from controls
(Pilinskaya 1970).  The levels of ziram in the store  and packing areas of
the workplace averaged 1.95 and 3.7 mg/m^, respectively,  but reached 71.3
mg/m^ in isolated cases.  Statistically significant abnormalities, were
observed in an in vitro study with cultured human lymphocytes at concentra-
tions of 0.06, 0.015, and 0.003 ppm, but not at 0.0006 ppm.  These changes
were significant at the p < 0.001 level and were dose-related (Pilinskaya
1971).  It was noted that at 0.003 ppm the changes were quantitatively
similar to the results found in vivo in the workers whose condition was
described by Pilinskaya (1970).  Pilinskaya, in his 1971 study, stated that
the types of aberrations induced in vivo and in vitro were also similar.
Ziraia exhibited a tendency for selective damage to chromosome 2.
      5.  Teratogenicity/Reproductive Effects

      a.  Type of Test   Teratogenicity/Reproductive Effects
          Species   Rats, male and female

          Dose/Route   50 or 10 mg ziram/kg body weight per day,
                       orally for 2, 4, or 6 months.

          Results   A series of experiments was performed on the
                    treated rats

                    (1) No effect was noted on reproduction during
                        the first two months of treatment.
                        Administration for longer periods resulted
                        in changes in both the mothers and the
                        offspring.  Six months after the beginning of
                        treatment five of the test females died, while
                        the two survivors became pregnant later than
                        the controls.

                    (2) The animals were mated at the end of the sixth
                        month of ziram treatment.  \11 females treated
                        with 50 mg/kg were infertile, wnils treatment
                        with 10 mg/kg "postponed" the date of pregnancy
                        in some of the test females.  Treated offspring
                        of treated parents exhibited reproductive changes
                        earlier than the parents.

                    (3) The offspring of rats treated for 2-4 months with
                        50 mg ziram had developmental anomalies.

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                                     21
                    (4) Untreated offspring  of  treated  parer    ,vere  mated
                        and produced 5  litters    One  of the    offspring
                        had developmental  anomalies  and 1    _er  had
                        decreased weight gain  (Ryazanova "  57a).
      The following effects of ziram were breifly  described  in  abstracts  or
reviews    embryotoxic to rats at a dose of 0.03 LJ>50  (Chepinoga  et  al.
1970, as reported in Chem Abstr 74 123308s),  embryotoxic  to  97.8,  22.6, and
4.4% of the rats tested with 250, 42, and 14  ng/kg  of  ziram,  respectively
(Antonovich et al. 1972, cursory translation),  and  teratogenic  and gonado—
toxic to rats, mice, and rabbits at unspecified doses  (Antonovich  et  al.
1972, as reported in Chem Abstr 73 24925s), caused  testicular atrophy in
some rats fed ziram for 2 years in concentrations  of 25-250  nig  and 2500
mg/kg of food (Hodge et al. 1956. as reported in Stenberg  and Rybakova
1967), reduced sperm motility in rabbits exposed to 5.0 mg/m^ ziram  dust  4
hours per day for 4 months (Enikeev 1967, as  reported  in  Chss: A.bstr
72 35486b), and substantially reduced the fertility and fecundity  of  female
mice when administered in doses of 50 mg/kg/day for 15 days  according to
Ghezzo et al. (1972, as reported in IARC 1976)  or  for  50  days according to
Ghezzo et al. (1972, as reported in NAS 1977).  No  effect  on the  fertility
of male mice was observed.  Ziram has also caused  the  following teratogenic
and reproductive effects in chickens:  stopped  egg production within  2 days
when administered in the diet at 200 ppm and  caused marked ovarian atrophy
after 7 days (Weppleman et al. 1980),  exhibited an LDso  of  0.031  mg/kg in
chick erabryos, and caused multiple hemorrhages  in  the  head and  trunk,  non-
development of the rostrum, legs, clawsr eyes,  and  less frequently of the
midbrain, disorders of the vascular walls, connective  tissue  proliferation
and changes in cartilaginous and osseous substances [Olefir  and Vinogradova
1968, as reported in Medlars (TOXBACK 65) 1983]; and retarded testicular
development in chicks of domestic fowl (Thornbex's 909 cockrels)  and  pro-
duced degeneration in the testes of adults administered 56 mg/kg  or 4 to  18
weeks (Rasul and Howell 1974)   It should also  be  noted that  the Office of
Pesticide Programs file contains a report for a negative  teratogenicity
study, claimed as confidential business information by the submitting com-
pany.
      6.  Other Effects

      a.  Animals

      Examples of non—oncogenic  caronic,  subchronic,  and  suoacute  effects
of ziram are listed in Tables 5  and 6.  Various  other  effects have been
described and include   the  inhibition of mitochondrial dehydrogenases in
yeast (Briquet et al. 1975), decreased hepatocyte  cytoplasmic RNA  and
decreased activity of liver  oxidation-reduction  enzymes in mice  receiving
maximum tolerated doses (Chernov et al. 1972,  as reported in Chem  Abstr
79 62413b), degenerative changes in the salivary glands, kidney, and liver
of rats [Mannari et al.  1974,  as reported  in DIALOG  (EXCERPTA  MEDICA)
1983], moderate contact hypersensitivity  in  guinea pigs (Matsushita et al.
1978, as reported in Chem Abstr  90 34683y),  moderate  eye  irritation in the

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                          Table  5   Effects  of Ziiora  Following  Subohronio  or  Subacnte  Exposure
  Species
                Roate
                                     Treatment
                                                          Results
                                                                                        Reference
    Rat
    Rat
    Rat
                 Orel      0, 300,  600. 1200.  2500, or
                          5000 ppm in diet  for 13 irks
                 Oral      Doso  (not  stated) administered
                          for 7 «k«
                Oral      413 mg/kg/day for 3 days
                                              Dody wt gain depressed more
                                              than 16% in males receiving
                                              1200-5000 ppm, and In females
                                              receiving 600-5000 ppm

                                              Ziram had toxic effect on
                                              liver and kidneys, decreased
                                              body wt, stimulated activity
                                              of p-glucoronidase and aryl-
                                              sulfatase   No changes in thy-
                                              roid

                                              Decreased excretion of urinary
                                              5-hydroxyindoleacetio acid
                                                                                             NTP 1983
                                              1969. as
                                 reported in Chem Abstr
                                 71 69657c
                                 Khaiklna ct at  1976, as
                                 reported in Chem Abstr
                                 85 73l18r
   Hi co
  Rabbit
Guinea Pig
                Oral      0, 300. 600, 1200. 2500 or
                          5000 ppm In diet for 13 «rks
Inhalation   (a) 14 7 mg/m1 dust 4 hr/day
            ,for 1 mo or (b) 5 mg/rn' dust 4
             hr/dny for 4 mos         •
                Oral
             4 mg/kg/day for 120 days
Dody wt gain depressed 26% or
more in males and females
receiving 2500 or 5000 ppm

50 and 20% died from exposures
(n) end (b), respectively
Survivors had increased reflex
tines and wt loss.

Increased free hlstamine in
blood. Inhibited histonminose
activity and decreased
hlstamlne-blndlng capacity of
                                                                                            NIT 1983
                                                                                            Enikccv J9fi7  as teported
                                                                                            in Chem Ahitr 7? 35486b
Khalklna et nl  1976, as
reported in Chem Abstr
85 73138r

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                                      Table 6   Effects of Ziram following Chronic Exposure
Species    Route
                               Treatment
                                                          Results
                                                                                               Reference
  Rat
  Rat
Oral
            Oral
  Rat
 House
           Oral
           Oral
Rabbit
           Oral
2500 and 250 ppm/day la diet
(-125 and 12 5 mg/kg/day) for
        0,  300,  or  £00  ppm la  feed  for
        2 yrs
         2  5 rag/kg/day  for  9  mos
2500 ppm produced growth retardation and
abnormal reflex   Doth doses produced
non-dose-rel»tod atrophy of testes and
hypertrophy of the thyroid

Doth doses produced. In males, two-fold
Increase in incidences of thyroid C-cell
hypcrplasift anil testicnlar hypcrplasla
over those of controls. In females, both
doses produced Increased Incidences of
retlnopathy of the eye,  Retlnopathy was
also seen in high dose males   None of
the effects were dose-related
                                 Transient immnnologlcal
                                 noted
                    0, 600 or 1200 ppm
                    {wo years
                            in  feed  for,
        15 or 30 mg/kg/dey  in  diet  for
        8 no s
                                                                              "changes" were
                                 In males, low dose produced increased
                                 Incidence of corpora amylacca of the
                                 brain (no data for high dose), in
                                 females  high dose produced Increased
                                 incidence of cystic follicles of the
                                 thyroid, both doses produced non-dose-
                                 rclnted increased incidences of cystic
                                 hyperplasla of the endonetrlal gland

                                 Doth doses produced decreased alkaline
                                 phosphatase
                                                                                                Hodge et al  1956, as reported
                                                                                                In Hayes 1982
                                                                                                NIP 19R3
                                           Shtenbcrg et at  1972, as
                                           reported in Hayes 19B2

                                           NIP 19R3
                                                                                                GhcJTO et nl  1972, as
                                                                                                reported In Chen Abstr
                                                                                                78 93310f
  Dog     Oral(T)    0 5, 5 0. and 25 mg/kg/day for
                    1 year
                                         25 ng/fcg  produced  convulsive  seizures
                                         and  death
                                                                            Hodge et al   1952,  as reported
                                                                            in Flshheln 1976

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                                     24
rabbit (Klignan and Rosenweig, as reported  in Hayes  1982),  le   openia  in
rabbits (Korablev 1965, as reported  in Pilinskaya  1971),  ery~_rocytopenia
and decreased hemoglobin in rabbits  and/or  guinea  pigs  [TaL  .ishvili  and
Nadirashvili 1980, as reported in MEDLARS  (TOSLINE)  1983],    i  increased
blood sugar, decreased tissue glycogen content,  and  loss  r - mobility of
hind limbs  in rats given 10 mg/kg i.p.   [Daily  et  al.   1TJ9,  as  reported in
MEDLARS (Toxback 65) 1983],  In addition,  ziram, like mc^t  dithiocarba-
mates, induces the accumulation of acetaldehyde  in the  olood  of  rats
receiving ethanol at the same time (van Logten  1972,  is reported in IARC
1976) .  This is not surprising, considering  the  structural  similarity  of
ziram to disulfuram (Antabuse) which  is known to suppress the second step
of ethanol  oxidation through blockage of aldehyde  dehydrogenase  (DeBruin
1976) and is used as an adjunct in combating alcohol  addiction.   The pos-
session of  a substituted N-atom appears  to be a  structural  requirement for
the alcohol intolerance phenomenon elicited  by  these  compounds.

      The mildew inhibitor Vancide 512 (90%  ziram  and 7.8%  zinc  salt of  2-
mercaptobenzothiazole) was tested by  the U.S. Army (1969)  in  skin and  eye
irritation  tests.  The commercial grade compound did not  cause  primary
irritation  of intact or abraded skin when  applied  for 24  hours  as either
the commercial powder or the commercial grade in acetone.   When applied  to
the eye, Vancide 512 powder caused severe  injury to  the cornea  and  to  the
conjunctiva, a l°b suspension of commercial grade Vancide  512  in propylene
glycol caused slight to moderate eye damage.
      b.  Humans                       •

      The majority of the human toxicity. and  epidemiological  data  are  from
Russian reports.

