297 916:
       ALDRIN /DIELDRIN
Ambient Water Quality Criteria
              Criteria and Standards Division
              Office of Water Planning and Standards
              U.S. Environmental Protection Agency
              Washington, D.C.

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                         CRITERION DOCUMENT



                          ALDRIN-DIELDRIN



 CRITERIA



                            Aquatic Life



      For aldrin/dieldrin the criterion to protect freshwater



 aquatic life as derived using the Guidelines is 0.0019 ug/1 as  a



 24-hour average and the concentration should not exceed  1.2 ug/1



 at any time.



      For aldrin/dieldrin the criterion to protect saltwater



.aquatic life as derived using procedures other than the  Guidelines



 is 0.0069 ug/1 as a 24-hour average and the concentration  should



 not exceed 0.16 ug/1 at any time.



                            Human Health



      For the maximum protection of human health from the potential



 carcinogenic effects of exposure to aldrin through ingestion  of



 water and contaminated aquatic organisms, the ambient water con-



 centration is zero.  Concentrations of aldrin estimated  to result



 in additional lifetime cancer risks ranging from no additional



 risk to an additional risk of 1 in 100,000 are presented in the



 Critrion Formulation section of this document.  The Agency is con-



 sidering setting criteria at an interim target risk level  in  the



 range of 10~5, 10~6, or 10~7 with corresponding criteria of 4.6 x



 10~2 ng/1, 4.6 x 10~3 ng/1, and 4.6 x 10~4 ng/1, respectively.



      For the maximum protection of human health from the potential



 carcinogenic effects of exposure to dieldrin through ingestion  of

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water; and .contaminated aquatic organisms,  the  ambient  water con-
centration :is zero.  Concent rat ions of dieldrin  estimated to re-
sult :in ^additional lifetime cancer risks  ranging from  no^addi-
tional risk to an additional risk of  1  in 100,000 are  presented in
the Criterion Formulation section of  this document.  The Agency is
considering setting criteria at  an interim target risk level in
the range  of 10~5, 10~6, or 10~7 with corresponding  criteria of
4.4 x lO-2 ng/1, 4.4 x 10~3 ng/1, and 4.4 x 10~4 ng^Jf respec-
tively.

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Introduction



     Aldrin and dieldrin have been two of the most widely



used domestic pesticides.  They are chlorinated hydrocarbon



compounds.  Although aldrin is used in greater quantity



than dieldrin, aldrin quickly transforms into dieldrin in



the environment.  Hence, there is concern with both compounds.



The primary use of the chemicals in the past was for control



of corn pests, although they were also used by the citrus



industry.  Uses are restricted to those where there is no



effluent discharge.



     Aldrin use in the United States peaked at 19 million



pounds in 1966 but dropped to about 10.5 million pounds



in 1970.  During that same period dieldrin use decreased



from 1 million pounds to about 670,000 pounds.  The decreased



use has been attributed primarily to increased insect resis-



tance to the two chemicals and to development and availability



of substitute materials.



     Aldrin and dieldrin have been the subject of litigation



bearing upon the contention that these substances cause



severe aquatic environmental change and are potential carcino-



gens.  In 1970, the U.S. Department of Agriculture cancelled



all registrations of these pesticides based upon a concern



to limit dispersal in or on aquatic areas.  In 1972, under



the authority of the Fungicide, Insecticide, Rodenticide



Act as amended by the Federal Pesticide Control Act of 1972,



USCS Section 135, et. sec., an EPA order lifted cancellation



of all registered aldrin and dieldrin for use in deep ground



insertions for termite control, nursery clipping of roots



and tops of non-food plants, and mothproofing of woolen




                              A-l

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textiles and carpets where there  is no effluent discharge*
In  1974, cancellation proceedings disclosed the severe hazard
to  human health  and suspension  of registration  of aldrin
and' dJie.ldrin use was ordered; production was  restricted
fLor. all pesticide products containing aldrin  or dieldziit.,
        , formulated products containing aldrin  and di.el.dtr.ijt
     imported, from Europe e.ac.h. year solely for subsurfcace:
.s,Q-iJL lo.ject.ion.- for termite- control.,.  Therefore.,  limits tfrat
      .^ aJL.1 neceiving: wa-tejc. uses,  must he* placed on addr.in.
       el^lr.in:.  The li ti.gat'i:on has produced, the.  evidentriarcy
       for th.e Administrator-' s conclusions that-  aldrin/dieldr.in
are c^rc.feno,genic in mice and. rats., approved the Agency's
e-xt-r:a:pAl-a,tion. to humans of. data, derived from  tests on an-imal.s,
a.jn;d- .a.f;fi,rmed, the conclusjons that aldrin. and  di.eldrin pose-
a SMteafc-a/nivlal. r:lsk of canc.er to humans, which consrtridt.ut.es.
an:  "'ijciainent; ha.zacd" to. man..
           n- and.  dieldrin are white crystralline  substances
    , ald:mn. melting, at 104°c and  die.-ldr.in melting  between
     to, l;7'7"QGu.  Hoth are; soluble  in organic solvents with:
          thej le-ast soluble of.  the- two.   The chemical name:
fojrr  al.drin i.s 1,  2,  3,  4,, 10",  10-hexachloro-l,  4,  4a, 5,- 8;, 8.a-
hex^ah;y.dEQr-l.,. 4:  5,  8-ex.o-dime.thanonaphathalene.  The chemical
name; for dieldrin is 1., 2, 3,  4,  10,  lO-hexachloro-6, 7—
epToxvy'-l, 4.-, 4a,  5,  6,  7, 8, Sia-octahydro-endo,  exo-1, 4:
5. ,, ai-d;imeit hanonaph t h a 1 ene- .
      Aldrin, i.s-, metabolic ally converted  to. dieldrin.   This,
Qpo.xida.tion has  been shown to  occur, in  several  species includ-
ing;  mamm-als: and  poultry, house^flies-,  locusts, soil microorgan-
     .,  a larg^e number of. Lepidoptera species, freshwater.
                                 A.-2

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fish (Gakstatter, 1968), and a number of freshwater inverte-
brates including protozoa, coelenterates, worms, arthropods,
molluscs, and lobsters.  The aldrin molecule is biologically
altered in the environment to a more stable and at least
equally toxic form, dieldrin.  Dieldrin is known to be meta-
bolically degraded as shown by Matsumura and Boush  (1967)
and Patil, et al. (1972); however, its persistence in the
environment is due to its extremely low volatility  (i.e.,
a vapor pressure of 1.78 x 10-7 mm mercury at 20°C) and
low solubility in water  (186 ;ug/l at 25 to 29°C) (Int. Agency
Res. Cancer, 1974).  In addition, dieldrin is extremely
apolar, resulting in a high affinity for fat which accounts
for its retention in animal fats, plant waxes, and other
such organic matter in the environment.  The fat solubility
of dieldrin results in the progressive accumulation in the
food chain which may result; in a concentration in an organism
which would exceed the lethal limit for a consumer.
     Many organisms not in direct contact with contaminated
water and sediment accumulate aldrin/dieldrin from the food
supply.  This biological concentration results in tissue
concentrations many times those found in the surrounding
environment (Sanborn and Yu, 1973).  Concentrations increase
in the food chain reaching the carnivores at the top including
man.
     Dieldrin is probably the most stable insecticide among
the cyclodienes  (i.e., isodrin-endrin; heptaclor-heptachlor
epoxide) .  The time required for 95 percent of the dieldrin
to disappear from soil has been estimated to vary from 5
to 25 years depending upon the microbial flora of the soil
                             A-3

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(Edwards, 1966).  Dieldrin applied at 100 ppm has  been  shown
to persist in soil for more than six years  (Westlake  and
San Antonio, 1960) , while at 25 ppm in a different  soil
type, a 50 percent loss was found at seven years  (Nash  and
Woolson, 1967).  When applied to sandy soil at a rate of
100 ppm, residues could be found 15 years later.  Matsumura
and Boush (1967) found that of 577 bacterial isolates collect-
ed from areas heavily contaminated with dieldrin,  10  isolates
would alter dieldrin to two to nine unidentified metabolites.
The microbes were members of Pseudomonas, Bacillus, and
Trichoderma genera. Subsequent microbiological studies  by
Wedemeyer (1968) revealed that Aerobacter aerogenes also
will alter dieldrin similarly to 6,7- trans-dihydroxydihydro-
aldrin.  Chacko, et al.  (1966) tested this capability of
17 species of fungi and actinomycetes.  Though most degraded
pentachloronitrobenzene  (PCNE) or DDT or both, none degraded
dieldrin.
     Patil, et  al. 1972, studied the metabolic transformations
of aldrin/dieldrin by marine algae, surface film, sediments,
and water.  They found that the insecticide was *not degraded
or metabolized  in sea water or polluted waters.  Some marine
algal populations were shown to degrade aldrin to dieldrin.
     Alterations of dieldrin by bacterial systems result
in the formation of at least one acidic product  (Matsumura
and Boush, 1967).  Once in the fatty tissue of organisms,
dieldrin remains stable, according to Sanborn and Yu  (1973).
However, dieldrin can be mobilized from fatty tissue as
demonstrated by Brockway  (1973); for example, when  fish
                              A-4

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are placed in an environment without dieldrin, there is
an elimination from the tissue (Brockway, 1973).  The elimina-
tion rate depends upon the diet with fasted fish eliminating
dieldrin more rapidly than fed fish because of the utilization
of fat stores (Grzenda, et al. 1972).
     The dieldrin eliminated from the tissues reenters the
water and thus becomes available for bioconcentration by
other organisms.  The movement of dieldrin among organisms,
water, and sediment is dynamic, with equilibrium attained  .
when the chemical concentration is constant.
                              A-5

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                          REFERENCES







Brockway, D.C. 1973.  The uptake, storage and release of



dieldrin and some effects of its release in the fish, Cichlo-



soma bimaculatum  (Linnaeus).  Diss. Abstr. Int. 33: 4323B.







Chacko, C.I., et al. 1966. Chlorinated.hydrocarbon pesticides:



Degradation by microbes.  Science 154: 893.







Edwards, C.A. 1966. Insecticide residues in soils.  Residue



Rev. 13: 83.







Gakstatter, J.H. 1968. Rates of accumulation of 14C-dieldrin



residues in tissues of goldfish exposed to a ssingle 'sublethal



dose of 14C-aldrin. Jour. Fish. Res. Board Can. 25: 1797.







Grzenda, A.R., et al. 1972.  The elimination and turnover



of 14C-dieldrin by different goldfish tissues.  Trans. Am.



Fish. Soc. 101: 686.







International Agency for Research on Cancer. 1974. Dieldrin.



IARC monographs on. the evaluation of carcinogenic risk of



chemicals to man: Some organochlorine pesticides. 5: 125.







Matsumura, F., and G.M. Boush. 1967. Dieldrin: Degradation



by soil microorganisms. Science 156: 959.







Nash, R.G., and.E.A. Woolson. 1967.  Persistence of chlorinated



hydrocarbon insecticides in soils.  Science 157: 924.




                              A-6

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Patil, K.C., et al. 1972. Metabolic transformation of DDT,



dieldrin, aldrin, and endrin by marine microorganisms. Environ.



Sci. Technol. 6: 631.







Sanborn, J.R., and C.C. Yu. 1973. The fate of dieldrin in



a model ecosystem. Bull. Environ. Contain. Toxicol. 10: 340.







Wedemyer, G. 1968. Partial hydrolysis of dieldrin by Aerebacter



aerogenes. Appl. Microbiol. 16: 661.







Westlake, W.E., and J.P. San Antonio. 1960. Insecticide



residues in plants, animals and soils. Page 105 in. The nature



and fate of chemicals applied to soils, plants, and animals.



U.S. Dep. Agric. 20: 9.
                              A-7

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AQUATIC LIFE TOXICOLOGY*



                       FRESHWATER ORGANISMS



Introduction



     Aldrin and dieldrin are members of a group  of  synthetic



cyclic hydrocarbons called cyclodienes.  The group  includes other



insecticides such as chlordane, heptachlor, endosulfan  and  endrin.



Until recently, aldrin and dieldrin were the most widely  used



domestic pesticides with aldrin being applied  in much greater



quantities than dieldrin.  However, these pesticides are  often



considered together since aldrin is rapidly converted in  animal  or



plant tissue and soil to dieldrin.  This conversion is  accom-



plished through the addition of an epoxide group to the aldrin



molecule.



     Since aldrin is rapidly converted to dieldrin  and  there are



no adequate data in all the criterion areas, no  criterion has been



developed for aldrin.  The following discussion  is  based  on diel-



drin data only except where specifically noted.
*The reader is referred to the Guidelines  for Deriving Water  Qual-



ity Criteria for the Protection of Aquatic Life  [43  FR 21506  (May



18, 1978) and 43 FR 29028 (July 5, 1978)]  in order  to better



understand the following discussion and recommendation.   The  fol-



lowing tables contain the appropriate data that  were found  in the



literature, and at the bottom of each table are  the  calculations



for deriving various measures of toxicity  as described in the



Guidelines.
                              B-l

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Acute Toxicity


     Sixty-seven acute  toxicity  tests  using  dieldrin are reported



in Table 1.  The tests  were  conducted  with ten  species  of fish



ranging from coldwater  fish  such as  the  rainbow trout,  coho and



chinook salmon to warmwater  fish such  as  the goldfish and carp.



All of the tests were static and none  included  measured concentra-


tions.  The adjustment  of a  48-hour  LC50  to  a 96-hour value was



necessary only for  the.  exposure  of the mosquitofish.



     Dieldrin is acutely toxic at low  concentrations.  Only 10 of



the 67 adjusted LC50 values  are  greater  than 10 ug/1 and a major-



ity of the values below 10 ug/1  are  in the range of  0.6 to 5.5



ug/1.  There are, however, species differences.  The most sensi-



tive fish tested was the rainbow trout with  96-hour  LC50 values



between 0.6 ug/1 and 5.4 ug/1.   The  other salmonids  (coho and



chinook salmon) had 96-hour  LC50 values  of 3.3  and  5.9  ug/l»  re-


spectively.  The most resistant  fishes were  the carp and the  gold-
      (

fish with 96-hour LC50  values of 33  and  22 ug/lr respectively.  In


the middle of the range, between the salmonids  and  the  carp,  were



fathead minnows  (range  9 to  20 ug/D and  the bluegill (range  4.8
      !                                                  I

to 17 ug/D.  Special attention  should be given to  the  data on the


guppy in the report by  Chadwick  and  Kiigemagi (1968) concerning
                                                        i

the development of  a toxicant delivery system.   To  determine  the


efficiency of the system, guppy  toxicity  tests  were  conducted over


an extended time period and  the  data are  included in Table 1.



Thirty-eight of the 67  test  results  are  from this study and range



from 1.3 to 5.5 ug/1.


      Thirteen fish species  were tested  and  23  tests were com-



pleted using aldrin.  The range  of the adjusted values  (1.2 to
                               B-2

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25.1 ug/1) is similar to the values obtained  for  dieldrin.   One

test, not included in the range, had a 96-hour LC50 value of 97

ug/lo  This test used the mosquitofish which  is well-known  for

pesticide-resistant wild populations.  When the geometric means

from Table 1 are divided by the sensitivity factor 3.9,  the

resulting Final Fish Acute Values are 1.6 and 2.4 ug/1  for  diel-

drin and aldrin, respectively.  Only 11 of the 67 dieldrin  tests

are lower than this concentration (1.6 ug/1)  and  of these 11,  8

are with the guppy (Chadwick and Kiigemagi, 1968) and are balanced

by 30 values above 1.6 ug/1.  The other three LC50 values are  for

the rainbow trout.  These results suggest that the adjustment  fac-

tors from the Guidelines are appropriate.

     Nineteen acute toxicity test results for dieldrin  and  inver-

tebrate species are presented in Table 2.  All of these  tests  were

conducted under static water conditions and the concentra-  tions
                                i
were not measured.  The adjusted concentrations range from  a 96-

hour LC50 value of 0.4 ug/1 for the stoneflies Pteronarcella badia

and Pteronarcys californica (Sanders and Cope, 1968) to  627 ug/1

for the crayfish (Sanders, 1972).  This wide  range in concentra-

tion of over 1,500 times demonstrates definite differences  in  in-

terspecific sensitivity to this compound.

     Intraspecific variation is apparent for  the  stonefly and

ostracod data.  This variation may have resulted  from differences

in experimental procedures used in stonefly testing and  Guideline

applications to the ostracod data.  Sanders and Cope  (1968) deter-

mined a 96-hour LC50 value of 0.5 ug/1 dieldrin at 15°C  for the

stonefly Pteronarcys californica.  They did not aerate  the  test

water.  Jenson and Gaufin (1964) used aeration and a slightly
                              B-3

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higher test temperature  of  15.5°C  and  determined  a much larger



(about 78 times) 96-hour LC50 value of 39  ug/1  for this species.



Since this insect  inhabits  well  oxygenated flowing water the non-



aerated static  test may  have potentiated  toxic  effects.  Hansen



and Kawatski  (1976) report  a 24-hour LC50  value of 185 ug/1 and a

      i

72-hour LC50  value of  12.3  ug/1  with the  ostracod Cypretta



kawatai.  These  tests  were  conducted under similar conditions but



were of different  duration.



     The geometric mean  of  the dieldrin data, 26  ug/lf was divided



by the sensitivity factor of 21  from the  Guidelines to obtain a



concentration of 1.2 ug/1.  This concentration  is higher than 3 of



the 1:9 adjusted  concentrations for the tested invertebrate species;



this result appears to support the procedures in  the Guidelines



for the sensitivity factor.
    i


     Results  of  13 acute toxicity  tests with  aldrin are also pre-



sented in Table  2.  Each test was  conducted  so  that data could be



compared with data obtained from similar  tests  with dieldrin.



Adjusted aldrin  96-hour  LC50 values range  from  1.1 ug/1 for the



•stonefly (Sanders  and  Cope, 1968)  to 32,609  ug/1  for the scud
      i                                                   '


(Ga.ufin, et al,  1965).   The cladocerans were  relatively more sen-



1966).  In all  other cases  the invertebrates  were relatively more



sensitive to  d.ieldrin.   For aldrin, the estimated concentration at



or below the  96-hour LC50 value  for 95 percent  of all invertebrate



species is 3,8  ug/1•



     Acute toxicity tests with aldrin  and  dieldrin have estab-



lished that these  compounds are  toxic  to  aquatic  life at low con-



centrations.  The  data indicate  that dieldrin is  slightly more



toxic than aldrin  for  both  fish  and invertebrates.  The Final Fish
                               B-4

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Acute Value is 1.6 ug/1  and  the  Final  Invertebrate Acute Value is


,1.2 ug/1.  Because the Invertebrate  Acute Value is the lowest, the


Final Acute Value is  1.2 ug/1.


Chronic Toxicity


     Two chronic toxicity tests  have been conducted with dieldrin.


.One was an embryo-larval exposure  using  steelhead (rainbow) trout


(Chadwick and Shumway, 1969).  This  species was the most sensitive


rspecies according to  the acute studies (Table 1).  The other


chronic exposure was  a three-generation  study using the guppy


(Roe-lpfs, 1971).  Fortunately, the 96-hour LC50 concentration is


.well-established for  this fish  (Table  1)  and is about 2.9 ug/1.


The geometric mean  (0.21 ug/1) of  the  two chronic concentrations


divided by the sensitivity factor  (6.7)  results in a 95 percent


protection concentration or  Final  Fish Chronic Value of 0.031


ug/1  (Table 3).  Since the two tested  species include the most


sensitive and a moderately sensitive species, the calculated con-


centration should confer adequate  protection for the non-tested


fish species.


     No chronic studies  were found for these important animals.
        i

Because of the lack of chronic data, it  is necessary to reexamine


the invertebrate test results.   All  of the acute invertebrate


values are greater than  the  fish geometric mean chronic concentra-


tion of 0.21  ug/1.  However,  three stonefly species have adjusted


acute values  (0.4 to  0.5 ug/1) which are  close to the fish geomet"


ric mean value.  These data  were obtained under static water con-


ditions without aeration and the dieldrin concentrations were not


measured.  More meaningful data  for  assessing the risk of chronic


exposure of dieldrin  to  stoneflies was obtained by Jensen and
                               B-5

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Gaufin (1966)o  They determined  a  30-day  LC50  value  of 2  ug/1/
based on measured concentrations,,  for  one of  the  three species, £.
californica  (Table  6),  in  flowing  water to which  stoneflies  are
adapted.  A  lower 30-day LC50 value of 0.2 ug/1 was  also  obtained
for another  stonefly Acroneuria  pacifica.  These  data indicate
that the insect chronic value might be less than  that calculated
for fisho  A lower  value might be  expected because the primary  use
of dieldrin  was as  an  insecticide.
     After applying the sensitivity factor the Final Fish Chronic
Value is 0.031 ug/1.   The  extent of protection for the inverte-
brates is unknown but  it can be  estimated from the acute  toxicity
test that many would be safe if  exposed at the concentration of
0.031 ug/1.
Plant Effects                                             *
     Four dieldrin  toxicity tests  using three  plant  species  were
found (Table 4).  The  alga, Scenedesmus quadricaudata, was  the
most sensitive species  tested with a 22 percent reduction in
biomass after exposure  to  100 ug/1 of  dieldrin (Stadnyk and
Campbell, 1971).  The  other species, diatom and water meal,  were
affected only at concentrations  100 times higher  than the alga.
Since fish and invertebrate species were  affected at concentra-
tions 100 times lower  than the alga, the  plants should be pro-
tected by the animal-derived data.
Residues
     Table 5 contains  the  results  of 10 residue studies with diel-
drin.  No comparable aldrin data were  found.   The 10 studies in-
clude plant,  invertebrate  and fish species.  The  range of the bio-
concentration factors  (BCF) are  from 128  for  an alga (Reinert,
                               B-6

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1972) to 68,286 for lake trout (Reinert, et al. 1974).   All  of  the



authors (except Reinert, et al. 1974) indicate that  an equilibrium



had occurred in their specific study.  An examination of the data



in the reports supports the conclusion of the  individual authors.



     The analysis of the residue data can be divided into two



broad groups, the plant-invertebrate and the fish data.   The



plant-invertebrate BCF values range from 128 to 5,558.   The  two



values representing the algal and diatom community accumulations



are perhaps the most ecologically applicable data  in this group.



The studies were conducted in open channels under  field  conditions



whereas the other algal study was a short-exposure laboratory



test.  The invertebrate BCF values show a comparatively  low  bio-



accumulation potential for the two species.



     The fish BCF values range from 2,385 to 68,286.  Although  all



but one of the authors report that equilibrium had occurred  in



each of their exposures, there seems to be a relationship between



length of exposure and total residue accumulation.   For  example,



guppies exposed for 32 days had a BCF of 12,708 while exposure  for



160 to 230 days resulted in a BCF of 28,408.   The  same relation-



ship may explain the high BCF for the lake trout.  The bioconcen-



tration of dieldrin by this species may become greater since the



fish had not reached an equilibrium when 'the study was terminated.



The channel catfish BCF is the lowest of the fish  values (Shannon,



1977a,b).  This is probably a result of the experimenter analyzing



dorsal muscle rather than whole fish as was done by  the  others.



     The residue limit established by the Food and Drug  Adminis-



tration (FDA) for dieldrin in domestic animal  feed  is 0.03 mg/kg,
                              B-7

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 and was used to calculate  the Residue Limited Toxicant Concentra-
tion (RLTC). : The FDA  domestic animal feed concentration of  0.03
 mg/kg .divided by the average fish bioconcentration factor  of
.15,482 gives a RLTC of 0.0000019 mgAg or 0.0019 iig/1.
      .The .lowest of .the Final Fish Chronic Value  (0.0.31 ug/D -,
:Final Invertebrate Chronic Value (none), Final Plant Value  (100
,ug-/D ...and 'the RLTC  (0.0019 ug/1) is -used to determine the  Final
 Chronic Value,.  Tor dieldrin the Final-Chronic Value is '0.0019
.ug/1.
' Ma:,scellan.e:ous
      Data•;presented ..in Table 6 do not conflict with the selection
 o.'f 0.001;9 ug/1 -:as .the  .Final 'Chronic Value.
                                B-8

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CRITERION FORMULATION



                      Freshwater-Aquatic Life



Summary of Available Data



     The concentrations below have been rounded  to  two  significant



figures.



     Final Fish Acute Value =1.6 ug/1



     Final Invertebrate Acute Value = 1.2 ug/1



          Final Acute Value = 1.2 ug/1



     Final Fish Chronic Value = 0.031 v.g/1



     Final Invertebrate Chronic Value = not  available



     Final Plant Value = 100 ug/1



     Residue Limited Toxicant Concentration  = 0.0019 ug/1.



          Final Chronic Value = 0.0019 ug/1



          0.44 x Final Acute Value = 0.53 ug/1



     The maximum concentration of dieldrin is the Final Acute



Value of 1.2 ug/1 which is based on the more acutely sensitive in-



vertebrate organisms.  Since 0.44 times the  Final Acute Value (0.44



x 1.2 ug/1 = 0.53 ug/D is not lower than the Final Chronic Value



(0.0019 ug/Df the latter is the recommended 24-hour average con-



centration.  No important adverse effects on freshwater aquatic



organisms have been reported to be caused by concentrations lower



than the 24-hour average concentration.



     CRITERION:  For dieldrin the criterion  to protect  freshwater



aquatic life as derived using the Guidelines is  0.0019  ug/1 as a



hour 24-average and the concentration should not exceed 1.2 ug/1



at any time.
                              B-9

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Table  1.  Freshwater fish acu.te values for aldrin/dieldrin
                                                            Adjusted
Bioasaay __Test
'Organism HfeifiS^Jl Cone.**
Rainbow trout, S U
Salmo gairdneri
Rainbow trout,
Salmo Rairdneri
Rainbow trout ,
Salmo gairdneri
Rainbow trout:,
Salmo gairdneri
Coho salmon,
Oncorhynchus kisutch
to
l!j Chinook salmon,
o Oncorhynchus tshawytscha
Goldfish,
Carassius auratus
Carp,
Cyprlnus carpio
Fathead minnow,
Pimephales promelas
Fathead minnow,
I'imephalea promelas
Fathead minnow,
Pimephales promelaa
Fathead minnow,
Pimephales promelas
Fathead minnow,
Pimephales promelas
Fathead minnow,
Pimophales promelas
S
S
S
S
S
S
S
S
S
S
S
S
S
U
U
U
u
u
u
u
u
u
u
u
u
u
Chemicai
Description - •
Dieldrin
90% dieldrin
85% dieldrin
85% dieldrin
85% dieldrin
90% dieldrin
90% dieldrin
90% dieldrin
15% dieldrin
90% dieldrin
90% dieldrin
85% dieldrin
85% dieldrin
85% dieldrin
85% dieldrin
Time
ms>
*
96
96
96
96
96
96
96
96
96
96
96
96
96
96
LCbU
• (^^v
9.9
2.4
1.1
10.8
6.1
41
60
18
18
36
,24 „ .
16
25
LC!>0
(uq/il
5.4
1.3
0.6
0.8
5.9
3.3
22
33
10
10
20
13
9
14
• Reference
Katz, 1961
Macek, et al.
1969
Macek, et al.
1969
Macek. et al.
1969
Katz, 1961
Katz, 1961
Henderson,
et al. 1959
Rao, et al.
1975
Henderson.
et al. 1959
Henderson .
et al. 1959
Tarzwell
Henderson, 1957
Tarzwell &
Henderson, 1957
Tarzwell &
Henderson, 1957
Tarzwell &
Henderson, 1957

-------
                   Table  1.   (Continued)
Organism
                        Bioaseay  Test      Cnemical       Tame      LC5U
Adjusted
XCiO
jug/11    Keterence
Fathead minnow,
Pimfcphales promelas
Hosquitofish,
Gambusia af finis
Guppy,
Poecilia
Cuppy,
Poecilia
Cuppy,
Poecilia
Guppy ,
Poecilia
CD
jjj Guppy,
i_i Poecilia
Guppy ,
Poecilia
Guppy ,
Poecilia
Guppy ,
Poecilia
Guppy ,
Poecilia
Guppy,
Poecilia
Guppy ,
Poecil la
Guppy,
Poecilia
Guppy,
Poecilia
reticulata

reticulata

reticulata

-rctlTrul-ata


-reticulata

reticulata

reticulata

reciculata

reticulata

reticulata

reticulata

reticulata

reticulata
S
S
S
S

S

S


S

S

S

S

S

S

S

S

S

u
u
"
u

u

u


u

u

u

u

u

u

u

u

u

85% dieldrin
957. dieldrin
"Technical
dieldrin
Technical
-->die-ldrin
"Technical
dieldrin
Technical
-d-fcel-drin

Technical
dieldrln
Technical
dieldrin
Technical
dieldrin
• Technical
dieldrin
Technical
dieldrin
Technical
dieldrin
Technical
dieldrin
Technical
dieldrin
Technical
dieldrin
grade
grade

grade

•grade


grade

grade

grade

grade

grade

grade

grade

grade

grade

96
48
-96
96

96

96


96

96

96

96

96

96

96

96

96

23
8
3
4

3

5


3

3

3

3

4

4

4

4

3


*
n

.9

.1


.9

.7

.2

.9

.2

.3

.3

.1

.5

13
3
*
^

2

1


2

2

1

2

2

2

2

2

1


•*
6

.1

.8


.1

.0

.7

.1

.3

.3

.3

.2

.9

Tarzwell &
-Henderson. 1957
Culley &
Ferguson, 1969
Chadwick &
Kiigeraagi. 1968
Chadwick &
Xilgemagl. 1968
Chadwick &
Kligemagl. 1963
Chadwick A
XHgenagl, 1958

Chadwick &
Kiigemagij 19.68
Chadwick &
Kii£emagi. 1968
Chadwick &
Kiigemagi, 1968
Chadwick &
Kiigemagi, 1968
Chadwick &
Kiigeraagi, 1968
Chadwick 6r
Kiigemagi. 1968
Chadwick &
Kiigemagi, 1968
Chadwick &
. Kiigemagi, 1968
Chadwick &
Kiigemagi, 1968

-------
                             Table   1.   (Continued)
         Organism
Bioassay  Test      Chemical
       _  ConCj.**   Description    jhrs)
                LC5U
                (uy/il
                                                                                         Adjusted
                                                                                         LCbO
                                                                                                   hetexence
Guppy,
Poecilia
                   reticulata
DO
I
!-•
tO
Guppy.
Poecilia
                   reticulaca
Guppy
Poecilia
                   reticulata
Guppy,
Poecilia
                   reticulata
Guppy,
Poecilia
                   reticulata
Guppy.
Poecilia

Guppy,
Poecilia
                   reticulata
                   reticulata
Guppy,
Poecilia
                  reticulata
Guppy.
Poecilia
                   reticulata
Guppy,
Poecilia
                   reticulata
Guppy,
Poecilia
                   reticulnta
Guppy,
Poecilia

Guppy,
Poecilia

Guppy.
Poecilia

Guppy.
Poecilia
                   reticulata
                   reticulata
                   reticulata
                  reticulata
   S


   S


   S


   S


   S


   S


   S


   S


   S


   S


   S


   S


   S


   S


   S
U


U


U


U


U


U


U


U


U


U


U


U


U


I)


U
Technical
dieldrin

Technical
dieldrin

Technical
dieldrin

Technical
dieldrin

Technical
dieldrin

Technical
dieldrin

Technical
dieldrin

Technical
dieldrin

Technical
dieldrin

Technical
dieldrin

Technical
dieldrin

Technical
dieldrin

Technical
dieldrin

Technical
dieldrin

Technical
dieldrin
grade  96


grade  96


grade  96


grade  96


grade  96


grade  96


grade  96


grade  96


grade  96


grade  96


grade, 96


grade  96


grade  96


grade  96


grade  96
4.7


3.2


2.9


2.6


2.9


2.4


2.6


2.3


2.7


2.3


2.7


2.7


4.8


6.1


3.2
2.6    Chadwick &
       Kiigemagi, 1968

1. 7    Chadwick &
       Kiigemagi. 1968

1.6    Chadwick &
       Kiigemagi, 1968

1.4    Chadwick &
       Kiigemagi. 1968

1.6    Chadwick &
       Kiigemagi, 1968

1.3    Chadwick &
       Kiigemagi. 1968

1.4    Chadwick &
       Kiigemagi, 1968

1.3    Chadwick &
       Kiigemagi, 1968

1.5    Chadwick &
       Kiigemagi. 1968

1.3    Chadwick &
       Kiigemagi. 1968

1.5    Chadwick &
       Kiigemagi, 1968

1.5    Chadwick &
       Kiigemagi. 1968

2.6    Chadwick &
       Kiigemagi. 1968

3.3    Chadwick &
       Kiigemagi. 1968

1.7    Chadwick &
       Kiigemagi. 1968

-------
                   Table   1.   (Continued)
                                                                      LC50
Adjusted
LCbO
(uq/i)    heterence











CD
1

(jJ















Guppy ,
Poecilia reciculaca
Guppy.
Poecilia reciculaca
Guppy,
Poecilia reciculaca
Guppy .
Poecilia reciculatd
Guppy.
Poecilia reciculaca
Guppy.
Poecilia reciculaca

Guppy.
Poecilia reciculata
Guppy.
Poecilia reciculaca
Guppy ,
Poecilia reciculaca
Guppy.
Poucilla reticulaca
Guppy.
Poecilia reciculoCa
Guppy .
Poecilia reciculata
Green uunfish,
l.epomis ey_anellus
Green bunt'isli.
l.epomis eyanellus
Green sun fish,
S

S

S

s

s

s


s

s

s

s

s

s

s
,
s

s
rf-"^T -TT
u

u

u

u

u

u


u

u

u

u

u

u

u

u

u
99+% dieldrin

99+% dieldrin

99+7. dieldrin

99+7. dieldrin

99+7. dieldrin

99+% dieldrin


99+7. dieldrin

99+% dieldrin

99+7. dieldrin

99+% dieldrin

90% dieldrin

Dieldrin

85% dieldrin

85% dieldrin

85% dieldrin
• • i , i'f
96

96

96

96

96

96


96

96

96

96

96

96

96

96
,
96
6.6

5.6

6.1

7.5

10

6.6


6.6

6.9

A. 7

7.5

25

21

6

11

8
3.6

3.1

3.3

4.1

5.5

3.6


3.6

3.8

2.6

4.1

14

11

3

6

A
Chadwick &
Kiigemagi, 1968
Chadwick &
Kiigemagi, 1968
Chadwick &
Kiigemagi, 1968
Chadwick &
Kiigemagi, 1968
Chadwick &
Kiigemagi. 1968
Chadwick &
Kiigemagi, 1968

Chadwick &
Kiigemagi, 1968
Chadwick &
Kiigemagi, 1968
Chadwick &
Kiigemagi. 1968
Chadwick &
Kiigemagi, 1968
Henderson.
et al. 1959
Cairns & Loos,
1966
Tarzwell &
Henderson, 1957
Tarzwell &
Henderson, 1957
Tarzwell &
I.cnomi s c
          Henderson, 1957

-------
                               Table 1.    (Continued)
CD
I
            Oraarjisro
Bluegill.
Lcpomis macrochirua

Bluegill.
Lepomls macrochlrua

Bluegill,
Lcpomis maci'ochiru3

Bluegill.
Lepomls macrochlrus

Bluegill.
Lepomls macrochirus

Bluegill,
Lepomiu macrochirus

Bluegill.
Lepornia macrochirus

Bluegill.
Lepomis macrochirus
           American  eel,
           AnjjuLHa  rostrata

           Rainbow crouc,
           Salino gairdnerl

           Rainbow Crouc,
           Sal mo j'.aircl fieri

           Rainbow trout,
           Saliiio galrdneri

           Rainbow trout.
           SaInio ga irdneri

           Colio salmon,
           Oncorliynclms klsucch
                                    Bioataay  Test      Chemical        Time
                                                                        (nra)
                                                                                 Adjusted.
                                                                       LCbc       LCiu
                                                                                 (ug/it   ^ heterence
S

s

s

s

s

s
s

s


s

s
s

s •

s

s
U

U

U

U

U

U
IJ

U


U

U
U

U

U

11
90% dleldrln

85% dieldrin

85% dieldrin

85% dleldrln

85% dieldrin

85% dieldrlp
85% dieldrin

85% dieldrin

Aldrin
Aldrin

88.4% aldrin
95% aldrin

95% aldrin

95% aldrin

88. *4% aldrin
.••i • "f
96

96

96

96

96

96
96

96


96

96
96

96

96

96
9

17

14

8.8

32

18
8

22


16

17.7
3.2

3.3

2.2

45.9
5

9

8

4.8

17

10
4

12


9

9.7
1.7

1.8

1.2

25.1
Henderson,
ec al. 1959
Macek,
ec al. 1969
Macek,
ec al. 1969
Macek,
ec al. 1969
Tarzwell &
Henderson, 1957
Tarzwell &
Henderson, 1957
Tarzwell &
Henderson, 1957
Tarzwell &
Henderson, 1957

RehwoldC,
ec al. 1977
Kacz. 1961
Macek.
ec al. 1969
Macek.
ec al. 1969
Macek,
ec al. 1969
Kacz. 1961

-------
                             Table  1.   (Continued)
03
I
          Organism
Chinook salmon,
Oncorhynchua tshawytscha

Goldfish.
Carassius auratua

Carp.
Cyprinus carpio

Carp.
Cyprinus carpio

Fathead minnow,
Pimephales promelas

Fathead minnow,
Pimephales promelas

Banded killifish,
Fundulus diaphanus

Mosquitofish,
Gambusia affinis

Mosquitofish,
Gambusia affinis

Guppy,
Poecilia reticulata

Guppy,
Poecilia reticulata

Uhite perch,
Koccjuis  americanus

Striped bass,
Morone  saxatilis

lilucgill.
Lcpomls macrochirus

BluegiJl.
l.upoiiiis macrochirus

assay
hod*_
S
S

S

S

S
S

S

S

S

S

S

S

S

S

S


Test
Cone .**
U
U

U

U

U
U

U

U

U

U

U

U

U

U

U


Chemical
Description
88.4% aldrin
88.4% aldrin

30% aidrin

Aldrin

88.4% aldrin
88.4% aldrin

Aldrin

95% aldrin

Aldrin

88.4% aldrin

Aldrin

Aldrin

Aldrin

88.4% aldrin

95% aldrin


Time
(nrs)
96
96
^
96

96

96
96

96

48

24

96

96

96

96

96

96


LCbo
(Uj/11
6.1
32

3.7

4

37
32

21

36

270

37

20

42

10

15

7.7

Adjusted
LC'jO
(uq/l)
3.3
17

2

2.2

20
17

11

16

97

20

11

23

7

8

4.2



Keterence
Katz, 1961
Henderson.
et al. 1959
Rao, et al.
1975
Rehwoldt,
et al. 1977
Henderson,
et al. 1959
Henderson,
et al. 1959
Rehwoldt ,
et al. 1977
Culley &
Ferguson, 1969
Krieger &
Lee. 1973
Henderson ,
et al. 1959
Rehwoldt,
et al. 1977
Rehwoldt,
et al. 1977
Rehwoldt,
et al. 1977
Henderson,
et al. 1959
Macek,
et al. 1969

-------
                               Table  1.  (Continued)
00
I
M
a\
                                              test      cnemicai        Time
                                    Method*   couc.**   Description    tnta)
          Adjusted
'LCb'i,      LC!>0
lug/I)     tuq/il     heterfence
Bluegill, S 11 95% aldrin 96
Lepomis macrochirus
Bluegill. S U 95% aldrin 96
Lepomis macrochirus

5.8 3.2 Macek-.
et al. 1969
A. 6 2.5 Macek,
et al. 1969
           *  S - static

           ** I) = unmeasured
                                                                          5.9
              Geometric mean of  adjusted valuesi   Dieldrin » 5.9 pg/1   LL± «• 1.6


                                                                       •

                                                    Aldrin - 9.4 »,g/l         - 2.4 Mg/l

-------
                             Table  2.   Freshwater intertebrate acute values for aldrtn/dieldrln
                                  Bioassay  Test      Chemical       Time
                                  Method*   Cone .**   Description    Hire)
                                                                               LCt>0
                                   Adjusted
                                   LCbO
                                    (ug/l>    Heterence
03.


-J
Cladoceran,                S        U
Daphnia carinata

Cladoceran,                S        U
Daphnia pulex

Cladoceran,                S        U
Simocephalus serrulatus

Cladoceran,                S        U
Simoccphalus serrulatus

Ostracod,                  S        U
Cypretta kawatai

Ostracod,                  S        U
Cypretta kawatai

Isopod,                    S        U
Asellus breicaudus

Scud.                      S        U
Gammarus fasciatus

Scud.                      S        U
Gammarus fasciatus

Scud,                      S        U
Ganimarus lacustris

Scud,                      S        U
Gammarus lacustris

Glass shrimp,              S        U
Palaemonetcs kadiakensis

Crayfish,          "       S        U
Orconecies nais

Mayfly,                    S        U
Ephemeralla grandis
                                                        Dieldrin

                                                     Technical grade  48
                                                     dieldrin
                                                     Dieldrin
                                                     Dieldrin
                                                     Dieldrin
                48
                48
                43
                                                      99+7. dieldrin   24
99+% dieldrin   72
                                                     Dieldrin


                                                     Dieldrin


                                                     Dieldrin


                                                     Dieldrin


                                                     Dieldrin


                                                     Dieldrin


                                                     Dieldrin


                                                     Dieldrin
                96


                96


                96


                96


                96


                96


                96


                96
130        110     Santharara,
                   et al.  1976

250        212     Sanders &
                   Cope, 1966

240        203     Sanders &
                   Cope. 1966

190        161     Sanders 6.
                   Cope, 1966

185         41     Hansen &
                   Kawatski, 1976

 12.3        6.3   Hansen &
                   Kawatski, 1976

  5          4     Sanders, 1972
640        542     Sanders, 1972


600        508     Sanders. 1972


700        593     Gaufin, et al.
                   1965

460        390     Sanders, 1969


 20         17     Sanders, 1972


740        627     Sanders. i972
  8          7     Gaufin, et al.
                   1965

-------
                   Table   2.   (Continued)
                                                                                 Adjusted
Uioabsay.
Organism ' Mgtnod*'
Stonefly, S
Acroneuria paclfica
Sconefly.
Claasaenta sabulosa
Stonefly,
Pteronarcella badia
Stonefly,
Pteronarcys callfornlca
Stonefly.
Pteronarcys callfornica
~"~~L- ' " . e - -_ .
CD
!
h* Cladoceran,
* Daphnia pulcx
Cladoceran,
Slmocephalus aerrulatua
Cladoceran,
Simocephalua serrulatus
Isopod.
Asellus bretcaudus
Scud .
Gammarus fasciatus
Scud.
Ganuuarus fasciatus
Scud, 	
Gammarus lacustris
Scud,
Ganuuarus lacuatris
Class shrimp.
S
S
S
S
S
S
S
S
S
S
S —
S
S
_ Test Cliemicai
Cone t** bebcri ption-
U
U
U
u
u
u
u
u
u
I)
u
- u -
u
u
100% dieldrln
Oieldrin
Dleldrin
100% dieldrln
Technical grade
dieldrin '
Aldrin
Aldrin
Aldrin
Aldrin
Aldrin
Aldrin
Aldrin
Aldrin
Aldrin
Aldrin
Time
(lira)
96
96
96
96
96
u
48
48
96
96
96
96
96
96
LCbu
24
0.58
0.5
39
0.5
28
23
32
8
4,300
5.600
38 . 500
9.800
50
^q/il
20
P. 5
0.4
33
0.4
24
19
27
7
3.642
4,743
32,609
8.301
42
inference
Jensen & .
Gaufln. 1964
Sanders &
Cope, 1968
Sanders &
Cope , 1968
Jensen &
Gaufin, '1964
Sanders &
Cope, 1968
Sanders &
Cope, 1966
Sanders & .
Cope. 1966
Sanders &
Cope, 1966
Sanders, 1972
Sanders. 1972
Sanders, 1972
Gaufln, et al
1965
Sanders, 1969
Sanders, 1972
Palaeiuonctett kadiakensia

-------
Table   2.  (Continued)
                                                            Adjusted
Organism
Mayfly.
Ephemerella grandis
Stonefly,
Acroneuria pacifica
Stonefly.
Pteronarcys californica
Sconefly.
Pteronarcys californica

* S = static
*"* U = unmeasured
CO
1 Geometric mean of ad
Bioassay
HetJiod*
S
S
S
S
Ttst Chemical
ConCj.** Description
U Aldrin
U Aldrin
U 93% aldrin
U Technical grade
aldrin
lusted values:
Dleldrln = 26 wg/l
Time LCbO
(t>r§) (ug/il
96 9
"96 143
96 180
96 1.3
^ - 1.2 pg/1
LCbO
(uq/i) heterence
8 Gaufin, et al.
1965
121 Jensen &
Gaufin. 1964
152 Jensen &
Gaufin, 1964
1.1 Sanders &
Cope, 19ba

                     Aldrin = 80 Mg/l
                                         80
3.8 Mg/l

-------
00
to
o
                         Table   3.  Freshwater fish chronic values  for  aldrln^dieldrin


                                                            CJuonic
                                                  Limits    value
           Orqaniarii                    ' jest*
           Steelhead trout,              E-L     0.12-0.39   Q.ll**        Chadwlck & Shniftway>  1969
           Salmo palrdnert

           Guppy,                        LC       0.2-1.0    0.4**         Roelbfs, 1971
           Poecilla reciculata
          *E-L - embryo-larval, LC - life cycle or partial life cycle

         **All chronic data are for dleldrin   .

           Geometric mean of chronic values = 0.21 cg/1     0.H - 0.031 (.g/1


           Lowest chronic value = 0.11 vg/1

-------
              Table  A.   Freshwater plant effects  for aldrin/dieldrin
CO
1
M
Organism
Alga.
Scenedesmus
quadrlcauHata
Diatom.
Navicula seminulum
Water meal,
Uolffia papulifera
Mater meal ,
Uolffia papulifera

Lowest plant value for
Concentration
Effect (uq/it
22% reduction
In blomass in
10 days
50% reduction
In growth In
5 days
Reduced popula-
tion growth in
12 days
Reduced popula-
tion growth in
12 days
dieldrin - 100 Mg/l
100
(dieldrin)
12,800
(dieldrin)
10.000
(dieldrin)
10.000
(aldrin)

Reference
Stadnyk £> Campbell. 1971
Cairns, 1968
Worthley & Schott, 1971
Worthley & Schott. 1971

Lowest plant value for aldrin = 10,000 pg/1

-------
               fattier S.-  Fice'sl^te"*' i-Gsiditi-a fclf
Onianism
                                                                  Time
                                                 12$
SceneJfesmus bbltqju'us

Community domiriaued by the alga;
tribonema minus

Community of  alga  arid diatoms
including Sfcieeoctorilum
subsecuridum,  SyneJria ulna,
                                               i.-iSlf
                                                                 4-6  wks    Rtis£ & tfc'ifttir'ej  i970f
4-6 wks     Rose  & Mclhtire, 1970
Epitnemifr sorex, Coccohe tg.
placeritula vaf •' englyptari
and Ni tzachi-a S£.