      Collective-farm female workers who used  a 707o  formulation  of  ziram  to
treat seed, suffered various difficulties, which  included  irritation of the
skin, nose, throat, and eyes, gastritis, reduced  hemoglobin,  vegetodys-
tonia, and slight hematological changes.  Several of  the women had  to  be
hospitalized 2-4 days following about 5 hours  of  exposure  to  the compound.
Some workers lost up to 4 days of work, but all recovered  completely
[Chernov 1968, as reported in Hayes 1982, and  in  MEDLARS (TOXBACK  65)
1983].  Less severe irritation was induced in  factory workers where levels
of ziram in the air ranged from 0 77 to 3.7 mg/m^ (Martson* and  Pilinskaya
1971, as reported in Hayes 1982).  Exposed workers in another study com-
plained of dermatitis, rhinitis, and conjunctivitis  of  an  allergic  nature
(Pilinskaya 1970).  Of 40 Italian workers, 22  complained of ear, nose,
throat, and epigastric pains.  They also had  bloody  sputum, nyperemia  of
the mucosa, ulcerations of the nasal septum,  pnlegm  in  the pharyngeal  pas-
sage, and some had difficulty in breathing. The symptoms were attributed  oy
the investigators to the irritative action of  ziram  powder, and  not to an
allergic reaction [Anneli Ducci 1966, as reported in  MEDLARS  (TOXBACK  65)
1983],  Another group of workers having prolonged occupational contact with
ziram had shifts in blood cholinesterase and  pseudocholinesterase  activi-
ties.  A tendency toward accumulation of acetylcholiae  in  the blood, along
with changes in the bioelectric activity of the muscles during voluntary
motion, indicate that ziram may be a cholmesterase  inhibitor in man and

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                                     25
that tnese procedures appear to be sensitive  enough  to  permi"  -airly detec-
tion of toxic effects of zirain [Komarova  and  Zotkina 1971,  ~   reported in
MEDLARS (TOSBACS 65) 1983] .

      Aplastic anemia and pseudotumor  cerebri (benign in4"  ^cranial  hyper-
tension) were diagnosed in a 14-year-old  girl who  had b~  a repeatedly
exposed to a number of herbicides  and  pesticides  (inclining ziram)  through
working in the fields of a tobacco company  for several  months  and through
living next to a potato farm that  was  frequently  sprayed  (Jenkyn et al.
1979).  Zirao was only one of the  agents  to which  the patient  was exposed,
but the diagnosis is of particular interest since  the compound causes
suppression of the hematopoetic organs in animals  (see  Section I.D.d.a.,
Other Effects).

      Seiaiconservative DNA systhesis in human lyrapnocytes  was  inhibited  by
56% following in vitro treatment with  1 ug/ml ziram  (Rocchi et al.  1980).
UV-induced unscheduled DNA synthesis was  also inhibited, but only by 21°b.

      Most workers in a ziram production  plant had enlarged livers,  and
18/29 workers had elevated alkaline phosphatase,  lactic dehydrogenase,
guanase, fructose 1-phosphate aldolase, and amylase  activities (Levin et
al.  1973, as reported in Cheia Abstr 83 151604q) .
  E.  Environmental Effects

      1.  Environmental Metabolism

      The metabolism of ziram has been  studied  in  papaya  plants,  rice
plants, and groundnut plants.  Known  amounts  of  radioactive  ziram were
applied to the leaves of the papaya plant,  and volatile products  formed
from residues of the compound on the  plant  were  measured  over  a period of
14 days (Hylin and Chin 1968).  Significant amounts  of radioactively
labelled carbon disulfide and carbon  dioxide  were  measured,  as were trace
amounts of trimethylamine.  Although  ziram  (or  at  least its  DDC ions)  is
known to be absorbed by intact leaves,  it was not  determined in this  study
if the decomposition occurred on the  surface  of  the  leaves or  in  the  outer
cell layers of the leaf.

      Kumarasamy and Raghu  (1976) sprayed ziram  on 25 day old  rice plants
at concentrations simulating normal agricultural applications   The rice
seeds were washed and cut into pieces which were extracted at  different
times after application.  Twenty four nours after  spraying,  the radioac-
tivity in the seeas was 3.3?o of the administered dose.  \t eignt  days, the
uptake was 8.2% of the dose.  The conversion  products of  ziram in the  seeds
at 24 hours and 8 days (with respective percentages  in parentheses)
included the alanine (16.4, 9.3) and  B-giucoside (16.9, 18.4) derivatives
of dimethyldithiocarfaamic acid, thiazolidine-2-thione-4-carboxylic acid
(3.8, 6.2), and an unidentified divalent sulfur  compound  (9.0, 11.1)
Unconverted ziras (and/or possibly thiram)  accounted for  16  and 17 1% of
the radioactivity at 1 and  8 days, respectively.

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                                     26
      In another study in groundnut plants, the same degrada*   :. products
were isolated (Raghu et al. 1976)   Twelve days after  spray     95% of  the
35S taken up by the plant (1.2% of the 35S activity) was p:   ,nt in the
shoots, most of wnich was identified as the alanine and B-   _coside deriva-
tives of dimethyldithiocarbamic acid.
      2.  Lethality

      Lethal doses of ziram in environmental species are listed in Table 7.
In a review of the literature, Strufe (1968) observed that, at concentra-
tions of 1-10 ppm for 12 to 72 hours, ziram kills numerous  species of adult
fish in addition to those listed in Table 6.  Young fish are  somewhat more
sensitive (lethal doses range from 0.5-1.5 ppm)  (Deschiens  and Floch 1962,
Lloyd 1960, Gretillat 1961, Gretillat and Lacan  1964, all reported in
Strufe 1968).  Lethal doses in aquatic fauna (crabs, crayfish, frog larvae,
dragonfly larvae, mosquito larvae) appear to be  of the same order of magni-
tude (Deschiens and Floch 1962, Gretillat 1962,  both reported in Strufe
1968).


                  Table  7.   Lethality of  Ziram in Environmental  Species
Species
Length of    Toxic Dose
Expo sure
                                 Reference
                                        - FISH -
Crassium
auratusa
Tilapia melanopleuraa
Epiplatus st) a
5 hrs
                  5-10 ppm
   5  hrs     LD50 5-10 ppm
   5  hrs      LDso 0.5-0.75 ppm
Bleak (Alburnus alburnus L.)t>     96 hrs     LC(I)50° 3-4 ppm

                                     - CRUSTACEANS -

Mitpera sinipes                   96 hrs     LC(I)sod 0.4 ppm

                                      - MOLLUSCS -

Dreissena polymorpha                5 d      LC5Q  1«3 ppm
Gretillat 1961, as
reported in Strufe
1968

Gretillat 1961, as
reported in Strufe
1968

Gretillat 1961, as
reported in Strufe
1968

Linden et al. 1979
                                    Linden et al. 1979
                                    Hoestlandt 1972

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                                     27
Table 7.  (continued)
Species                          Length of    Toxic  Dose              Reference
                                 Exposure


                                     - WILD BIRDS -

Red-winged blackbird6
(Agelaius phoeniceus)                         LDfQ 100 mg/kg  (56-     Schafer  1972
                                              178, 95% conf.
                                              limits }

                                       - PLANTS -
Pistia stratiotes               Not  stated   LD^Q                    Gretillat 1961,  as
                                                                     reported  in  Strafe
                                                                     1968


     aTested an water.  No other conditions stated.

     ^Tested in brackish water under  static conditions  at 10°C.  Test
compound was mixture of ziram (22.5%) and carbendazim  (2.5%).

     C(I) = Initial concentration.

     ^Tested in brackish water under  static conditions  at 21°C.  Test
compound was mixture of ziram (22.5%) and carbendazim  (2.5%).

     eDosed by gavage
      3.  Reproduction

      No studies were found which would  indicate the reproductive toxicity
of ziram in environmental species.
      4.  Behavior

      No data were found.



      5.  Growth and Development

      Ziram has been shown to be an inhibitor of growth or metabolic
processes of bacteria.  Suzuki and Nakajima  (1967, as reported  in Chem
Abstr 70'26633d) demonstrated that 20 ppm of ziram completely inhibited the
growth of bacteria isolated from pulp white water, Hansen  (1972) tested the
antibacterial effects of ziram in 211 strains of bacteria  and concluded
that the compound has an innibitory effect, particularly in  the gram-
positive organisms, Vaishnav and Brown (1976, as reported  in Chem Abstr

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                                     28
91 187939g) reported tnat ziraia  (concentration  not  stated)  re  _;ed  the  02
consumption of cultures of a mixture of  oil—degrading bacter    zo nearly
zero, and Azad et al. [1971, as  reported in DIALOG  (CAB Abs   -cts 72-83)
1983] reported that ziram, tested at concentrations  rangir_  -rom 0.00005—
0.05%, depressed both, microbial  decomposition of  organic  _  -ter and
nitrification processes in loam  soil at  the higher  and n  -iun
concentrations.

      There is also evidence that ziram  reduces growta and  development  of
plants.  George et al. (1970) treated  seeds of  the barley variety C 164
with ziram at concentrations of  250 and  500 ppm for  1 and 2 hours.   Ziram
inhibited germination of the seeds by  60-97.5%  on day 5 after  treatment and
by 28-89.5"$ on day 10 after treatment.   The rate  of  inhibition was
proportional to concentration and duration of treatment.  Fifteen days
after treatment with 500 ppm, germination was inhibited by  20  and 28% for
the 1- and 2-hour treatment periods.   In addition,  all the  ziram treatments
markedly reduced the height of the seedlings to between 8.6  and 32.9% that
of the controls.  Similar, but less severe, effects  were  reported in a
later study in barley by Zutshi  and Kaul (1975).

      Ziram, at a concentration  of 0.16% active ingredient,  reduced the
number and size of fruits on apple trees, while the  foliage  remained
undamaged (Kirby et al. 1968, as reported in Chem Abstr 69  26234d),  and,
when sprayed on the pollen of peach trees at 0.1  and 0.2%,  reduced
germination [Pinzauti 1982, as reported  in DIALOG (CAB Abstracts 72-83)
1983].
      6.  Population and Community Effects

      No data were found.



      7.  Abiotic Effects

      No data were found.


      8.  Other Effects

          a.  Effect on Plants

              — At 10 ppm, ziram  is  toxic to  several  species  of  water
                plants including  Pistia  stratiotes  (Gretillat  1961,  as
                reported in Strufe 1968).  However, ziram applied  at
                molluscicidal concentration  [not  stated  in  this  paper, but
                Hadler (1982) reports that ziram  is effective  against most
                aquatic snails at 3-5 ppm in.  water] has  no  effect  on Lotus,
                Nvm-phaea, water grasses, and  reeds  (Gretillat  and  Lacan
                1964, as reported in Strufe 1968).

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                                     29
                Different species of algae are susceptible t   .ram and are
                danaged by the active ingredient at mollusc    lal
                concentration (Deschiens and Floch 1962, a    sported in
                Strufe 1963).
                Ziram, at 0 16% active ingredient, mere ..ad  russeting of
                the fruits of apple trees (Kirby et al. 1968,  as reported
                in Chem Abstr 69 26234d).
                Ziram, administered to peach trees during the  vegetative
                period, experimentally reproduced th.e characteristic
                symptoms of external necrosis which appear from November to
                January (Grosclaude et al. 1969, as reported  in Chem Abstr
                72.65880O .
      b.  Effects on Other Organisms

          - Nishiuchi and Yoshida (1972, as reported in Chem Abstr
            79 74562n) reported that ziram is toxic to tadpoles (no data
            available), and Zazhivilov [1972, as reported in MEDLARS
            (Toxback 65) 1983] found that, under experimental conditions,
            the compound inhibited the function of the epithelial cilia of
            the frog esophagus.

          - Ziram is reportedly somewhat repellent to wild pigeons (Becker
            1966, as reported in Chem Abstr 67 72803v), and reportedly to
            other species of wildlife (Soyez 1981, as reported in Chem
            Abstr 95 75491f).

          - At the dose recommended for spraying crops, ziram was slightly
            toxic to honeybees on ingestion, and more toxic on contact
            [Arzone and Vidano 1980, as reported in DIALOG (CAB Abstracts
            72-83) 1983]
  F.  Standards and Regulations

      No effect levels for ziram, as demonstrated in the rat and dog, are
12.5 and 5 mg/kg body weight, respectively, and a temporary ADI (allowable
daily intake) of 0.025 mg/kg for man was established and subsequently
lowered to 0.005 mg/kg on the basis of reported teratogenic, genotoxic, and
pre—carcinogenic properties (WHO/FAO 1967, 1970, as reported in Vetorazzi
1979).

      The use of ziram is permitted in the U.S. in rubber articles wnich
come in contact with food at levels not to exceed 1.5% by weight (USEPA
1980, as reported in USEPA 1983a)

      Tolerances for residues of ziram (calculated as zinc ethylenebis
dithiocarbamate in or on raw agricultural commodities are established in
the U.S  as follows   7 ppm in or on apples, apricots, beans, beets  (with
or without tops) or beet greens alone, blackberries, blueberries

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                                     30
(huckelbernes) ,  boysenbernes, broccoli, brussel  sprouts,  c   ;age,
carrots, cauliflower, celery, cherries, collards,  cranberri   ,  cucumbers,
dewberries, eggplants, gooseberries, grapes, kale, kohlrao-   .ettuce,
loganberries, melons, nectarines, onions, peaches, peanut"  pears, peas,
peppers, pumpkins, quinces, radishes (with  or without  tor  / ox  radish  tops,
raspberries, rutabagas (with or without tops) or rutaba;   tops,  spinach,
squash, strawberries, summer squash, tomatoes,  turnips  with  or  without
tops) or turnip greens, youngberries, 0.1 ppm in or or  almonds,  pecans
(USEPA 1980a, as reported  in USEPA 1983a) .
  G.  Other Relevant Information

      Alamanni et al. (1982, as reported in Chem Abstr 97  9056lp)  state
that ethylenethiourea (ETU) was present as a contaminant in  ziram  between
the concentrations of 0 57 and 0.82%.  ETU is reported to  be a mutagen,
teratogen, and carcinogen  (Lewis and Tatkin 1982) and is normally
associated with ethylene bis dithiocarbamate fungicides, not the N,N—
dimethyldithiocarbamate class of fungicides of which ziram is a member.
The possibility of an error in the abstract must be considered, especially
since this was the only reference found that links till and ziram.

      The EPA Catalog of Data Supporting Pesticide Registrations (USEPA
1977) contains a listing of information or tests submitted to the  USEPA
Office of Pesticide Programs Company Data Library.  The catalog is  indexed
according to chemical, formulation, and data type.  The contents of  the
ziram section of the catalog are summarized in Table 8.  Listed first are
the tests submitted for ziram as the single active ingredient or for a
product containing ziram as a single active ingredient.  Next are  tests on
ziram mixed with a second  active ingredient.  The data types include
product chemistry, residue chemistry, environmental chemistry, efficacy,
phytotoxicity, human and domestic animal safety, fish and  wildlife  safety,
benificial insect safety,  and accident exposure data.  In  Table 8  the
different formulations are grouped according to data type.

      It should be noted that this list was compiled in 1977 and does not
include more recent information.
 II.  Preliminary Risk Assessment

      Zinc, bis (dithmethylcaroaisodithioato-S, S')-,   (T-4)-
      CAS Registry Number   137-30-4

  A.  Exposure Assessment

      Ziram is produced and used in fairly hign volumes.  \ccording to the
aost recent data available, 1,880,000 pounds of ziran were produced in the
U.S. in 1981 (USITC 1982, as reported in USEPA 1983a).  Production of ziram
has been declining since 1979 when the reported production volume was

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                                   31

         Taole  8    Tests Saoaitted in Support of Ziram Registz -ion
Data Type
Formulation
Descr ptorsa
Product chemistry

   Physical-chemical
   properties

Residue chemistry
Efficacy
       -Ziram-


Technical chemical


Technical chemical


Dust

Wettable powder
                        Unspecified formulated
                           product
Wettable powder/dust
                        Unspecified formulated
                           product
Apples, cabbages,
   potatoes

Figs, strawberries

Raspberries, beans
   (green), cucumbers,
   strawberries,
   tomatoes

Almonds, beans  (green),
  cranberries, cucumbers,
  figs, strawberries,
  tomatoes
Almonds/shot hole
   fungus, apricots/
   brown rot, apricots/
   shot hole, beans
   (Blue!ake)/Sclerotina
   j>. clerotiorun,
   strawberries/gray
   mold, strawberries/
   strawberry fruit
   rot, peaches/peach
   leaf curl, raspber-
   ries/not specified

Almonds/almond scab,
   almonds/brownrot
   blossom blight,
   almonds/leaf blight,
   almonds/peach scab, •
   almonds/shot hole,
   apples/bullseye rot,
   blueberries/mummy
   berry, blueberries
   (low bush)/blossom
   blight, cranberries/
   cranberry fruit rot,
   peaches/leaf curl,
   peaches/shot hole,
   pecans/pecan scab
   pine trees/fusiform
   rust, strawberries/
   gray mold

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                                     32
Taole 8  (continued)
Data Type
     Formulation
Des  , ptors£
Environmental
   chemistry

Phytotoxicity
Efficacy
            -Ziram-(continued)

     Wettable powder/
        dust

     Unspecified formulated
        product

-Ziram _in Combination with. Maneb^-

     Dnspecified formulated
        product
Beans  (green),
   cucumbers,  tomatoes

Apples, peaches
Almonds/almond  scab,
   almonds/shot hole,
   peach.es/peach  leaf
   curl
Efficacy
—Ziram in Combination with Ferbam0—

     Wettable powder/dust
Almonds/shot hole;
   celery
          -Ziram in Combination with Zinc  2-Mercaptoben2othiazolate—
Product chemistry

   Physical-chemical
   properties
   Storage stability

Efficacy
Efficacy

   Sanitizer test
   for non-food
   contact surfaces

   Unclassified
   test type
     Wettable powder


     Wettable powder

     Technical chemical  (in—can
        paint preservatives)

     Wettable powder  (in-can
        paint preservatives)
     Wettable powder
     Wettable powder
                        Flowable concentrate
Unspecified bacteria


Mold, B. subtilisd.
   S^ faecalis. S_
   aureus, P, aerugi-
   nosa
Unspecified bacteria,
   mold
E. coli, S. cholerae-
   suis. S.. typaosa,
   S.. schottmueller,
   Vf. glutinosum,
   V{. audouini, S^.
   fructicola, T.
   gypseum, M. avreus,
   A. faecalis, P_.
   ammoniae

M. audouzai,  S_.
   fructola
   Fongicidal test
     Flowable concentrate

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                                     33
Table 8. (continued)
Data Type
Formulation
                                                    Descriptors3-
          —Ziram in Combination with Zinc 2—Me reap to?: enzothiazolate—  (continued)
   Soil burial test
   on fabrics treated
   with, fungicides
   Fabric preservative
   on wool

   Fabric sanitizing
   test

   Paper mold—proof ing
   test

   Adhesive preser-
   vation test

   Paper mill slime
   control test
   Cooling water slime
   control test
   Fungus proofing
   test for latex
   coated products

Efficacy
Human and domestic
   animal safety

   Oral
   Primary eye
   irritation
Flowable concentrate
Flowable concentrate
Flowable concentrate
Flowable concentrate
Flowable concentrate
Flowable concentrate
Flowable concentrate
Flowable concentrate
Unspecified formulated
   product (in—can
   paint preservatives
          o
Unspecified formulated
   product (preservation
   method)
V/ettable powder

Flowable concentrate


Wettable powder


Flowable concentrate

Flowable concentrate
Acute toxicity—

                  o
Subicute dermal      Flowable concentrate
sensitization

Residues on paper    Wettable powder
                                                    B. subtilis, P.
                                                    aeruginosa. mildew


                                                    Natural fauna
                                                    Rat
                                                    Albino rat, pigeon,
                                                    albino rabbit

                                                    Albino raboit
                                                       Albino rabbit

                                                       Albino rat
                                                        o
                                                       Guinea pig

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                                     34
Table 8. (continued)

Data Type
                        Formulation
          Desc"
     -Ziram in Combination with Petroleum Distillate,  Oi  _.._,  Solvent,  or
             Hydrocarbons, Aliphatic  Hydrocarbons.  Para"  inic Oil-
Efficacy
                        Unspecified formulated
                           product
          Blueberries/mummy
             berry
        -Ziram in Combination with  Copper  Sul.fate.  Calcium Oxide-
Efficacy
                        Unspecified formulated
                           product
          Pecans/pecan scab
   -Ziram in Combination with Ferbam,  Manganous  Dimethyldithiocarbamate-

Efficacy                Wettable powder                 Apples/not  specified,
                                                           fruit trees/not
                                                           specified
Phytotoxicity           Yfettable powder                 Apples
   —Ziram in Combination wit h Zinc 2—Mercaptobenzothiazolate.  Zinc  Oxide-
Efficacy

Human and domestic
   animal safety

   Acute oral
   Acute primary dermal
      irritation
   Acute eye irritation
   Acute toxicity -
      inhalation
Fish and wildlife
   safety
   Aquatic exposure
   LC50
                        In—can spray pre-
                           servatives
                        Wettable powder
                            Wettable powder

                            Wettable powder
                            Wettable powder
                            Wettable powder
          Unspecified bacteria
         Albino rat
         Albino rabbit

         Albino rabbit
         Rat
         Fathead minnow
Descriptors are as follows
     Residue chemistry — by  commodity  name
     General efficacy - by site  and  pest
     Phytotoxicity - by plant  or  crop  name
°'-tanganous ethylenebisdithiocarbamate
cFemc dimethyl dithiocarbamate
      organism glossary
   faecal is = Al call genes, faecal is
   terreus = Aspergillus terreus
   subtilis = Bacillus subtilis
   coli =
                                          P.
                                          1-
                                          S.
ammoniac
aureus =
         = Proteus ammoniae
_  	   Eschenchia coli
}!. aado'mni = Microsporum audouini
M. avreus = Micrococcus avreus
M. glutinosum = Metarrhizmm glutinosum
P_  aeruginosa = Pseudomonas aeruginosa
   	   Staphlococcus aureus
   choleraesuis = Salmonella choleraesuis
5>. faecal is = Streptococcus f aecalis
^. fructicola = Sclerotina fmeticola
j>. scnottmueller = Salmonella  schottaueller
^. typhosa = Sa_liaone_ll_a typhosa
T. gypseum = Trichophyton gypseum

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3,765,000 pounds.  Recent importation data were not availaole   ^at 1977
figures indicate that at least 10,000-100,000 pounds %ere  iir   rted during
that year (USEPA 1983o, as reported in USEP4 1983a)

      Ziram is used mainly as a rubber accelerator and a  I  gicide (USEPA
1983a), and in small quantities in animal glue and adhes-  33 which are used
in food-contact articles, non-food-contact paper coatin s,  industrial
cooling water, latex-coated articles, neoprene, paper  -zd  paperboard, and
textiles and plastics (IARC 1976).  Ziram is also an offective  molluscicide
(Hadler 1982).  There is no evidence that the compound is  used  as a
chemical intermediate.

      Of the 2,231,000 pounds of ziram produced in 1978,  approximately
400,000 pounds (18%) were used for fungicidal purposes (SRI International
1980, as reported in USEPA 1983a).  Of the 400,000 pounds, 300,000 pounds
were used on deciduous fruits and 100,000 pounds were used on vegetables.
These figures  suggest that probably over 1,000,000 pounds  are used in the
rubber industry.

      Occupational monitoring data for ziram were not found.  Based on the
National Occupational hazard survey, NIOSH (1980, as reported  in USEPA
1983a) projected that 27,889 workers were occupationally  exposed to ziram,
the majority of whom were employed in the fabricated rubber products
industry.  However, this survey did not include workers engaged in the
manufacturing  of ziram or those using the compound as a pesticide, thus  the
number of exposed workers could be even larger.