Cladoceran, 1,395 3 Rftihert, 1972
Paphnia magna
Freshwater mussel, 1,030 7-21 Bedford & Zabitc. I973f
Lampsi lis siliguoidea
Ci> .
1 Steelhead trout (newly hatched 3,225 35 Ghadwick & Shumway, 1969
^ alevin)f,
Sal mo gairdneri
Lake trout (year ling) ,-
Salvelinus riamaycttsh
Channel catfish',
ictatluru's punctatus
Channel catfish,
Ictalurus punctatus
Guppy
Poecilia rcticulata
Cuppy ,
Poecilia reticulata
Organism
Man
68,286** 152 Reiner t. ec al. 1974
2,385*** 70 Shatiiioh, 19776
2,993*** 28 Shannon. 1977a
9,862 32 Reinert., 1972
28.787 160-230 Rbelofs. 1971
Maximum Permissible Tissue Concentration
Concentration
Action Level or Effect (ing/kg) Reference
Fish and shellfish - 0.3 FDA Admin. Guideline
                               smoked,- frozen or canned
                                                                             7420.08

-------
                         Table  5,  (Continued)
03
I
M
LO
Organism
Man
Domestic animals
Rainbow trout,
Sal mo gairdneri
Rainbow trout,
Salmo gairdneri

Act ion" Level or Effect
Fish and shellfish -
raw edible portion
Animal feed
Altered amonia
detoxifying mechanism
- Altered phenylalanine
metabolism
Concentration
(mg/kg)
0.3
0.03
0.36 of
diet
0.36 of
diet
Reference
FDA Admin. Guideline
7420.09
FDA Admin. Guideline
7426.04
Mehrle & Bloomfield.
1974
Mehrle & DeClue.
1972 '
*  All bioconcentration factor data are for dieldrin

** May not be at equilibrium

***Data are for dorsal muscle.

   Geometric mean bioconcentration factor for all species =3,238

   Geometric mean whole fish bioconcentration factor -  15,482
   Lowest residue concentration = 0.03 nig/kg
                                                            ;
                                                           -,482
                                                                  0.0000019  mg/kg or  0.0019  ng/1

-------
Table  6.
                                    freshwater data for aldrinj'dieldrin
Organism  '
                        Test
                                                            Result
Amoeba,
Acanthamoeba
casFeTlanti

Tubtficids (mixture),
Tubifex and
timrioOrilua

Aquatic insects
                       Oieldrln

       6 days  No effect on survival    10.000    Prescott. et al.   1977
      96 hrs   LC50
       6 mos   Bioconcentratlon in
               naturally exposed
               animals
Stonefly.                30 days
Pteronarcys californica
CD
K>
it^.
Stonefly.
Acroneuria pacifica
Midge .
Chironomus tentans
Rainbow trout,
Salino gairdneri
30 days
24 hrs
17-23
days
Rainbow trout,
Salmo gairdneri
               LC50
                                  LC50
                                  I.C50
                                  Lethal muscle tissue
                                  bioconcentration
     1AO days  Altered concentrations
               of 11 amino acids
  6,700    bitten & Goodnight,  1966



  4.620    Buikley. et al.  1974



      2    Jensen & Gaufin. 1966',


      0.2  Jensen & Gaufin. 1966


      0.9  Karnak 6. Collins. 1974


  3,348    Holden. 1966
  1 mg/kg/ Mehrle, et al.  1971
     wk
Rainbow trout,
Salino gairdneri

Rainbow trout,
Sano
Carp.    ........
Cypriiuis carpio

Channel catfish.
Ic-talurus ptinctatus
IIlack bnl]head.
lcr,-ilt
     140 days  Increased lipid
               control
0.2 mg/kg/ Macek. et al.  1970
     wk
     168 days  Equilibrium bioaccumu-  0.2 mg/kg/ Macek, et al.   1970
               lation of 1.05 ppm           v;k
      96 hrs   1007. mortality of
               embryos

     210 days  Reduced growth
      36 hrs   I.C50
  5,000    Halone & Blaylock, 1&70-


 4 pg/g of Argyle, 1975
   diet
 (dry wt.)

      2.5  Kcrguson. c-t al.  1965

-------
                              Table  6.  (Continued)
          Organism
          Green  sunfish,
          Leggings  cyanellus

          Green  sunfish,
                                   Teet
                                                                      Kesuit
                        Ill hrs   Concentration In blood   5.65 wg/g Hogan & Roelofs, 1971
                                  at death

                        111 hrs   Concentration in brain  10.31 ug/g Hogan & Koelofs. 1971
                                  at death
          Walleye,                embryonic   Behavioral  aberrations
          Stizostedion vitreum    atage  of    of  yolk  sac fry
                                  develop.
Toad (tadpoles),
Bufo woodhoust

Frog (tadpoles),
Pseudacris triseriata
                                    96  hrs    I.C50


                                    96  hrs    I.C50
                             12.2  Hair. 1972



                            150    Sanders, 1970


                            100    Sanders, 1970
CO
          Amoeba,
          Aienthamoeba
          casteTIani

          Cladoceran,
          Daphnia magna

          Mayfly,
          ll£xageni_a bilineata

          Stonefly,
          Pteronarcys californica
          Stonefly ,
          Acroneuria
                                          Aldrin

                          6 days  No effect on survival    10,000    Prescott, et al.  1977
Midge,
Chiconomus sp.

Carp,
Cyp_r_hois_ carpio

Black bullhead,
Ict.'ilurus mel as

blaegill,
        macrochirus
                          3 days


                          3 days


                         30 days


                         30 days


                          3 days
Bioconcencration


Bioconcencration


LC50


LC50


Bioconcentration
  14.100    Johnson, et al.  1971


1   6.300    Johnson, et al.  1971


       2.5  Jensen i< Gaufin, 1966


      22    Jensen 6> Gaufin, 1966


   4,600    Johnson, et al.  1971
                                             Significant  increase  of     180    McBride & Richards,  1971
                                             sodium  in  profused  gill
                                    36  hrs    LC50
                                                               12.5  Ferguson, et al.  1965
                                             Aldrin  50% inhibition      30
                                             dose  or Na+-K+ ATPase
                                                                     Yap. et al.  1975

-------
                              'fable  6.



                                   Test                                  flesult
          Organism                 Duration
          Lowesic aldrin  value = 2.5
          Toad (tadip,ole§},          9$hrs(   LC5Q                          \$Q    ganders.  19.7.0.
          t>itfo wobdhoua'ii                      "                             '"     ••':-;--  •-••>
          LovjesiU dieldrln  value -0.2  yg/
6v

-------
                       SALTWATER ORGANISMS


Introduction


     Aldrin and dieldrin are chlorinated cyclodiene compounds  that


have in the past, been two of the most widely used insecticides.


Aldrin was applied to soils and foliage using soil injection or


aerial techniques; since leaching by water was minimal/  soil


erosion and sediment transport were the two major routes .for


aldrin to enter aquatic environments.  Aldrin and dieldrin  are


often considered together, because aldrin is rapidly  converted to


dieldrin by metabolism by plants and animals or by photo- decom-


position.  Therefore, although aldrin and dieldrin are  considered


separately for purpose of comparison, dieldrin is of  the greater


concern in the aquatic environment.


     The acute toxicities of aldrin and dieldrin and  the persis-


tence and bioaccumulation potential for dieldrin have been  studied
                                            •

using estuarine plants and animals.  Bioaccumulation  by estuarine


organisms and/or subsequent transfer to other animals in estuarine


food-webs have been documented in field-studies and laboratory


experiments.  Long-term test results indicate that dieldrin is


chronically toxic to estuarine fishes and crabs, although the


exact mechanism of toxicity is not known.


Acute Toxicity


     All species of saltwater fish tested were sensitive to acute


exposures to aldrin (13 species) or dieldrin  (16 species) .(Table  7)


In flow-through exposures, the unadjusted 48- or 96-hour LC50


values for six fishes ranged from 2.0 to 7.2 ug aldrin/1 (Butler,


1963; Earnest and Benville, 1972; Korn and Earnest; 1974; and


Lowe, data sheets).  The unadjusted acute LC50 values for eight



                              B-27

-------
fishes exposed  to  dieldrin differed and ranged from 0.66 to 24.0

ug/1  in flow-through  tests (Butler, 1963;  Earnest and Benville,

1972; Korn  and  Earnest,  1974;  Lowe, data sheets;  Parrish, et al.


1973; Schoettger,  1970;  and Wade,  1969).  Generally,  LC50 values


for ^aldrin  are  slightly  higher than those for dieldrin in tests


where the same  species were tested, but for practical purposes,


the acute toxicities  for these two chemicals can be considered the


same •..
       i                                                  *
      Es.tuarine  invertebrate species are acutely sensitive to both
       1                                                  i
aldrin and.  dieldrin,  but there is  greater differences in reported


LC50  values for these species  than for fishes (Table  8).'  Unad-


justed invertebrate LC50 or EC50 values ranged from 0.37 to 33.0


ug aldrin/1 and 0.28  to  240.0  ug dieldrin/1.  The most sensitive


species tested  was the commercially important pink shrimp; the


24-h:our LC50 value for aldrin  was  0.37 ug/1, while the 48-hour


LC50  value  for  dieldrin  was 0.28 ug/1  (unmeasured), and the 96-


ho.ur  LC50 value was 0.7  ug/1 (measured) in flowing water exposures


(•Lowe, data sheets; Parrish., et al. 1973).  Other crustaceans were


less  sensitive  and their acute LC50 values ranged from 3.0 to


.240.0 ug/1  (Butler, 1963;  Lowe, data sheets; Parrish, et al. 1973;


Schoettger,  1970).


      Acute  toxicity test conditions can affect the results of


tests with  fishes  and invertebrates.  For example, LC50 values


based on static exposures of aldrin or dieldrin with  three fish


and two invertebrate  species are higher than LC50 values based on


flow-through exposures where comparable data are available


(Earnest and Benville.,  1.072; Eisler, 1969, 1970b; Lowe, data


sheets; and Parrish,  et  al. 1973).  In addition,  LC50 values for
                               B-28

-------
dieldrin based on unmeasured concentrations were higher  than  those



based on measured concentrations in tests with sheepshead minnows



and two shrimp species (Eisler, 1969; Parrish, et  al.  1973).



Therefore, if relative sensitivities of species are  to be under-



stood, knowledge of test procedures is necessary.



Chronic Toxicity



     No entire life-cycle or embryo-larval tests have  been  re-



ported for aldrin or dieldrin.  However, results (Table  11) of



long-term exposures of invertebrate species and a  fish species  to



dieldrin in food (Klein and Lincer, 1974) or water  (Epifanio,



1971; Lane and Livingston, 1970) indicate a need for such data.



The LC50 value of dieldrin to the sailfin molly after  34 weeks  of



exposure was approximately one-fourth that after 48-hours  (Tables



7 and 11).  Fiddler crabs (Uca pugilator) fed 100  ng dieldrin/g



for 15 days (Table 11) demonstrated unusual running  behavior



(Klein and Lincer, 1974).



Plant Effects



     Information on the sensitivity of aquatic plants, including



algae and rooted vascular plants, indicates that they  are much



less sensitive than are fish and invertebrate species.  Product-



ivity and growth rates were reduced at concentrations  of approxi-



mately 950 to 1,000 ug/1 in three 4- to 36-hour static tests  using



one alga and mixed-population communities (Batterton,  et al.  19'71;



Butler, 1963).



Residues



     Bioconcentration factors (BCF) for dieldrin (Tables 10 and



11) range from 400 to 8,000 for fish or shellfish  (Epifanio,  1973;



Lane and Livingston, 1970; Mason and Rowe, 1976; Parrish, 1974;
                              B-29

-------
and Parrish, et al. 1973).  Bioconcentration  factors  for  oysters



were higher for long exposure periods because  dieldrin  concentra-



tions in tissues reached  steady-state after extended  periods



(several weeks) of exposure (Mason and Rowe,  1976;  Parrish,  1974;



Parrish, et al. 1973).  Therefore, long  exposures  are necessary to



attain steady-state bioconcentration factors.   After  34 weeks  of



exposure to dieldrin, sailfin mollies exhibited BCF's of  3,867 to



4,867 in muscle; BCF's  for liver, brain, gill,  intestine,  and



blood ranged from 10,500  to 50,000  (Lane and  Livingston,  1970).



Spot exposed to dieldrin  for 35 days, depurated the chemical  to



non-detectable body-burdens within 13 days of  holding in  dieldrin-



free saltwater  (Parrish,  et al. 1973).   Concentrations  in  edible



tissues- were slightly less (about 15 percent)  than concentrations



in whole spot; however, concentrations in  liver were  two  to  13



times that in spot muscle.



Data Interpretation and Use of Guidelines



     Acute toxicity of  aldrin and dieldrin will be underestimated



by static tests and by  toxicity tests in which the concentration



of aldrin or dieldrin is  not measured by chemical  analysis.   After



applying adjustment factors for test conditions,  the  variability



in sensitivity of fishes  to aldrin and dieldrin was reduced  so



they differed by less than a factor of 50  for  all  species.   When



the geometric mean of the LC50 value for aldrin is divided by the



Guideline's species sensitivity factor of  3.7,  a value  of  1.4  ug/1



results.  The Guidelines  adjustment factors  for test  conditions



and species sensitivity seem reasonable  because none  of the  geo-



metric mean adjusted LC50 values  for any species is lower  than the
                               B-30

-------
Final Fish Acute Value of 1.4 ug aldrin/1 although some  are  close.



The Guidelines are designed to obtain a Final Acute Value  that



provides an estimate of an LC50 value that  is less than  that of  95



percent of all fish species.  When the geometric mean of the LC50



value for dieldrin is divided by the Guidelines species  sensi-



tivity factor of 3.7, a Final Fish Acute Value of 0.85 ug/1  re-



sults,,  This value is lower than the geometric mean adjusted LC50



values for 13 of 16 species tested.  Therefore, since the  Guide-



lines are designed to provide a Final Fish  Acute Value which is



lower than or equal to the LC50 value of 95 percent of the



species, the test conditions and sensitivity adjustment  factors



appear appropriate.



     Invertebrate acute values must also be adjusted  for test con-



ditions and species sensitivities.  When the Final Invertebrate



Acute Value is obtained from the geometric  mean of the adjusted



LC50 values divided by the species sensitivity factor of 49,  a



Final Invertebrate Acute Value of 0.084 ug  aldrin/1 results.   The



adjustment factors seem reasonable because  the geometric mean ad-



justed LC50 values for six of the seven tested species are greater



than the Final Invertebrate Acute Value; the adjusted LC50 value



of 0.074 ug/1 for pink shrimp is only slightly lower.



     The geometric mean of the adjusted LC5C values for  dieldrin,



when divided by the species sensitivity factor of 49, gives  a



Final Invertebrate Acute Value of 0.16 ug dieldrin/1.  The adjust-



ment factors seem reasonable because the geometric mean  adjusted



LC50 values for seven of the eight tested species are greater than
                              B-31

-------
the Final Invertebrate  Acute  Value.;  the adjusted LC50 value for



one test with pink  shrimp  was less  than the Final Invertebrate



Acute Value.



     Dieldriri was bioconcentrated  in edible portions of fish and



shellfish by; 2,000  to 8,000 times  the concentration in water.   The



acceptable residue  level,  0.03 ug/g  for animal feed, divided; by



the geometric mean-  bioconcentration  factor of 4,367 for whole



fish,, gives* a' Residue Limited Toxicant Concentration (RLTC) of



0.,006:9 ug/'l«
                               B-32

-------
CRITERION FORMULATION
                      Saltwater-Aquatic Life
Summary of Available Data
     The concentrations below have been rounded  to  two  significant
figures.
     Final Fish Acute Value = 0.85 ug/1
     Final Invertebrate Acute Value = 0.16 ug/1
          Final Acute Value = 0.16 ug/1
     Final Fish Chronic Value = not available
     Final Invertebrate Chronic Value = not available
     Final Plant Value = 950 ug/1
     Residue Limited Toxicant Concentration = 0.0069 ug/1
          Final Chronic Value = 0.0069 ug/1
          0.44 x Final Acute Value = 0.070 ug/1
     No saltwater criterion can be derived for dieldrin using  the
Guidelines because no Final Chronic Value for either fish  or
invertebrate species or a good substitute for either value  is
available.
     However, results obtained with dieldrin and  freshwater
organisms indicate how a criterion may be estimated.  For
freshwater organisms the Final Fish Chronic Value divided  by  the
Final Fish Acute Value is 0.031/1.6 = 0.019.  When  this value  is
multiplied times the saltwater Final Fish Acute  Value,  an
estimated Final Fish Chronic Value of 0.85 x 0.019  = 0.016  ug/1  is
obtained.  Therefore, the Final Chronic Value of  0.0069 ug/lf
based on the RLTC, should not cause adverse chronic effects on
fish or invertebrate species.
                              B-33

-------
      To. estimate: a criterion  for  dieldrin,  the  maximum concen-
tration is. the Final, Acute Value  of: 0.16- ug/1 and the 24-hour.
average concentration- is the  Final Chronic  Value of- 0.0069  ug/1.
No  important': adverse effects;  on saltwater aquatic organisms  have
been, re.pQ,r,teid to- be; caused; by concentrations" lower* than the
2.4.--hour, ave.rag.ei- concentration-:.
      GHfcTEKEON:;   Eor; dieldrin the/ criterion  to.  protect saltwater
aquatsiar Ifijffe as§  decdived. us-ing- procedures: other  than the Guidelines
iissi Oiiv03016^ ug^lt as'j as 2;4-^hour. averager and- the  concentration- should-
nts.tr reaccee'd,; Oi..16ft  ug/1; at any time:.

-------
Table  7.    Marine  fish acute values  for aldrin/dieldrin







03
1
U)
cn






B
Organism H

American eel,
Anguilla rostrata
Mummlchog,
Fundulus heteroclitus
Mummichog,
Fundulus heteroclitus
Striped killifish.
Fundulus majalis
Atlantic silverside,
Menidia menidia
Threespine stickleback,
Gasterosteus aculeatus
Threespine stickleback,
Gasterosteus aculeatus
Striped bass,
Morone saxatilis
Spot,
Lciostomus xanthurus
Shiner perch,
Cyma togas ter aggregata
Shiner perch,
C^iiiato^aster aggregata
Dwarf perch,
Micrometrus minimus
Dwarf perch,
MLcrometrus minimus
111 uehedil ,
Thalassoma bifasciatum
Uhite mullet,
Mu^il cureina
ioaeeay
etfiod*

S
S
S
S
S
S
S
FT
Ft
S
FT
S
FT
S
FT
Teat
Cone***

U
U
U
U
U
U
U
U
'U
U
U
U
U
U
U
Time
Ihra)
Aldrin
96
96
96
96
96
96
96
96
48
96
96
96
96
96
48
LCSO
lug/l|

5.0
8.0
4.0
17.0
13.0
39.8
27.4
7.2
3.2
7.4
2.26
18.0
2.03
12.0
2.8
Adjusted
LC50

2.73
4.37
2.19
9.29
7.11
21.76
14.98
5.54
2.0
4.05
1.74
9.84
1.56
6.56
1.75
                                                            heier fence
                                                            Eisler, 1970b
                                                            Eisler, 1970b
                                                            Eisler. 1970a
                                                            Eisler,  1970b
                                                            Eisler,  1970b
                                                            Katz,  1961
                                                            Katz.  1961
                                                            Korn & Earnest. 1974
                                                            Lowe, undated
                                                            Earnest & Benville,
                                                            1972

                                                            Earnest & Benville,
                                                            1972

                                                            Earnest & Benville,
                                                            1972

                                                            Earnest & lienville,
                                                            1972

                                                            Eisler, 1970b

-------
                       7,    (Continued)
           vTest.
Mttjiod*_  Cone,**    Jii£S)
                                                                      'Adjusted
                                                                                        .cfc










03
1
co
CT\
















Striped mullet,
Mujjil cephalua
Striped jnulJlet,
Mugil cepjialus
Northern puffer-5-'
Sphaeroidus maculatus

American eel,' :
Anpuilla rostrata
Chi'iro'ok aalnion,'' ' :
Oncorhyncluis tshawytacha
Sheepsh&ad minnow. •
Cyp_rinodou varie^ntua
Sheejpuheud minnow, •"
Cygrinodon vuriegatus
SheepsheiH minnow.
Cygrinodon varie^-atua
Munmiichog,
Kiindulus heteroclltus
Munuiiichog , • ' •
Kniululus heterocll tua
Mimimi cliog ,
Kundtilti.s heterocll tua
Striped killifish.
l-'undnlus majalis
Sail fin molly,
I'oucilia Ijlipinna
A 1 1 antic si Iverside,
S
,
FT

S


S

PC

S

FT

FT

S

S

S

S

S

S
U

U

U


U

U

U

U

M

U

U

U

U

U

U
96

48
_,.:,
96

Dieldrin
96

96

48

48

96

96

96

96

96

48

96
100.0
; ;-,
2.0
.•: ••'
36.0


0.9

1.47

5 . 82***

24.0

10.0

5.0

16.0

5.0

4.0

10.81***

5.0
54.67

1.25

19.68


0.49

1.13

2.58

15.0

10.0

2.73

8.75

2.73

2.19

4.79

2.73
Eisler. I970b
f .-;.... ••••• :-:i.- .i
Lowe, undated
' • ^ - • •-* .'
Eisler. 1970b


Eisler. i970b

Schoettger, 1970

Wade. 1969

Lowe, undated

Parrish. et al. 1973

Eisler. 1970a

Eisler. 1970b

Eisler. 1970b

Eisler. 1970b

Wade. 1969

Eisler. 1970b
tloaiilla

-------
7.   (Continued)
Bioassay
Oiqjinism Method*
Threespine stickleback,
Gasterosteus aculeatus
Threespine stickleback,
Gasterosteus aculeatus
Striped bass.
Morone saxatilis
Spot,
Leiostomus xanthurus
Shiner perch,
Cymatogaster aggregata
Shiner perch.
^ C^r.ia togas ter aggregata
-j Dwarf perch,
Micrometrus minimus
Dwarf perch,
Micrometrus minimus
Bluehead ,
Tlialassoma bifasciatum
White mullet,
Mugil curema
Striped mullet,
Mui>il cephalus
Striped mullet,
Mugil cephalus
Striped mullet,
Mugi 1 cepliai us
Striped mullet.
S

S

FT

FT

S

FT

S

FT

S

FT

FT

FT

FT

S
Teat
Conc^**
U

U

U

U

U

U

U

U

U

U

U

U

U

U
Time
(lirst
96

96

96

24

96

, 96

96

96

96

48

48

48

48

96
LC50
(iiq/j \
15.3

13.1

19.7
*
3.2

3.7

1.5

5.0

2.44

6.0

7.1

3.2

3.2

0.66

23.0
Adjusted
LCbO
Juq/1)
8.36

7.16

15.17

1.63

1.53

1.16

2.73

1.88

3.28

4.43

2.0

2.0

0.41

12.57
Kfeierei.ce
Katz. 1961

Katz, 1961

Korn & Earnest, 1974

Lowe, undated

Earnest & Benville,
1972
Earnest & Benville,
1972
Earnest & Benville,
1972
Earnest & Benville,
1972
Eisler, 1970b