      Inhalation and skin contamination are the most likely routes of
occupational  exposure to the compound.  Occupational exposure  to ziram has
been demonstrated in Russian production plants where levels of  ziram dust
ranging from 0.5 to 130 mg/m^ have been detected (Enikeev  1967,as reported
in Chem Abstr  72 35486b, Pilinskaya 1970, Marsten and Pilinskaya 1971, as
reported in USEPA 1983a).  According to Narsten and Pilinskaya  (1971), the
technological  stages at which workers come in contact with ziram are in
packaging, drying, and warehousing the finished product.   Until more data
is obtained,  similar exposure in U.S. industry must be considered a
possibility.

      Consumer exposure to ziram may occur through the use of the compound
as pesticide  or through the ingestion of contaminated fruits and
vegetables.  However, limited studies have demonstrated that residues of
the pesticide  are easily washed off treated fruits and vegetables (Ryaznova
1967, as reported in Chem Abstr 71 2469z, Villa et al. 1976, as reported in
Chem Abstr 88  16949u), indicating that routine household washing of produce
may limit the  quantities of ziram ingested.

      Environmental monitoring data were not found.  There was  no
indication in the literature of whether or not ziram is released into the
environment from the pesticide and rubber industries.  Environmental
contamination is expected, however, through the use of ziram as a fungicide
(soil contamination, primarily) and a molluscicide (*ater  contamination)

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                                     36
      Once released inco the environment, ziram may persist  f    about  a
month..  Under experimental conditions, ziraia  residues  disap^   red  from
sprayed vegetables (stored at 4°C) in about 30 days  (Villa     al.  1976),  in
the field, persistence on the leaves of woody plants was £_    ffeeks  for 10
of the 12 species studied (Neely 1970).  In water, ziram - , persist  for
30-45 days,  depending on pH  (Gretillat 1961,  as reported  .a  Stmfe  1968)
and other factors such as photolysis, biodegradation,  s rption
characteristics and uptake by aquatic organisms.

      A low concentration of ziram in water,  exposed to sunlight each  day,
remained biologically active for 45 days (Deschiens and Floch  1965, as
reported in Strufe 1968), indicating that photodegradation of  ziram is
probably minimal.  There is  some evidence that ziram is biodegradable
(Raghu 1976, as reported in  Chem Abstr 89 37937z, Etges et al.  1965),
however biodcgradability of  the compound may  be limited by its toxicity to
microorganisms (Sect- I.E.5.Growth and Development).   Sorption studies have
demonstrated that in water,  ziram adsorbs to  mud particles in  varying
degrees (Paulini 1963, Gonnert and Strufe 1962, both reported  in Strufe
1968), and would therefore be available to bottom-feeding organisms,  in
particular.   If taken up by  aquatic organisms, ziram would not be  expected
to bioaccumulate (Vetorazzi  1979).

      The presistence of ziram in soil would  depend on factors similar to
those which govern the persistence of the compound in  the water.  However,
the availabile data for the  mobility of ziram through  the soil are
conflicting.  Some investigators found the compound to be immobile  in  soil
(Munneke 1961, Helling et al. 1974, both, reported in Singhal and Bansal
1978; Kenaga 1980), while others observed high mobility (Singhal and Bansal
1978).  Singhal and Bansal (1978) suggested that the mobility  of ziram may
depend on its concentration  (the excess of supersaturate would be more
mobile) since they had applied high concentrations in  their  assays    It is
also possible that different analytical techniques could account for  the
conflicting results of at least two of the studies.  In any  case, this
suggests the possibility of  at least some leaching and subsequent
contamination of ground water by ziram.

      In summary, the data suggest the possibility of  the release of
significant quantities of ziram into the workplace and the environment
(especially during its use as a fungicide), with workers in  the rubber and
pesticide industries and agriculture having the greatest exposure
potential.  Once released into the environment, the compound would  probably
not persist longer than a few weeks due to chemical and/or biological
degradation.  Occupational and environmental  monitoring data from  the  U.S.
and data on environmental releases from manufacturing  and use  sites are
needed for further assessment of the exposure potential of ziram.
  B.  Human Health Risk Assessment

      Ziram is carcinogenic, mutagenic, and teratogenic  in  animals,  and
apparently causes chromosomal abnormalities in humans.   These  effects.

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                                     37
coupled with the relatively hign production volume  of  the  co^   _nd  and  its
wiaespread use in industry and agriculture, constitute  a po*  .  lal  risk to
human health.

      In an NTP (1983) bioassay, ziram was carcinogenic  i   jale,  but  not
female, F344/N rats, inducing a statistically  significar.   increase  (p <
0.05) in the incidence of C-cell carcinomas of  the  thyr  _d at an  oral dose
of 22 mg/kg/day for 103 weeks.  The effect was  dose-re.ated.  Ziram also
produced a statistically significant  increase  (P  <  0 35)  in the incidence
of alveolar adenomas in female, but not male,  B6C3Fi mice  (NTP  1983).
However, the interpretation of the results of  the mouse  study was
complicated by a respiratory (Sendai) virus infection.

      These rather equivocal positive results  are supported by  the  fact
that the thyroid is recognized as a target organ  for the  thiocarbdinate
compounds as a class (NTP 1983), and that unidentified metabolites  of
ziram have been detected in the thyroid of female rats 24  hours after a
single dose of ziram was administered by gavage (Izmarova  and Marinov 1972,
as reported in NTP 1983).  In addition, tetrazaethylthiuram disulfide,  a
metabolite of ziram, has been associated with  squamous metaplasia in  the
thyroid of rats (Lee et al. 1978, as reported  in NTP 1983).

      In several older studies in rats, ziram  induced fibrosarcomas  and
tumors of the thyroid and the liver (Section I.D.3, Carcinogenicity),  some
statistically significant, some not, and in older studies  in mice,  the
compound was non-oncogenic.  Some of these studies  were considered  by IARC
(1976) to be qualitatively or quantitatively inadequate, however, their
significance should be reevaluated in light of  the  NTP  (1983) results.

      The oncogenicity of ziram by the oral route is particularly relevant
to potential consumer exposure via ingestion of contaminated produce,
however the compound apparently has not been tested for oncogenicity  via
inhalation or skin application, the two most probable routes of worker
exposure.  This data would be useful for a more complete assessment  of
occupational risk.

      In experimental systems, the mutagenicity of  ziram is  equivocal
(Table 4) .  However, abnormal chromosomes or chroiaatids were reported in
5.9% of the lymphocytes cultured from workers with  known exposure to  the
compound in a ziram manufacturing facility (Pilinskaya 1970), and these
effects were essentially repeated in vitro (Pilinskaya 1971).   Similar
epidemiological data for U.S. workers would be useful.

      Teratogenic and reproductive effects have been reported in  rats,
rabbits, mice and chickens at various doses, mostly by  the oral route
(Section I.4.D, Teratogenicity/Reproductive Effects).  Moreover,  one
inhalation study was reported in wnich raboits, exposed to 5 cig/m^  of ziram
dust 4 aours a day for 4 months, displayed testicular atrophy (Enikeev
1967, as reported in Chem Abstr 72 35486b).  This exposure level  was  almost
in the range of the levels detected in the work atmosphere by Pilinskaya
(1970) of 1.95 and 3.7 mg/m3.  However, Marsten and Pilinskaya  (1971)
reviewed the clinical records of women employed in  a ziram manufacturing
plant and did not detect any disturbances in reproductive  functions.

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                                     38
      la animals, ziraa is of moderate  to high  acute  oral  tc    ity,  accord-
ing to the scale of Gossel^n st al.  (1977), with,  oral LDfQ     -ies  ranging
from 400-1400 ng/lg in various species.

      Various non-oncogenic cnronic,  subchronic ana  suba  _.e  effects  have
been described in animals and humans  (Section I.D.6,  Ot  jr  Effects).
Observed effects in animals include  supression  of the ^.amatopoetic  system,
degenerative changes in the liver, kidney,  and  salivary  glands,  and  contact
hypersensitivity.  In humans exposed  in Russian and  Italian industries,
observed effects include irritation  of  the  skin,  eyes, and  respiratory
tract, slight hematological changes,  and enlarged livers with elevated
liver enzyme activities.  One group  of  workers  had shifts  in  blood  cho-
linesterase and  pseudocholinesterase  activities (accumulation of acetylcho—
line), indicating that ziram may be  a cholinesterase  inhibitor in  man
[Komarova and Zotkina 1971, as reported in  JffiDLARS (Toxback 65)  1983].

      The effects of ziram on the health of animals  and  humans suggest that
workers and consumers should avoid exposure to  the compound.   In addition
to the data needs mentioned above, monitoring data in the U.S.  workplace
and in fruits and vegetables treated  with ziram would be useful  in  further
assessment of the health risk imposed on humans by the compound.
  C.  Environmental Assessment

      Monitoring data that would  indicate the  extent  to which  ziram  is
released into the environment were not found.  The probability of  ziram
contamination of the environment  is  indicated  by  the  use of  the  compound  as
a fungicide which is sprayed on various crops, and as a molluscicide which
is added to aquatic systems.  The high production volume and the use of the
compound in the rubber industry also  suggest the  possibility of  industrial
release.  Once released, the biological activity  of ziram  could  persist for
as long as a month in both water  and  soil.

      Ziram is lethal to aquatic  species at concentrations of  0.5—10 ppm
depending on age and species, the young usually being more sensitive than
the adults.  These species include fish, crustaceans, amphibians,  insects,
molluscs, and certain aquatic plants  (Deschiens and Floch  1962,  Gretillat
1962, Gretillat and Lucan 1964, Lloyd 1960, all reported in  Strufe 1968)
The letnal concentrations are within  the range recommended for molluscici-
dal activity   \vailaole data for terrestrial  animals >vas  limited  to tne
oral LDso in the rea-wingea olackoira of 100 mg/kg (Scnafer  1972).  More-
over, in experimental animals, the compound *as of moderate  to nigh acute
oral toxicity (Taole 3)

      Ziram has been shown to be  an  inhibitor  of  growth and metabolic
processes of bacteria in water (Suzuki and Nakajima 1967,  as reported  in
Chem Abstr 70 26633d) and soil [Azad  et al. 1971, as  reported  in DIALOG
(CAB Abstracts 72-33)].  At concentrations of  0 05% (500 ppm), microoial
decomposition of organic matter and  nitrification processes  in loam  soil

-------
                                     39
were depressed.  This could limit biodegradation  of  the  comr  . z.d.   Ziram
also reduced growth and development of barley plants  (at  25   .ad  500  ppm)
and fruit trees (at 1000-2000 ppm).

      All of the effects mentioned above  indicate  that e   ironmental
release of ziram could result in  injury to a wide  spect_-_a of environmental
species.  Environmental monitoring data and reproducti e  toxicity  data  for
environmental species would be particularly useful for further assessment
of the extent of the hazard.

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                                   40

III.   References

  A.   Literature Cited

  Alamanni U,  DeLuca G, Mura M, Alamanni 31.  1982.  Prese_  , of
  ethylenethiourea in fruits, vegetables and their conime.- ;ial derivatives.
  Boll Chim Unione Ital Lab Prov Parts Sci 33(S1) 43-54   (As reported in
  Chem Abstr 97 90561p)

  Andiranova MM, Alekseev IV.  1970.  Carcinogenic properties of the
  pesticides sevin,  manefa, ziram and zineb.  Vopr Pitan 29 71-74.  (As
  reported in IARC 1976)

  Antonovich EA, Cernov 0V, Salmosh LV et al.  1972.  Comparative
  toxicologic assessment of dithiocarbamates.  Gig Sanit  50(9) 25-30.  (As
  reported in Chem Abstr 78 249255s)

  Armeli Ducci IG.  1966.  Problems in occupational medicine and industrial
  hygiene in the production of zinc dimethyldithiocarbamate (ziram).  Med
  Lavoro 57(8-9) 537-541.  [As reported in MEDLARS (Toxback 65) 1983]

  Arzone A,  Vidano C.  1980.  Laboratory investigations on the action of
  acephate dialifos and ziram on honeybees.  Apicoltore Noderno 71(2) 37-
  43.  [As reported in DIALOG (CAB Abstracts 72-83) 1983]

  Azad MI, Khan AA,  Saleem M.  1971.  Effect of zinc and  copper fungicides
  on soil microbiological processes.  J Agric Res 9(3) 218-221.  [As
  reported in DIALOG (CAB Abstracts 72-83) 1983]

  Becker K,   1966.  Influencing the breeding of wild pigeons with
  chemicals.  Z Angew Zool 53(2) 237-256.  (As reported in Chem Abstr
  67-72803v)

  Benes V, Sram R.  1969.  Mutagenic activity of some pesticides in
  Drosophila melanogaster.  Ind Med 38(12) 50-52.

  Brieger H, Hodes WA.  1949.  Toxicity of dithiocarbamates and the hazard
  of exposure to these compound.  In   Proceedings of the 9th International
  Congress on Industrial Medicine, London, Sept 13—17, 1948.  Bristol  John
  Wright if Sons, pp. 598-602.  (As reported in Strufe 1968)

  Briquet M, Sabadie-Pialoux N, Goffeau A.  1976   Ziram,  a sulfhydryl
  reagent and specific inhibitor of yeast mitochondrial dehydrogenases.
  Arch Biochem Biopnys 174 684-694.

  Budnikov GK, Toropova VF, Ulakhovich NA, Viter IP.  1974.
  Electrochemical benavior of dithiocarbamates on a mercury electrode.
  III.  Polarographic study of fungicides of dithiocarbamate type in
  organic solvents.   Zh Analyt Shim 29 1204-1209.  (As reported in USEPA
  1983a)

  Bnlkan AI.  1974.  Acute poisoning with ziram.  Sud Med Ekspert 17 51.
  (As reported in Hayes 1982)

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                                   41
Chepinoga OP, Chernov 0V, Samosh LV et al.  1970.   Possible    astomogenic,
nutagenic, and eiabryotropic effects of some carbamate  pest,  _des.   Vop
Gig Toksikol Pestits Tr Nauch Sess Akad Med Nauk SSSR  196"  -29-134.   (As
reported in Caen Abstr 74 123308s)

Chernov 0V.  1968.  A case of occupational poisoning v a  the  dimethyl-
dithiocarbamate of zinc (ziram).  Gigiena Truda i Pro" Zabolevaniya
12(12) 48.  [As reported in Hayes 1982. and in MEDLAT3 (Toxback  65)  1983]

Chernov 0V, Khitsenko II. 1969.  Blastomogenic properties  of  some  deriva-
tives of dithiocarbamic acid,  Vop Onkol 15 71-74.   (As reported in  IARC
1976)

Chernov 0V, Khitsenko II, Balm PN.  1972.  Blastomogenic  properties  of
some derivatives of dithiocarbamic acid and their metabolites.   Onkolo—
giya  (Kiev) 3 123-126. ~ (As reported in Chem Abstr  79  62413b)

Dailey RE, Leavens CL, Walton MS.  1969.  Effect of certain dimethyl-
dithiocarbanate salts on some intermediates of the  glycolytic  pathway in
vivo.  J Agr Food Chem 17(4) 827-828.  [As reported in MEDLARS (Toxback
65) 1983]

DeBruin A.  1976.  Biochemical  toxicology of environmental agents.   New
York  Elsevier North Holland Biomedical Press, pp.  398-399.

DeLorenzo F, Staiano N, Silengo L, Cortese R.  1978.   Mntagenicity of
diallate, sulfallate, and triallate and relationship between  structure
and mutagenic effects of carbamates used widely in  agriculture.  Cancer
Res 38 13-15.

Deichmann WB, Gerarde HW.  1969.  Toxicology of drugs  and  chemicals.  New
York   Academic Press, p. 668.

Deschien R, Floch H.  1962.  Vergleichende Untersuchung der mollusciciden
Wirkung von Kupfer- u. Zink-dimethyldithiocarbainat  in  der Bilharziose-
Prophylaxe.  Bull Soc Pathol Exot 55 807.  (As reported in Strufe 1968)

Donner M.  1981.  Use of Drosophila as indicator of risk chemicals  in
rubber factory.  SGF Publ 57 47-53.  [As reported in JDEDLARS  (TOXLINE)]

Dun's Marketing Services.  1982.  The billion dollar directory
Parsippany, NJ   Dun and Bradstreet Inc., pp. 2049,  2061.   (As reported
in USEPA 1983a)

Eisenfarand G, lingerer 0. Preussiaann R.  1974   Rapid formation of  carci-
nogenic N-nitrosamines by interaction of nitrite *ith  fungicides derived
from dithiocarbamic acid in vitro under simulated gastric  conditions  and
in vivo in the rat stomach.  Food Cosmet Toxicol 12(2) 299-232.   [As
reported in DIALOG (EXCERPTA MEDICA) 1983]

Engst R, Scnnaak W.  1974   Residues of dithiocarbamate fungicides and
their metabolites on plant foods.  Residue Rev 52 45-67.   (As  reported in
Fishbein 19'76)

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                                   42
Enikeev V Kh.  1967.  Hygiene and toxicology in the product   -> of ziram.
Mater Nauch-Prakt Konf Molodykn Gig Sanit Vrachei, llth.   .  149-150.   (As
reported in Chem Abstr 72 35486b)

Enikeev V Kh.  1968.  Problems of #ork hygiene in the p   action of
ziran.  Gig Tr Prof Zabol 12 12-16.  (As reported in H  33 1982)

Etges FJ, Bell EJ, Gilbertson DE.  1965.  Bacterial tsgradation of some
molluscicidal chemicals.  Am J Trop Med Hyg 14(5) 8 6-851.

Fahrig R.  1974.  Chemical carcinogenesis assays.  Publ No 10.  Montesano
R, Tomais L, eds.  Lyon   International Agency for Research on Cancer, p.
161.

Fishbein L.  1975.  Chromatography of environmental hazards, vol.3   Pes-
ticides  676-692.  (As reported in USEPA 1983a)

Fishbein L.  1976.  Environmental health aspects of fungicides.  I.
Dithiocarbamates.  J Toxicol Environ Health 1 713-715.

Fishbein L, Zielinski WL, Jr.  1967.  Chromatography of carbamates.
Chromat Rev 9 37-101.  (As reported in USEPA 1983a)

George ME, Kirpal S, Aulakh S, Dhesi JS.  1970.  Morphological and cyto-
logical changes induced in barley (Hordeum vulgare) seedlings following
seed treatment with fungicides.  Can J Genet Cytol 12 415-419.

Ghezzo F, Coradini L, Guglielmini C, Ninfo V.  1972.  L'azione tossica
die ditiocarbamati su sistemi enzimatici.  Quad Sclavo Diagn 8 485-494.
(As reported in IARC 1976, MAS 1977, Chem Abstr 78 93330f)

Goen RL, Coyner EC, Gibson T, Steele RV, Brown SL.  1980.  SRI
International.  Chemical use standard encoding system (ChemUSES).  Final
report.  SRI Project CRU-5722.  Washington, DC   Office of Pesticides and
Toxic Substances, U.S.  Environmental Protection Agency.  Contract No.
68-01-4109, Research Request No. 9.  (As reported in USEPA 1983a)

Gonnert R, Strufe R.  1962.  Comparative investigations of some mullusci-
cides.  Ciba Foundation Symposium  Bilharziasis, p, 326.  (As reported in
Strufe 1968)

Goring CAI, Hamaker JW.  1972.  Fungicides.  In   Organic chemicals in
the soil environment, vol.2.  New York   Marcel Dekker, Inc., pp.597—598,
608- 629

Gossenn RE, Hodge HC, Smith RP, Gieason MN.  1977   Clinical toxicology
of commercial products, 4th ed.  Baltimore, MD   The Williams ? Wilkias
Co., p. 201.

Gretillat S.  1961.  Zinkdimethyldithiocarbaiaat (Ziram), ein neues Molluskizid
Bull World Health Org 25 581.  (As reported in Strufe 1968)

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                                   43
Gretillat S, Lacan A   Efficacite du ziraine  (Dimethyldithic   .oamate  de  zinc)
sur les getes a rsullusques en riviere  et  toxicite pour  let  -oissons.
Bull World Health Org 30 413.   (As reported  in Strife 19f

Grosclaude MC, Detienne G, Roux JJ.  1969    Winter necr  _s  of peach
twigs.  Experimental reproduction of symptoms followin, pesticide  treat-
ments.  Rev Zool Agr Pathol Veg 68(1-3) 26-36.   (As reported in  Chem
Abstr 72:658SOt)

Gunther FA, Gunther JD, eds.  1971.  Chemistry of pesticides.  In-  Resi-
due reviews, vol. 36   New York   Springer-Verlag, pp.  16-19, 210-224.

Hadler MR.  1982.  In   Kirk-Othmer encyclopedia of chemical  technology,
3rd ed., vol. 18.  New York   John Wiley  ? Sons, p. 304.

Hansen JC.  1972.  The effect of some  sulphur and mercury containing
fungicides on bacteria.  Chemosphere 4 159-162.

Hawley GG.  1977.  The condensed chemical dictionary, 9th ed. New York.
Van Nostrand Reinhold Company, p.  943.

Hayes WJ.  1982.  Pesticides studies in man.  Baltimore.  Williams  £  Wil-
kins, pp.606-607, 615-622.

Hedenstedt A, Rannug U, Ramel C, Wachtmeister CA.  1979   Mutagenicity
and metabolism studies on 12 thiuram and dithiocarbamate compouds used as
accelerators in the Swedish rubber industry.  Mutation Res 68 313-325.

Heinisch KF.  1974.  Dictionary of rubber.   New York   John Wiley q Sons,
pp. 528-529   (As reported in USEPA 1983a)

Helling CS, Dennison GD, Kaufman DD.  1974.  Fungicide movement  in  soils.
Phytopathology 64 1091-1100.  (As reported in Singhal and Balsal 1978)

Hemminke K, Falck K, Vainio H.  1980.  Comparison of alkylation  rates and
mutagenicity of directly acting industrial and laboratory chemicals.
Arch Toxicol 46 277-285.

Hodge HC, Maynard EA, Downs W, Blanchet HJ,  Jr., Jones CK.   1952.  Acute
and short-term toxicity tests of ferbam and  ziram.  J Am Pharm Assoc, Sci
Ed 41.662-666.  (As reported in Hayes 1982)

Hodge HC, Maynard EA, Downs WL, Coye RD, Steadman LT.  1956.  Chronic
oral toxicity of ferric dimethyldithiocarbamate  (ferbam) and zinc
dinethyldithiocarbamate (ziram)   J Pharmacol Esp Ther 118 174-1S1.   (As
reported in NTP 1983, Hayes 1982, I ARC 1976, Scenberg ana Ryoakova 1967)

Hoestlandt H.  1972.  Lutte contre 1'invasion de la moule d'eau  douce,
Dreissena polymor-plia Pallas, par insecticides et molluscicides.  Int  Ver
Theor Angew Linaiol, Verh 18(2) 961-967.

Hylin JW, Chin BH.  1968.  Volatile metabolites  from dimethyldithiocarba-
mate fungicide residues.  Bull Environ Contain Toxicol 3(6) 322-332.

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                                   44
IARC.  1976b.  International Agency for Researcn on  Cancer   Ziram.   In
IARC monographs on the evaluation of the carcinogenic ris!   _  chemicals
to man 12 259-270   Lyon, France   World Health Organiza"   -    (Also,  as
reported in DSEPA 1983a)

Innes FILM, Ulland BM, Valeno MG, Petmcelli L, Fishbe  _ L,  Hart ER,  et
al.  1969.  Bioassay of pesticides and industrial che icals  for tumori-
genicity in mice   a preliminary note.  J Nat Cancer Inst 42 1101-1114.
(As reported in IARC 1976).