Butler, 1963

Lowe, undated

Lowe, undated

Lowe, undated

Eisler, 1970b

-------
        Organism
                             T.    (Continued)
Bipassay  Teat

Method* ;
        Northern puffer,
        Sphaeroldfcs maculatus
            U
                                                               LC50
                                                                         Adjusted
                                                                              1 •• •--
34,0      18.59    Elsier.  19,70b
   •:.      I:.'-'      ' * 1 - - '  A ••" •' '-
CO
 I
u>
op
        *  S = static; FT f flow-through


        **  M = measured; U ° unmeasured


        ***Geotnecric mean of 18 means


           Geometric mean of adjusted values:
                aldrin =  5.2  jig/1




                dieldrin  =3.2  pg/1

            1.4

-------
              Table  8.   Marine invertebrate acute values :for  aldrin/dleldrln
t
Orcjanisjji £

Eastern oyster,
Crassostrea virginica
Sand shrimp,
Crangdon septemspinosa
Hermit crab,
Pagurus longicarpus
Crass shrimp,
Palaemonetes vulgaris
Korean shrimp,
Palaemon macrodactylua
CD
^ Korean shrimp,
(£> Palaemon macrodactylus
Pink shrimp,
Penacus duorarum
Blue crab (juvenile) ,
Callinecte£ sapidus

Eastern oyster.
Crassostrea virginica
Eastern oyster,
Crassostrea virginica
Eastern oyster,
Crassostcea virginica
Eastern oyster.
Crassostrea virginica
Sand shrimp,
Ik' rin if crab,
licassay

FT

S

S

S

S


FT

FT

FT


FT

FT

FT

Ft

S
S
Test
Cone.*

U

U

U

U

U


U

U

U

•
U

U

U

M

U
U
Time
Aldrin
96

96

96

96

96


96

24

48

Dieldrin
96

24

24

96

96
96
LC50

25.0***

8.0

33.0

9.0

0.74


3.0

0.37

23.0


34 . 0***

15.0***

240 . 0***

31.2***

7.0
18.0
Adjusted
LCbO

19.25

6.78

27.95

7.62

0.63


2.3

0 . 074

7.62


26.2

3.0

48.0

31.2

5.9
15.2
Kctfctence

Butler. 1963

Eisler. 1969

Eisler. 1969

Eisler. 1969

Schoettger. 1970


Schoettger, 1970

Lowe, undated

Lowe, undated


Butler, 1963

Lowe, undated

Lowe, undated

Parrluli. ct al. 1973

Eisler, 1969
Eisler, 1969
Pa^urus lon^lcjirpus

-------
                        Table   8.   (Continued)
                        Biodusay  Teat
                        Method*
    Time
          Adjusted
LC50      IX. 50
                 ii__ hfeterenre
(irass shrimp.
i'alaeiiioiietes vulj-.irla
(iraaa shrimp,
I'ijiaeiiionetes pujjlo
Korean shrimp,
I'alaeiiion macrodacljlus
Korean shrimp.
I'.-j 1 ciiMiiuu iiiacrodactyl us
1'Jnk shrimp.
Penaeus duo fa rum
I'lnk shriinp.
to Fenaeus duoraruin
1
** Brown shrimp,
Fencieus a^tecus
lilue crab (juvenile).
Calllnccles :>a(>idus

s u

FT M

S U

FT U

FT M

FT U


FT U

FT U


96 50 ;0

96 8.64

96 16.9

96 6.9

96 0.7

48 0.28


48 3 . 2

48 240.0


42.4

8.64

14.3

5.3

0.7

0.093


1.06

79.5


Elsler. 1969

Parrlsh, et al.

Sehoettger. 1970

Schoettger, 1970

Parribli , et al .

Lowe, undated


Lowe, undated

Lowe, undated




1973





1973









*  S - static; FT -  flow-through

** M = inc.-
-------
00
I
                               9.   Marine plant effects for  aldrin/dieldrin
Organ lain
Alga.
Agmenellum
quadrupl Lea turn
Phytoplankcon
community
Ettect
Reduced
growth
rate
84.6-84.8%
decrease In
productivity
after 4 hrs
Concentration
(uq/ij Reference
950*: Batterton, et al. 1971
1,000**' Butler, 1963
          *   Dieldrin


          **  Aldrin


             Lowest  plant value =, 950 pg/1

-------
                                                              J
              Table  10,  Marine residues for aldrin/dieldrin
Organism
Eastern oyster,
Crassostrea virgintca
Crab,
Leptodius floridanus
Sailfin molly,
Pqecilia latipinna
Spot,
I.elostomus xanthurus
Organism
Man
to
1
M Man
Domestic animals
Bioconcentration Factoi
TIME
(days)
netetence
8,000** 392 Parrish, 1974
400*** 16 Epifanlo, 1973
4,367 238 Lane & Livingston,
1970
2,300** 35 Parrish, et al. 1973
Maximum Permissible Tissue Concentration
Action Level or Effect
Fish and shellfish -
smoked, frozen or canned
Fish and shellfish -
raw edible portion
Animal feed
Concentration
-- • (mg/kg)
0.3
0.3
0.03
Reference
FDA Admin. Guideline
7420.08
FDA Admin. Guideline
7420.09
FDA Admin. Guideline
7426.04
    All data are for dieldrin
**
    Edible tissue

*** Converted from dry to wet weight basis

    Ccomctric mean whole fisli bioconcentration factor
                                                    4,367
    Geometric mean bioconcentration factor for all species (does not include edible portion of
    fish) = 2,409
Lowest residue concentration = 0.03 mg/kg
                                                           0.0000069 mg/kg or 0.0069 ug/1

-------
                              Table   11.  Other marine data for aldrln/dieldrin*
CD

.U
U>
           Organ!am
Teat
Duration  ptfect
Alga,
Skeletonema costatum
Alga,
Tetraaelrais chuii
Alga.
Isochrysis galbana
Alga,
Oltsthodlacus luteua
Alga,
Cyclotella nana
Alga.
Amphldlnium carter!
Clam,
Rang! a cuneata
Eastern oyster,
Crassostrea virginica
Eastern oyster,
Crassostrea virginica
Brown shrimp.
Crangou crangon
Shore crab,
Carcinus macnus
Fiddler crab.
lie a pugilator
Crab larvae.
Leptodius floridanus
2 hrs
2 hrs
2 hrs
2 hrs
2 hrs
2 hrs
72 hrs
7 days
7 days
48 hrs
48 hrs
IS days
18 days
1,588**
859**
824**
490**
481**
98**
Bioconcentration
factor - 1.600
Bioconcentrat ion
factor <* 2,070
Bioconcentration
factor - 2,880
LC50
LC50
Dieldrin in food
affected running
Bioaccumulated al
consuming food wi
                                                                       Result
           Crab larvae,            6 days
           Leptodivis flortdanus
          213 ng/kg

          LC50,  approximately
          - 1
            peierencfc

            Rice & Sikka,  1973


            Rice & Sikka,  1973


           .Rice & Sikka.  1973


            Rice & Sikka.  1973


            Rice & Sikka,  1973


            Rice & Sikka.  1973


            Petrocelli.  et al. 1973


            Mason & Rowe.  1976


            Mason & Rowe,  1976
 >10,  <33    Portroann & Wilson.  1971


 >10,  <33    Portmann & Wilson.  1971


  0.1  tig/g  Klein & Liueer.  1974
>r

  217  ng/g  Epifanio,  1973



            Epifanio,  1971

-------
        Oranic*
                           Table   11. (Continuet»)



                                Test                                i**Ult
        Blue cfife.              10 days   Bioaccuaulated 4 to         «      Pe trope 111, ft al. lf||
        Calltn«(CUa aapidu»               1  tiuwi  (h* daily
        —-•--"—•---- -----  -               dose  in  fQod

        S.llfln molly,          34 wk.    LC50                   ?|.|  O.O   Lag* % Llvin^ton. 1970
        Poacilta latiplnna                                                                      r
        Winter flounder.         -r        1.21 pg/kg in egga          -      Smith 6> Cole.
        Raeudopleuronectea                 caused  &&t reduction
        |pftri-gi>nug"^-"--"'-t'7                 in"f?rtil'i?§ti«ii"J
                                                    to contrqla
D



I
        *  All data are for dieldrln

        ** Correccion faccor> (0.1) for dry weight analys^a,

-------
Cairns, J., Jr. 1968.  The effects of dieldrin on diatoms.



Mosquito News  28: 177.








Car ins,- J. , Jr. , and J.J. Loos. 1966.  Changes in guppy



populations resulting from exposure to dieldrin.  Prog.



Fish-Cult. 28: 220.








Chadwick, G.G., and U. Kiigemagi. 1968.  Toxicity evaluation



of a technique for introducing dieldrin into water.  Jour.



Water.. Pollut. .Co.ntrol Fed. 40:'76.








Chadwick, GIG., .and .D.L. Shumway. 1969.  Effects of dieldrin



on the growth  and development of steelhead  trout.  Page



90 in The  biological impact of pesticides in the environment.



Environ. Health Sci. Set. No.  1. Oregon State University.








Culley, D..D.,  and D.E. Ferguson. 1969.  Patterns of insecticide



res.*i.s.tence in  the mosquito fish, Gambusia affinis.  Jour.



Fi'sh -Res.  Board Can. 26: 2395.








Earnest, R.D., and P.E. Benville, Jr. 1972.  Acute toxicity



of four organochlorine insecticides to two  species of  surf



perch.  Calif. Fish Game. 58:  127.








Eisler, R. 1969.  Acute toxicities of insecticides to .marine



decapod crustaceans.  Crustaceana 16: 302.
                               B-46

-------
Eisler, R. 1970a.  Factors affecting pesticide-induced toxicity



in an estuarine fish.  U.S. Bur. Sport Fish. Wildl. Tech.



Pap. 45.







Esiler, R. 1970b.  Acute toxicities of organochlorine and



organophosphorus insecticides to estuarine fishes.  U.S.



Bur. Sport Fish. Wildl. Tech. Pap. 46.







Epifanio, C.E. 1971.  Effects of dieidrin in seawater on



the development of two species of crab larvae, Leptodius



floridanus and Panopeus herbstii.  Mar. 3icl. 11: 356.







Epifanio, C.E. 1973.  Dieldrin uptake by larvae of the crac,



Leptodius floridanus.  Mar. 3iol. 19: 320.







Ferguson, D.E., et al. 1955.  Tolerance -o five chlorinated



hydrocarbon insecticides in two species of fish from  a transect:



of the lower Mississippi River.  Jour. Miss. Acad. Sci.



11: 239.







Gaufin, A.R., et al. 1965.  The toxicity of  ten organic



insecticides to various aquatic invertebrates.  Water Sewage



Works 12: 276.







Hair, E.M. 1972.  Effects of dieldrin or. walleye egg  develcprr.ent,



hatching and fry survival.  Thesis.  Chic State "nive.r si ty,



Columbus.
                              3-4'

-------
Hansen, C.R., Jr., and J.A. Kawatski. 1976.  Application



of 24-hour postexposure observation to acute toxicity studies



with invertebrates.  Jour. Fish. Res. Board Can. 33: 1198.







Henderson, C., et al. 1959.  Relative toxicity of ten chlor-



inated hydrocarbon insecticides to four species of fish.



Trans. Am. Fish. Soc. 88: 23.







Hogan, R.L., and E.W. Roelofs. 1971.  Concentrations of



dieldrin i:n the blood and brain of the green sunfish, Lepomis



cyarv.ellus, at death.  Jour. Fish. Res. Board Can. 28: 610.







Holder, .A.W. 1966.  Organochlorine insecticide residues



in salmonid fish.  Jour. Appl. Ecol. 3: 45.







Jensen, L.D., and A.R. Gaufin, 1964.  Effects of ten organic



insecticides on two species of stonefly naiads.  Trans.



Am. Fish. Soc. .93: 27.







Jensen, L.D.., and A..R. Gaufin. 1966.  Acute and long-term



effects of organic insecticides on two species of stonefly



naiads.  Jour. Water Pollut. Control Fed. 38: 1273.







Johnson, B.T., et al. 1971.  Biological magnification and



degradation of DDT and aldrin by freshwater invertebrates.



Jour. Fish. Res. Board Can. 28: 705.
                              B-48

-------
Karnak, R.E., and W.J. Collins. 1974.  The susceptibility
to selected insecticides an acetylcholinesterase activity
in a laboratory colony of midge larvae, Chironomus tentans.
Bull. Environ. Contain. Toxicol. 12: 62.

Katz, M. 1961.  Acute toxicity of some organic insecticides
to three species of salmonids and to the threespine sticleback.
Trans. Am. Fish. Soc. 90: 264.

Klein, M.L., and J.L. Lincer. 1974.  Behavioral effects of
dieldrin upon the fiddler crab, Uca pugilator.  Pages 181-
196 JLri J. Vernberg and W.B. Vernberg, eds.  Pollution and
physiology of marine organisms.  Academic Press, New York.

Korn, S., and R. Earnest. 1974.  Acute toxicity of twenty
insecticides to striped bass, Morone saxatilis.  Calif.
Fish Game. 60: 128.

Krieger, R.I., and P.W. Lee. 1973.  Inhibition of  ir\ vivo
and iri vitro epoxidation of aldrin, and potentiation of
toxicity of various insecticide chemicals by  Diquat in two
species of fish.  Arch. Environ. Contain. Toxicol.  1: 112.

Lane, C.E., and R.J. Livingston. 1970.  Some  actue and chronic
effects of dieldrin on the sailfin molly, Poecilia latipinna.
Trans. Am. Fish. Soc. 99: 489.
                              B-49

-------
Lowe, J.I.  Results of toxicity tests with fishes and macro-



invertebrates.  Data sheets available from U.S. Environ.



Prot. Agency, Environ. Res. Lab. Gulf Breeze, Fla.








Macek, K.J., et al. 1969.  The effects of temperature on



the susceptibility of bluegills and rainbow trout to selected



pesticides.  Bull- Environ. Contain. Toxicol. 4: 174.







Macek, K.J., et al. 1970.  The uptake, distribution and


                       14          14
elimination of dietary   C-DDT and   C-Dieldrin in rainbow



trout.  Trans. Am.. Fish. Soc. 99: 689.








I-?* lone, C.R., and B.C. Blaylock. 1970.  Toxicity of insecticide



formulations to carp embryos reared :in vitro.  Jour. Wildl.



Manage. 34: 4.60.








Mason, J.W., and R. Rowe.  1976.  The accumulation and loss

          I


of dieldrin and endrin in  the eastern oyster. Arch. Environ.



Contain. Tpxic.ol. 4: 349.








McBride, R.K., and B.D. Richards. 1975.  The effects of



some herbicides and pesticides on sodium uptake by isolated



perfused gills from the carp, Cyprinus carpio.  Comp. Biochem.



Physiol. 51C: 105.








Mehrle, P.M., and R.A. Bloomfield. 1974.  Ammonia detoxifying



mechanisms of rainbow trout altered by dietary dieldrin.



Toxicol. Appl. Pharmacol.  27: 355.
                               B-50

-------
Mehrle, P.M., and M.E. DeClue. 1972.  Phenylalaraine metabolism



altered by dietary dieldrin.  Nature 238: 462.







Mehrle, P.M., et al. 1971.  Serum amino acids in rainbow



trout, Salmo gairdneri as affected by DDT and dieldrin.



Comp. Biochem. Physiol.  38B: 373.







Parrish, P.R. 1974.  Arochlor 1254, DDT and ODD, and dieldrin:



accumulation and loss by American oysters, Crassostrea virginica



exposed continuously for 56 weeks.  Proc. Natl. Shellfish.



Assoc. 64.







Parrish, P.R., et al. 1973.  Dieldrin:  Effects on several



estuarine organisms.  Pages 427-434 ir\ Proc. 27th Annu.



Conf. S.E. Assoc. Game Fish Comm.







Petrocelli, S.R., et al. 1973.  Uptake and accumulation



of an organochlorine insecticide  (dieldrin) by an estuarine



mollusc, Rangia cuneata.  Bull. Environ. Contain. Toxicol.



10: 315.







Petrocelli, S.R., et al. 1975.  Biomagnification of dieldrin



residues by food-chain transfer from clams to blue crabs



under controlled conditions.  Bull. Environ, Contam. Toxicol.



13: 108.
                              B-51

-------
 Portmann,  J.E.,  and K.W. Wilson. 1971.  The toxicity of

 140  substances to the brown shrimp and other marine animals.

 Pages 1-9  iri shellfish Info. Leaflet No. 22.  Ministry Agric.

 Fish.  Food.   Fish.  Lab, Burnham-on-Crouch, Essex.



 Prescott,  L.M.,  et  al. 1977.  The effects of pesticides,

 polychlbrinated  biphenyls and metals on the growth and repro-

 duction  of Acanthamoeba castellanii.  Bull. Environ. Contam.

 Tdxiol.  18: 29.
                                                      4 •


 Rao,  T.S..., et al.  1975.  Median tolerance limits of some

 chemicals  to freshwater fish, Cyprinus carpio.  Indian Jour.

 Environ. Health  17: 140.



 Rehwoldt,  R.E., :et  al. 1977.  Investigations into acute

 toxici'ty and .some chronic effects of selected herbicides

 and ;pes"trci'd:es'on several freshwater fish species.  Bull.

 Environ. Contam.  Toxico.l. 18: ;361.



 'Reinert, R.E. 197.2.  Accumulation of dieldrin in an alga

 •Scenedesmus  obligus,  Daphnia magna and the guppy, Poecilia

..re^ticulata.   Jour.  Fish. Res. Board Can. 29: 1413.



 Reinert, R.E., et al. 1974.  Dieldrin. and DDT:  Accumulation

 from water arid food by lake trout, Salvelinus namaycush

 in the laboratory.  Proc..l7th Conf. Great Lakes Res. 52.
                               B-52

-------
Rice, C.P., and B.C.  Sikka.  1973.  Fate of dieldrin in selected
species of marine algae.   Bull. Environ. Contain. Toxicol.
9: 116.

Roelofs, T.D. 1971.  Effects of dieldrin on the intrinsic
rate of increase of the guppy, Poecilia reti.culata Peters.
Thesis. Oregon State University, Corvallis.

Rose, F.L., and C.D.  Mclntire. 1970.  Accumulation of dieldrin
by benthic algae in laboratory streams.  Hydrobiologia 35: 481.

Sanders, H.O. 1969.  Toxicity of pesticiedes to the crustacean,
Gammarus Lacustris.  Bur. Sport Fish. Wildl. Tech. Pap.
No. 25.

Sanders, H.O. 1970.  Pesticides toxicities to tadpoles of
the western chorus frog,  Pseudacris triseriata and Fowler's
toad, Bufo woodhousii fowleri.  Copeia 2: 246.

Sanders, H.O. 1972.  Toxicity of some insecticides to four
species of malacostracan crustaceans.  Bur. Sport Fish.
Wildl. Tech. Pap. No. 66.

Sanders, H.O., and O.B. Cope. 1966.  Toxicities of several
pesticides to two species of cladocerans.  Trans. Am. Fish.
Soc. 95: 165.
                              B-53

-------
Sanders, H.O.,  and O.B.  Cope.  1968.  The relative  toxicities


of several pesticides to naiads of three species of stoneflies.


Limnol. Oceariogr.  13: 112.





Santharam, K.R.,  et al.  1976.   Toxicity of some insecticides


to Daphnia caarin-a-ta King, an; importan link, in the  food chain


in the. freshwater' ecosystems..   Indian Jour. Ecol.  3:  70.





Scho.ettger, R.A.  1970.   Progress in sport fishery  research.


Fish-Pestle.  Res.. Lab.  U.S.  Dep. Inter. Bur. Sport Fish Wildl.


Re sour., Publ.  1.06.





Shannon:,. L...R:., 1977a.   Accumulation and elimination of dieldrin
                 9

in muscle' tissue  of channel  catfish.  Bull. Environ.  Contain.


TOrxdcol.. 1.7'r  637.





Shannon:,- L...K.. 1.9-7 7;b.   Equilibrium between uptake and  elimina-


tion-, of dieldrin- b.y; channel  catfish, Ictalurus punctatus.


Bull.. Environ.  Contain.  Toxicol. 17: 278.





Smith, R.M;.,  and; C.F. Cole.  1973.  Effects of egg  concentrations


of DDT and- dieldtin on development in winter flounder, Pseudo-


p-leuronectes  amer icanus.  Jour. Fish. Res. Board Can. 30:  1894.





Stadynyk, E.,, and-• R...&... Campbell. 1971.  Pesticide  effect


on growth and" •  C assimilation in a freshwater alga.  Bull.


Environ. Contain.  Toxicol. 6: 1..
                               B-54

-------
Tarzwell, C.M., and C.  Henderson.  1957.  Toxicity of dieldrin
to fish.  Trans. Am. Fish.  Soc.  86: 245.

U.S. Food and Drug Administration.  1973.  Administrative
Guideline 7402.08, Section  D.

U.S. Food and Drug Administration.  1973.  Administrative
Guideline 7420.09, Section  A.

U.S. Food and Drug Administration.  1977.  Administrative
Guideline 7426.04, Section  A.

Wade, R.A. 1969.  Ecology of junvenile tapon and effects
of dieldrin on two associated species.  U.S. Bur. Sport
Fish. Wildl. Tech. Pap. 41.

Whitten, B.K., and C.J. Goodnight.  1966.  Toxicity of some
common insecticides to tubificids.   Jour. Water Pollut.
                                       j
Control Fed. 38: 227.

Worthley, E.G., and C.D. Schott. 1971.  The comparative
effects of CS and various pollutants on freshwater phytoplankton
colonies of Wolffia papulifera Thompson.  Dep. Army. Edgewood
Arsenal Biomed. Lab. Task IW662710-AD6302.

Yap, H.H., et al. 1975.  I_n vitro inhibition of fish brain
ATPase acitivity by cyclodiene insecticides and related
compounds.  Bull. Environ.  Contam.  Toxicol. 14: 163.
                               B-55

-------
                     ALDRIN AND DIELDRIN


Mammalian Toxicology and Human Health Effects


Introduction


     During the past decade, considerable information has


been generated concerning the toxicity and potential carcino-


genicity of the two organochlorine pesticides aldrin and


dieldrin.  These two pesticides are usually considered to-


gether since aldrin is readily expoxidized to dieldrin in


the environment.  Both are acutely toxic to most forms of


life including arthropods, mollusks, invertebrates, amiphi-


bians, reptiles, fish, birds, and mammals.  Dieldrin is


extremely persistent in the environment.  By means of bio-


accummulation it is concentrated manyfold as it moves up


the food chain.

                                                 •
     Aldrin and dieldrin are manmade compounds belonging


to the group of cyclodiene insecticides.  They are a sub-


group of the chlorinated cyclic hydrocarbon insecticides


which include DDT, BHC, etc.  They were manufactured in


the United States by Shell Chemical Company until the U.S.


EPA prohibited their manufacture in 1974  (39 FR 37246) under

the Federal Insecticide, Fungicide and Rodenticide Act.