Izmirova N.  1972.  A study of the water-soluble and chloroform-soluble
metabolites of 35S-ziram by means of paper chromatography.   Eksp Med  Mor-
fol 11 240-243   (As reported Chem Abstr 79 62341g and  in NTP  1983).

Izmirova N, Marinov V   1972.  Distribution and excretion of 35S-ziram
and metabolic products in 24 hours following oral administration of the
preparation to female rats.  Eksp Med Morfol 11 152-156.  (As  reported in
Chem Abstr 79 1052m)

Japanese Ministry of Agriculture and Forestry.  1975.   Noyaku  yoran
(agricultural chemicals annual), 1975, division of plant disease preven-
tion, Tokyo, Takeo Endo,  pp.  17-18, 254, 267-268.  (As reported in  IARC
1976)

Jenkyn LR, Budd RC, Fein SH, Cornell CJ.  1979.  Insecticide/herbicide
exposure, aplastic anemia, and pseudotumor cerebri.  Lancet 2.368.

Kada T, Hirano K, Shirasu Y.  1980.  Screening of enviornmental chemical
mutagens by the Rec-Assay system with Bacillus sub tilis.  In   Chemical
mutagens.  Principles and methods for their detection,  vol.  6.  de Serres
FJ, Hollaender A, eds.  New York   Plenum Press, pp. 149-173.

Kas'yanenko AG, Koroleva NS, Ryabova IM, Shevtsova VM.  1977.  Mutations
in Verticillium induced by pesticides.  Izv Akad Nauk Tadzh  SSR Otd Biol
Nauk 1 22-27.  (Trans, from Russian)

Kenaga EE.  1980.  Predicted bioconcentration factors and soil sorption
coefficients of pesticides and other chemicals.  Ecotox Environ Safety
4 26-38.

Ehaikina BI, Shilina VF, Ivanitskn VA.  1976.  Characteristics of the
metabolism of biogenic amines in warm—blooded animals under  the effect of
pesticides of various chemical types.  Vopr Pitan 3  47-50.   (As reported
in USEPA 1983a)

Eirby \HM, Bennett M, Sharpies RO.  1968.  Phytotoxicity of dithiocarua-
rnate fungicides on Worcester Pearmain.  Ann Rep East Mailing Res Sta
Kent, 1967.  pp.  177-181.  (As reported in Chem Abstr  69 26234d)

Kligman AM, Rosenweig W.  1948.  Studies with new fungistatic  agents.
II.  For treatment of superficial mycoses.  J Invest Dermatol  10 59-68.
(As reported in Hayes 1982)

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Slisenko MA., Ve's.shtein MS   1973.  Determination of  ziram,  c  ^razin-II,
tetramethylthiuram disulfide  (TMTD),  and  their  degradation  products
(tetramethylthiourea, dime thy lammonmia dimethylditniocarb    ;e,  and  sul-
fur) in water using tmn-layer chroiaatography.  Metody  0    _.  Pestits.
Vode.  1 60-64.  (As reported in USEPA 1983a, and  in Ch<=   lostr
82 39300r)

Komarova AA, Zotkina VP.  1971.  Application of elect_omyography and of
certain parameters of acetylcholme metabolism  for  t^e  evaluation of the
condition of workers engaged  in the manufacture of  ziram.   Gig Tr Prof
Zabol 15(9) 17-20. [As reported in MEDLARS  (Toxback  65) 1983]

Korablev MV,  1965.  Pharmacology and toxicology of  derivatives  of
dithiocarbamic acid.  Author's abstract of  doctoral  dissertation (in Rus-
sian), Saunas Medical Institute.  (As reported  in Pilinskaya  1971)

Kumarasamy R, Raghu K.  1976.  Conversion of the fungicide, ziram in Tice
plants.  Agr Biol Chem 40(11) 2297-2298.

Kurnnny AI, Kondratenko TI.  1972.  Effect of  fungicides  (dithiocarbamic
acid derivatives) on chromosomes of bone  marrow cells in mice.   Tsitol
Genet 6(3) 225-228.  [As reported in MEDLARS (TOXBACK 65) 1983]

Levin AI, Garkavenko OS, Frolova VG.  1973.  Diagnostic significance of
the determination of soiae type-specific enzymes for  early recognition of
occupational liver disorders  and evaluation of  the  effectiveness of  pro-
phylactic nutrition.  Sovrem  Jletody Kim-Lab Issled  Diagn Prof Zabol 14-
17.  (As reported in Chem Abstr 83 15l604q)

Lee C, russell J, Minor J.  Oral toxicity of ferric  dimethyldithiocarba-
mate (ferbam) and tetramethylthiuram disulfide  (thiram) in  rodents.   J
Toxicol Environ Health 4(1) 93-106. (As reported in  NTP 1983)

Lewis RJ, Tatkin RL, eds.  1982.  Registry  of toxic  effects of chemical
substances, 1980 ed., vol. 2.  Cincinnati,  OH:  National Institute for
Occupational Safety and Health, p. 838.

Linden E, Bengtsson B-E, Svanberg 0, Sundstrom G.  1979.  The  acute  toxi-
city of 78 chemicals and pesticide formulations against two brackish
water organisms, the bleak (Alburnus alburnus) and  the  Harpacticoid
(Nitocra s-pinipes)   Chemosphere 11/12 843-851.

Lloyd R.  1960.  The toxicity of zinc sulphate  to rainbow trout.   Ann
Applied Biol 48 84.  (As reported in Strufe 1968)

Lowen rfS.  1961   Determination of thiram »n ferbam.  J \ssoc  Off \gric
Chem 44 584-589.  (As reported in Fishoein  1976)

Mannari UM, Pala V, Burlando F et al.  1974.  Morpnologic  alterations  in
the salivary glands, estraorbital lacrymal  glands,  liver and  kidney  of  rats
caused by some toxic czapounds and industrial dusts.  Pathologica (Italy)
66-961-962.  Us reported in  DIALOG (ECOSRPTA MEDICA) 1983]

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Martin H, Worthing CR.  1974.  Pesticide manual,  4th.  ed. Br   .ah.  Crop
protection council   p   520

Martson' LV, Pilinskaya '-IA.  1971.  Hygienic charaterist     of working
conditions in the production of ziram.  Gig Sanit 36(3)    /    (As
reported in USEP4 1983a, and in Hayes 1982).

Matsushita T, Yoshioka M, Aoyama K, Yamashita T.  19"3.  Experimental
study on contact hypersensitivity by dithiocarbamat   fungicides ferbam,
ziran and their related compounds.  Acta Med Univ -agoshima  20(2)  99-106.
(As reported in Chem Abstr 90 34683y)

McLeod HA, McCully KA,  1969.  Head space gas procedures for screening
food samples for dithiocarbamate pesticide residues.  J Ass  Off Analyt
Chen. 1226-1230.  (As reported in USEPA 1983a)

Moriya M, Eato K, Shirasu Y, Kada T.  Mutagenicity screening of pesti-
cides in microbial systems.  IV.  Mutagenicity of dimethyldithiocarba-
mates and related fungicides.  Mutation Res 54 221.

Munnecke DW.  1967.  In   Fungicides, vol. 1.  Torgeson DC,  ed.  New
York  Academic, pp. 509-559.  (As reported in Goring  and flamaker 1972)

Munneke DE.  1961.  Movement of non-volatile, diffusible fungicides
through columns of soil.  Phytopathology 51 595-599.  (As  reported in
Singhal and Bansal 1978)

Neal RA, Kanatake T, Hunter AL, Catignani G.  1977   Monooxygenase
catalyzed activation of thiono-sulfur containing compounds to reactive
intermediates.  In   Microsomes and drug oxidation. Ullrich  V, ed.
Oxford, England.  Pergamon Press, pp. 467-475.   (As reported in NTP 1983)

Neely D   1970.  Persistence of foliar protective fungicides.  Phyto-
pathology 60(7) 1583-1586.

NIOSH.  1980.  National Institute for Occupational Safety  and Health.
Projected number of exposures to chemical and physical hazards.  Cincin-
nati, OH   U.S. Department of Health, Education, and Welfare.  (As
reported in USEPA 1983a)

Nishiuchi Y, Yoshida K.  1972.  Toxicity of agricultural chemicals to
tadpoles.  II.  Noyaku Seisan Gijutsu 29 23-28.  (As  reported in Chem
Abstr 79 74562n)

Nitsche I, Siemrova J, Ballschmiter K, Selenka F   1975    Studies on the
metabolism of dialkyl dithiocaroamates.  In   Pesticides.  Lectures held
at the IUPAC Third International Congress of Pesticide Chemistry, Helsinki,
3-9 July 1974.  Koivistoinen P, Scientific Chairman.  Stuttgart   Georg
Thieme Puolisners, pp.292-297.

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NTIS.  1968   National Technical Information Service.   Eval -  -xOn  of
carcinogenic, teratogemc and mutagenic activities  of  sele   ;a  pesticides
and industrial cnenicals, vol. 1, carcinogenic  study.   Wa   agton, DC
US Department of Commerce    (AS reported  in IARC  1976)

NTP   1983a.  National Toxicology Program.  NTP technic  . report on  the
carcinogenesis bioassay of ziram (CAS No. 137-30—4).   Pasearch  Triangle
Park, NC   Department of Health and Human Services.   NTP TR 238.

NTP.  1983b.  National Toxicology Program.  FYI-OTS-0783-0252.  Bethesda,
MD. National Institutes of Health.

Olefir AI, Vinogradova VKh.  1968.  The embryotropic  effect of  the pesti-
cides Sevin and zirata.  Vrachebnoe Delo 11 103-106.  [As  reported in
MEDLARS (TOXBACS 65) 1983]

Paulini E.  1963.  World Health Org Bilharziasis  Research Nol/inf/10,39
or 12,25.  (As reported in Stmfe 1968)

Pilinskaya MA.  1970.  Chromosome aberrations in  individuals coming  in
contact with ziram under industrial conditions.   Genetika 6 157—163.
(Also reported in Hayes 1982)

Pilinskaya MA.  1971.  Cytogenetic effects of the fungicide ziram  on cul-
tured human lymphocytes in vitro.  Genetika 7(6)  138-143.  (Also reported
in Hayes 1982)

Pinzauti M.  1982.  The toxicity of various fungicides  in relation to
pollen and bees.  Frutticoltura 44(6/7) 31-38.  [As reported in DIALOG
(CAB Abstracts 72-83) 1983]

Primo Yufera E,  Carrasco JM, Martinez RM.  1967.  Pesticide contamination
of agvricultural produce.  I.  Residual contents  of malathion,  ziram,
Lebaycid, Kelthane, and Tedion on fruits  and changes up  to harvest tine.
Rev Agroquim Tecnol Aliment 7(1).98-104.  (As reported  in Chem Abstr
67*42620r)
                                                     0
Predzdziecki Z.   1969.  Biochemical changes in  the  organs of rats  treated
with some pesticides.  Rocz Panstw Zakl Hig 20(2) 231-248,  (As reported
in Chem Abstr 71 69657c)

Raghu K.  1976.   Radiotracer study of the fate  and  persistence of  organic
fungicides used as seed dressing on grain.  Part  of a  coordinated program
of isotopic tracer aided studies of foreign residues  in  food.   IAEA-R-
1188F   (As reported in Chem ^bstr 89 37937z)

Raghu K, Sumarasamy R. Rao SR, Murthy NBK, Sane PV.  1976.  Metabolism of
labelled ziram in groundnut plants and its microoiological degradation.
In.  Trace contaminants of agriculture, fisheries and  food in developing
countries.  Vienna   International Atomic Energy Agency, pp. 37-39


                        o

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                                   48
          y JR. Poorniica P, Maj under SS.  1970.  Rapid  cole   -atric method  for
estimation of ferbaa and ziram residues on grains.  J.  Ass   -if. Analyt.
Chem. 53 1043-1044.  (\s reported in US EPA 19S3a)

Rasul AR,  Howell JM.  1974   The toxicity of some dithi--  -rbamate  com-
pounds in young and adult domestic fowl.  Toxicol Appl  _armacol
30(1) 63-78.  [As reported in DIALOG (EXCERPTA iMEDICA   1983]

Rocchi P,  Perocco P, Alberghini W, Fini A, Prodi G.  1980.  Effect of
pesticides on scheduled and unscheduled DNA synthesis of  rat  thymocytes
and human lymphocytes.  Arch Toxicol 45 101-108.