They are currently manufactured by Shell Chemical Company


in Holland.  Prior to 1974, both insecticides were available


in the United States in various formulations for broad-spectrum


insect control.  They were used for control of soil pests

and grasshoppers, protection of vegetables and fruits, and


control of disese vectors including locusts and termites
                              C-l

-------
(Int. Agency Res. Cancer, 1974a,b).  In 1974, the U.S.EPA

restricted the use of aldrin/dieldrin to termite control

by direct soil injection and non-food seed and plant treatment,

     Early work by Treon and Cleveland in 1955 suggested

that aldrin and dieldrin may have tumor-inducing potential,

especially in the liver.  Since that time, several conflicting

reports of the hepatocarc.inogenicity in mice, rats, and

dogs have appeared in literature.  Studies have been carried

out mainly by the U.S. Food and Drug Administration, the

National Cancer Institute, and by the manufacturer, Shell
                                   i
Chemical Company.  There has been much debate over the type

and significance of hepatic damage caused by aldrin and

dieldrin.  IIY order to ascertain the human risks associated

with aldrin and dieldrin, evaluations of the toxic effects

of. these pesticides have been carried out on workers in
        i
the Shell Chemical Company.  The evaluations include epide-

miological studies in addition to the more routine toxicity

studies..  However,: it is felt that the number of workers

with high exposures was too small and the time interval

too short, to determine whether or not aldrin and dieldrin

represent a cancer threat to humans.

     The objective of this report is to examine published

studies so as to utilize the most relevant data to develop

a criterion for human risk assessment.
                              C-2

-------
                           EXPOSURE



     Exposure to aldrin and dieldrin is from contaminated



waters, food products, and air.  Because of its persistence,



dieldrin has become widespread in the aquatic environment.



It is also spread great distances by wind.  Since aldrin



and dieldrin are used throughout much of the world beyoimd



the United States, it must be assumed that imported food



stuffs, such as meat products, contain residues of these



pesticides.



     Use of aldrin and dieldrin peaked at 19.3 million Ibs.



in 1966, and 3.6 million in 1956, respectively (39 FR 37251).



The subsequent decline in dieldrin use was due, in part,



to increased resistance of boll weevils to chlorinated insect-



icides  (Table 1).  The use of dieldrin was preferred to



aldrin because it required less application due to its persis-



tance.
                              C-3

-------
                              TABLE 1
Year
  Aldr in
(1,000 Ibs)
 Dieldrin
(1,000 Ibs)
1950
1951
1952
1953
1954
1955
1956
1957
1958
1.959
1960
1961
1962
1963
1964
1965
1-966
1967
1968
1969
1.970
L971
1972
1973 (to July 1) .
1973 estimated (to Dec. 31)
1973
1974 (to July 1)
1,456
3,288
814
1,234
2,993
4,372
6,495
2,431
4,971
5,566
8,109
9,26
10,886
12,152
12,693
14,278
19,327
18,092
13,690
9,902
8,909
11,615
11,868
8,721
(10,000)
9,900
9,700
0
185
750
1,135
1,777
2,585
8,635
2,673
3,074
3,008
2,650
2,764
2,990
2,685
2,052
1,814
1,908
1,478
1,332
1,206
749
705
740
432
(576)




'Domestic  sales  of aldrin and dieldrin from 1950  through  July 1,
1974  (3.9  FR,  19T4);...
                             C-4

-------
Ingestion from Water



     Aldrin and dieldrin have been applied to vast areas



of agricultural land and aquatic areas in the United States



and in most parts of the world.  These pesticides have there-



fore found their way into most fresh and marine waters.



Unlike DDT, aldrin and deildrin are somewhat more soluble



in water (27 and 186 mg/1, respectively) (Park and Bruce,



1968).  Gunther, et al. (1968) reported dieldrin to be slightly



more soluble at 250 mg/1.



     In early studies  (Weaver, et al. 1965), dieldrin was



found in all major river basins (mean concentration 7.5



ng/1) in the United States and it was found more often than



any other pesticide.  It was also found in the Mississippi



delta (U.S. Dep. Agric. 1966) at 10.0 ng/1 while aldrin



was found as high as 30 ng/1.  Marigold and Schulze (1969)



reported aldrin and dieldrin at 40 and 70 ng/1, respectively,



in streams in the western United States.  Leichtenberg,



et al.  (1970) found levels of dieldrin and aldrin as high



as 114 and 407 ng/1, respectively, in surface waters in



the United States.



     More recently, dieldrin has been reported to be present



in many fresh waters in the United States with mean concentra-



tions ranging from 5 to 395 ng/1 in surface water and from



1 to 7 jjg/1 in drinking water  (Epstein, 1976) .



     In 1975 a survey in the United States of aldrin, diel-



drin, DDT, and DDT metabolite levels in raw and drinking



water was carried out  (U.S.EPA, 1976).  Dieldrin was found



in 117 of 715 samples analyzed (Table 2).  The six samples
                              C-5

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   in the highest range were all taken from the same location,

  three from raw waters and three from finished waters.  Three

  of these .six samples also contained aldrin in concentration

  of 15 to 18 ng/1.
                                TABLE 2

           Dieldrin Concentrations in Raw and Drinking Water
                            (U.S.  EPA,  1976)


No. of Samples     598         94          13           4            6
ng/1                 4       4-10       11-20       21-29       56-110



       .-Harris, et al.  (1977) summarized the distribution of

  various chemicals in drinking water in several cities in

  the United States.  Dieldrin was found in concentrations

  of 1 ng/l in Seattle, Washington, and Cincinnati, Ohio;

  2 ,ng/l in Miami, Florida, and Ottumwa, Iowa; and as high

  as 50 ng/1 in New Orleans, Louisiana.

       It has been estimated  (MacKay and Wolkoff, 1973) that

  unlike many chlorinated hydrocarbons that evaporate rapidly

  firom shallow waters, dieldrin has by far the longest half-

  lii'fe of these compounds in water 1 meter in depth.  They

  calculated that the half-life for aldrin and dieldrin would

  be 10.1 days and 723 days, respectively, compared to 3.5

  days -for DDT and 289 days for lindane. This long half-life

  in water combined with the potential for bioconcentration

  by aquatic organisms such as micororganisms, phytoplankton,

  mollusks, and fish further enhances the hazard of these

  two pesticides  (Wurster, 1971).
                                 C-6

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Ingestion from Food
     Although aldrin is readily converted to dieldrin, diel-
drin itself is stable and persistent in the environment.
Because it is lipophilic, dieldrin accumulates in the food
chain (Wurster,. 1971).  The persistence of aldrin and diel-
drin in different soils varies with the type of soil and
with movement to other areas by water, wind, etc.(Matsumura
and Boush, 1967).  Dieldrin has been shown to be one of
the most persistent of all the organochlorine pesticides
(Nash and Woolson, 1967).
     It has been estimated that 99.5 percent of all human
beings in the United States have dieldrin residues in their
tissues (U.S. EPA, 1971).  Although there are other origins
of contamination, these residue levels are mainly due to
                         «
contamination of foods of animal origin (Wurster, 1971).
The levels of aldrin/dieldrin in several types of food have
been summarized by Edwards (1973), Matsumura (1974) , and
Manske and Johnson (1975).  The overall concentration of
dieldrin in the diet in the United States has been calcu-
lated to be approximately 43 ng/g of food consumed (Epstein,
1976).  Table 3 lists the estimated daily dietary intake
for aldrin and dieldrin of a 16-to 19-year-old male (Natl.
Acad. Sci., 1975).
     A bioconcentration factor (BCF) relates the concentration
of a chemical in water to the concentration in aquatic organisms,
but BCF's are not available for the edible portions of all
four major groups of aquatic organisms consumed in the United
States.  Since data indicate that the BCF for lipid-soluble
                              C-7

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                                            TABLE 3




                                   Daily Dietary intake  (ing)
                    1965          1966          1967         1968         1969        1970


    Aldrin         0.001        0.002        0.001        trace         trace        trace

V   Dieldrin       0.005        0.007        0.001        0.004         0.005        0.005
00                                   	                        	

-------
compounds is proportional to percent lipids* BCF's can be

adjusted to edible portions using data on percent lipids

and the amounts of various species consumed by Americans.

A recent survey on fish and shellfish consumption in the

United States (Cordle, et al. 1978) found that the per capita

consumption is 18.7 g/day.  From the data on the 19 major

species identified in the survey and data on the fat content

of the edible portion of these species (Sidwell, et al.

1974), the relative consumption of the four major groups

and the weighted average percent lipids for each group can

be calculated:

                          Consumption  '     Weighted Average
     Group                 (Percent)          Percent Lipids

Freshwater fishes             12                  4.8

Saltwater fishes              61                  2.3

Saltwater molluscs             9                  1.2

Saltwater decapods            18                  1.2

Using  the percentages for consumption and lipids for each

of these groups, the weighted average percent lipids is

2.3 for consumed fish and shellfish.

     Measured steady-state bioconcentration factors were

obtained for dieldrin using five species:
                              C-9

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Organisms

Eastern  oyster,
Crassostrea  virginica
       Percent Adjusted
BCF    Lipids    BCF       Reference
8,000
1.5   12,266   Parrish,  1974
Spot,
Leiostomus xanthurus
Lake trout (yearling) ,
Salvelinus namaycush
Channel catfish,
Ictalurus punctatus
Channel catfish,
Ictalurus punctatus
2,300
68,286
2,385
2,993
3.1
14.9
3.2
3.2
1,706
10,540
1,714
2,151
Parrish
1973
Reinert
et al.
Shannon
Shannon
, et al
1974
, 1977b
, 1977a
Each of these measured BCF's was adjusted from the percent

lipids of the test species to the 2.3 percent lipids that is

the weighted average  for consumed fish and shellfish.  The

geometric mean was obtained for each species, and then for

all species.  Thus, the mean bioconcentration factor for

dieldrin and the edible portion of all aquatic-organisms

consumed by Americans is calculated to be 4,500.

     No useful measured bioconcentration factor can be obtained

for aldrin because it is rapidly converted to dieldrin by

aquatic organisms.  In addition, because aldrin is converted

to dielrin in soil, aquatic organisms are rarely exposed

to aldrin.

     However, the equation "Log BCF =0.76 Log P - 0.23"

can be used  (Veith, et al. Manuscript) to estimate the BCF

for aquatic organisms that contain about eight percent lipids

from the octanol-water partition coefficient (P).  Based

on an octanol-water partition coefficient of 1,000, a steady-

state bioconcentration factor for aldrin would be estimated

to be 110.  An adjustment factor of 2.3/8.0 = 0.2875 can
                              C-10

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be used to adjust the estimated BCF from the 8.0 percent


lipids on which the equation is based to the 2.3 percent


lipids that is the weighted average for consumed fish and


shellfish.  Thus, the weighted average bioconcentration


factor for aldrin and the edible portion of all aquatic


organisms consumed by Americans would be calculated to be


110 x 0.2875 = 32.


Inhalation


     Aldrin and dieldrin enter the air through various mech-


anisms such as spraying, wind action, water evaporation,


and adhesion to particulates.  Stanley, et al. (1971) reported


levels of aldrin and dieldrin in air samples in nine cities


in the United States.  One sample of the air in Iowa City,

     »                           '              3
Iowa had detectable levels of aldrin (8.0 ng/m ), and 50


samples taken in Orlando, Florida had detectable amounts


of dieldrin, the largest being 29.7 hg/m .  Various other


studies of the air carried out during the 1960's were sum-


marized by Edwards (1973).


     In a study conducted by the U.S. EPA from 1970 to 1972


(Epstein, 1976), dieldrin was found in more than 85 percent


of the air samples tested.  The mean levels ranged from


1 to 2.8 ng/m3.  From these levels, the average daily intake


of dieldrin by respiration was calculated to be 0.035 to


0.098 pg.


     Although aldrin/dieldrin are no longer used in the


United States, there is still the possibility of air borne


contamination from other parts of the world.  Edwards (1973)


showed that dieldrin has been transported long distances
                              C-ll

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in the air.  Exposure due to inhalation of aldrin and diel-



 drin from the application of these pesticides was,  of course,



 much greater before the restriction of their use.  Pesticide



 applicators and indiviudals living near agricultural areas



 were exposed to aldrin/dieldrin through inhalation.



      In a recent report, Domanski, et al. (1977)  reported



 no increase in dieldrin concentration in adipose tissue



 of cigarette smokers as compared to non-smokers although



 tobacco has high residues of pesticides and is stored many



 years before use.



 Dermal



      Dermal exposure to aldrin or dieldrin is limited to



 those involved in manufacturing or application of these



 pestic.ides.  Wolfe, et al.  (1972) reported that exposure



 to workers, both manufacturers and applicators, was mainly



 through dermal absorption rather than from inhalation.



 Due to the ban on manufaturing of the pesticides in the



 United States, the possibilities of dermal exposure have



 been greatly reduce.



                        PHARMACOKINETICS



 Absorption



      Heath and Vandekar (1964) , using   Cl-dieldrin (4 percent



 in arachis oil)  showed that absorption by the upper part



 of the gastroinestinal tract begins almost immediately after



 oral administration in rats and that the absorption varies



 with the solvent used.  Barnes and Heath (1964) demonstrated



 that the LD50 varies with the dieldrin-to-solvent ratio.



 Heath and Vandekar  (1964)  also demonstrated that absorption



 is by the poartal vein and not the thoracic lymph duct.




                              '  C-12

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Initially, dieldrin is widespread but within a few hours


it is redistributed in favor of the fat.  They also stated


that following oral treatment at 25 mg/kg,   Cl-dieldrin


could be recovered from the stomach, small intestine, large


intestine, and feces after 1 hour.


Distribution


     It is well known that dieldrin has a low solubility
                                                    h
in water and a high solubility in fat.  At 1 and 2 hours


after treatment, Heath and Vandekar (1964) detected the


highest concentration of   Cl-dieldrin in fat tissue.  They


also reported high concentrations in the liver and kidney -


with moderate concentrations in the brain at these times.


     Deichmann, et al.(1968) studied the retention of diel-


drin in blood, liver, and fat.  Female Osborne-Mendel rats


were fed a diet containing 50 mg/kg dieldrin (87 percent
                                                        •

purity).  The rats were killed on various days of feeding


up to 183 days.  The concentration of dieldrin in the blood


and liver increased for nine days and then leveled off until


the end of the six-month period.  The concentration of diel-


drin in the fat took approximately 16 days to reach a level


that was maintained throughout the experiment.  The fat


had the highest concentrations of dieldrin followed by the


liver.  The mean concentration in the fat was 474 times '


that in the blood, while the concentration in the liver


was approximately 29 times the blood concentration.


     Walker, et al. (1969) studied the distribution of diel-


drin in rats and dogs over a two-year period.  Dieldrin


(99 percent purity) was incorporated into the diet of CFE
                               C-13

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   male and female rats at 0.1, 1.0, and 10 rag/kg and was fed
   to dogs in gelatin capsules at concentrations equivalent
   to 0.1 and 1.0 mg/kg of their daily dietary intake.  The
   authors measured the dieldrin residues in whole blood, fat,
   liver, and brain and found signifrcantly increased concentra-
   tions in all tissues compared to those in the controls (Table 4)
                                 TABLE 4
      fe-.H  Mean Geometric Dieldrin Concentration (mg/kg)  in Rats
                                104 weeks
Dietary
Level (mg/kg) Blood
Males



Females



0
0.1
1.0
10.0
0
0.1
1.0
10.0
0.0009
0.0021
0.0312
0.1472
0.0015 '
0.0065
0.0861
0.3954
Fat
0.0598
0.02594
1.493
19.72
0.3112
0.8974
13.90
57.81
Liver
0.0059
0.0159
0.01552
1.476
0.0112
0.0348
0.4295
2.965
Brain
0.0020
0.0069
0.1040
0.4319
0.0077
0.0224
0.2891
1.130
(Walker,  et al.  1969)
        The concentrations in the tissues increased with an
   increase in the dietary concentrations, and the concentra-
   tions  in the  female rats were considerably higher than those
   in the males.   The  dieldrin concentrations reached a plateau
   by the end of  the 6th month and remained fairly constant
   for the remaining 18 months.
        In dogs,  the blood concentrations increased in both
   treatment groups of the first 12 weeks.  With the higher
   dose (1.0 mg/kg/diet)  the concentration leveled off between
   18 and 30 weeks of  treatment.  However, with the lower dose
   (0.1 mg/kg/diet)  the plateau was reached between 12 and
                                  C-14

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18 weeks.  In the group receiving 1.0 mg/kg/diet the dieldrin
concentration in the blood increased significantly during
the final 6 weeks of exposure.   The dieldrin concentrations
in the liver and brain were also dose-related but, as opposed
to the results from the rats,  showed no significant sex
differences.  As in other studies, the concentration in
the fat was much greater than  that in the liver, which in
turn, was greater than in the  brain.
     Additional studies on the distribution of dieldrin
were carried out by Robinson,  et al. (1969).  In this study
Carworth rats were fed dieldrin (99+ percent purity) at
10 mg/kg in their diet for 8 weeks.  At the end of this
time, they were returned to a  dieldrin-free diet and killed
randomly in pairs up to 12 weeks after withdrawal of the
dieldrin diet.  The fatty tissue clearly had the highest
concentration of dieldrin followed by the liver, brain,
and blood.  Concentrations of  dieldrin in fat returned to
control levels after 12 weeks  and the decline in dieldrin
concentrations was approximately exponential in nature.
     Matthews, et al. (1971) investigated the distribution
of dieldrin and some of its metabolites in several organs
and tissues of both male and female Charles River rats.
Three animals of each sex were fasted for eight hours and
                                           14
then given 3 g of food containing 10 mg/kg   C-dieldrin
(96 percent purity).  The animals were killed after nine
days and dieldrin and metabolic product concentrations were
determined.  In general, the amount of radioactivity per
gram was higher for the female rats.  The kidneys and stomachs
                              C-15

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    of the males contained more radioactivity than those of

    the females.  Levels in the lungs and intestines showed

    similar differences.  The other organs and tissues of the

    females had three to four times the radioactivity of the

    males.  In the females, storage was predominantly as dieldrin,

    but in males other metabolites, identified as keto dieldrin,

    and trans-dihydro-aldrin, and a polar metabolite were detected

    in various tissues.

       -  Hayes (1974) determined the concentration of dieldrin

    in the fat, liver, kidney, brain, muscle, and plasma following

    a single oral dose in rats.  Male Sprague-Dawley rats were

    given 10 mg/kg dieldrin (86 percent purity)  by stomach tube.

    The animals were killed at various intervals up to 240 hours

    and the dieldrin concentration in the tissues was determined.

    The concentrations in the brain at 4 and 16 hours were 1.5

    and 1.0 jug/g, respectively.  Hayes assigned a value of one

    to the concentrations in the brain and calculated the ratio

    of the concentrations in other tissues to the concentrations

    in the brain at 4 and 16 hours (Table 5).


                            TABLE 5
  Hr.  Brain
          Muscle
             Liver
            Kidney
             Plasma
             Fat
 4
16
1.00+0
1.00+0
0.62+0.05
0.55+0.06
2.30+0.11
3.17+0.25
1.55+0.22
2.02+0.56
0.20+0.02
1.35+1.11
 7.20+1.18
17.96+3.23
                                  C-16

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The concentrations in the tissues remained relatively con-



stant for 24 hours and began to decline at 48 hours.  No



further samples were taken until 240 hours when all the



dieldrin concentrations were below 0.2 pg/g except the con-



centration in the fat which was 5 pg/g.



     In a study done in 1963 on 30 individuals from three



different states, the concentrations of chlorinated hydro-



carbon pesticides in body fat were determined (Dale and



Quinby, 1963).   Twenty-eight individuals were from the general



population while one had previous DDT exposure and one had



aldrin exposure.  The mean (—SE) for the general population



was 0.15—0.02 ,ug/g dieldrin while the aldrin exposure was



0.36 jug/g dieldrin (see discussion on aldrin metabolism



to dieldrin in the Metabolism section of this report).



     In a study of aldrin and dieldrin concentrations in



71 workers involved in pesticide manufacturing, Hayes and



Curley (1968) measured the plasma, fat, and urine concent-



rations by gas-liquid chromatography.  Their findings were



in accordance with the earlier animal studies.  The fat



contained the highest concentration of the pesticides followed



by the urine and plasma.  The mean concentrations of diel-



drin in the fat, urine, and plasma of the pesticide workers



were 5.67+1.11, 0.242+0.0063, and 0.0185+0.0019 mg/g respect-



ively.  These were significantly different from those re-



ported for the general population.  The authors reported



a high correlation between total hours or intensity of .exposure



and concentration of dieldrin.  However, no correlation



could be found between dieldrin concentrations and amount



of sick leave.




                             I C-17   .

-------
     Another study  (Hunter, et al. 1969) involving adult
males ingesting 10, 50, or 211 jig dieldrin per day for 18
or 24 months again  found a relationship between the dose
and the length of exposure and concentration of dieldrin
in the fat and blood.  In general, the concentration of
dieldrin in the samples increased during the first 18 months
and either leveled  off or rose slightly during the remaining
time.  The control  and 10 ;ug groups, both of which were
given 211 ;ug/day for the final 6 months, demonstrated a
rise in concentrations similar to the rise demonstrated
by those who were given 211 jug/day initially.  The authors
stated that there was no effect on the general health of
the individuals receiving the dieldrin for the two-year
test.
     In the above-mentioned studies, blood concentrations
of aldrin or dieldrin were determined using whole blood
(Deichmann, et al.  1968; Robinson, et al. 1969; Hunter,
et al. 1969; Walker, et al. 1969), or plasma (Hayes and
Curley, 1968).  Mick, et al.  (1971) measured the aldrin
and dieldrin concentrations in erythrocytes, plasma, and
the alpha-and beta-lipoprotein fractions of the blood of
six aldrin workers  after the workers had formulated 2 million-
pounds of aldrin over a five-week period.  The six workers
were exposed to aldrin by both inhalation and dermal contact.
The blood samples were collected at the conclusion of the
five-week exposure  and blood plasma concentrations as high
as 312 ng/1 were measured.  No immediate health problems
were reported during this time.  In all cases, dieldrin
                              C-18

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concentrations were higher than the aldrin concentrations
due to the epoxidation of aldrin to dieldrin.  The dieldrin
residue in the plasma averaged approximately four times
higher than that in the erythrocytes.  As the dieldrin residue
in the blood increased, the amount in the plasma became
proportionally higher.  In addition, the beta-lipoprotein
fraction usually contained more dieldrin than the alpha
fraction.
     The work of Mick, et al. (1971) was confirmed in part
by Skalsky and Guthrie (1978) .  Using labelled pesticides
of 98 percent purity incubated with various fractions of
human blood £n vitro Skalsky and Guthrie were able to demon-
strate that dieldrin and DDT bind to albumin and beta-lipopro-
tein.
Metabolism
     Aldrin and its epoxidation product, dieldrin, are both
cyclopentadiene insecticides.  Since epoxidation of aldrin
to dieldrin was first reported by Radomski and Davidow in
1953, there have been many reports in the literature of
the ability of various organisms  (i.e., soil microorganisms,
plants, fish, and animals, including man) to epoxidize this
type of double bond.  Winteringham and Barnes (1955) first
reported this reaction with aldrin in mice.  Wong and "Terriere
(1965) were able to demonstrate the iin vitro conversion
of aldrin to its epoxide, dieldrin, using microsomes* from
*In this document microsomes refers to the cell-free homo-
genized liver  (including soluble enzymes and microsomes)
and not to purified microsomes.
                               C-19

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male and female rats.  The reaction was NADPH-dependent
and the enzymes were heat-labile.,  Winteringham and Barnes
also showed that males converted alrdin to dieldrin at a
higher rate.  No other metabolic products were detected,
although the authors noted that polar products could have
been overlooked by the methods used.  Nakatsugawa, et al.
(1965) confirmed the work of Wong and Terriere using micro-
somes from male rats and rabbits.  They also demonstrated
a requirement for NADPH and stated that dieldrin was not
further metabolized by the microsomes.  They reported that
lung homogenate was only one-tenth as active as liver in
epoxidase activity and that no activity was detected in
the kidney, spleen, pancreas, heart, or brain.
    , Korte  (1963) identified one of the metabolic products
of aldrin as aldrin diol in studies with rabbits.  Heath
and Vandekar (1964) reported the existence of a somewhat
polar metabolite which is excreted in the feces.  They stated
that the feces are the main route of excretio'n and that
little dieldrin is excreted unchanged.  They were able to
detect other polar metabolites in both urine and feces.
                              14
     Ludwig, et al.  (1964) fed  C-aldrin to male rats at
4.3 jug/day for three months.  The compounds excreted into
the urine consisted of aldrin, dieldrin, and unidentified
hydrophilic metabolic products.  These unidentified products
made up 75 percent of the dose excreted in the feces and
95 percent excreted in the urine.  Two different products
were found  in the feces and two in the urine.  Two of these
                              g-20

-------
four products appeared to be identical by paper and thin-
layer chromatography.
     Korte and Arent (1965)  isolated six urinary metabolites
                                 14
from rabbits treated orally with   C-dieldrin for 21 weeks.
The major metabolite (86 percent) was one of the two enantio-
morphic isomers of 6,7 trans-dihydroxy-dihydro-alrdin.
     Richardson, et al. (1968)  were able to identify two
metabolites in urine and feces from male CF rats fed a diet
containing 100 mg/kg dieldrin for seven months.  Metabolites
were isolated from the urine and feces collected during
the last month.  They determined that the urinary metabolite
had a keto group on the number 12 carbon and the epoxide
was unchanged.  The fecal metabolite was a mono-hydroxyder-
ivative of dieldrin at either the 4a or 4 position.  A similar
study was carried out  (Matthews and Matsumura, 1969) in
which male rats were fed a diet of 20 mg/kg purified dieldrin
for one month, with the dosage increased to 100 mg/kg for
18 days while the urine and feces were collected.  Two metabo-
lites were isolated from the feces and two from the urine.
The major fecal metabolite was similar to the mono-hydroxy-
derivative isolated by Richardson, et al. (1968) in the
feces.  The major urinary metabolite was identical to the
ketone compound identified by Richardson, et al. in the
urine.  The minor urinary and fecal metabolites were ident-
ical and similar to the 6,7 trans-dihydroxy-dihydro-aldrin
described by Korte and Arent (1965).
                              C-21

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     Matthews and Matsumura  (1969) also conducted in vitro
                  14
experiments using   C-dieldrin incubated with rat liver
microsomes and various co-factors.  Thin-layer chromatography
of the water-soluble components producted six metabolites
in addition to the unchanged dieldrin.  Analysis of the
water-soluble metabolites revealed a glucoronide conjugate
which accounted for approximately 45 percent of the radio-
activity.  Comparsion of the Revalues for the in vivo and
iji vitro studies showed that the minor urinary/fecal metabo-
lite (i.e., the 6, 7 trans-dihydroxy-dihydro-aldrin) was
produced in vitro and that the metabolite freed from the
glucoronic acid was also present in the in vitro system
in the unconjugated form.
     The products identified by Richardson, et al.  (1968)
                                                             0
and Matthews and Matsumura (1969) represent an oxidized
form of dieldrin in the urine and an oxidated, dechlorinated
metabolite in the feces which had lost the intact dieldrin
ring system.
     Hedde, et al. (1970) were able to isolate six metabolic
                                          14
products in the urine of sheep dosed with   C-dieldrin.
Three castrated sheep were given unlabelled dieldrin orally
                                            14
at 2 mg/kg for five days before dosing with   C-dieldrin.
Four other sheep were fed a single oral dose of labelled
dieldrin at 20 mg/kg.  Urine and feces were collected up
to six days after treatment with the labelled dieldrin.
Although other determinations were made, only the urine
was analyzed quantitatively.  After hexane extraction of
pH 1 followed by other clean-up procedures, the four hexane-
                               C-22

-------
soluble metabolites were separated on Sephadex LH-20 gel.


The LH-20 was again used to separate the two water soluble


metabolites after they were purified by several procedures,


including paper chromatography.  The authors postulated


that these water-soluble metabolites were a glucoronic acid


conjugate of the transdiol and an unidentified conjugate


of glucoronic acid and, possibly, glycine.


     Feil, et al (1970) were able to identify two to the


hexane-soluble metabolites found by Hedde, et al. (1970)


in sheep urine.  One was the 6,7-trans-dihydroxy-dihydro-


aldrin described by Richardson, et al (1968) and the other


was the 9-,momo-hydroxy-derivative.  Further work on the


metabolism of dieldrin (Matthews, et al.  (1971) is discussed


in the Distribution section of this report where details


of treatment are given.  Matthews, et al. documented the
               •

production of several metabolites of dieldrin including


the 6,7-trans-dihydroxy-dihydro-aldrin and a second unident-


ified polar metabolite excreted in the feces.  The mono-


hydroxy-lated compound represented the greatest percentage


of the radioactivity extracted from the feces of both male


and female rats.  In male rats, the chloroform extract of


the urine consisted of the keto-metabolite described by


Klein, et al. (1968).  Also, initially, trans-dihydroxy-


dihydro-aldrin was found in the urine of the male rats along


with unchanged dieldrin.   Most of the radioactivity extracted


from the urine of the female rats was in the form of the


trans-dihydroxy-dihydro-aldrin, and initially contained


up to 20 percent dieldrin.
                              C-23

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     The metabolism  and  excretion of dieldrin appears to
be more rapaid  in male than in female rats.  Investigators
attribute  this  to the males' ability to produce the more
polar metabolites, especially the keto-product which is
excreted into the urine.
     A recent paper  has  appeared on the comparative meta-
bolism of  dieldrin in rodents.  Baldwin, et al. (1972) treated
                               14
a male CFE rat  with  3 mg/kg of   C-labelled dieldrin and
two male CF1 mice with 10 mg/kg.  The urine and feces were
collected  for the following seven or eight days.  The authors
reported that the CFE rat excreted the pentachloroketone
derivative in the urine  but that the CFl mice did not.
Conversely, the mice produced an unidentified urinary metabolite
which'the  rat did not.   The 6,7-trans-dihydorxy-dihydro-
aldrin was found in  the  feces of the mice and the rat, and
a dicarboxylic  derivative was found in the urine of all
three animals.
     A review of the literature on the metabolism of diel-
drin and endrin in rodents has been compiled by Bedford
and Hutson (1976) .  They summarized the four known metabolic
products of dieldrin as  they 6,7-trans-dihydroxy-dihydro-
aldrin (trans-diol) and  the tri-cyclic dicarboxylic acid
(both of which  are products of the trans-formation of the
epoxy group), the syn-12-hydroxy-dieldrin (a mono-hydro-
derivative) ,  and the pentachloroketone.
     In comparing dieldrin metabolism in acute of short-
term studies versus chronic, low-dose exposure, it must
be mentioned that organochlorine compounds, including diel-
                              C-24

-------
drin, have been shown to induce the mixed function oxidases
(MFO) found in the liver (Kohli, et al. 1977).  It is there-
fore possibel, in the long-term animal studies, that investi-
gators have been observing the results of high levels of
these enzymes and that the percentages and amounts of certain
metabolites may be misleading.  Baldwin, et al. (1971) in
a limited study, were able to show some inducability in
the CFE male rat but not in the CFl male mouse.  They induced
the enzymes by prefeeding the animals for 21 days with low
doses (i.e., 10 or 25 mg/kg in diet) of dieldrin.  If the
results of the Kohli, et al. study are to be accepted, then
one may assume that since man is subject to chronic, low-
dose exposure to many MFO inducers  (including various organo-
chlorine pesticides), this exposure may affect studies of
dieldrin metabolism.
Excretion
     As mentioned in the Distribution and Metabolism sections
of this report, aldrin and/or dieldrin are excreted mainly
in the feces and to some extent in the urine in the form
of several metabolites that are more polar than the parent
compounds.  Usually, a plateau is reached in most tissues
when the dose is held relatively constant.  However, if
the dosage increases, the body concentrations will increase
and vice versa.
     The early work of Ludwig, et al.  (1964) demonstrated
that male Wistar rats administered daily with low doses
of   C-labelled aldrin  (4.3/jg for 12 weeks) excreted appro:
mately nine times as much of the radioactivity in the feces
                               C-25

-------
as in the urine.  After about two weeks of treatment, the



rats were excreting 80 percent of the daily dose of aldrin



and this increased to 100 percenc after eight weeks.  Twenty-



four hours .after, the final dose  (12 weeks), the animals



had excreted 88 percent of the total radioactivity fed.



This increased to 98 percent after six weeks and greater



than 99 percent after 12 weeks.  It appears that after eight



weeks of feeding aldrin, a saturation level was attained



which did not increase with continued feeding at the same



concentration.  The concentrations in the body decreased



rapidly once the feeding was terminated.


                                          14
     In a study with rabbits administered   C-deildrin orally



over a,21-week period (total dose 56 to 58 mg/kg), Korte

   '. .,'                                    ^

and Arent (1965) reported somewhat conflicting results.



At the end of the feeding (22nd week) 42 percent of the



total radioactivity had been excreted with two to three



times as much in the urine as in the feces.  The level in



the feces was negligible after 24 weeks while the amount



in the urine was up to 43 percent at 52 weeks.



     It must be kept in mind that aldrin is metabolized



to dieldrin which is then converted to more polar metabo-



lites for excretion.  It is possible that the increased



amount of radioactivity noted by Korte and Arent in the



feces after treatment with aldrin could be due to the less



polar aldrin or deldrin as compared to the more polar metabo-



lites excreted in the urine or to a basic in metabolism



of deildrin in the rabbit.
                               C-26

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     The work of Robinson, et al. (1969) on the metabolism



of dieldrin has been summarized in the Metabolism section



of this report.  These investigators also studied the loss



of dieldrin (99+ percent purity) from the liver, blood,



brain, and adipose tissue of male CFE rats fed 10 mg/kg



in their diet for eight weeks.  Figure 1 illustrates the



loss of dieldrin from these tissues.  During the period



of observation, approximately 99 percent of the dieldrin



was excreted at various rates from the tissues.  However,



it must be noted that the analysis was performed by gas-



liquid chromatography and that later investigators  (Matthews,



et al. 1971) have found liver can contain approximately



30 percent of products other than dieldrin, a fact which



may have been overlooked by Robinson, et al.  The fat and



brain contained greater than 99 percent dieldrin and the



excretion times correspond to those for the rat observed



by Korte and Arent, in their work six years earlier.



     It can be seen from Figure 1 that three of the four



slopes for dieldrin loss were not linear and that with the



blood and liver, loss was rapid at first and then slowed



down.  Estimates for the half-life of dieldrin in the liver



and blood were 1.3 days for the period of rapid elimination



and 10.2 days for the slower period.  The estimated half-



life for dieldrin was 10.3 days in the adipose tissue and



3.0 days in the brain.



    In the study of   C-dieldrin metabolism in sheep (Hedde,



et al. 1970) mentioned in the Metabolism section of this



report, the excretion of dieldrin or its metabolites was
                              C-27

-------
                01
                0-01
             o
             o
             Ul


             "S 0001

             e
              0-0001
                    t

                    V.
                                     Blood
        cXI04«542«xp(-0-535l)

         .+ 298 exp (-005291)
         -

       -X
                         2O    40
                                   60
                        _J

                        80
                                                °"
                            a
                            o

                            X

                            ^

                             §
                                             §
                                             a
                                              0001
                                                   \
e«07lexp(-O54t)

  -f 0-233 exp(-O068t)
                                                        20    tO   60
             G
200


10-0
                 -o
                 o-,
              o
              
-------
higher in the feces than in the urine.  This ratio varied
considerable due partially to the different doses used.
The authors noted that in two very fat sheep the ratio of
labelled dieldrin in feces to urine was greater than 10
to 1 but in two thin sheep receiving the same dose, it was
slightly greater than 1 to 1.  The amount of radioactivity
                    14
that was exhaled as   CO^ was only 0.25 percent of the total
dose.  This indicates that virtually none of the dieldrin
is broken down to CO^.  With the sheep, less than 50 percent
of the total radioactivity was recovered after the five
or six days of collection.
    Several investigators have shown that removal of diel-
drin from the diet results in rapid loss of dieldrin or
metabolites from the body, especially the adipose tissue.
Barren and Walton (1971) further studied the loss of diel-
drin from the body of the rat and also looked at the role
of dieldrin in the diet with respect to loss from the adi-
pose tissue.  For this study, male Osborne-Mendel rats were
fed a diet containing 25 mg/kg dieldrin (99+ percent purity)
for 8 weeks.  They were then placed on a normal diet and
                                14
given four daily, oral doses of   C-dieldrin equivalent
to 25 mg/kg in their diet.  After these four days, one-half
of the animals were then returned to the dieldrin diet (25
mg/kg) while the rest remained on the normal diet.Groups
of five animals were sacrificed on the four days when they
received the labelled-dieldrin and on days 7, 9, 11, 16,
and 23 after the conclusion of the eight-week feeding.
The concentration of dieldrin found in the adipose tissue
from the rats receiving the dieldrin diet was approximately
                              C-29

-------
50 ;ug/g and remained  at  this level throughout the 23 days
following the feeding period.  The concentrations in the
rats on the normal diet  decreased to 4 >ig/g at day 23.
The authors reported  that the half-life of dieldrin in the
adipose tissue was about 4.5 days/ which is somewhat lower
than the 10.3 days calculated by Robinson, et al. (1969)
with rats fed only 10 mg/kg dieldrin.
    Cole, et al.  (1970)  measured the appearance of   C-dieldrin
    14
and   C-endrin in the urine and feces of male Holtzman rats
for seven days after a single intravenous dose of 0.25 mg/kg
of either chemical.  They reported that greater than 90
percent of the radioactivity occured in the feces.  Approx-
imately 80 percent of the total dose of labelled dieldrin
was excreted in the feces after the seven days, compared
with approximately 100 percent for the endrin.  Cole, et
al.  (1970) conducted a  similar experiment during a four-
day period using bile-fistula rats.  They also reported
that these rats produced patterns of excretion similar to
those observed in the first experiment.
    In a comparison of the excretion of dieldrin in the
CF1 mouse and CFE rat, Baldwin, et al. (1972) found that
after seven or eight days the amount of labelled dieldrin
excreted was similar to  both species.  Also, the feces contained
approximately two times  as much radioactivity as the urine,
and 50 to 70 percent of  the total activity was excreted
during the collection period.  As mentioned in the Meta-
bolism section of this report, the proportion of metabo-
lites varied between the mouse and the rat.
                              C-30

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    Although there has been extensive work done on the meta-



bolism and excretion of dieldrin in animals, there is under-



standably less known about the fate of dieldrin in humans.



Early work by Cueto and Hayes (1962) demonstrated that diel-



drin and some of its metabolites could be detected in the



urine of occupationally exposed workers.  A later report



by Cueto and Biros (1967)  compared the levels of dieldrin



and other chlorinated insecticides in the urine of 5 men



and 5 women in the general population to that of 14 men



with different degrees of occupational exposure.  The concen-



trations of dieldrin found in the urine of men and women



in the general population were 0.8 — 0.2 mg/1, and 1.3 —



0.1 mg/1, respectively.  The concentrations found in male



workers with low, medium,  and high degrees of exposure were



5.3 mg/1 (5), 13.8 mg/1 (4), and 51.4 mg/1  (5), respectively



(numbers in parentheses represent the number of individuals



per sample).  The degrees of exposure were only expressed



as relative and no data on the exposures were given.



    Hayes and Curley (1968) measured the plasma, fat, and



urine concentration of various chlorinated pesticides in



workers with occupational exposure to these chemicals.



In 14 urine samples, aldrin was present at less than 0.2



mg/1 and dieldrin was present at 1.3 to 66.0 mg/1.  This



is compared to the mean for dieldrin in the general popu-



lation of 0.8 — 0.2 mg/1 determined in the same laboratory



by Cueto and Biros (1967).



    A study by Hunter, et al. (1969) concluded that dieldrin



had a relatively long half-life in humans.  This compares
                              C-31

-------
with  a  half-life  of  less  than  ten days reported  in animal
                                 (t


studies.   In  the  Hunter,  et  al. study, 12 human  volunteers



ingested various  doses  of dieldrin for up to 24  months.



The blood  and adipose concentrations were determined over



this  time  and the blood levels were followed for eight additi-



onal  months after termination of the treatment.  The authors



reported that during this period concentrations  of dieldrin



in the  blood of three of  the volunteers did not  change sign-



ificantly.  (These concentrations were not given.)  In the



other nine subjects, the  half-life of dieldrin in the blood



ranged  from 141 to 592  days with a mean of 369 days.  These



estimates  were made on  a  limited number of samples.



    Jager  (1970)  reported that DeJonge, in an unpublished



report, studied the half-life of dieldrin in the blood of



15 aldrin/dieldrin workers who were transferred  to other



areas.  Prior to  transfer, these workers had had high ex-



posures to the pesticides and concentrations of  aldrin/diel-



drin  in their blood had reached equilibrium.  Measurements



of the dieldrin blood concentrations were taken  every six



months  for three  years  following the transfer.   The mean



half-life was 0.73 years  (approx. 266 days).  This is somewhat



in agreement with the estimates of Hunter, et al.  (1969)



of 369 days based on limited data.



    It has been reported  by these and other authors (Robin-



son, et al.  1969; Walker, et al. 1969) that there is a



direct relationship between the concentration of dieldrin



in the blood and  that in  adipose and other tissues.  It



seems likely that the half-life in the blood may reflect



the overall half-life in  other tissues.





                               C-32

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                           EFFECTS  •-.-..•;•'.:•/•-• ^; ^.. .
Acute, Subacute, and Chronic Toxicity
    The acute toxicity of aldrin and dieldrin has been ex-
tensively summarized by Hodge, etal. (1967) and Jager (1970)
In many cases, aldrin and dieldrin are considered similar
due to the rapid conversion of aldrin to dieldrin (see Meta-
bolism section) .  Dieldrin, in turn, is metabolized to a
variety of more polar products.  In"some cases, the toxi-
city of the metabolites has been compared to the parent
compound but this information is rather sparse  (Soto and
Deichmann, 1967).
    After ingestion, aldrin and dieldrin are rapidly absorb-
ed from the gastro-intestinal tract.  Following absorption,
the pesticides are transported from the liver* to different
sites in the body.  They have been found at various levels
in the brain, blood  (including erythrocytes), liver, and
especially the adipose tissue  (Mick, et al. 1971; Walker,
et al. 1969).  In addition, dieldrin has been shown to cross
the placenta to the fetus  (Hathaway, et al. 1967).  Hunter,
et al. (1969) demonstrated that a relationship  between in-
take and storage exists and that a plateau  is maintained
in the tissues unless the dose changes considerably.
    It was shown early that the pesticide-to-solvent ratio
affects the LD50  (Barnes and Heath, 1964) and that some
variation is caused by the solvent employed  (Heath and Vand-
ekar, 1964).  There is a pronounced variation in toxicity
related to route of administration.  Toxicity is highest
by the intravenous route, followed by oral,  then dermal.
                              C-33

-------
 This  is most likely due to the  high blood and central ner-
 vous  system concentrations produced from intravenous injec-
 tion.   Oral and  dermal  toxicity is lower due to lower blood
 concentrations brought  about by resorption and storage in
 adipose tissue.   For  most  species the acute oral toxic dose
 is between  20 and 70  mg/kg.  This includes the rat, mouse,
 dog, monkey,  sheep,  and man (Hodge, et al. 1967).
    With both aldrin  and dieldrin, toxicity in animals appears
 to be related to the  central nervous system.  According
 to Hodge:

    "...a characteristic pattern has been described of stimu-
     lation,  hyperexcitability,  hyperactivity, incoordina-
     tion,  and exaggerated body movement, ultimately leading
     to convulsion, depression,  and death."
     There  apparently is a direct correlation between blood
 concentrations and  clinical signs of intoxication.  Keane,
 et al.  (1969) reported  that in  dogs, fed daily doses of
 dieldrin, the first signs  of muscle spasms occurred at 0.38
 to 0.50 jug/ml blood and convulsions at 0.74 to 0.84 jug/ml.
     The symptoms of  intoxication in man are similar to
 those found  in mice,  rats,  and  dogs.  Jager (1970) described
 the symptoms  resulting  from oral or dermal exposure that
occur from  20 minutes to 24 hours as:
    "...headache, dizziness, nausea, general malaise, vomiting,
     followed later by  muscle.twitching, myoclonic jerks
     and even convulsions.  Death may result from anoxemia."
Changes in  the electroencephalogram (EEC) usually result
after insecticide intoxication  and generally return to normal
after recovery (Hootsman,  1962).  The transitory change
                               C-34

-------
in the EEC has been challanged by several investigators
(see Burchfiel, et al. (1976)  for recent summary).  Work
carried out in Rhesus monkeys (Burchfiel, et al. 1976) using
technical grade dieldrin (4 mg/kg, i.v. one time or 1 mg/kg
i.m.  administeredonce a week for 10 weeks) demonstrated
                                                0
that dieldrin can alter the EEC for up to 1 year.
     The acute lethal dose of aldrin in man was reported
by Jager (1970) and Hayes (1971)  based on the summary of
Hodge, et al.  (1967) to be 5 g or 70 mg/kg respectively.
However, Hodge, et al. only speculated on possible human
toxic effects from a 1-year feeding study in monkeys.  It
is known that persons have recovered from acute oral doses
of 26 mg/kg aldrin and 44 mg/kg dieldrin so that the acute
lethal human dose must be somewhat higher (Hayes, 1971).
     The sub'acute or chronic toxicity of low doses of aldrin
and dieldrin to mice, rats, dogs and, to some extent, monkeys,
has been reported in many of the carcinogenicity studies
included herein.  The resulting effects include shortened
life span, increased liver-to-body weight ratio, various
changes in liver histology, and induction of hepatic enzymes.
Another effect that has been observed is teratogenicity
(Ottolenghi, et al. 1974).
     Some information is available concerning the subacute
or chronic exposure of humans to aldrin and dieldrin.  Based
on information gained from monitoring workers at the Shell
Chemical Company, Jager (1970) reported that 33.2 /ig/kg/day
can be tolerated by workers for up . to 15 years.  Above this
level some individuals may show signs of intoxication, al-
                              C-35

-------
though others can  tolerate  two  times this level.  In another
study involving 12 volunteers who ingested dieldrin for
up to two years, 3.1 ;ug/kg/day  was tolerated and produced
no increase in plasma alkaline  phosphatase activity (Hunter,
et al. 1969).
Synergism and/or Antagonism
     Since aldrin and dieldrin  are metabolized by way of
the mixed function oxidases (MFO), it must be assumed that
any inducer or inhibitor of these enzymes will affect the
metabolism of aldrin or dieldrin.  Dieldrin and other organ-
ochlorine pesticides have been  reported to induce the MFO
(Kohli, et al. 1977).  Baldwin, et al.  (1972) reported that
prefeeding low doses of dieldrin to rats altered the meta-
bolic products produced after acute dosing.  Several reports
have appeared on the combined effect of aldrin or dieldrin
on the storage of DDT in tissues (Street, 1964; Street and
Blau, 1966; and Deichmann,  et al.  1969).
     In the Deichmann, et al. (1969)  study, when aldrin
was given along with DDT or  after a plateau had been reached
in the blood and fat by chronic DDT feeding, the retention
of DDT by the blood and fat increased considerably.  The
authors suggest that this increase in tissue dieldrin concen-
trations is due to a reduced rate of excretion of DDT.
     Walker, et al.  (1972)  fed groups of mice 50 or 100
mg/kg/diet DDT or a mixture of  5 mg/kg/diet dieldrin and
50 mg/kg/diet DDT for 112 weeks.  The highest incidence
of tumors was in the dieldrin/DDT group, although it is
difficult to determine whether  the effect between dieldrin
and DDT was additive or synergistic.
                              036