Ryazanova RA.  1967a. The effect of the toxic chemicals ziram  and  zineb
on reproductive function in experimental animals.   Hyg  Sanit
32(1,2,3,) 137- 192.

Ryazanova RA.  1967b.  Health evaluation of agricultural  products  treated
with ziram and zineb.  In   Vop Gig Pitan.  Shitskova AP,  ed.  Moscow,
USSR  Mosk Nauch-Issled Inst Gig, pp.32-38.  (As reported in  Chem  Abstr
71.2469z)

Sandmeyer EE.  1981.  Organic sulfur compounds.  In  Patty's  industrial
hygiene and toxicology, 3rd revised ed., vol. 2A  Clayton GD,  Clayton FE,
eds.  New York   John Wiley ? Sons, pp. 2066-2061,  2101.2117.

Sax NI.  1975.  Dangerous properties of industrial  materials,  4th  ed.
New York Van Nostrand Reinhold Company, p. 1252.

Schafer EW.  1972.  The acute oral toxicity of 369  pesticidal, pharma-
ceutical and other  chemicals to wild birds   Toxicol Appl Pharmacol
21 315-330.

Sen NP, Donaldson BA, Charbonneau C.  1974.  Formation  of nitrosodimethy—
lamine from the interaction of certain pesticides and nitrite.  IARC SCI
PTJBL  (United Nations) 9 75-79.  [As reported in DIALOG  (EXCERPTA IffiDICA)
1983]

Shirasu Y, Moriya, Kato K, Furuhashi A, Kada A.  1976.  Mutagenicity
screening of pesticides in the microbial system.  Mutation Res 40  19-30.

Shtenberg AI, Ashmenskas Yu I, Kusevitskiy LA.  1972.   Immunobiological
reactivity changes  under the influence of some pesticides belonging to
the groups of carbamate and dithiocarbamate compounds.  Vopr Pitan 31 58-
63.   (As reported  in Hayes 1982)

Shtenberg AI, Rybakova MN.  1967   The effect of certain  pesticides on
the endocrine system.  Hyg Sanit 32(1,2,3) 94-99

Siebert D, Zisuneraann FK, Leiaperle E.  Genetic effects  of fungicides.
Mutation Res 10 533-543.

Singhal JP, Bansal  V.  1978.  Studies of the mobility of  pesticides by
soil  thin layer chromatography.  Soil Sci 126(6) 360-363.

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                                   49
Sit-tig M, ed.  1980.  Pesticide manugacutring and  toxic mat  .^als  control
encyclopedia.  Park Ridge, NJ   Noyes Data Corporation, pr    771-773.   (As
reported in USEPA 1983 a)

Smith SB, Fianegan JK, Larson PS, Sahyoun PF, Dreyfuss  -, Haag HB.
1953.  Toxicologic studies on zinc and disodium ethyle  .  oisdithiocarfaa-
mates.  J Pharmacol Exper Therap 109 159-166. (As  reported in NTP  1983)

Soyez JL (inventor), 1981 (Jan 2). Reducing the dairagege  caused to wild
animals by chemical treatments in agriculture. French Fr  Demande
2,458,218.  (As reported  in Chem Abstr 95 75491f)

SRI International.  1980.  Chemical econonics handbook.   Menlo Park, CA.
SRI International, pp.  573.50011, 573.5003H.  (As reported  in USEPA
1983a)

SRI International.  1983.  Directory of chemical producers - U.S.A.
Menlo Park, CA   SRI International, p.  975.  (As  reported in USEPA
1983a)

SRI International.  1983a.  Rubber-processing chemicals data base.
Prepared for U.S. Environmental Protection Agency, Industrial Environmen-
tal Research Laboratory,  Cincinnati, OH.  (As reported  in USEPA 1983a)

Strufe R.  1968.  Problems and results of residue  studies after applica-
tion of molluscicides.  Residue Rev 24 79-168.

Supin GS, Klisenko MA, Vekshtein MS.  1973.  Polarographic determination
of residual amounts of fungicides as dithiocarbonic acid  derivatives.
Khim.  Sel. Khoz. 11 840-842. (As reported in USEPA 1983a)

Suzuki S, Nakajima T. 1967   Microbial damage by sulfur compounds  (germi—
cidal effects of sulfur compounds).  Kogyo Yosui 103 50-53.   (As reported
in Chem Abstr 70 26633d)

Taktakishvili SD, Nadirashvili TA.  1980.  Characteristics of the  deposi-
tion of erythrocytes in the spleen of various laboratory  animals.
Soobshch Akad Nauk Gruz SSR 97 465-468.  [As reported in  MEDLARS (T02-
LINE) 1983]

Taylor R, Son PN.  1982.  Rubber Chemicals.  In   Kirk-Othmer encydlo-
pedia of chemical technology, 1982, 3rd ed., vol   20.  New York   John
Wiley ? Sons, p. 343.  (As reported in USEPA 1983a)

Tewari SN, Singh R.  1979.  Identification and detection  of  carbamate
pesticides in autopsy tissues using thin—layer chromatograpny.
Fresenius' Z Anal Chen 294(4) 287.  (As reported in Chem  Abstr 91  336llg)

Trotz SI, Pitts JJ.  1981.  Industrial antimicrobial agents.  In   Eirk-
Othmer encyclopedia of chemical tecnnology, 1981, 3rd ed., vol. 13.  New
York.  John Wiley ? Sons, pp.  243, 246.  (As reported  in USEPA 1983a)

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                                   50
TsapjiO \G, Polishcnux DI, Men'shov AA, Khokhol'kova GA.  19"    Comparative
hygienic evaluation of orchard sprayers.  Hyg Sanit 35(4-6"  290-292.

U.S. Code of Federal Regulations.  1974   Protection of     ironment,
title 40, part. 180 116.  Washington, DC   U.S. Governn     Printing
Office, p.  249.  (As reported in LARC 1976)

U.S. Army.  1969.  TSCA FYI-OTS-0883-0252 supp.  Prir^ry irritation
evaluation of mildew inhibitors G-4 and Vancide 512   Edgewood Arsenal,
MD  U.S. Army Environmental Hygiene Agency, llpp. Special  study No. 33-
009-69/70.

USEPA.  1973. U.S. Environmental Protection Agency.  EPA compendium of
registered pesticides, vol.2.  Fungicides and nematocides,  part 1.
Washington, DC   U.S. Government Printing Office,
p. I-z-ll-00.01-z-ll-00.07.  (As reported in IARC 1976 and  USEPA 1983a)

USEPA.  1977.  U.S. Environmental Protection Agency.  Catalog of tests
submitted in support of ziram (zinc dimethyl dithiocarbamate).  Catalog
#034805-770910.  Washington, DC.  Office of Pesticide Programs, USEPA.

USEPA.  1980.  U/S. Environmental Protection Agency.  Code  of federal
regulations.  Title 21, food and drugs.  Parts 175.105. 177.2600 and
178.3120.  Washington, DC   Office of the Federal Register, pp.  109,
124, 267, 268, 249, 250.

USEPA.  1983a.  U.S. Environmental Protection Agency.  Production expo-
sure profile   ziram.  Technical directive 5.48.  Washington, DC   U.S.
Environmental Protection Agency.

USEPA.  1983b.  U.S. Environmental Protection Agency.  Computer printout
(CISIS)   Production statistics for chemicals in the nonconfidential ini-
tial TSCA. inventory.  Washington, DC.  Office fo Toxic Substances, USEPA.
(As reported in USEPA 1983a).

USITC.  1978. U.S. International Trade Commission.  Synthetic organic
chemicals.  U.S. production and sales, 1977.  Washington, DC   USITC, p.
235.  USITC Publication 920.  (As reported in USEPA 1983a)

USITC.  1979. U.S. International Trade Commission.  Synthetic organic
chemicals.  U.S. production and sales, 1978.  Washington, DC   USITC, p.
213.  USITC Publication 1001.  (As reported in USEPA 1983a)

USITC,  1980. U.S. International Trade Commission.  Synthetic organic
chemicals.  U.S. production and sales, 1979   Washington, DC   USITC, p.
175,  USITC Publication 1099.  (As reported in USEPA 1983a)

USITC.  1981. U.S. International Trade Commission.  Synthetic organic
chemicals.  U.S. production and sales, 1980.  Washington, DC.  USITC, p.
175.  USTTC Publication 1183.  (As reported in USEPA 1983a)

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                                   51
USITC   1982. U.S  International Trade Commission.   Synthet    organic
chemicals.  U.S. production and sales, 1931.  Washington, "    USITC,
p. 155.  USITC Publication 1292    (As reported  in USEPA 1    a)

Vaishnav DD, Brown LR.  1976.  The effects of biocides    che  microbial
degradation of crude oil.  Dev Ind Microbiol 18 597-7-    (As  reported  in
Chen Abstr 91 187939g)

van Hoof F, Heyndrickx A.  1973.  Thin-layer chroma :ographic-spectrophoto
flurometric methods for the determination of dithio- and thiocarbamates
after hydrolysis and coupling with NBD-C1.  Ghent Rijks- univ  Fac Lanbl Med
38 911-916.  (As reported in USEPA 1983)

van Logten MJ.  1972.  De dithiocarbamaat—alcohol—reactie bij  di rat.
Terbcrg,The Netherlands   Bedrijf FA. Lammers,  p. 40.  (As reported  in
IARC 1976)

Vekshtein MSh, Khitsenko II.  1971.  The metabolism  of ziram in warm-
blooded animals.  Gig Sanit 36 23-27.  (As reported  in Hayes 1982)

Vekshtein US, Klisenko JIA.  1970.  Identification and quantitative deter-
mination of some dialkyl dithiocarbamates and their  metabolites in dif-
ferent media of vegetable and animal origin.  Vopr Pitan 29  56-61.   (As
reported in Fishbein 1976)

Vettorazzi G.  1979.  Ziram.  In   International regulatory  aspects  for
pesticide chemicals, vol. I.  Pesticides.  Boca Raton, FL    CRC Press,
Inc., pp. 98-100, 138-139, 1*6, 148.

Villa P, Orecchio F, Piersanti S.  1976.  Dithiocarbamate pollution  of
vegetables.  Experimental study.  Acta Med Rom  14 97-103.  (As reported
in Chem Abstr 88 16949u)

Vekshtein MS, Klisenko JIA.  1970.  Identification and quantitative deter-
mination of some dialkyl dithiocarbamates and their  metabolites in dif-
ferent media of vegetable and animal origin.  Vopr Pitan 29  56-61.   (As
reported in Fishbein 1976)

Weed RM, McCallan SEA, Miller LP.  1953.    Factors  associated with  the
fungitoxicity of ferbam and nabam.  Contrib Boyce-Thompson Inst 17 299-
304.  (As reported in Fishbein 1975)

Weppelman RM, Long RA, Van Iderstine A et al.   1980.  Antifertility
effects of dithiocarfaamates in laying hens.  Biol Repro 23 40—46

WHO. 1975a. tforla Health Organization.  Evalaations  of some  pesticide
residues in food.  Wld Hlth Org Pest Res Ser, No. 4, pp.  261-262.   (As
reported in IARC 1976)

WHO.  1975b.  World Health Organization.  Pesticide  residues in food.
Report of the 1974 Joint Meeting of the FAO Working  Party of Experts on
Pesticide Residues and the WHO Expert Committee on Pesticide Residues.
    filth Org Techn Rep Ser. No. 574, pp.  26-28,  (As reported in IARC 1976)

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                                   52
WHO/FAO   1965   World Health. Oiganization/ Food and Agricu   re Organi-
zation.  Evaluation of the to—ic.ity of pesticide residues    food.
Geneva   World Fealtii Organization.  (As reported in Fish   a 1976)

WHO/FAO.  1967   World Health Organizaton/Food and Agri   cure Organization.
Evaluations of some pesticide residues in food.  WHO F'  - Addit Ser 68.30
234.  (As reported in Vettorazzi 1979)

WHO/FAO.  1970.  World Health Organizaton/Food and Agriculture Organization.
Evaluations of some pesticide residues in food, AGP 197081/12/1;  WHO Food
Addit Ser 71.42, 272, 1971.  (As reported in Vettorazzi 1979)

Windholz M, Budavari S, Stroumtsos LY, Fertig MN.  1976.  The Merck
index.  Rahway, NJ   Merck ? Company, p.  9843.