-------
     Clark and Krieger (1976) studied the metabolism and
tissue accumulation of   C-labelled aldrin (99.3 percent
purity) in combination with an inhibitor of oxidative bio-
transformation (i.e., SKF 525-A).  They reported that pre-
treatment of male Swiss-Webster mice with either 50 or 100
mg/kg SKF 525-A significantly "increased the accumulation
of radioactivity in the blood, brain, kidney, and liver.
The SKF 525-A blocked the epoxidation of aldrin to dieldrin.
However, the authors did not feel that differences in meta-
bolite formation or excretion alone could account for the
increased accumulation in the tissues.
Teratogenicity
                                                14
     In 1967, Hathaway, et al. established that   C-dieldrin
could cross the placenta in rabbits.  Eliason and Posner
                            14
(1971a,b)  demonstrated that   C-dleldrin crossed the placenta
in the rat and that the concentration in the maternal plasma
increased as gestation progressed.  Deichmann (1972)  reported
that 25 mg/kg/diet aldrin and dieldrin fed to mice for six
generations markedly affected such parameters as fertility,
gestation, viability, lactation,  and survival of the young,
while mice fed lower doses showed fewer or no effects.
     In a study by Ottolenghi, et al. (1974)  pregnant golden
hamsters and pregnant CD-I mice were given single oral doses
of purified aldrin, dieldrin, or  endrin at one-half the
LD50 (hamsters 50, 30, 5 mg/kg, and mice 25,  15, 2.5 mg/kg,
respectively).  The hamsters were treated orally on day
seven,  eight, or nine of gestation and the mice on day nine.
All three pesticides caused a significant increase in fetal
                              C-37

-------
 death  in  hamsters  treated  on  days  seven and eight.  Only
 dieldrin  gave  significant  results  on day nine.  Hamsters
 treated on  day eight  also  had the  highest number of anomalies
 (i.e., open eye, webbed  foot,  cleft palate, and others).
 These  increased anomalies  were noted for all three pesticides.
 The  three pesticides  also  reduced  the fetal weight in the
 hamsters  treated on the  three different days.  No significant
 difference  was observed  in the weight or survival of fetuses
 of treated  and control mice;  however, a teratogenic effect
 was  observed in mice  for all  three pesticides.  It was less
 pronounced  in  the  mice than in the hamsters.  The author
 reasoned  that  the  reduced  teratogenic effect in mice may
 be due to the  lower doses  used in  the mice.
   'Two  later studies on  the  teratogenicity of dieldrin
 have reached different conclusions.  The studies of Chernoff,
 et al. (1975)  and  Dix, et  al.  (1977) both concluded that
 dieldrin  was not teratogenic.  Chernoff, et al. tested diel-
 drin  (87  percent purity) and  the photo-product, photodiel-
 driri  (95  percent, purity) in CD-I mice and CD rats orally
 at doses  lower than those  used by  Ottolehghi, et al. (1974).
The  actual  doses of dieldrin  based on 87 percent purity
were 1.3, 2.6,  and 5.2 mg/kg/day over a ten-day period  (i.e.,
days 7 to 16 of gestation).   The compounds were dissolved
 in peanut oil.  The control animals also received peanut
oil.   The highest  doses of dieldrin produced 41 percent
mortality in rats.  In mice the highest doses induced signi-
 ficant increases in liver-to-body.weight ratios, reduced
 the weight  gain, and  produced  some fetal toxicity.  Photodiel-
                               C-38

-------
drin at 0.6 mg/kg/day for 10 days also induced a significant
increase in the liver-to-body weight ratio in rats but caused
no fetal toxicity.  However, no teratogenic effects were
observed in the mice or rats at any of the doses employed.
     Dix, et al. (1977) examined the use of two solvents
(corn oil and dimethylsulfoxide (DMSO))  with various doses
of dieldrin in CF1 mice.  The corn oil groups received 1.5
or 4.0 mg/kg/day of 99 percent pure dieldrin orally with
suitable controls of corn oil or no treatment,  The DMSO
groups received 0.25, 0.5, or 1.0 mg/kg/day with similar
controls.  Both solvent groups were treated on days 6 through
14 of gestation.  In the corn oil group, young (7-week)
virgin animals were used and the pregnancy rate was very
low.  With the few animals that survived to term, the only
significant effect was delayed ossification in the mice
administered the 4 mg dose.  The DMSO experiments were con-
ducted with older animals (ten weeks) of proven fertility.
These animals demonstrated a significant increase in inci-
dences of delayed ossification and extra ribs.  However,
the DMSO controls also had a high incidence of these two
anomalies.  The authors attributed this to the toxic effect
of this solvent.  DMSO also produced a reduction in maternal
and fetal body weights whereas the corn oil did not.  No
differences were observed in the mean litter size, number
of resoprtions, or fetal death with either solvent.
                              039

-------
Mutagenicity

     Relatively little work has been done on the mutageni-

city of aldrin or dieldrin.  Of the limited data available,

most are concerned with the mutagenicity of dieldrin.  This

may be sufficient, since aldrin is readily converted to

dieldrin in both in vivo and j.£ vitro systems.  Fahrig (1973)

summarized the microbial studies carried out up to 1973

on aldrin, dieldrin, and other organochlorine pesticides

including DDT and the metabolites of DDT.  Aldrin and diel-

drin gave negative results with gene conversion in Sacchar-

omyces cerevisae, back-mutation in Serratia marcescens,

forward mutation (Gal Rs)  in Eschericia coli and forward

mutation to streptomycin resistance in E^ coli.  It is impor-

tant to note that DDT and  several of its metabolites also

gave negative results in these microbial tests and that

no mention of any type of  activation system (i.e., mammalian

liver enzymes) was made in this summary.

     Bidwell, et al. (1975) reported in an abstract that

dieldrin was not found to  be mutagenic in five strains of

Salmonella typhimurium with or without the addition of a

liver activation system, although the authors did not give

dose levels.  They also stated that dieldrin was negative

in the host-mediated assay, blood and urine analysis, micro-

nucleus test, metaphase analysis, dominant lethal test,

and heritable translocation test.  The doses used were 0.08,

0.8, and 8.0 mg/kg in corn oil with corn oil used as the

control and triethylene melamine  (0.5 mg/kg five times)

serving as the positive mutagenic control.  The pesticide

was given orally on a subacute basis.
     i •

                               C-40

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     Three reports on the mutagenicity of aldrin or dieldrin

have recently been published.  The first examined the mutagen-

icity of dieldrin and several other pesticides with four

strains of S^ typhimurium (i.e., TA1535, TA1536, TA1537,

and TA1538) with the addition of a rat liver activating

system (Marshall, et al.  1976) .  The second, an in-depth

study of nearly 200 pesticides,  utilized several microbial

indicators and, in some cases, the addition of an activating

system (Shirasu, et al.  1977).   The third study dealt pri-

marily with strains of S^ typhimurium (TA1535, TAlOO, and

TA98) plus a mouse liver activating system (Majumdar, et

al. 1977) .

     In the Marshall, et al.  (1976) study, dieldrin was

tested at only one concentration, 1000 ug per plate, with

and without the addition of phenobarbital-induced rat liver

homogenate.  In all four strains tested, no increase in

mutagenicity was observed at this concentration.

     Shirasu, et al. (1977)  assayed aldrin with metabolic

activation using £_._ coli B/r WP2 try-hcr+ and WP try-hcr~

and S^ typhimurium strains TA1535, TA1537, TA98, and TAlOO.

Dieldrin was assayed without metabolic activation using

the E^ coli WP2 hcr + , WP2 her" and S^ typhimurium TA1535,
                                              »
TA1536, TA1537, and TA1538.   According to the authors, both

aldrin and dieldrin were considered non-mutagenic in these

tests.

     Majumdar, et al.  (1977), on the other hand, have reported

that dieldrin was somewhat mutagenic for S_._ typhimurium

strains TA1535, TAlOO, and TA98 without metabolic activation
                              C-41

-------
and  that  it  was  strongly mutagenic  for  all  three strains
when  liver enzymes  from Aroclor-1254*-induced mice were
added to  the mixtures.
      In summarizing the limited  microbial mutagenicity studies
on aldrin and dieldrin, it  must  be  mentioned that the only
reference to any mutagenicity  in the Majumdar studies con-
tains several notable  inconsistencies.  The inconsistencies
are:  (1)  the cultures  used  were  grown for 24 hours rather
than  the  recommended 16 hours;  (2)  the  plates were incubated
for 72 hours rather than the conventional 48 hours; and
(3) the control  values  for  TA1535 and TA98 were not consis-
tent  with those  recommended by Ames, et al.  (1975).
      It is not possible to  say that these inconsistencies
    '-» •,'
could account for the  positive mutagenic findings but they
should be taken  into consideration  in view of the fact that
several other similar,  although  not identical, studies re-
ported no mutagenic findings with dieldrin.  It should be
kept  in mind that mice  apparently metabolize dieldrin differ-
ently than do rats  (see the Metabolism  section of this report).
It is possible that the use of the  mouse liver enzymes by
Majumdar, et al. (1977)  may be producing a mutagenic metabolite
not seen  in  other studies.
      Studies on  the mutagenic effects of dieldrin in organ-
isms  other than  microorganisms were also somewhat varied.
Scholes (1955) reported that dieldrin had no effect on onion
root  mitosis.  However,  Markaryan  (1966) observed an increase
*Aroclor-1254 is a  mixture  of PCB's, which  induce the MFO
in liver  (Ames,  et   al.  1975).
                               C-42

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 in the cytogenic effects of dieldrin in mouse bone marrow
 nuclei and Bunch and Low (1973)  reported chromosomal aberra-
 tions in semi-domestic mallard ducks.
      .gecently,  Majumdar, et al.  (1976)  studied (1) the effect
 of dieldrin on  chromosomes in mouse bone marrow iin vivo
 and in'cultured human WT-38 lung cells, and (2) the cyto-
 pathic effect of dieldrin on the cultured human WI-38 cells.
 They reported a decrease in the mitotic index in both the
 iS v^-vo mouse bone  marrow and in vitro human lung cells
 with the increasing concentration of dieldrin used.  In
 each test, an increase in chromosome aberrations was observed
 with the lowest doses employed (1 mg/kg in mouse bone marrow
 and 1 jug/ml in  human cell cultures).  The authors also re-
 ported a dose-  and  time-dependent cyt:otoxic effect on the
 WI-38 human 'lung cells.
      In addition, Ahmed, et al.  (1977)  measured unscheduled
• DNA synthesis (UDS)  in SV-40 transformed VA-r4 human fibro-
 blasts in vitro with and without an uninduced rat liver
 activating system using  aldrin,  dieldrin, DDT, and other
 pesticides.   Both aldrin and dieldrin produced a significant
 increase in UDS either with or without the activating system
 at all £he doses used.
 Carcinogenicity        —
      During the 1960's and the early part of the 1970's,
 numerous studies on the  carcinogenicity of aldrin and diel-
 drin appeared in literature.  These reports include studies
 on mice, rats,  dogs,  and monkeys.   Of these species,  mice
 appear to be the most susceptible to aldrin/dieldrin.  Various
                               C-43

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strains of both sexes have been examined at different dose



levels.  The effects range from benign liver tumors to hepat-



ocarcinogenicity with transplantation confirmation to pul-



monary metastases.  The data on carcinogenicity have been



evaluated and discussed extensively, mainly by Epstein (1975a,b,



1976).



     Six major studies using various strains of mice have



been carried out mainly by long-term feeding at low doses



(i.e., 0.1 to 20 mg/kg in the diet).  The earliest of these



studies was conducted by the U.S.  Food and Drug Administ-



ration (FDA) (Davis and Fitzhugh, 1962) .  Using C-jHeB/Fe



(C-aH) mice, both males and females were fed either aldrin



or dieldrin at 10 mg/kg in the diet for two years.  Both aldrin



and dieldrin shortened the average life span by two months.



The experimental and control group death rate was high,



possibly due to overcrowding.  Significantly more hepatomas



were observed in the treated groups than in the controls



for both sexes.  In addition, the number of mice with tumors



may have been underestimated due to the high mortality which



left fewer animals for evaluation.



     In an FDA followup study, Davis (1965) examined 100



males and females of the C-jH mice treated with aldrin or



dieldrin at the same concentrations as the first study.



Again, survival was reduced compared to the control group



and there was an increase in benign hyperplasia and benign



hepatomas.  A re-evaluation of the histological material



of both of these studies was carried out by Rueber in 1973



(Epstein, 1975a,b, 1976) .  He concluded that the hepatomas
                              C-44

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were malignant and that both aldrin and dieldrih were hepato-
carcinogenic for male and female, CoH mice.
     In a 1964 abstract/ Song and Harville reported some
indication of hepatocarcinogenicity in CjH ancj CBA mice
with aldrin (15 mg/kg) and dieldrin (15 mg/kg) although
minimal data are given.  Epstein (1975a,b, 1976) reviewed
an unpublished study of MacDonald, et al. on technical grade
dieldrin in Swiss-Webster mice.  The authors concluded that
dieldrin was noncarcinogenic but that there was some quest-
ions as to the type of lesions.
     Walker, et al. (1972) conducted a multi-part study
of dieldrin in CF1 mice of both sexes.  In this study, the
dieldrin used was 99+ percent pure and 4-aminq-2,3-dimethy-
lazobenzene (ADAB) was used as the positive control.  In
ttte first part of the study, diets were prepared containing
0, 0.1, 1.0, and 10 mg/kg dieldrin although 0.01 mg/kg diel-
drin was found in the control  (0 mg/kg) diet along with
low concentrations of other pesticides.  The treatment groups
were made up of 600, 250, 250, and 400 mice respectively
and contained equal numbers of males and females.  The ADAB
group, which contained 50 mice equally divided as to sex,
received 600 mg/kg/diet for six months.  Initially, the animals
were housed five to a cage, but after the sixth week they
were placed in individual cages.  The pqsitive controls
were maintained separately from the other groups.  After
nine months, the mice receiving 10 mg/kg in the diet dieldrin
demonstrated palpable intrar-abdominal masses, and by the
fifteenth month, half the males and females in the group
                              C-45

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had died or had been killed when the masses became large.
This period of 15 months is short compared to the 20 to
24 months that elapsed before one-half of the control group
had died.  The life spans of members of the 0.1 mg/kg and
1.0 mg/kg groups were similar to those of the controls.
All the ADAB mice were dead by the 15th month.
     An increased number of liver tumors was observed at
all the concentrations of dieldrin including 0.1 mg/kg,
with the highest increase occurring in the 10 mg/kg group.
The tumors were classified by the authors as type (a) "...solid
cords of closely packed parenchymal cells with a morphology
and staining affinity little different from the rest of
the parenchyma" or  (b) "...areas of cells proliferating
in confluent sheets and often with foci of necrosis.  These
lesions were distinguished from the previous types of growth
by the presence of areas of papilliform and adenoid formations
of liver cells with wide and irregular vascular channels
within the growth."  This classification appears somewhat
arbitrary.  Nonetheless, the presence of tumors was dose-
related and effects were detected at the lowest dieldrin
level tested (0.1 mg/kg).  In addition to the increase in
hepatic tumors there was an increase in the incidence of
tumors at other sites.
     In the second part of the Walker, et al. (1972) study,
groups of 30 male and 30 female CFl mice received ethylene
oxide-sterilized diets containing 1.25, 2.5, 5, 10, or 20
mg/kg dieldrin for 128 weeks.  The control group consisted
of 78 males and 78 females and the conditions and observa-
                              G-46

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tions were similar to those in the first experiment.  In

this part of the study, the mice that received 20 mg/kg

dieldrin in the diet had a high mortality rate.  About 25

percent of the males and 50 percent of the females showed

signs of intoxication and died during the first 3 months.

Liver masses were detected at 36 weeks, and all the mice

either died or were killed at 12 months.  Masses were not

detected until 40 weeks in the 10 mg/kg mice, 75 weeks in

the 5 mg/kg mice, and 100 weeks in the 2.5 mg/kg mice.

In the 10 and 20 mg/kg groups, few animals were available

for examination due to the acute toxieity or their being

used in another study.  The 5 mg/kg group had a higher incidence

of tumors than the 2.5 mg/kg group.

     The third part of the study was carried out under simi-

lar conditions.  Groups of 60 mice received gamma-irradiated
                      i
diets containing 0 or 10 mg/kg/diet dieldrin for 120 weeks.

Also, groups of 48 mice received gamma-irradiated diets

and litter for 110 weeks or unsterilized diets and litter

for 104 weeks.  The authors stated that; liver enlargement

occurrence and mortality were similar to those of the previous

study.

     The next section of the Walker, et al.  (1972) study

concerned the combined effect of dieldrin and DDT treatment

on CFl mice.  Initially, the mice were fed diets containing

200 mg/kg DDT or 10/200 mg/kg dieldrin/DDT.  This resulted

in high mortality.  The diets were subsequently reduced

to 50 and 100 mg/kg DDT and 5/50 mg/kg dieldrin/DDT.  There

were 47 males and 47 females in the control group and 32
                              C-47

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males and 32  females  in  each of the treatment groups.  In



mice on the 5/50 mg/kg diet and 100 mg/kg DDT diet, liver



enlargements  were detected after 65 weeks of exposure.



Both of these doses were toxic to males but only the 5/50



mg/kg dose was  toxic  to  females.  At 50 mg/kg DDT, masses



were detected by the  96th week but the mortality was similar



to that of the  controls.  In this experiment, the highest



incidence of  liver tumors was in the dieldrin/DDT group.



However, because only one combination was tested, it is



difficult to determine whether the effect was synergistic



or additive.  In a re-evaluation of the experiment, Reuber



(see Epstein, 1975a,b, 1976), believes that Walker, et al.



(1972) over-estimated the incidence of liver tumors in the



control and DDT groups,  thus minimizing the effect of the



combined dieldrin/DDT.



     In the last section of the Walker, et al.  (1972) study,



groups of 58 mice were fed dieldrin at 10 mg/kg for 2, 4,



8, 16, 32, and  64 weeks  and sacrificed after 2 years.  The



control group consisted  of 156 mice.  All groups were equally



divided between males and females.  In the mice receiving



dieldrin for 64 weeks, liver enlargements were detected



after 60 weeks  in six males and two females.  These enlarge-



ments remained  after  the termination of the feeding.  No



other enlargements were  detected and the mortality of all



the groups was  similar throughout the 2 years.  It is import-



ant to note that type b  tumors were detected after only



4 or 8 weeks of treatment and that the liver enlargements



did not appear  after  the feeding was terminated.
                              C-48

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     A similar study of dieldrin and other chemicals in



CFl mice was carried out by the same group (Thorpe and Walker,



1973).  The treatment groups were comprised of 30 males



and 30 females and the controls of 45 mice of each sex.



Dieldrin was tested at one concentration  (10 mg/kg/diet)



only, and the animals were not sacrificed when abdominal



masses were large as in the previous studies.  The study



was terminated after 100 weeks of feeding.  The authors



reported that there were no signs of intoxication in the



dieldrin groups; however, mortality increased after 22 months



of exposure.  Also liver enlargements were detected in both



sexes by the 50th week.  In this study, the cumulative tumor



incidence and the number of dead mice were given at 17,



21, 25, and 26 months.  Dieldrin at 10 mg/kg produced a



high incidence of liver tumors.  All the males and one-half



the females that had died by 17 months had liver tumors.



By the end of the study, 100 percent of the males and 87



percent of the females had liver tumors.



     In a recent evaluation of both aldrin and dieldrin



by the National Cancer Institute, aldrin and dieldrin were



found to produce hepatic carcinomas in male mice.  Female



mice responded to low doses of dieldrin, but showed no effects



from aldrin.  No carcinomas were observed in either male



or female rats of two different species (43 FR 2450 when



the subjects were exposed to both aldrin and dieldrin.



In the study on mice, groups of 50 male and 50 female BgC-jF-^



mice were fed either aldrin (technical grade) or dieldrin



(technical grade) at various doses.  The females received
                              049

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aldrin at 3 and 6 mg/kg/diet and the males received aldrin



at 4 and 8 mg/kg.  Both  sexes were given dieldrin at 2.5



and 5 mg/g.  Aldrin controls consisted of 20 untreated males



and 10 females and dieldrin controls had 20 animals per



group.  In addition, pooled controls consisted of 92 males



and 78 females.  The animals were fed the pesticide diets



for 80 weeks and then observed for 10 to 13 weeks.  All



survivors were killed at 90 to 93 weeks.



     In the male mice administered aldrin, there was a signif-



icant, dose-related increase in the incidence of hepatic



carcinomas.  The values  were: matched controls 3/20 (15



percent); pooled controls 17/92 (19 percent); 4 mg/kg 16/49



(33 percent); and 8 mg/kg 25/45 (56 percent).  The mean



body weights of the aldrin- and dieldrin-fed mice were similar



in the control and treated groups. - There was a dose-related



mortality in female mice at the high dose of aldrin.  With



the male mice fed dieldrin, a significant increase in hepatic-



carcinomas was observed  in the 5 mg/kg group.  The incidences



were 12/50  (24 percent)  for the 2.5 mg/kg group and 16/45



(36 percent) for the 5 mg/kg group.



     There have also been six carcinogenicity studies of



aldrin and/or dieldrin done in various strains of rats.



In an early paper by Treon and Cleveland (1955) aldrin and



dieldrin were fed to male and female Carworth rats at 2.5,



12.5, and 25 mg/kg.  The authors reported a significant



increase in mortality and an increase in liver-to-body weight



ratios at all concentrations tested.  No data on tumor in-



cidences were given, although some liver lesions were detected,
                              C-50

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Later Cleveland (1966)  summarized the work on aldrin and



dieldrin conducted at the Kettering Laboratory.  Although



little data and details were given, Cleveland stated that



aldrin and dieldrin were not tumorigenic in their rat studies.



     A study was carried out by the U.S. Food and Drug Admin-



istration on aldrin and dieldrin in rats and dogs (Fitzhugh,



et al. 1964) to determine the toxicity of these pesticides.



Groups of 12 male and 12 female Osborne-Mendel rats were



fed diets containing either aldrin (99+ percent purity)



or dieldrin (100 percent purity) at 0, 0.5, 2, 10, 50, 100,



or 150 mg/kg for two years.  The animals were housed individually



and the survivors were killed after two years.  None of



the dose levels of aldrin or dieldrin affected the growth



of the rats but both chemicals at 50 mg/kg or greater reduced



the survival.   A significant increase in liver-to-body weight



ratios was observed in both males and females for several



doses of both chemicals.  The authors reported no increase



in liver tumors; however, there was a high incidence of



multiple site tumors at lower concentrations of both aldrin



and dieldrin.



     Deichmann, et al.   (1967) carried out a study in which



5 mg/kg aldrin  (technical grade) was fed to male and female



Osborne-Mendel rats, either individually or in combination



with 200 mg/kg aramite, 200 mg/kg DDT, and 1000 mg/kg methoxy-



chlor.  There were 30 males and 30 females in each treatment



group and they were housed in pairs.  No increase in mor-



tality over the controls was observed in any of the treated



groups.  Aldrin alone had no significant effect on liver-
                              C-51

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to-body weight ratio, but an increase in the ratio was noted



in the groups treated with the pesticide mixtures.  The



authors state that one-half  (13 females and 2 males) of



the aldrin-treated rats had one tumor; however, only the



tumors in survivors were listed.



     Walker, et al.  (1969) fed dieldrin (99+ percent purity)



to Carworth rats at concentrations of 0, 0.1, 1.0, and 10



rng/kg in the diet for two years.  There were 25 males and



25 females in each treatment group and 45 rats of each sex



in the control group.  The animals were housed individually



and dying animals were killed and examined.  The authors



reported that some irritability, tremors, and convulsions



occurred after two to three months but that the animals



remained in good health for the two years.  None of the



dieldrin doses had any effect on body weight.  Mortality



was the same for the control and treated groups; however,



all the groups had an overall, high rate of mortality.



This resulted in only a few animals being available for



examination at the conclusion of the feeding.  At 1 and



10 mg/kg there were increases in liver-to-body weight ratios.



Only one male rat and four female rats at the 10 mg/kg level



demonstrated any liver cell changes.  However, at the 0.1



and 1.0 mg/kg levels there were high but not significant



increases in total tumors even though few animals were examined



histologically.



       In another study with the Osborne-Mendel rat, Deichmann,



et al. (1970) examined aldrin, dieldrin, and endrin in a



lifetime exposure.  Aldrin (technical, 95 percent) and dieldrin
                               C-52

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(technical*, 100 percent active ingredients) were fed in

the diet to groups of 50 males and 50 females.  The concentra-

tions during the first two weeks were 10, 15, and 25 mg/kg

aldrin and 10, 15, and 25 mg/kg dieldrin.  After this time

all the dose concentrations were doubled for the remainder

of the treatment time.  The control groups contained 100

rats of each sex.  Any animals that appeared ill were sacrificed,

Both aldrin and dieldrin produced some dose-related toxicity,

tremors, and clonic convulsions, especially in females.

However, these doses had no effect on mean gain in body

weight although some animals had marked loss of weight.

The mean survival rate was somewhat lower in the aldrin

and dieldrin rats; again, predominantly in females receiving

the high concentrations.  There were significant increases

in liver-to-body weight ratios in males fed aldrin at 30

and 50 mg/kg and dieldrin at 30 mg/kg and a significant

decrease in liver-to-body weight ratios in females fed aldrin

at 20 mg/kg.  A moderate increase in hepatic centrilobular

cloudy swelling and necrosis was observed in both male and

female rats fed aldrin and dieldrin as compared to the controls.

However, there was no increase in the number of liver tumors

or other site tumors.  In fact, a decrease in total tumors

was observed in both the males and females fed aldrin and

dieldrin.  The authors stated that this was possibly due

to increased microsomal enzyme activity.  It should be noted

that limited re-evaluation of this data was carried out
*This is somewhat contradictory since "technical" diel-
drin is actually 85 percent  pure.
                              C-53

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by Reuber who disagreed with the findings of Deichmann,



et al.  (1970).  However, he re-evaluated only one group



(dieldrin, 30 mg/kg) and there has been no independent re-



evaluation of the material.



     A  two-year study by the National Cancer Institute (1976) (43



FR 2450) studied the effects of technical grade aldrin and



dieldrin on Osborne-Mendel and Fisher 344 rats.  The first



part of the study used groups of 50 Osborne-Mendel rats



of each sex for aldrin  (30 or 60 mg/kg) and dieldrin (29



or 65 mg/kg).  Aldrin was fed to the males for 74 weeks.



The rats were then observed for an additional 37 to 38 weeks.



All survivors were killed at 111 to 113 weeks.  The same



doses of aldrin were administered to the female rats for



80 weefcs, followed by 32 to 33 weeks of observation.  All



survivors were killed at 111 to 113 weeks.  The dieldrin



rats were treated for 59 weeks at 65 mg/kg followed by 51



to 52 weeks of observation, or 80 weeks at 29 mg/kg followed



by 30 to 31 weeks of observation.  All survivors were killed



at 110  to 111 weeks.  For both pesticides, the controls



consisted of 10 untreated rats of each sex plus pooled controls



consisting the matched control groups combined with 58 untreated



males and 60 untreated females from similar bioassays of



other chemicals.



     During the first year of the rat studies, the mean



body weights for the aldrin-and dieldrin-fed rats did not



differ  from those of the controls.  However, during the



second  year, the body weights of the treated rats were lower
                              C-54

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than those of the untreated.   For both aldrin and dieldrin,


no significant increase in hepatic carcinomas was observed


in either sex.  There was a significant increase in adrenal


cortical adenoma in the low-dose aldrin- and dieldrin-treated


female rats.


     In the second part of the study on rats, 24 male and


24 female Fisher 344 rats were fed purified dieldrin at


2, 10, or 50  mg/kg for 104 to 105 weeks.  Matched controls


consisted of  24 rats of each sex.  All survivors were killed


at 104 to 105 weeks.  The body weights of the treated and


control rats  were similar and survival was not greatly affected.


The high-dose males and females demonstrated signs of intox-


ification at  76 and 80 weeks, respectively.  A variety of


neoplasms occurred in both the control and treated rats;


however, there were no significant dose-related increases
                         •

in the neoplasms.


     There has been minimal work on the carcinogenicity


of aldrin or  dieldrin in dogs.  A limited, short-term study


was conducted by Treon and Cleveland  (1955).  Aldrin and


dieldrin were fed to two male and two female beagles at


1 and 3 mg/kg/diet.  The dogs were killed between 15 and


16 months.  Although the growth rates of the treated dogs


were similar  to those of the controls, liver weights were


increased at 1 mg/kg.  These doses were toxic to the dogs


and mortality was high.  The study provides few data on


the necropsy and the treatment was too short to adequately


evaluate carcinogenicity.
                             C-55

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     In another study using dogs, Fitzhugh, et al. (1964)



treated 26 animals with aldrin or dieldrin at dosages of



0.2 to 1.0 mg/kg/day, 6 days a week, up to 25 months.  At



doses of 0.5 mg/kg and greater, toxic effects including



weight loss, convulsions, and death were observed.  At 1



mg/kg/day or higher no animals survived over 49 days, and



at 2.5 and 10 mg/kg/day all dogs died within 10 weeks.



However, dogs fed 0.2 mg/kg/day of aldrin and dieldrin showed



no ill-effects during the 2 years of the study.  In the



dogs fed aldrin at 1.0 mg/kg/day and dieldrin at 0.5 mg/kg/day,



fatty degeneration was observed in the liver and kidneys.



This study also was too short-termed to determine tumori-



genic properties of aldrin and dieldrin.  The number of



animals surviving at the end of the study was inadequate



to make any type of evaluation.



     A third short-termed study on dieldrin in dogs was



carried out by Walker, et al.  (1969) .  Dieldrin (99+ percent



purity) was administered to groups of five male and five



female dogs in gelatine capsules at 0.005 and 0.05 mg/kg/day.



After two years, the health and body weight of the treated



dogs, as compared to the controls, was normal.  A variety



of physiological tests confirmed the general good health



of the dogs.  In dogs- administered the higher concentration



of dieldrin, liver-to-body weight ratios were increased



significantly over the controls.  The report stated that



no lesions were seen in the tissues but provided no data



on this.



     There has been one report on the effects of dieldrin



on Rhesus monkeys.  The work of Zavon in 1970, which appears





                               C-56  •           >.

-------
to be unpublished, has been summarized by Epstein (1975b).
Epstein reports that six control monkeys (five male, one
female) and groups of five monkeys each received 0,  0.1,
0.5, 1.0, and 1.75 mg/kg dieldrin in their diet for 5.5
to 6 years.  The group at 1.75 mg/kg received 5.0 mg/kg
for 4 months, then 2.5 mg/kg for approximatley 2.5 months,
and then 1.75 mg/kg for the remainder of the exposure.
Epstein further states that four of the monkeys died during
the study, two of which had received 5 mg/kg.  The remaining
animals survived until they were killed.  No data on his-
tology are given although it is reported that no differences
were observed between control and treated monkeys.
     Versteeg and Jager (1973) summarized health studies
carried out on pesticide workers in the Shell plant in Holland,
These workers had occupational exposure to aldrin/dieldrin
over periods of up to 12.3 years with a mean of 6.6 years.
The average time that had elapsed from the end of exposure
was 7.4 years (maximum, 16 years).  The average age of the
group was 47.4 years.  The report states that 233 long-term
workers were involved in this study and that no permanent
adverse effects (including cancer) on the workers' health
were observed.
     Epstein (1975a) states that the epidemiological aspects
of the study carried out by Shell have been reviewed by
several experts who have criticized the study as inadequate
due to the number of workers at risk and the short duration
of exposure and/or time after exposure.
                              C-57

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                    CRITERION FORMULATION


 Existing Guidelines and Standards

     Prior to 1974, aldrin and dieldrin were approved for

use on 46 agricultural crops and for treatment of soil around

fruits, grains, nuts, and vegetables (Int. Agency Res.

Cancer, 1974a,b).  In 1974 the registration of aldrin and

dieldrin was suspended on the basis of adverse health affects

in rodents (39 FR 37251).  As a result, production  is restricted

for all pesticide products containing aldrin or dieldrin.

Aldrin and dieldrin can  no longer be used for spraying and

dusting, or for mothproofing in which the residues  are dis-

charged into waterways.  All uses in structures occupied

by humans or livestock,  uses upon turf, and any use involving
                                                   f
application to any aquatic environment are also restricted.

Aldrin and dieldrin can  be used for termite treatment which

involves direct application to the soil and therefore little

movement of the pesticides.  They may also be used  for treat-

ment of some non-food seeds and plant dipping during trans-

plantation.

     The current exposure level for both aldrin and dieldrin

set by the Occupational  Safety and Health Administration

is an air time-weighted  average (TWA) of 250 ;ug/m   for skin

absorption (37 FR 22139).  In 1969, the U.S. Public Health

Service Advisory Committee recommended that the drinking

water standards for both aldrin and dieldrin be 17 /ag/1

(Mrak, 1969).  Also, the U.N. Food and Agriculture  Organization/World

Health Organization's acceptable daily intake for aldrin

and dieldrin is 0.0001 mg/kg/day (Mrak, 1969).
                               C-58

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Current Levels of Exposure



     The people of the United States are exposed to aldrin



and dieldrin in air, water, and food.  As mentioned earlier,



aldrin or dieldrin has been found in more than 85 percent



of the air samples tested by the U.S. EPA (Epstein, 1976).



The levels were as high as 2.8 ng/m  resulting in an intake



of up to 0.098 jug/day.  Dieldrin can travel great distances



in the air, especially when absorbed to particulate matter.



Thus people can potentially be exposed to pesticide treat-



ments from other countries.



     Waters recently sampled in the United States contained



aldrin or dieldrin in amounts up to 0.05 jig/1 (Harris, et



al. 1977).  The standard diet in the United States has been



calculated to contain approximately 43 ng/g of dieldrin.



According to Epstein  (1976) tolerances for dieldrin in cattle-



meat fat, milk fat, meat, and meat by-products have been



petitioned for at levels of 0.3, 0.2, and 0.1 ppm respectively.



Special Groups at Risk



     Children, especially infants, have a high dairy product



diet that has been shown to contain dieldrin  (Manske and



Johnson, 1975).  It has also been demonstrated that human



milk contains dieldrin residues and that some infants may



be exposed to high concentrations of dieldrin from that



source alone  (Savage, 1976).



     In early studies, Curley, et al. (1969) and Zarvon,



et al.  (1969) reported that dieldrin and several other chlori-



nated hydrocarbon pesticides were present in the tissues



of stillborn infants.  Curley, et al. also reported that
                              C-59

-------
dieldrin and other pesticides could be  found  in  the  blood

of newborn infants.

     No work has been carried out on neonatal  animals with

either aldrin or dieldrin; however, due  to  the sensitivity

of neonatal animals to other carcinogens, this should be

an area of great concern.
Basis and Derivation  of Criterion
     The aldrin and dieldrin carcinogenicity data of Walker,

et al. (1972) and  the National Cancer Institute  (1976) were

analyzed using a linear dose-response model to calculate

that concentration of dieldrin in water  which  is estimated

to result in an excess lifetime  risk of  10"  in man  (see

Appendix I).  It should be noted that Walker,  et al. study

used 99 percent pure dieldrin while the  NCI study used techni-

cal grade dieldrin.

     Under the .Consent Decree in NRDC vs. Train, criteria

are to state "recommended maximum permissible  concentrations

(including where appropriate, zero) consistent with  the

protection of aquatic organisms, human  health, and recreation-

al activities."  Both aldrin and dieldrin are  suspected

of being human carcinogens.  Because there  is  no recognized

safe concentration for a human carcinogen,  the recommended

concentration of aldrin/dieldrin in water for  maximum protection

of human health is zero.

     Because attaining a zero concentration level may be

infeasible in some cases and in  order to assist  the  Agency

and States in the  possible future development  of water quality

regulations, the concentrations  of aldrin and  dieldrin corre-
                             C-60

-------
     spending to several incremental lifetime cancer risk levels

     have been estimated.   A cancer risk level provides an estimate

     of the additional incidence of cancer that may be expected

     in an exposed population.   A risk of 10~  for example, indi-

     cates a probability of one additional case of cancer for

     every 100,000 people exposed, a risk of 10   indicates one

     additional case of cancer  for every million people exposed,

     and so forth.

          In the Federal Register notice of availability of draft

     ambient water quality criteria, EPA stated that it is con-

     sidering setting criteria  at an interim target risk level

     of 10" , 10   or 10   as shown in the table below.
Exposure Assumptions           Risk Levels and Corresponding Criteria^ '

                               0_      1£~7         1£~6        1£~5

2 liters of drinking water
and consumption of 18.7
grams of fish and shellfish (2)

     Aldrin                    0   4.6 x 10"4   4.6 x 10~3  4.6 x 10~2


     Dieldrin                  0


Consumption of fish
and shellfish only.

     Aldrin                    0   4.6 x 10~4   4.6 x 10~3  4.6 x 10"2
                                     ng/1         ng/1        ng/1

     Dieldrin                  0   4.5 x 10~4   4.5 x 10~3  4.5 x 10~2
                                     ng/1         ng/1        ng/1

     (1)  Calculated by applying a modified "one hit" extrapolation

     model described in the FR 15926, 1979.  Appropriate bioassay

     data used in the calculation of the model are presented

     in Appendix I.  Since the extrapolation model is linear


                                   C-61
ng/1
4.4 x 10~4
ng/1
ng/1
4.4 x 10~3
ng/1
ng/1
4.4 x 10~2
ng/1

-------
    to low doses, the additional lifetime risk is directly propor-

    tional to the water concentration.   Therefore, water concen-

    trations corresponding to other risk levels can be derived

    by multiplying or dividing one of the risk levels and corres-

    ponding water concentrations shown  in the table by factors

    such as 10, 100, 1,000, and so forth.

    (2)   99.9 percent of aldrin exposure results from the consump-

    tion of aquatic organisms which exhibit an average bioconcen-

    tration potential of 4500 fold.  The remaining 0.1 percent

    of aldrin exposure results from drinking water.

         Ninety-eight percent of dieldrin exposure results from

    the consumption of aquatic organisms which exhibit an average

    bioconcentration potential of 4500  fold.  The remaining

    2 percent of dieldrin exposure results from drinking water.
      0
         Concentration levels were derived assuming a lifetime
0
    exposure to various amounts of aldrin/dieldrin, (1)  occurring

    from the consumption of both drinking water and aquatic

    life grown in water containing the  corresponding aldrin/dieldrin

    concentrations and, (2) occurring solely from the consumption

    of aquatic life grown in the waters containing the corresponding

    aldrin/dieldrin concentrations.

         Although total exposure information for aldrin and

    dieldrin is discussed and an estimate of the contributions

    from other sources of exposure can  be made, this data will

    not be factored into the ambient water quality criteria

    formulation because of the tenuous  estimates.  The criteria

    presented, therefore, assume an incremental risk from ambient

    water exposure only.
                                  C-62

-------
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                               C-76

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                          APPENDIX 1

            Summary and Conclusions Regarding  the
           Carcinogenicity of Aldrin and Dieldrin*
     Aldrin has induced liver tumors  in males  and  females

of three strains of mice according to  reports  of four  separate

chronic feeding studies.  It has failed to  induce  a  statisti-

cally significant carcinogenic response in  rats at any site

according to reports of five studies  in two different  strains.

In two bacterial assays with and without activation  (S.  Typhi-

murium and E. Coli) it was found to be non-mutagenic,  but

it did produce unscheduled DNA synthesis in human  fibroblasts

with and without activation.  The induction of hepatocellular

carcinoma in both male and female mice from the administration

of aldrin leads to the conclusion that it is likely  to be

a human carcinogen.

     Dieldrin, which is readily formed from aldrin in  the

environment and by metabolism of aldrin in  rats, mice,  fish,

and many other species, has produced liver  tumors  in four

strains of mice according to six reports of chronic  feeding

studies and possible liver tumors in an unpublished  study

with a fifth strain.  In rats it has failed to induce  a

statistically significant excess of tumors  at  any  site in

six chronic feeding studies in three strains.  It was found

to be mutagenic in  S. typhimurium after metabolic activation

with mouse liver enzymes, but it was not mutagenic in  two
*This summary has been prepared and approved by the Carcinogens
Assessment Group, U.S. EPA, on July 25, 1979.

-------
other studies of  the  same  bacterial  strain  with  a  rat  liver


enzyme activation mixture.  The  induction of  hepatocellular


carcinomas  in mice  leads to the  conclusion  that  dieldrin


is likely to be a human carcinogen.


     Both aldrin  and  dieldrin have been  found  to be  non-


mutagenic in several  test  systems as  follows:  a) gene  conver-


sion in SA cerevisie;  b) back mutations  in  S.  marcescens


and c)  foward mutations at two loci  in £_._ coli.  Several


other organochlorine  pesticides  which produce  mouse  liver


tumors are also non-mutagenic in the  same systems.


     The induction  of  liver tumors in mice  of  both sexes


by aldrin and dieldrin is  sufficient  evidence  that they


are likely to be  human carcinogens.


     The water quality criterion for  aldrin is based on


the hepatocellular  carcinoma incidence in male B6C3F1  mice


of the low dose group  in the NCI chronic test, and on  the


response in the 0.1 ppm group of female CF-1 mice  in the


Walker, et al. (1972) experiment (because aldrin in converted


to and stored as  dieldrin  in fish).   It  is  concluded that


the water concentration of aldrin should be less than  4.6

    _2
x 10   ng/1 in order  to keep the lifetime cancer risk  below

  — 5
10  .  For dieldrin the criterion is  based  on  the  response


in the 0.1 ppm group of female CF-1 mice in the  Walker,


et al.  (1972)  experiment.  The corresponding concentration

                        _2
for dieldrin is 4.4 x 10   ng/1.
                              C-78

-------
             Summary of  Pertinent Data for Aldrin







     The water quality criterion for aldrin  is derived  from



the hepatocellular carcinoma response of  the B6C3F1 male



mice given the low dose of aldrin in the  NCI bioassay test,



and on the response in the 0.1 ppm group  of  female CF-1



mice in the Walker, et al. (1972) experiment.  In the NCI



study, a time-weighted average dose of 4  ppm was given  in



the feed for 80 weeks and the animals were observed for



an additional 10 weeks before terminal sacrifice.  The  inci-



dence of hepatocellular carcinoma was 3/20 and 16/49 in



the control and treated groups, respectively.  The slope



of the one-hit dose-response curve for aldrin is calculated



from the following parameters:



               n  =16        Le = 90 weeks



               Nfc =49        le = 80 weeks



               n  = 3         d = 4 ppm x 0.13 = 0.52 mg/kg/day



               N  = 20        L = 90 weeks
                c


                              w = 0.035 kg



     With these parameters the slope of the one-hit dose-



response curve for aldrin is 6.349 (mg/kg/day)~  .



     The conversion of aldrin to dieldrin in fish results



in the accumulation of dieldrin residues  in fish exposed



to aldrin.   This makes it necessary to consider  the risk



resulting from intake of dieldrin stored  in fish due to



the presence of aldrin in water.  Thus, the criterion for



aldrin also depends upon the one-hit dose-response curve



for dieldrin, which has a slope of 183.6  (mg/kg/day)~  as



calculated  previously from the talker, et al. (1972) study.
                              C-79

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     The equation describing the risk due to aldrin in water

is derived from the general relationship

         P = BUD   and    D = 1/70 kg,  thus
              ri

         P = Bu 1/70 kg    and
              rl
where
            P{70 kg) = BHI



            P = individual lifetime risk  (set at 10~  for criterion
                calculation)

            I = average daily human intake of the substance
                in question

           Bu = estimated slope of the human one-hit dose-response curve
            n
        70 kg = average weight of humans

        Since aldrin in water leads to the accumulation of

   dieldrin residues in fish, the equation describing the risk

   due to aldrin is

   Pa (70 kg) = BRa CQ (2.0 l/day)+ BRa Cfl Rad  (0.0187 kg/day) +

                  BHd Ca Rad (°-0187 k9/day)

   where

           P  = risk due to aldrin (set at 10   for criterion
            a   calculation)

          Bu  = 6.349 (mg/kg/day)~ , the aldrin dose-response slope
           tia
          BHd = 183.6 (mg/kg/day)~ , the dieldrin dose-response slope

           C  = criterion concentration for aldrin  (to be calculated)
            a
           R  = 32 I/kg, the fish bioconcentration of aldrin
                from aldrin

          R , = 4468 I/kg, the fish bioconcentration of dieldrin
           a    from aldrin

    2.0  I/day = average daily intake of water for humans

0.0187 kg/day = average daily intake of fish for humans
                              C-tfO

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The term containing Rad represents intake of dieldrin  resulting



from the presence of aldrin in the water, and  is thus  multiplied



by the dieldrin dose-response slope.  R  , is estimated by
                                       aci


assuming that in the absence of conversion to  dieldrin,



aldrin would bioconcentrate 4500 times (as dieldrin does),



and that since aldrin only accumulates 32 times, the remainder



of the expected aldrin residues are being stored as dieldrin.



     The result is that the water concentration of aldrin


                            -2
should be less than 4.6 x 10   ng/1 in order to keep the



individual lifetime risk below 10  .
                              C--dl

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             Summary  of  Pertinent  Data  for  Dieldrin







      The water quality criterion for dieldrin is based on



 the hepatocellular carcinoma response of the female CF-1



 mice given 0.1 ppm of dieldrin continuously in the diet



 in  the experiment of Walker, et al. (1972).  In that group



 the incidence of type a and type b liver tumors in the 0.1



'ppm group of females was 24 out of 90 animals, whereas in



 the controls it was  39  out of 297 animals.  Assuming a fish



 bioconcentration factor of 4500,  the parameters of the dose-



 response model are:



           nfc = 24             d = 0.1 ppm x 0.13 = 0.013 mg/kg/day



           Nfc = 90             L = 132 weeks



           n   = 39             w = 0.025 kg
           c


           NC = 297            R = 4500



           Le = 132 weeks      F = 0.0187 kg/day



           le = 132 weeks



      With these parameters the slope of the one-hit dose-



 response curve for dieldrin is 183.6 (mg/kg/day)



      The result is that the water concentration should be


                   _o
 less  than 4.4  x 10   ng/1 in order to keep the individual



 lifetime risk  below  10~ .
                                                          <3PO 860 727



                              C-JJ2

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