Wolfe HR,,  Durham WF.  1966.  Proceedings of the Second Eastern Washing-
ton Fertilizer and Pesticide Conference, Washington State University, pp.
14-21.  (As reported in Deichman and Gerard 1969)

Wolfe JR, Jr.  1971.  Vulcanization.  IN   Encyclopedia of polymer sci-
ence and technology, vol. 14.  Bikalis NM, ed.  New York   Interscience,
pp.  740-741, 747-748.  (As reported in IARC 1976)

Worthing CR, ed.  1979.  The pesticide manual.  A world compendium, 6th
ed.  British Crop Protection Council, p.551.   (Also reported in USEPA
1983a)

Zazhivilov AG.  1972.  Effect of pesticides on the function of the cili-
ated epithelium of the esophagus in frog   Zh Ushn Nos Gorl Bolez 32 74-
75.  [As reported in MEDLARS (Toxback 65) 1983]

Zutshi U, Kaul BL.  1975.  Studies on the cytogenetic  activity of some
common fungicides in higher plants.  Cytobios 12 61-67.

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                                   53
B.  Secondary Sources Searched

    1.  Books

American Conference of Governmental Industrial Eygienis      1979.  TLVs.
Threshold limit values for chemical substances in  #ork - ^om  air  adopted by
ACGIH for 1979.  Cincinnati, OH   American Conference of Governmental
Industrial Eygienists.

American Conference of Governmental Industrial Eygienists.   1980.  Docu-
mentation of the threshold limit values for substances  in workroom air
adopted by ACGIH for 1980.  Cincinnati, OH   American Conference of
Governmental Industrial Hygienists.

Arena JM.  1979,  Poisoning, 4th ed.  Springfield   Charles  C.  Thomas.

Barton D, Ollis WD, eds.  1979.  Comprehensive organic  chemistry  The
synthesis and reactions of organic compounds.  New York   Pergamon Press.

Bennett H, ed.  1974.  Concise chemical and technical directory.  New
York   Chemical Publishing Co., Inc.

Chemical Technology   An encyclopedic treatment.   1972.  New York
Barnes and Nobel Books.

Choudhary G, ed.  1981.  Chemical hazards in the workplace.  American
Chemical Society Symposium series 149.  Washington, DC.  American Chemi-
cal Society.

Clayton GD, Clayton FE, eds.  1981.  Patty   Industrial hygiene and tech-
nology, 3rd ed., vol. Ila and lib.  New York   Interscience  Publishers.

Cone MV, Baldauf MF, Martin FM.  1979-1981.  Chemicals  identified in
human biological media, a data base.  Washington,  DC   Office of Toxic
Substances, U.S. Environmental Protection Agency   EPA 560/13-80-036A.B,
EPA 560/13-70-001, EPA 560/5-81-008A,B.

Dean JA.  1979.  Lange's handbook of chemistry, 12th ed.  New York
McGraw-Hill Book Company.

Dreisbach RH.  1980.  Handbook of poisoning   prevention, diagnosis and
treatment.  Los \ltos, CA   Lange Medical Publications.

Faith WL, Keys DB, Clark RL.  1975.  Industrial chemicals, 4th  ed.  New
York   Joan Wiley and Sons, Inc.

Fishbein L.  1979.  Studies in environmental science,  4.  Potential
industrial carcinogens and tautagens.  New York   Elsevier Scientific
Publishing Company.

Goodwin BL.  1976.  Handbook of intermediary metabolism of aromatic com-
pounds.  London   Chapman and Hall.

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                                   54
Goring CA.I, Hamaker JW, eds.  1972.  Organic  chemicals  in  t    soil
environment, vol 2   New York   Marcel Dekker,  Inc.

Grant J, ed.  1979   Hackh's chemical dictionary,  4th  ed    ^few York
McGraw-Hill Book Company.

Guenzi WD, ed.  1974.  Pesticides  in soil  and water.   ..idison,  WI    Soil
Science Society of America.

Hamilton A, Hardy H.  1974.  Industrial  toxicology, 3rd ed.   Littleton,
MA.  PSG Publishing Company, Inc.

Hawley GG.  1981.  Condensed chemical dictionary.  New York    Van
Nostrand Reinhold Company.

Hayes WH Jr.  1975.  Toxicology of pesticides.  Baltimore, MD  Williams
and Wilkins Company.

International Labour Office.  1971.  Encyclopedia  of occupational health
and safety, vol. 1-2.  New York:  McGraw-Hill Book Company.

International Technical Information Institute.  1975   Toxic  and
hazardous industrial chemicals safety manual  for handling  and disposal
with toxicity and hazard data.  Tokyo, Japan    International  Technical
Information Institute.

Kent JA, ed.  1974.  Reigel's handbook of  industrial chemistry, 7th  ed.
New York   'Van Nostrand and Reinhold Company.

Leo A, Hansch C, Elkins.  1971.  Partition coefficients and their uses.
Chem. Rev. 71(6) 525-616.

Lipsett CH.  1963.  Industrial wastes and  salvage.  conservation and
utilization.  New York   Atlas Publishing Co.,  Inc.

Lowenheim FA, Moran MK.  1975.  Industrial chemicals, 4th  ed.   New York.
John V/iley and Sons, Inc.

Mackison FW, Stricoff RS, Partridge LJ,  eds.  1981.  NIOSH/OSHA
occupational health guidelines for chemical hazards.  Washington, DC
U.S. Department of Health and Human Services.

McGraw-Hill Encyclopedia of Science and Technology.  1977.  New York
McGraw-Hill Book Company.

Menzie CM.  1969   Metabolism of pesticides.  Special scientific report -
wildlife no. 127   Washington, DC   U.S. Department of the Interior,
Bureau of Sport Fisheries and Wildlife.

National Academy of Sciences.  1977   Drinking water and health.
Washington. DC   National Academy of Sciences.

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National Cancer Institute   1961-1973.   Survey of compound:   nch have been
tested for carcinogenic activity   National Institutes of r  __th. Public
Health Service Publication No. 149.  Washington, DC   Gov  uent Printing
Office.

National Cancer Institute.  1978.  Survey of compounds   -ich have been
tested for carcinogenic activity.  Washington, DC   U ~  Government
Printing Office.  NIE Publication 80-453.

Pollack JRA, Stevens R.  1965-1978.  Dictionary of organic compounds.
New York   Oxford University Press.

Radding SB, Liu DH, Johnson EL, Mill T.  1977.  Review of the
environmental fate of selected chemicals.  Washington, DC   U.S. Environ-
mental Protection Agency.  EPA 560/5-77-003.

Ross RH, Kemp HT, Ryon MG, Hammons AS, Ensminger JT.  1979.  Chemicals
tested for phytotoxicity.  Oak Ridge, TN.  Oak Ridge National  Laboratory.
ORNL/EIS-155, vol. 1 and 2.

Sax NI.  1979.  Dangerous properties of  industrial materials,  5th ed.
New York   Van Nostrand Reinhold Company.

Searle CE, ed.  1976.  Chemical carcinogens.  ACS monograph 173.
Washington, DC.  American Chemical Society.

Shackelford WM, Keith LH.  1976.  Frequency of organic compounds
identified in water.  Athens, GA   Office of Research and Development,
U.S. Environmental Protection Agency.  EPA-600/4-76-062.

Shepard TH.  1980.  Catalog of teratogenic agents.  Baltimore, MD   Johns
Hopkins University Press.

Sittig Jf.  1975.  Environmental sources  and emissions handbook.  Park
Ridge, NJ   Noyes Data Corporation.

Sittig M.  1981.  Handbook of toxic and hazardous chemicals.   Park Ridge,
NJ   Noyes Data Corporation.

USEPA.  1979.  U.S. Environmental Protection Agency.  Toxicology
handbook, mammalian and aquatic data.  Books 1 and 2, P680-196884.
Washington, DC   U.S. Environmental Protection Agency.

Verschueren K.  1977.  Handbook of environmental data on organic
chemicals.  New York.  Van Nostrand Reinhold Company.

Weast RC, Astle MJ, eds.   1980.  Handbook of chemistry and physics, 60th
ed.  Cleveland. OH-  The Chemical Rubber Company.

Weiss G, ed.  1980.  Hazardous chemicals data book.  Park Ridge, NJ   Noyes
Data Corporation.

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i-nlkiascn G, Stone FGA, Abel  F,7,  eds.   1982    Comprehensive    janometallic
chemistry   New York   Pergamon Press

Wiswesser WJ, ed.  1976.  Pesticide  index.   College  Park,  D
Entomological Society of  \nenca.

Worthing CR.  1979.  Pesticide manual,  6th ed.  Briti;   Crop  Protection
Council.

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       2.  Data Bases
 File

 JEDLARS
   TOXLJNE
   TOX65
   TOX74
   CANCEELINE
   CANCERPROJ
   MEDLINE
   IDE
   RTECS
   CHEMLINE
  BACK77
  BACK75
  BACK71
  BACK66

LOCKHEED/DIALOG

  AGRICOLA 79-
  AGRICOLA 70-78
  APTIC
  ASFA
  BIOSIS PREVIEWS 69-76
  BIOSIS PREVIEWS 77-80
  BIOSIS PREVIEWS 81-
  CA SEARCH 67-71
  CA SEARCH 72-76
  CA SEARCH 77-79
  CA SEARCH 80-81
  CA SEARCH 82-
  CAB
  CHEM.  IND.  NOTES
  CHEM NAJSE
  COMP.  DISS. ABS.
  CONF.  PAPERS INDEX
  ENVIROLINE
  EXCERPTA MEDICA IN-PROCESS
  EXCERPTA MEDICA 74-79
  EXCERPTA fffiDICA 80-
  FEDERAL  REGISTER
  NTIS
  PHARMACEUTICAL NEWS INDEX
  POLLUTION ABS.
  SCISEARCH 74-77
  SCISEARCH 78-80
  SCISEARCH 81-PRESENT
  SSIE
  WATERNET
Number of  References
           142
           189
           201
            5
            0
            1
            1
            1
            1
            4
            5
           10
            2
            1
           12
            0
            0
           100
           59
           25
           183
           211
           156
           92
           58
           241
            5
            1
            1
            1
            2
            0
           39
           19
            0
           10
            0
            2
            4
            1
            2
            2
            0
"ate of Search.
   May 10, 1983
         It

         19

         It

         t9

         tt

         tt

         It

         ft

         It
         ft

         It

         tt

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        It

        It
        tt

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File                               Number  of  References       D  -j of Search

ORBIT
  CRECORD                                      0                       "

SYRACUSE RESEARCH CORPORATION

  DATALOG                                      2
  CHEJfFATE                                     0

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  C.  Searcn Strategy

      Ziraia

      Search terns included  collective  index  names,  synon;  .,  CAS Registry
Number, and CHEMLINE and CHEilNAME  nomenclature,   ill  hit- _iOm each data
base were "dumped" and the  computer printouts were  scar   d  for pertinent
references.

-------